Trial Outcomes & Findings for An Investigational Immuno-therapy Study of Nivolumab Combined With Ipilimumab Compared to Nivolumab by Itself After Complete Surgical Removal of Stage IIIb/c/d or Stage IV Melanoma (NCT NCT03068455)

NCT ID: NCT03068455

Last Updated: 2021-09-20

Results Overview

RFS was defined as the time between the date of randomization and the date of first recurrence (local, regional or distant metastasis), new primary melanoma (including melanoma in situ), or death (from any cause), whichever occurred first. Median values based on Kaplan-Meier Estimates.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 1844 participants
• Primary outcome timeframe: From randomization to Primary Completion Date (up to approximately 3 years)
• Results posted on: 2021-09-20

Participant Flow

1844 participants randomized and 1833 treated. Reasons not treated: 1 disease progression; 2 participants withdrew consent; 1 poor/non-compliance; 4 participants no longer met study criteria; 3 not reported

Participant milestones

Measure	Arm A: Nivo + Ipi Arm A: nivolumab 240 mg IV Q2 weeks plus ipilimumab 1 mg/kg IV Q6 weeks (for 1 year of study drug treatment)	Arm B: Nivo Arm B: nivolumab 480 mg IV Q4 weeks (for 1 year of study drug treatment) with nivolumab placebo on Weeks 3, 7, 11, 15, 19, 23, 27, 31, 35, 39, 43, \& 47 and ipilimumab placebo on Weeks 1, 7, 13, 19, 25, 31, 37, 43, \& 49
Pre-treatment Period STARTED	920	924
Pre-treatment Period COMPLETED	916	917
Pre-treatment Period NOT COMPLETED	4	7
Treatment Period STARTED	916	917
Treatment Period COMPLETED	364	561
Treatment Period NOT COMPLETED	552	356

Reasons for withdrawal

Measure	Arm A: Nivo + Ipi Arm A: nivolumab 240 mg IV Q2 weeks plus ipilimumab 1 mg/kg IV Q6 weeks (for 1 year of study drug treatment)	Arm B: Nivo Arm B: nivolumab 480 mg IV Q4 weeks (for 1 year of study drug treatment) with nivolumab placebo on Weeks 3, 7, 11, 15, 19, 23, 27, 31, 35, 39, 43, \& 47 and ipilimumab placebo on Weeks 1, 7, 13, 19, 25, 31, 37, 43, \& 49
Pre-treatment Period Disease progression	0	1
Pre-treatment Period Participant withdrew consent	1	1
Pre-treatment Period Poor/non-compliance	0	1
Pre-treatment Period Participant no longer meets study criteria	1	3
Pre-treatment Period Not reported	2	1
Treatment Period Disease progression	166	208
Treatment Period Study drug toxicity	317	104
Treatment Period Adverse Event unrelated to study drug	15	7
Treatment Period Participant request to stop therapy	33	20
Treatment Period Participant withdrew consent	5	10
Treatment Period Poor/non-compliance	3	0
Treatment Period Participant no longer meets study criteria	1	3
Treatment Period Other reasons	12	4

Baseline Characteristics

An Investigational Immuno-therapy Study of Nivolumab Combined With Ipilimumab Compared to Nivolumab by Itself After Complete Surgical Removal of Stage IIIb/c/d or Stage IV Melanoma

Baseline characteristics by cohort

Measure	Arm A: Nivo + Ipi n=920 Participants Arm A: nivolumab 240 mg IV Q2 weeks plus ipilimumab 1 mg/kg IV Q6 weeks (for 1 year of study drug treatment)	Arm B: Nivo n=924 Participants Arm B: nivolumab 480 mg IV Q4 weeks (for 1 year of study drug treatment) with nivolumab placebo on Weeks 3, 7, 11, 15, 19, 23, 27, 31, 35, 39, 43, \& 47 and ipilimumab placebo on Weeks 1, 7, 13, 19, 25, 31, 37, 43, \& 49	Total n=1844 Participants Total of all reporting groups
Age, Continuous	53.8 Years STANDARD_DEVIATION 14.6 • n=5 Participants	54.6 Years STANDARD_DEVIATION 13.7 • n=7 Participants	54.2 Years STANDARD_DEVIATION 14.2 • n=5 Participants
Sex: Female, Male Female	405 Participants n=5 Participants	387 Participants n=7 Participants	792 Participants n=5 Participants
Sex: Female, Male Male	515 Participants n=5 Participants	537 Participants n=7 Participants	1052 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	22 Participants n=5 Participants	22 Participants n=7 Participants	44 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	359 Participants n=5 Participants	376 Participants n=7 Participants	735 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	539 Participants n=5 Participants	526 Participants n=7 Participants	1065 Participants n=5 Participants
Race/Ethnicity, Customized Race · White	907 Participants n=5 Participants	911 Participants n=7 Participants	1818 Participants n=5 Participants
Race/Ethnicity, Customized Race · Black or African American	4 Participants n=5 Participants	1 Participants n=7 Participants	5 Participants n=5 Participants
Race/Ethnicity, Customized Race · American Indian or Alaska Native	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized Race · Asian	3 Participants n=5 Participants	5 Participants n=7 Participants	8 Participants n=5 Participants
Race/Ethnicity, Customized Race · Other	6 Participants n=5 Participants	6 Participants n=7 Participants	12 Participants n=5 Participants

PRIMARY outcome

Timeframe: From randomization to Primary Completion Date (up to approximately 3 years)

Population: All randomized participants with completely resected stage IIIb/c/d or stage IV no evidence of disease (NED) melanoma

RFS was defined as the time between the date of randomization and the date of first recurrence (local, regional or distant metastasis), new primary melanoma (including melanoma in situ), or death (from any cause), whichever occurred first.

Median values based on Kaplan-Meier Estimates.

Outcome measures

Measure	Arm A: Nivo + Ipi n=918 Participants Arm A: nivolumab 240 mg IV Q2 weeks plus ipilimumab 1 mg/kg IV Q6 weeks (for 1 year of study drug treatment)	Arm B: Nivo n=922 Participants Arm B: nivolumab 480 mg IV Q4 weeks (for 1 year of study drug treatment) with nivolumab placebo on Weeks 3, 7, 11, 15, 19, 23, 27, 31, 35, 39, 43, \& 47 and ipilimumab placebo on Weeks 1, 7, 13, 19, 25, 31, 37, 43, \& 49
Recurrence-free Survival (RFS) - All Randomized Participants	NA Months Median not reached as Kaplan-Meier plot did not reach 0.5 probability of recurrence-free survival	NA Months Median not reached as Kaplan-Meier plot did not reach 0.5 probability of recurrence-free survival

PRIMARY outcome

Timeframe: From randomization to Primary Completion Date (up to approximately 3 years)

Population: All randomized participants with PD-L1 expression level \< 1% and with completely resected stage IIIb/c/d or stage IV no evidence of disease (NED) melanoma. PD-L1 expression levels based on Interactive Response Technology (IRT)

RFS was defined as the time between the date of randomization and the date of first recurrence (local, regional or distant metastasis), new primary melanoma (including melanoma in situ), or death (from any cause), whichever occurred first.

