Trial Outcomes & Findings for Study of Secukinumab Compared to Ustekinumab in Subjects With Plaque Psoriasis (NCT NCT02826603)

Last Updated: 2019-07-09

Results Overview

Number of participants who achieved ≥ 90% reduction in PASI compared to baseline. Logistic regression analysis of PASI 90 response at Week 12 PASI is a combined assessment of lesion severity and affected area into a single score: 0 (no disease) to 72 (maximal disease). Body is divided into 4 areas for scoring (head, upper limbs, trunk, lower limbs; each area is scored by itself and scores are combined for final PASI. For each area, percent of skin involved is estimated: 0 (0%) to 6 (90-100%), and severity is estimated by clinical signs, erythema, induration and desquamation; scale 0 (none) to 4 (maximum). Final PASI = sum of severity parameters for each area\* area score weight of body region(head: 0.1, upper limbs: 0.2, trunk: 0.3, lower limbs: 0.4).

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

1114 participants

Primary outcome timeframe

Week 12

Results posted on

2019-07-09

Participant Flow

Overall, 1353 patients were screened of which 1102 patients completed the Screening phase; 251 patients were screen failures

The randomized set was defined as all patients who were randomized at the baseline visit. Unless otherwise specified, mis-randomized patients were excluded from the randomized set. Mis-randomized patients were those who were screen failures, but had been randomized by the Investigator before eligibility was assessed, but had not been treated

Participant milestones

Participant milestones
Measure	Secukinumab 300mg (2 x 150 mg) Secukinumab 300mg s.c. injection (2 150mg pre-fiilled syringes)	Ustekinumab 2 x 45mg or 90mg Ustekinumab s.c. 45 mg or 90 mg (depending on body weight) using 45mg pre-filled syringes (1 or 2 syringes)
Overall Study STARTED	550	552
Overall Study COMPLETED	489	488
Overall Study NOT COMPLETED	61	64

Reasons for withdrawal

Reasons for withdrawal
Measure	Secukinumab 300mg (2 x 150 mg) Secukinumab 300mg s.c. injection (2 150mg pre-fiilled syringes)	Ustekinumab 2 x 45mg or 90mg Ustekinumab s.c. 45 mg or 90 mg (depending on body weight) using 45mg pre-filled syringes (1 or 2 syringes)
Overall Study Adverse Event	17	9
Overall Study Lack of Efficacy	4	9
Overall Study Lost to Follow-up	13	12
Overall Study Noncompliance with treatment	0	2
Overall Study Physician Decision	1	7
Overall Study Pregnancy	1	2
Overall Study Protocol Violation	3	3
Overall Study Withdrawal by Subject	20	19
Overall Study Death	2	0
Overall Study New therapy for study indication	0	1

Baseline Characteristics

Study of Secukinumab Compared to Ustekinumab in Subjects With Plaque Psoriasis

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Secukinumab 300mg (2 x 150 mg) n=550 Participants Secukinumab 300mg s.c. injection (2 150mg pre-fiilled syringes)	Ustekinumab 2 x 45mg or 90mg n=552 Participants Ustekinumab s.c. 45 mg or 90 mg (depending on body weight) using 45mg pre-filled syringes (1 or 2 syringes)	Total n=1102 Participants Total of all reporting groups
Age, Continuous	45.4 years STANDARD_DEVIATION 14.09 • n=5 Participants	45.3 years STANDARD_DEVIATION 14.16 • n=7 Participants	45.4 years STANDARD_DEVIATION 14.12 • n=5 Participants
Age, Customized <65 years	488 Participants n=5 Participants	494 Participants n=7 Participants	982 Participants n=5 Participants
Age, Customized >=65 years and <75 years	60 Participants n=5 Participants	48 Participants n=7 Participants	108 Participants n=5 Participants
Age, Customized >=75 years	2 Participants n=5 Participants	10 Participants n=7 Participants	12 Participants n=5 Participants
Sex: Female, Male Female	194 Participants n=5 Participants	176 Participants n=7 Participants	370 Participants n=5 Participants
Sex: Female, Male Male	356 Participants n=5 Participants	376 Participants n=7 Participants	732 Participants n=5 Participants
Race/Ethnicity, Customized Caucasian	416 Participants n=5 Participants	410 Participants n=7 Participants	826 Participants n=5 Participants
Race/Ethnicity, Customized Black	21 Participants n=5 Participants	24 Participants n=7 Participants	45 Participants n=5 Participants
Race/Ethnicity, Customized Asian	60 Participants n=5 Participants	57 Participants n=7 Participants	117 Participants n=5 Participants
Race/Ethnicity, Customized Native American	34 Participants n=5 Participants	41 Participants n=7 Participants	75 Participants n=5 Participants
Race/Ethnicity, Customized Pacific Islander	1 Participants n=5 Participants	5 Participants n=7 Participants	6 Participants n=5 Participants
Race/Ethnicity, Customized Unknown	4 Participants n=5 Participants	2 Participants n=7 Participants	6 Participants n=5 Participants
Race/Ethnicity, Customized Other	14 Participants n=5 Participants	13 Participants n=7 Participants	27 Participants n=5 Participants