Median based on Kaplan-Meier Estimates.

Outcome measures

Measure	Arm A: Nivo + Ipi n=347 Participants Arm A: nivolumab 240 mg IV Q2 weeks plus ipilimumab 1 mg/kg IV Q6 weeks (for 1 year of study drug treatment)	Arm B: Nivo n=350 Participants Arm B: nivolumab 480 mg IV Q4 weeks (for 1 year of study drug treatment) with nivolumab placebo on Weeks 3, 7, 11, 15, 19, 23, 27, 31, 35, 39, 43, \& 47 and ipilimumab placebo on Weeks 1, 7, 13, 19, 25, 31, 37, 43, \& 49
Recurrence-free Survival (RFS) - All Randomized Participants With PD-L1 Expression Level < 1%	33.15 Months Interval 22.21 to Upper limit not calculable as upper CI bound does not cross 50% threshold	27.63 Months Interval 19.81 to Upper limit not calculable as upper CI bound does not cross 50% threshold

SECONDARY outcome

Timeframe: From randomization to date of death (up to approximately 45 months)

Population: All randomized participants with completely resected stage IIIb/c/d or stage IV no evidence of disease (NED) melanoma

OS is defined as the time between the date of randomization and the date of death. Median based on Kaplan-Meier Estimates.

Outcome measures

Measure	Arm A: Nivo + Ipi n=918 Participants Arm A: nivolumab 240 mg IV Q2 weeks plus ipilimumab 1 mg/kg IV Q6 weeks (for 1 year of study drug treatment)	Arm B: Nivo n=922 Participants Arm B: nivolumab 480 mg IV Q4 weeks (for 1 year of study drug treatment) with nivolumab placebo on Weeks 3, 7, 11, 15, 19, 23, 27, 31, 35, 39, 43, \& 47 and ipilimumab placebo on Weeks 1, 7, 13, 19, 25, 31, 37, 43, \& 49
Overall Survival (OS) - All Randomized Participants	NA Months Median not reached as Kaplan-Meier plot did not reach 0.5 probability of overall survival	NA Months Median not reached as Kaplan-Meier plot did not reach 0.5 probability of overall survival

SECONDARY outcome

Timeframe: From randomization to date of death (up to approximately 45 months)

Population: All randomized participants with PD-L1 expression level \< 1% and with completely resected stage IIIb/c/d or stage IV no evidence of disease (NED) melanoma

OS is defined as the time between the date of randomization and the date of death. Median based on Kaplan-Meier Estimates.

Outcome measures

Measure	Arm A: Nivo + Ipi n=347 Participants Arm A: nivolumab 240 mg IV Q2 weeks plus ipilimumab 1 mg/kg IV Q6 weeks (for 1 year of study drug treatment)	Arm B: Nivo n=350 Participants Arm B: nivolumab 480 mg IV Q4 weeks (for 1 year of study drug treatment) with nivolumab placebo on Weeks 3, 7, 11, 15, 19, 23, 27, 31, 35, 39, 43, \& 47 and ipilimumab placebo on Weeks 1, 7, 13, 19, 25, 31, 37, 43, \& 49
Overall Survival (OS) - All Randomized Participants With PD-L1 Expression Level < 1%	NA Months Interval 41.72 to Median not reached as Kaplan-Meier plot did not reach 0.5 probability of overall survival	NA Months Median not reached as Kaplan-Meier plot did not reach 0.5 probability of overall survival

SECONDARY outcome

Timeframe: From randomization to Study Completion Date (up to approximately 45 months)

Population: All randomized participants with variable PD-L1 expression levels (see data table for details). PD-L1 expression levels based on clinical database.

RFS was defined as the time between the date of randomization and the date of first recurrence (local, regional or distant metastasis), new primary melanoma (including melanoma in situ), or death (from any cause), whichever occurred first.

Median based on Kaplan-Meier Estimates.

Outcome measures

Measure	Arm A: Nivo + Ipi n=920 Participants Arm A: nivolumab 240 mg IV Q2 weeks plus ipilimumab 1 mg/kg IV Q6 weeks (for 1 year of study drug treatment)	Arm B: Nivo n=924 Participants Arm B: nivolumab 480 mg IV Q4 weeks (for 1 year of study drug treatment) with nivolumab placebo on Weeks 3, 7, 11, 15, 19, 23, 27, 31, 35, 39, 43, \& 47 and ipilimumab placebo on Weeks 1, 7, 13, 19, 25, 31, 37, 43, \& 49
Recurrence-free Survival (RFS) by Baseline Tumor PD-L1 Expression < 1% Tumor PD-L1 Expression	33.18 Months Interval 22.21 to Upper limit not calculable as upper CI bound does not cross 50% threshold	25.33 Months Interval 19.81 to Upper limit not calculable as upper CI bound does not cross 50% threshold
Recurrence-free Survival (RFS) by Baseline Tumor PD-L1 Expression ≥ 1% Tumor PD-L1 Expression	NA Months Median not reached as Kaplan-Meier plot did not reach 0.5 probability of recurrence-free survival	NA Months Median not reached as Kaplan-Meier plot did not reach 0.5 probability of recurrence-free survival
Recurrence-free Survival (RFS) by Baseline Tumor PD-L1 Expression ≥ 5% Tumor PD-L1 Expression	NA Months Median not reached as Kaplan-Meier plot did not reach 0.5 probability of recurrence-free survival	NA Months Median not reached as Kaplan-Meier plot did not reach 0.5 probability of recurrence-free survival
Recurrence-free Survival (RFS) by Baseline Tumor PD-L1 Expression < 5% Tumor PD-L1 Expression	NA Months Interval 31.18 to Median not reached as Kaplan-Meier plot did not reach 0.5 probability of recurrence-free survival	NA Months Interval 27.63 to Median not reached as Kaplan-Meier plot did not reach 0.5 probability of recurrence-free survival
Recurrence-free Survival (RFS) by Baseline Tumor PD-L1 Expression Non-quantifiable Tumor PD-L1 Expression	NA Months Interval 22.41 to Median not reached as Kaplan-Meier plot did not reach 0.5 probability of recurrence-free survival	NA Months Interval 10.87 to Median not reached as Kaplan-Meier plot did not reach 0.5 probability of recurrence-free survival

SECONDARY outcome

Timeframe: From randomization to start of next therapy or second next therapy (up to approximately 45 months)

Population: All randomized participants

Time to next therapy was defined as the time from the date of randomization to the start date of next systemic therapy. Participants who did not receive next treatment were censored at the last known alive date.

Time to second next therapy was defined as the time from the date of randomization to the start date of second next systemic therapy. Participants who did not receive second next treatment were censored at the last known alive date.

Outcome measures

Measure	Arm A: Nivo + Ipi n=920 Participants Arm A: nivolumab 240 mg IV Q2 weeks plus ipilimumab 1 mg/kg IV Q6 weeks (for 1 year of study drug treatment)	Arm B: Nivo n=924 Participants Arm B: nivolumab 480 mg IV Q4 weeks (for 1 year of study drug treatment) with nivolumab placebo on Weeks 3, 7, 11, 15, 19, 23, 27, 31, 35, 39, 43, \& 47 and ipilimumab placebo on Weeks 1, 7, 13, 19, 25, 31, 37, 43, \& 49
Time to Next-Line Therapies - All Randomized Participants Time to next therapy	NA Months Median not reached because of an insufficient number of participants receiving next therapy	NA Months Median not reached because of an insufficient number of participants receiving next therapy
Time to Next-Line Therapies - All Randomized Participants Time to second next therapy	NA Months Median not reached because of an insufficient number of participants receiving second next therapy	NA Months Median not reached because of an insufficient number of participants receiving second next therapy

SECONDARY outcome

Timeframe: From randomization to start of next therapy or second next therapy (up to approximately 45 months)

Population: All randomized participants with PD-L1 expression level \< 1%

Time to next therapy was defined as the time from the date of randomization to the start date of next systemic therapy. Participants who did not receive next treatment were censored at the last known alive date.

Time to second next therapy was defined as the time from the date of randomization to the start date of second next systemic therapy. Participants who did not receive second next treatment were censored at the last known alive date

Outcome measures

Measure	Arm A: Nivo + Ipi n=349 Participants Arm A: nivolumab 240 mg IV Q2 weeks plus ipilimumab 1 mg/kg IV Q6 weeks (for 1 year of study drug treatment)	Arm B: Nivo n=351 Participants Arm B: nivolumab 480 mg IV Q4 weeks (for 1 year of study drug treatment) with nivolumab placebo on Weeks 3, 7, 11, 15, 19, 23, 27, 31, 35, 39, 43, \& 47 and ipilimumab placebo on Weeks 1, 7, 13, 19, 25, 31, 37, 43, \& 49
Time to Next-Line Therapies - All Randomized Participants With PD-L1 Expression Level < 1% Time to next therapy	NA Months Median not reached because of an insufficient number of participants receiving next therapy	NA Months Median not reached because of an insufficient number of participants receiving next therapy
Time to Next-Line Therapies - All Randomized Participants With PD-L1 Expression Level < 1% Time to second next therapy	NA Months Median not reached because of an insufficient number of participants receiving second next therapy	NA Months Median not reached because of an insufficient number of participants receiving second next therapy

SECONDARY outcome

Timeframe: From start of first next systemic therapy to start of second next systemic therapy (up to approximately 28 months)

Population: All randomized participants who received first and second next systemic therapy

Time from next treatment to second next treatment was defined as the time from the start date of next systemic therapy to start date of second next systemic therapy. No censoring rules were applied here as analysis was only performed for the subset of participants who received second next treatment.

Outcome measures

Measure	Arm A: Nivo + Ipi n=81 Participants Arm A: nivolumab 240 mg IV Q2 weeks plus ipilimumab 1 mg/kg IV Q6 weeks (for 1 year of study drug treatment)	Arm B: Nivo n=81 Participants Arm B: nivolumab 480 mg IV Q4 weeks (for 1 year of study drug treatment) with nivolumab placebo on Weeks 3, 7, 11, 15, 19, 23, 27, 31, 35, 39, 43, \& 47 and ipilimumab placebo on Weeks 1, 7, 13, 19, 25, 31, 37, 43, \& 49
Time From Next Therapy to Second Next Therapy - All Randomized Participants	4.60 Months Interval 0.8 to 23.7	4.80 Months Interval 0.0 to 27.7

SECONDARY outcome

Timeframe: From start of first next systemic therapy to start of second next systemic therapy (up to approximately 28 months)

Population: All randomized participants with PD-L1 expression level \< 1% who received first and second next therapy

Time from next treatment to second next treatment was defined as the time from the start date of next systemic therapy to start date of second next systemic therapy. No censoring rules were applied here as analysis was only performed for the subset of participants who received second next treatment.

Outcome measures

Measure	Arm A: Nivo + Ipi n=35 Participants Arm A: nivolumab 240 mg IV Q2 weeks plus ipilimumab 1 mg/kg IV Q6 weeks (for 1 year of study drug treatment)	Arm B: Nivo n=46 Participants Arm B: nivolumab 480 mg IV Q4 weeks (for 1 year of study drug treatment) with nivolumab placebo on Weeks 3, 7, 11, 15, 19, 23, 27, 31, 35, 39, 43, \& 47 and ipilimumab placebo on Weeks 1, 7, 13, 19, 25, 31, 37, 43, \& 49
Time From Next Therapy to Second Next Therapy - All Randomized Participants With PD-L1 Expression Level < 1%	4.44 Months Interval 0.8 to 23.7	5.04 Months Interval 0.9 to 27.7

SECONDARY outcome

Timeframe: From randomization to progression event (up to approximately 45 months)

Population: All randomized participants

PFS2 was defined as the time from randomization to the progression date on next-line systemic therapy or the end date of next-line systemic therapy (if progression date not available) or death from any cause (if both progression date and end date not available), and to last known alive date in case of no event (ie, censoring), meaning either (1) no subsequent systemic therapy and no death OR (2) subsequent systemic therapy but no progression date nor end date available and no death.

Outcome measures

Measure	Arm A: Nivo + Ipi n=920 Participants Arm A: nivolumab 240 mg IV Q2 weeks plus ipilimumab 1 mg/kg IV Q6 weeks (for 1 year of study drug treatment)	Arm B: Nivo n=924 Participants Arm B: nivolumab 480 mg IV Q4 weeks (for 1 year of study drug treatment) with nivolumab placebo on Weeks 3, 7, 11, 15, 19, 23, 27, 31, 35, 39, 43, \& 47 and ipilimumab placebo on Weeks 1, 7, 13, 19, 25, 31, 37, 43, \& 49
Progression-free Survival (PFS) on Next-line Therapy - All Randomized Participants	NA Months Median not reached as insufficient progression events among participants	NA Months Median not reached as insufficient progression events among participants

SECONDARY outcome

Timeframe: From randomization to progression event (up to approximately 45 months)

Population: All randomized participants with PD-L1 expression level \< 1%.

PFS2 was defined as the time from randomization to the progression date on next-line systemic therapy or the end date of next-line systemic therapy (if progression date not available) or death from any cause (if both progression date and end date not available), and to last known alive date in case of no event (ie, censoring), meaning either (1) no subsequent systemic therapy and no death OR (2) subsequent systemic therapy but no progression date nor end date available and no death.