PRIMARY outcome

Timeframe: Week 12

Population: The Full analysis set (FAS) is all patients from the randomized set assigned to study treatment. Following the intent-to-treat principle, patients were analyzed according to the treatment assigned at randomization. If the actual randomization stratum was different to the assigned stratum in IRT, the actual stratum was used in the analyses.

Outcome measures

Outcome measures
Measure	Secukinumab 300mg (2 x 150 mg) n=550 Participants Secukinumab 300mg s.c. injection (2 150mg pre-fiilled syringes)	Ustekinumab 2 x 45mg or 90mg n=552 Participants Ustekinumab s.c. 45 mg or 90 mg (depending on body weight) using 45mg pre-filled syringes (1 or 2 syringes)
Participants Who Achieved Psoriasis Area and Severity Index (PASI) 90 Response at Week 12	366 Participants	265 Participants

PRIMARY outcome

Timeframe: Week 12

Population: The full analysis set (FAS) population was used for this analysis. The FAS included all participants to whom treatment was assigned. Only participants from the FAS, who had values at a given week, were included in the analysis for that week.

Investigator's Global Assessment uses a scale (IGA mod 2011) that rates disease from a score of 0 (clear skin) to 4 (severe disease)

Outcome measures

Outcome measures
Measure	Secukinumab 300mg (2 x 150 mg) n=550 Participants Secukinumab 300mg s.c. injection (2 150mg pre-fiilled syringes)	Ustekinumab 2 x 45mg or 90mg n=552 Participants Ustekinumab s.c. 45 mg or 90 mg (depending on body weight) using 45mg pre-filled syringes (1 or 2 syringes)
Participants With IGA Mod 2011 0 or 1 at Week 12	397 Participants	306 Participants

SECONDARY outcome

Timeframe: Week 12

Population: FAS

Number of participants who achieved ≥ 75% reduction in PASI at Week 12 compared to baseline.

Outcome measures

Outcome measures
Measure	Secukinumab 300mg (2 x 150 mg) n=550 Participants Secukinumab 300mg s.c. injection (2 150mg pre-fiilled syringes)	Ustekinumab 2 x 45mg or 90mg n=552 Participants Ustekinumab s.c. 45 mg or 90 mg (depending on body weight) using 45mg pre-filled syringes (1 or 2 syringes)
Participants Who Achieved Psoriasis Area and Severity Index (PASI) 75 Response at Week 12	484 Participants	409 Participants

SECONDARY outcome

Timeframe: Week 4

Population: FAS

Number of participants who achieved ≥ 75% reduction in PASI at Week 4 compared to baseline.

Outcome measures

Outcome measures
Measure	Secukinumab 300mg (2 x 150 mg) n=550 Participants Secukinumab 300mg s.c. injection (2 150mg pre-fiilled syringes)	Ustekinumab 2 x 45mg or 90mg n=552 Participants Ustekinumab s.c. 45 mg or 90 mg (depending on body weight) using 45mg pre-filled syringes (1 or 2 syringes)
Participants Who Achieved Psoriasis Area and Severity Index (PASI) 75 Response at Week 4	221 Participants	90 Participants

SECONDARY outcome

Timeframe: Week 16

Population: FAS

Number of participants who achieved 100% reduction in PASI at Week 16 compared to baseline.