Outcome measures

Measure	Arm A: Nivo + Ipi n=349 Participants Arm A: nivolumab 240 mg IV Q2 weeks plus ipilimumab 1 mg/kg IV Q6 weeks (for 1 year of study drug treatment)	Arm B: Nivo n=351 Participants Arm B: nivolumab 480 mg IV Q4 weeks (for 1 year of study drug treatment) with nivolumab placebo on Weeks 3, 7, 11, 15, 19, 23, 27, 31, 35, 39, 43, \& 47 and ipilimumab placebo on Weeks 1, 7, 13, 19, 25, 31, 37, 43, \& 49
Progression-free Survival (PFS) on Next-line Therapy - All Randomized Participants With PD-L1 Expression Level < 1%	NA Months Median not reached as insufficient progression events among participants	NA Months Interval 35.94 to Median not reached as insufficient progression events among participants

Adverse Events

Arm A: Nivo + Ipi

Serious events: 374 serious events

Other events: 868 other events

Deaths: 122 deaths

Arm B: Nivo

Serious events: 242 serious events

Other events: 844 other events

Deaths: 121 deaths

Serious adverse events

Measure	Arm A: Nivo + Ipi n=916 participants at risk Arm A: nivolumab 240 mg IV Q2 weeks plus ipilimumab 1 mg/kg IV Q6 weeks (for 1 year of study drug treatment)	Arm B: Nivo n=917 participants at risk Arm B: nivolumab 480 mg IV Q4 weeks (for 1 year of study drug treatment) with nivolumab placebo on Weeks 3, 7, 11, 15, 19, 23, 27, 31, 35, 39, 43, \& 47 and ipilimumab placebo on Weeks 1, 7, 13, 19, 25, 31, 37, 43, \& 49
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to central nervous system	0.00% 0/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.11% 1/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to liver	0.00% 0/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.11% 1/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to lymph nodes	0.44% 4/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.11% 1/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to meninges	0.11% 1/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.00% 0/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastasis	0.44% 4/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.11% 1/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastatic malignant melanoma	0.33% 3/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.22% 2/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Blood and lymphatic system disorders Anaemia	0.22% 2/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.22% 2/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Blood and lymphatic system disorders Haemolytic anaemia	0.11% 1/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.00% 0/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Blood and lymphatic system disorders Lymphadenopathy	0.00% 0/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.33% 3/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Blood and lymphatic system disorders Lymphadenopathy mediastinal	0.22% 2/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.00% 0/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Blood and lymphatic system disorders Neutropenia	0.22% 2/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.00% 0/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Blood and lymphatic system disorders Splenic lesion	0.00% 0/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.11% 1/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Blood and lymphatic system disorders Thrombocytopenia	0.22% 2/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.11% 1/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Cardiac disorders Acute coronary syndrome	0.11% 1/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.00% 0/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Cardiac disorders Acute myocardial infarction	0.11% 1/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.11% 1/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Cardiac disorders Atrial fibrillation	0.44% 4/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.00% 0/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Cardiac disorders Atrial flutter	0.11% 1/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.11% 1/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Cardiac disorders Cardiac failure	0.00% 0/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.11% 1/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Cardiac disorders Cardio-respiratory distress	0.11% 1/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.00% 0/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Cardiac disorders Cardiomegaly	0.11% 1/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.00% 0/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Cardiac disorders Myocardial infarction	0.00% 0/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.11% 1/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Cardiac disorders Myocarditis	0.33% 3/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.00% 0/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Cardiac disorders Palpitations	0.11% 1/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.00% 0/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Cardiac disorders Pericardial effusion	0.11% 1/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.00% 0/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Cardiac disorders Pericarditis	0.11% 1/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.00% 0/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Cardiac disorders Tachycardia	0.11% 1/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.00% 0/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Endocrine disorders Addison's disease	0.11% 1/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.00% 0/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Endocrine disorders Adrenal insufficiency	1.1% 10/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.22% 2/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Endocrine disorders Adrenocortical insufficiency acute	0.00% 0/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.11% 1/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Endocrine disorders Adrenocorticotropic hormone deficiency	0.00% 0/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.11% 1/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Endocrine disorders Goitre	0.00% 0/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.11% 1/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Endocrine disorders Hyperparathyroidism	0.00% 0/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.11% 1/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Endocrine disorders Hyperparathyroidism primary	0.00% 0/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.11% 1/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Endocrine disorders Hyperthyroidism	0.55% 5/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.00% 0/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Endocrine disorders Hypophysitis	2.6% 24/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.98% 9/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Endocrine disorders Hypothyroidism	0.22% 2/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.11% 1/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Endocrine disorders Lymphocytic hypophysitis	0.33% 3/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.00% 0/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Endocrine disorders Primary adrenal insufficiency	0.11% 1/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.00% 0/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Endocrine disorders Thyroiditis	0.22% 2/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.11% 1/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Endocrine disorders Thyroiditis acute	0.11% 1/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.11% 1/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Endocrine disorders Thyrotoxic crisis	0.11% 1/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.00% 0/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Eye disorders Orbital myositis	0.11% 1/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.11% 1/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Eye disorders Papilloedema	0.00% 0/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.22% 2/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Eye disorders Retinal detachment	0.00% 0/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.11% 1/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Eye disorders Retinal tear	0.11% 1/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.00% 0/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Gastrointestinal disorders Abdominal pain	0.11% 1/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.11% 1/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Gastrointestinal disorders Abdominal pain upper	0.00% 0/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.11% 1/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Gastrointestinal disorders Ascites	0.00% 0/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.11% 1/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Gastrointestinal disorders Autoimmune colitis	0.87% 8/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.22% 2/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Gastrointestinal disorders Autoimmune pancreatitis	0.11% 1/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.00% 0/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Gastrointestinal disorders Colitis	3.2% 29/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.76% 7/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Gastrointestinal disorders Colitis microscopic	0.11% 1/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.00% 0/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Gastrointestinal disorders Colitis ulcerative	0.11% 1/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.00% 0/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Gastrointestinal disorders Constipation	0.11% 1/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.00% 0/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Gastrointestinal disorders Diarrhoea	2.0% 18/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.76% 7/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Gastrointestinal disorders Duodenitis	0.11% 1/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.11% 1/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Gastrointestinal disorders Enteritis	0.11% 1/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.11% 1/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Gastrointestinal disorders Enterocolitis	0.22% 2/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.00% 0/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Gastrointestinal disorders Epigastric discomfort	0.00% 0/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.11% 1/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Gastrointestinal disorders Gastric ulcer	0.22% 2/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.00% 0/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Gastrointestinal disorders Gastritis	0.44% 4/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.11% 1/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Gastrointestinal disorders Gastrooesophageal reflux disease	0.00% 0/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.11% 1/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Gastrointestinal disorders Ileus	0.00% 0/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.11% 1/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Gastrointestinal disorders Immune-mediated enterocolitis	1.7% 16/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.76% 7/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Gastrointestinal disorders Impaired gastric emptying	0.00% 0/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.11% 1/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Gastrointestinal disorders Inguinal hernia	0.11% 1/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.00% 0/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Gastrointestinal disorders Mallory-Weiss syndrome	0.11% 1/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.00% 0/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Gastrointestinal disorders Melaena	0.00% 0/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.11% 1/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Gastrointestinal disorders Nausea	0.22% 2/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.00% 0/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Gastrointestinal disorders Oesophageal obstruction	0.11% 1/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.00% 0/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Gastrointestinal disorders Oesophageal spasm	0.11% 1/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.00% 0/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Gastrointestinal disorders Pancreatic cyst	0.11% 1/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.00% 0/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Gastrointestinal disorders Pancreatitis	0.22% 2/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.44% 4/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Gastrointestinal disorders Pneumatosis intestinalis	0.00% 0/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.11% 1/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Gastrointestinal disorders Retroperitoneal fibrosis	0.11% 1/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.00% 0/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Gastrointestinal disorders Small intestinal obstruction	0.00% 0/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.11% 1/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Gastrointestinal disorders Small intestinal perforation	0.11% 1/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.00% 0/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Gastrointestinal disorders Ulcerative gastritis	0.11% 1/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.00% 0/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Gastrointestinal disorders Umbilical hernia	0.11% 1/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.00% 0/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Gastrointestinal disorders Upper gastrointestinal haemorrhage	0.22% 2/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.00% 0/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Gastrointestinal disorders Vomiting	0.11% 1/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.00% 0/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
General disorders Asthenia	0.11% 1/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.00% 0/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
General disorders Chills	0.11% 1/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.00% 0/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
General disorders Complication associated with device	0.00% 0/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.11% 1/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
General disorders Fatigue	0.66% 6/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.00% 0/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
General disorders Gait disturbance	0.00% 0/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.11% 1/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
General disorders General physical health deterioration	0.11% 1/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.00% 0/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
General disorders Granuloma	0.11% 1/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.00% 0/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
General disorders Lithiasis	0.00% 0/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.11% 1/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
General disorders Malaise	0.11% 1/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.00% 0/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
General disorders Mass	0.11% 1/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.00% 0/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
General disorders Nodule	0.00% 0/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.11% 1/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
General disorders Non-cardiac chest pain	0.11% 1/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.00% 0/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
General disorders Polyserositis	0.00% 0/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.11% 1/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
General disorders Pyrexia	1.3% 12/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.55% 5/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Hepatobiliary disorders Autoimmune hepatitis	1.5% 14/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.11% 1/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Hepatobiliary disorders Cholangitis sclerosing	0.11% 1/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.00% 0/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Hepatobiliary disorders Cholecystitis	0.22% 2/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.00% 0/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Hepatobiliary disorders Cholelithiasis	0.11% 1/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.00% 0/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Hepatobiliary disorders Hepatic function abnormal	0.00% 0/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.11% 1/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Hepatobiliary disorders Hepatitis	0.66% 6/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.44% 4/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Hepatobiliary disorders Hepatotoxicity	0.44% 4/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.00% 0/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Hepatobiliary disorders Hypertransaminasaemia	0.00% 0/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.11% 1/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Hepatobiliary disorders Immune-mediated hepatitis	0.66% 6/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.00% 0/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Hepatobiliary disorders Liver disorder	0.22% 2/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.11% 1/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Hepatobiliary disorders Nodular regenerative hyperplasia	0.11% 1/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.00% 0/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Hepatobiliary disorders Venoocclusive liver disease	0.11% 1/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.00% 0/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Immune system disorders Autoimmune disorder	0.00% 0/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.11% 1/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Immune system disorders Drug hypersensitivity	0.11% 1/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.00% 0/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Immune system disorders Sarcoidosis	0.76% 7/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.11% 1/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Infections and infestations Adrenalitis	0.11% 1/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.22% 2/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Infections and infestations Arthritis bacterial	0.00% 0/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.11% 1/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Infections and infestations Atypical pneumonia	0.33% 3/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.00% 0/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Infections and infestations Bacterial infection	0.11% 1/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.00% 0/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Infections and infestations Bronchiolitis	0.00% 0/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.11% 1/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Infections and infestations Bronchitis	0.22% 2/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.22% 2/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Infections and infestations Bronchitis viral	0.11% 1/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.00% 0/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Infections and infestations Bursitis infective	0.22% 2/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.00% 0/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Infections and infestations Campylobacter colitis	0.11% 1/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.11% 1/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Infections and infestations Cellulitis	0.44% 4/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.55% 5/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Infections and infestations Chronic sinusitis	0.00% 0/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.11% 1/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Infections and infestations Clostridium difficile colitis	0.11% 1/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.00% 0/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Infections and infestations Cystitis	0.11% 1/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.00% 0/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Infections and infestations Cytomegalovirus infection reactivation	0.00% 0/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.11% 1/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Infections and infestations Dengue fever	0.00% 0/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.11% 1/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Infections and infestations Device related infection	0.11% 1/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.00% 0/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Infections and infestations Diarrhoea infectious	0.11% 1/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.00% 0/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Infections and infestations Encephalitis	0.44% 4/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.22% 2/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Infections and infestations Endocarditis enterococcal	0.11% 1/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.00% 0/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Infections and infestations Enterovirus infection	0.11% 1/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.00% 0/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Infections and infestations Erysipelas	0.55% 5/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.33% 3/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Infections and infestations Fournier's gangrene	0.11% 1/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.00% 0/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Infections and infestations Gastroenteritis	0.22% 2/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.11% 1/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Infections and infestations Gastrointestinal infection	0.00% 0/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.11% 1/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Infections and infestations Groin abscess	0.11% 1/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.00% 0/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Infections and infestations Haematoma infection	0.00% 0/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.11% 1/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Infections and infestations Herpes oesophagitis	0.11% 1/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.00% 0/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Infections and infestations Infected bite	0.11% 1/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.00% 0/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Infections and infestations Infection	0.11% 1/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.00% 0/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Infections and infestations Localised infection	0.00% 0/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.11% 1/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Infections and infestations Lower respiratory tract infection	0.33% 3/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.11% 1/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Infections and infestations Meningitis	0.22% 2/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.00% 0/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Infections and infestations Meningitis aseptic	0.22% 2/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.00% 0/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Infections and infestations Myelitis	0.11% 1/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.00% 0/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Infections and infestations Pharyngitis	0.00% 0/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.11% 1/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Infections and infestations Picornavirus infection	0.00% 0/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.11% 1/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Infections and infestations Pneumonia	1.2% 11/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.22% 2/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Infections and infestations Pneumonia klebsiella	0.11% 1/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.00% 0/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Infections and infestations Postoperative wound infection	0.11% 1/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.00% 0/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Infections and infestations Respiratory tract infection	0.11% 1/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.11% 1/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Infections and infestations Sepsis	0.33% 3/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.00% 0/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Infections and infestations Septic shock	0.22% 2/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.11% 1/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Infections and infestations Sinusitis	0.11% 1/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.11% 1/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Infections and infestations Skin infection	0.11% 1/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.00% 0/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Infections and infestations Subcutaneous abscess	0.00% 0/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.22% 2/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Infections and infestations Tonsillitis	0.11% 1/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.00% 0/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Infections and infestations Tracheitis	0.11% 1/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.00% 0/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Infections and infestations Urinary tract infection	0.22% 2/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.11% 1/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Infections and infestations Urosepsis	0.33% 3/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.00% 0/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Infections and infestations Varicella zoster virus infection	0.00% 0/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.11% 1/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Infections and infestations Vascular device infection	0.11% 1/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.11% 1/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Infections and infestations Vestibular neuronitis	0.00% 0/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.11% 1/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Infections and infestations Viral infection	0.11% 1/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.00% 0/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Infections and infestations Wound infection	0.00% 0/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.11% 1/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Injury, poisoning and procedural complications Clavicle fracture	0.11% 1/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.00% 0/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Injury, poisoning and procedural complications Facial bones fracture	0.00% 0/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.11% 1/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Injury, poisoning and procedural complications Fall	0.00% 0/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.11% 