Outcome measures

Outcome measures
Measure	Secukinumab 300mg (2 x 150 mg) n=550 Participants Secukinumab 300mg s.c. injection (2 150mg pre-fiilled syringes)	Ustekinumab 2 x 45mg or 90mg n=552 Participants Ustekinumab s.c. 45 mg or 90 mg (depending on body weight) using 45mg pre-filled syringes (1 or 2 syringes)
Participants Who Achieved Psoriasis Area and Severity Index (PASI) 100 Response at Week 16	250 Participants	147 Participants

SECONDARY outcome

Timeframe: Week 16

Investigator's Global Assessment uses a scale (IGA mod 2011) that rates disease from a score of 0 (clear skin) to 4 (severe disease)

Outcome measures

Outcome measures
Measure	Secukinumab 300mg (2 x 150 mg) n=550 Participants Secukinumab 300mg s.c. injection (2 150mg pre-fiilled syringes)	Ustekinumab 2 x 45mg or 90mg n=552 Participants Ustekinumab s.c. 45 mg or 90 mg (depending on body weight) using 45mg pre-filled syringes (1 or 2 syringes)
Participants With IGA Mod 2011 0 or 1 at 16 Weeks	432 Participants	326 Participants

SECONDARY outcome

Timeframe: Week 12

Population: FAS

Number of participants who achieved 100% reduction in PASI at Week 12 compared to baseline.

Outcome measures

Outcome measures
Measure	Secukinumab 300mg (2 x 150 mg) n=550 Participants Secukinumab 300mg s.c. injection (2 150mg pre-fiilled syringes)	Ustekinumab 2 x 45mg or 90mg n=552 Participants Ustekinumab s.c. 45 mg or 90 mg (depending on body weight) using 45mg pre-filled syringes (1 or 2 syringes)
Participants Who Achieved Psoriasis Area and Severity Index (PASI) 100 Response at Week 12	210 Participants	111 Participants

SECONDARY outcome

Timeframe: Week 16

Population: FAS

Number of participants who achieved ≥ 75% reduction in PASI at Week 16 compared to baseline.

Outcome measures

Outcome measures
Measure	Secukinumab 300mg (2 x 150 mg) n=550 Participants Secukinumab 300mg s.c. injection (2 150mg pre-fiilled syringes)	Ustekinumab 2 x 45mg or 90mg n=552 Participants Ustekinumab s.c. 45 mg or 90 mg (depending on body weight) using 45mg pre-filled syringes (1 or 2 syringes)
Participants Who Achieved Psoriasis Area and Severity Index (PASI) 75 Response at Week 16	506 Participants	441 Participants

SECONDARY outcome

Timeframe: Week 16

Population: FAS

Number of participants who achieved ≥ 90% reduction in PASI at Week 16 compared to baseline.

Outcome measures

Outcome measures
Measure	Secukinumab 300mg (2 x 150 mg) n=550 Participants Secukinumab 300mg s.c. injection (2 150mg pre-fiilled syringes)	Ustekinumab 2 x 45mg or 90mg n=552 Participants Ustekinumab s.c. 45 mg or 90 mg (depending on body weight) using 45mg pre-filled syringes (1 or 2 syringes)
Participants Who Achieved Psoriasis Area and Severity Index (PASI) 90 Response at Week 16	423 Participants	299 Participants

SECONDARY outcome

Timeframe: Week 52

Population: FAS

Number of participants who achieved ≥ 90% reduction in PASI at Week 52 compared to baseline.