1/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Injury, poisoning and procedural complications Fracture	0.11% 1/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.00% 0/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Injury, poisoning and procedural complications Graft complication	0.11% 1/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.00% 0/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Injury, poisoning and procedural complications Head injury	0.11% 1/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.00% 0/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Injury, poisoning and procedural complications Infusion related reaction	0.22% 2/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.33% 3/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Injury, poisoning and procedural complications Joint dislocation	0.11% 1/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.00% 0/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Injury, poisoning and procedural complications Joint injury	0.11% 1/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.00% 0/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Injury, poisoning and procedural complications Lower limb fracture	0.00% 0/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.11% 1/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Injury, poisoning and procedural complications Meniscus injury	0.00% 0/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.11% 1/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Injury, poisoning and procedural complications Overdose	0.00% 0/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.11% 1/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Injury, poisoning and procedural complications Patella fracture	0.11% 1/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.00% 0/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Injury, poisoning and procedural complications Post lumbar puncture syndrome	0.00% 0/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.11% 1/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Injury, poisoning and procedural complications Post procedural haematoma	0.00% 0/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.11% 1/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Injury, poisoning and procedural complications Procedural pneumothorax	0.00% 0/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.11% 1/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Injury, poisoning and procedural complications Road traffic accident	0.11% 1/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.00% 0/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Injury, poisoning and procedural complications Skin laceration	0.00% 0/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.11% 1/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Injury, poisoning and procedural complications Spinal fracture	0.11% 1/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.00% 0/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Injury, poisoning and procedural complications Subdural haematoma	0.11% 1/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.00% 0/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Injury, poisoning and procedural complications Tendon rupture	0.11% 1/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.00% 0/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Injury, poisoning and procedural complications Traumatic liver injury	0.11% 1/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.00% 0/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Injury, poisoning and procedural complications Wound complication	0.00% 0/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.22% 2/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Injury, poisoning and procedural complications Wound dehiscence	0.00% 0/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.11% 1/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Investigations Alanine aminotransferase increased	0.22% 2/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.00% 0/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Investigations Amylase increased	0.11% 1/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.00% 0/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Investigations Blood creatine phosphokinase increased	0.11% 1/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.00% 0/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Investigations Blood creatinine increased	0.11% 1/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.00% 0/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Investigations Electrocardiogram abnormal	0.11% 1/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.00% 0/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Investigations General physical condition abnormal	0.11% 1/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.11% 1/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Investigations Hepatic enzyme increased	0.11% 1/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.00% 0/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Investigations Lipase increased	0.11% 1/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.00% 0/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Investigations Transaminases increased	0.22% 2/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.11% 1/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Investigations Troponin I increased	0.11% 1/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.00% 0/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Metabolism and nutrition disorders Decreased appetite	0.11% 1/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.00% 0/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Metabolism and nutrition disorders Dehydration	0.11% 1/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.11% 1/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Metabolism and nutrition disorders Diabetes mellitus	0.11% 1/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.22% 2/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Metabolism and nutrition disorders Diabetes mellitus inadequate control	0.11% 1/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.00% 0/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Metabolism and nutrition disorders Diabetic ketoacidosis	0.11% 1/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.11% 1/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Metabolism and nutrition disorders Diabetic metabolic decompensation	0.11% 1/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.00% 0/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Metabolism and nutrition disorders Fulminant type 1 diabetes mellitus	0.00% 0/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.11% 1/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Metabolism and nutrition disorders Hyperglycaemia	0.44% 4/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.44% 4/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Metabolism and nutrition disorders Hypoglycaemia	0.11% 1/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.00% 0/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Metabolism and nutrition disorders Hypokalaemia	0.22% 2/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.00% 0/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Metabolism and nutrition disorders Hyponatraemia	0.11% 1/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.22% 2/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Metabolism and nutrition disorders Steroid diabetes	0.44% 4/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.00% 0/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Metabolism and nutrition disorders Type 1 diabetes mellitus	0.22% 2/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.22% 2/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Metabolism and nutrition disorders Type 2 diabetes mellitus	0.11% 1/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.00% 0/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Musculoskeletal and connective tissue disorders Arthralgia	0.11% 1/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.22% 2/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Musculoskeletal and connective tissue disorders Arthritis	0.11% 1/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.11% 1/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.11% 1/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Musculoskeletal and connective tissue disorders Muscular weakness	0.11% 1/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.00% 0/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	0.11% 1/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.00% 0/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Musculoskeletal and connective tissue disorders Musculoskeletal pain	0.11% 1/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.00% 0/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Musculoskeletal and connective tissue disorders Myopathy	0.00% 0/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.11% 1/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Musculoskeletal and connective tissue disorders Myositis	0.22% 2/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.22% 2/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Musculoskeletal and connective tissue disorders Myositis-like syndrome	0.11% 1/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.00% 0/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Musculoskeletal and connective tissue disorders Osteoarthritis	0.11% 1/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.22% 2/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Musculoskeletal and connective tissue disorders Polyarthritis	0.00% 0/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.11% 1/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Musculoskeletal and connective tissue disorders Polymyalgia rheumatica	0.22% 2/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.00% 0/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) B-cell lymphoma	0.00% 0/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.11% 1/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Basal cell carcinoma	1.5% 14/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	2.5% 23/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Bowen's disease	0.33% 3/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.11% 1/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant melanoma	0.33% 3/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.76% 7/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant melanoma in situ	0.11% 1/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.00% 0/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant neoplasm progression	1.6% 15/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	1.1% 10/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Marginal zone lymphoma	0.11% 1/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.00% 0/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Melanoma recurrent	0.66% 6/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.11% 1/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to breast	0.00% 0/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.11% 1/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasm malignant	0.22% 2/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.00% 0/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasm progression	0.00% 0/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.11% 1/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Oesophageal carcinoma	0.11% 1/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.00% 0/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Oesophageal squamous cell carcinoma	0.00% 0/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.11% 1/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Oncocytoma	0.00% 0/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.11% 1/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Papilloma	0.00% 0/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.11% 1/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Plasma cell myeloma	0.00% 0/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.11% 1/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Plasmacytoma	0.00% 0/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.11% 1/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Prostate cancer	0.11% 1/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.33% 3/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Recurrent cancer	0.11% 1/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.00% 0/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Schwannoma	0.00% 0/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.11% 1/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Skin cancer	0.11% 1/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.00% 0/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Squamous cell carcinoma	0.87% 8/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	1.3% 12/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Squamous cell carcinoma of skin	0.22% 2/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.22% 2/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Transitional cell carcinoma	0.11% 1/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.00% 0/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumour haemorrhage	0.00% 0/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.11% 1/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Uterine leiomyoma	0.00% 0/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.11% 1/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Nervous system disorders Acute disseminated encephalomyelitis	0.11% 1/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.00% 0/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Nervous system disorders Amnesia	0.11% 1/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.00% 0/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Nervous system disorders Autoimmune neuropathy	0.11% 1/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.00% 0/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Nervous system disorders Carotid artery dissection	0.11% 1/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.00% 0/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Nervous system disorders Cerebral infarction	0.00% 0/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.11% 1/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Nervous system disorders Cerebrovascular accident	0.00% 0/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.11% 1/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Nervous system disorders Encephalitis autoimmune	0.11% 1/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.00% 0/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Nervous system disorders Encephalopathy	0.22% 2/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.00% 0/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Nervous system disorders Epilepsy	0.00% 0/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.11% 1/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Nervous system disorders Facial paresis	0.11% 1/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.00% 0/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Nervous system disorders Guillain-Barre syndrome	0.00% 0/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.11% 1/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Nervous system disorders Haemorrhage intracranial	0.00% 0/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.11% 1/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Nervous system disorders Headache	0.22% 2/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.44% 4/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Nervous system disorders Hypertensive encephalopathy	0.11% 1/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.00% 0/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Nervous system disorders Intracranial aneurysm	0.00% 0/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.11% 1/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Nervous system disorders Intracranial pressure increased	0.11% 1/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.00% 0/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Nervous system disorders Meningism	0.00% 0/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.11% 1/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Nervous system disorders Miller Fisher syndrome	0.11% 1/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.00% 0/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Nervous system disorders Monoparesis	0.11% 1/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.00% 0/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Nervous system disorders Myasthenia gravis	0.22% 2/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.00% 0/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Nervous system disorders Myasthenic syndrome	0.00% 0/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.11% 1/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Nervous system disorders Myelitis transverse	0.11% 1/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.00% 0/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Nervous system disorders Neuropathy peripheral	0.00% 0/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.11% 1/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Nervous system disorders Optic neuritis	0.11% 1/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.00% 0/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Nervous system disorders Paraesthesia	0.00% 0/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.11% 1/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Nervous system disorders Peripheral motor neuropathy	0.00% 0/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.11% 1/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Nervous system disorders Peripheral sensory neuropathy	0.11% 1/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.00% 0/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Nervous system disorders Polyneuropathy	0.11% 1/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.00% 0/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Nervous system disorders Radiculopathy	0.11% 1/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.00% 0/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Nervous system disorders Seizure	0.11% 1/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.00% 0/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Nervous system disorders Spinal cord compression	0.00% 0/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.11% 1/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Nervous system disorders Syncope	0.22% 2/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.00% 0/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Nervous system disorders Transient ischaemic attack	0.22% 2/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.00% 0/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Psychiatric disorders Anxiety	0.00% 0/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.11% 1/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Psychiatric disorders Completed suicide	0.11% 1/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.00% 0/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Psychiatric disorders Delirium	0.11% 1/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.00% 0/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Psychiatric disorders Depression	0.22% 2/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.33% 3/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Psychiatric disorders Mania	0.11% 1/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.00% 0/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Psychiatric disorders Mental disorder	0.11% 1/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.00% 0/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Renal and urinary disorders Acute kidney injury	0.44% 4/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.44% 4/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Renal and urinary disorders Autoimmune nephritis	0.00% 0/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.22% 2/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Renal and urinary disorders Calculus bladder	0.00% 0/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.11% 1/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Renal and urinary disorders Calculus urinary	0.00% 0/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.11% 1/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Renal and urinary disorders Haematuria	0.00% 0/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.11% 1/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Renal and urinary disorders Nephritis	0.11% 1/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.33% 3/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Renal and urinary disorders Nephrolithiasis	0.22% 2/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.00% 0/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Renal and urinary disorders Renal colic	0.00% 0/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.11% 1/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Renal and urinary disorders Renal failure	0.22% 2/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.00% 0/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Renal and urinary disorders Renal impairment	0.00% 0/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.11% 1/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Renal and urinary disorders Tubulointerstitial nephritis	0.00% 0/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.11% 1/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Renal and urinary disorders Ureterolithiasis	0.11% 1/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.11% 1/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Renal and urinary disorders Urinary retention	0.11% 1/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.00% 0/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Reproductive system and breast disorders Benign prostatic hyperplasia	0.00% 0/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.11% 1/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Reproductive system and breast disorders Prostatitis	0.11% 1/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.00% 0/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Respiratory, thoracic and mediastinal disorders Acute pulmonary oedema	0.11% 1/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.00% 0/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Respiratory, thoracic and mediastinal disorders Asthma	0.00% 0/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.11% 1/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Respiratory, thoracic and mediastinal disorders Bronchitis chronic	0.11% 1/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.00% 0/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Respiratory, thoracic and mediastinal disorders Cough	0.11% 1/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.00% 0/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Respiratory, thoracic and mediastinal disorders Diaphragmatic spasm	0.00% 0/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.11% 1/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.22% 2/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.00% 0/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Respiratory, thoracic and mediastinal disorders Epistaxis	0.00% 0/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.11% 1/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Respiratory, thoracic and mediastinal disorders Immune-mediated pneumonitis	0.44% 4/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.00% 0/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Respiratory, thoracic and mediastinal disorders Interstitial lung disease	0.00% 0/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.11% 1/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Respiratory, thoracic and mediastinal disorders Laryngeal oedema	0.11% 1/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.00% 0/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Respiratory, thoracic and mediastinal disorders Lung disorder	0.11% 1/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.00% 0/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Respiratory, thoracic and mediastinal disorders Organising pneumonia	0.00% 0/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.11% 1/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.22% 2/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.00% 0/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Respiratory, thoracic and mediastinal disorders Pneumonitis	0.98% 9/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.33% 3/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.44% 4/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.00% 0/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Respiratory, thoracic and mediastinal disorders Pulmonary mass	0.11% 1/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.00% 0/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Respiratory, thoracic and mediastinal disorders Pulmonary sarcoidosis	0.11% 1/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.00% 0/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Respiratory, thoracic and mediastinal disorders Respiratory disorder	0.00% 0/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.11% 1/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.00% 0/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.11% 1/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Skin and subcutaneous tissue disorders Angioedema	0.00% 0/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.11% 1/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Skin and subcutaneous tissue disorders Dermatitis allergic	0.00% 0/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.11% 1/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Skin and subcutaneous tissue disorders Drug eruption	0.11% 1/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.11% 1/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Skin and subcutaneous tissue disorders Drug reaction with eosinophilia and systemic symptoms	0.11% 1/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.00% 0/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Skin and subcutaneous tissue disorders Pemphigoid	0.00% 0/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.22% 2/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Skin and subcutaneous tissue disorders Psoriasis	0.00% 0/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.11% 1/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Skin and subcutaneous tissue disorders Rash	0.33% 3/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.22% 2/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Skin and subcutaneous tissue disorders Rash maculo-papular	0.11% 1/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.11% 1/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Skin and subcutaneous tissue disorders Subcutaneous emphysema	0.00% 0/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.11% 1/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Skin and subcutaneous tissue disorders Toxic skin eruption	0.22% 2/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.11% 1/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Vascular disorders Capillary leak syndrome	0.11% 1/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.00% 0/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Vascular disorders Deep vein thrombosis	0.22% 2/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.11% 1/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Vascular disorders Hypertension	0.22% 2/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.11% 1/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Vascular disorders Lymphoedema	0.00% 0/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.11% 1/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Vascular disorders Orthostatic hypotension	0.11% 1/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.00% 0/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Vascular disorders Shock	0.00% 0/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.11% 1/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)

Other adverse events

Measure	Arm A: Nivo + Ipi n=916 participants at risk Arm A: nivolumab 240 mg IV Q2 weeks plus ipilimumab 1 mg/kg IV Q6 weeks (for 1 year of study drug treatment)	Arm B: Nivo n=917 participants at risk Arm B: nivolumab 480 mg IV Q4 weeks (for 1 year of study drug treatment) with nivolumab placebo on Weeks 3, 7, 11, 15, 19, 23, 27, 31, 35, 39, 43, \& 47 and ipilimumab placebo on Weeks 1, 7, 13, 19, 25, 31, 37, 43, \& 49
Endocrine disorders Adrenal insufficiency	6.1% 56/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	0.76% 7/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Endocrine disorders Hyperthyroidism	19.7% 180/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	10.7% 98/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Endocrine disorders Hypophysitis	10.0% 92/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	1.2% 11/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Endocrine disorders Hypothyroidism	23.9% 219/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	15.2% 139/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Gastrointestinal disorders Abdominal pain	11.1% 102/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	9.2% 84/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Gastrointestinal disorders Abdominal pain upper	6.2% 57/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	4.0% 37/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Gastrointestinal disorders Constipation	11.8% 108/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	9.7% 89/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Gastrointestinal disorders Diarrhoea	36.9% 338/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	33.2% 304/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Gastrointestinal disorders Dry mouth	10.8% 99/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	9.8% 90/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Gastrointestinal disorders Nausea	23.8% 218/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	20.4% 187/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Gastrointestinal disorders Vomiting	10.9% 100/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	8.4% 77/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
General disorders Asthenia	18.0% 165/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	16.0% 147/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
General disorders Fatigue	38.0% 348/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	36.9% 338/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
General disorders Influenza like illness	6.3% 58/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	5.1% 47/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
General disorders Pyrexia	12.9% 118/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	9.2% 84/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Infections and infestations Nasopharyngitis	11.9% 109/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	11.0% 101/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Infections and infestations Upper respiratory tract infection	7.5% 69/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	9.4% 86/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Injury, poisoning and procedural complications Infusion related reaction	6.1% 56/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	5.0% 46/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Investigations Alanine aminotransferase increased	14.6% 134/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	9.4% 86/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Investigations Amylase increased	9.3% 85/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	4.0% 37/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Investigations Aspartate aminotransferase increased	12.0% 110/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	7.6% 70/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Investigations Blood creatine phosphokinase increased	6.1% 56/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	5.5% 50/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Investigations Lipase increased	13.1% 120/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	6.3% 58/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Metabolism and nutrition disorders Decreased appetite	11.6% 106/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	6.9% 63/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Metabolism and nutrition disorders Hyperglycaemia	5.6% 51/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	5.3% 49/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Musculoskeletal and connective tissue disorders Arthralgia	18.3% 168/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	23.2% 213/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Musculoskeletal and connective tissue disorders Back pain	10.3% 94/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	10.5% 96/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Musculoskeletal and connective tissue disorders Myalgia	10.8% 99/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	8.8% 81/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Musculoskeletal and connective tissue disorders Pain in extremity	5.1% 47/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	5.7% 52/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Nervous system disorders Dizziness	7.3% 67/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	7.0% 64/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Nervous system disorders Headache	29.5% 270/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	23.3% 214/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Psychiatric disorders Anxiety	3.5% 32/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	5.1% 47/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Psychiatric disorders Insomnia	9.6% 88/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	8.2% 75/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Respiratory, thoracic and mediastinal disorders Cough	17.7% 162/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	18.3% 168/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Respiratory, thoracic and mediastinal disorders Dyspnoea	8.0% 73/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	8.1% 74/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	5.7% 52/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	4.7% 43/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Skin and subcutaneous tissue disorders Pruritus	37.0% 339/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	26.0% 238/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Skin and subcutaneous tissue disorders Rash	28.2% 258/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	25.5% 234/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Skin and subcutaneous tissue disorders Vitiligo	5.3% 49/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	6.1% 56/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)
Vascular disorders Hypertension	4.6% 42/916 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)	5.1% 47/917 • All-cause mortality was assessed from first dose to study completion date (up to approximately 45 months). Serious Adverse Events and Non Serious Adverse Events above 5% were assessed from first dose to 100 days post last dose (up to approximately 15 months)

Additional Information

Bristol-Myers Squibb Study Director

Bristol-Myers Squibb

Phone: Please email:

Email: Clinical.Trials@bms.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place

Restriction type: LTE60