Outcome measures

Outcome measures
Measure	Secukinumab 300mg (2 x 150 mg) n=550 Participants Secukinumab 300mg s.c. injection (2 150mg pre-fiilled syringes)	Ustekinumab 2 x 45mg or 90mg n=552 Participants Ustekinumab s.c. 45 mg or 90 mg (depending on body weight) using 45mg pre-filled syringes (1 or 2 syringes)
Participants Who Achieved Psoriasis Area and Severity Index (PASI) 90 Response at Week 52	402 Participants	330 Participants

Adverse Events

AIN457 300 mg

Serious events: 29 serious events

Other events: 216 other events

Deaths: 2 deaths

UST 45/90 mg

Serious events: 21 serious events

Other events: 229 other events

Deaths: 0 deaths

All Patients

Serious events: 50 serious events

Other events: 445 other events

Deaths: 2 deaths

Serious adverse events

Other adverse events

Additional Information

Study Director

Novartis Pharmaceuticals

Phone: +1 (862) 778-8300

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (ie, data from all sites) in the clinical trial.
Publication restrictions are in place

Restriction type: OTHER

Serious adverse events
Measure	AIN457 300 mg n=550 participants at risk Secukinumab 300mg s.c. injection in 2 150mg pre-fiilled syringes	UST 45/90 mg n=552 participants at risk Ustekinumab s.c. 45mg or 90 mg (depending on body weight) (using 45mg pre-filled syringes)	All Patients n=1102 participants at risk All Patients from both arms
Blood and lymphatic system disorders Lymphadenopathy	0.18% 1/550 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for approximately 52 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of 52 weeks	0.00% 0/552 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for approximately 52 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of 52 weeks	0.09% 1/1102 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for approximately 52 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of 52 weeks
Cardiac disorders Angina pectoris	0.18% 1/550 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for approximately 52 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of 52 weeks	0.00% 0/552 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for approximately 52 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of 52 weeks	0.09% 1/1102 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for approximately 52 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of 52 weeks
Cardiac disorders Atrial fibrillation	0.55% 3/550 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for approximately 52 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of 52 weeks	0.00% 0/552 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for approximately 52 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of 52 weeks	0.27% 3/1102 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for approximately 52 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of 52 weeks
Cardiac disorders Myocardial ischaemia	0.18% 1/550 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for approximately 52 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of 52 weeks	0.00% 0/552 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for approximately 52 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of 52 weeks	0.09% 1/1102 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for approximately 52 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of 52 weeks
Cardiac disorders Ventricular tachycardia	0.36% 2/550 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for approximately 52 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of 52 weeks	0.00% 0/552 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for approximately 52 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of 52 weeks	0.18% 2/1102 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for approximately 52 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of 52 weeks
Gastrointestinal disorders Anal fissure	0.18% 1/550 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for approximately 52 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of 52 weeks	0.00% 0/552 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for approximately 52 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of 52 weeks	0.09% 1/1102 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for approximately 52 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of 52 weeks
Gastrointestinal disorders Colitis erosive	0.18% 1/550 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for approximately 52 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of 52 weeks	0.00% 0/552 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for approximately 52 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of 52 weeks	0.09% 1/1102 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for approximately 52 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of 52 weeks
Gastrointestinal disorders Colitis ulcerative	0.18% 1/550 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for approximately 52 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of 52 weeks	0.00% 0/552 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for approximately 52 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of 52 weeks	0.09% 1/1102 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for approximately 52 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of 52 weeks
Gastrointestinal disorders Haemorrhoids	0.00% 0/550 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for approximately 52 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of 52 weeks	0.18% 1/552 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for approximately 52 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of 52 weeks	0.09% 1/1102 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for approximately 52 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of 52 weeks
Gastrointestinal disorders Pancreatitis acute	0.18% 1/550 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for approximately 52 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of 52 weeks	0.00% 0/552 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for approximately 52 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of 52 weeks	0.09% 1/1102 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for approximately 52 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of 52 weeks
General disorders Sudden cardiac death	0.18% 1/550 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for approximately 52 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of 52 weeks	0.00% 0/552 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for approximately 52 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of 52 weeks	0.09% 1/1102 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for approximately 52 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of 52 weeks
Hepatobiliary disorders Cholecystitis	0.18% 1/550 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for approximately 52 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of 52 weeks	0.00% 0/552 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for approximately 52 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of 52 weeks	0.09% 1/1102 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for approximately 52 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of 52 weeks
Immune system disorders Anaphylactic reaction	0.18% 1/550 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for approximately 52 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of 52 weeks	0.00% 0/552 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for approximately 52 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of 52 weeks	0.09% 1/1102 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for approximately 52 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of 52 weeks
Immune system disorders Drug hypersensitivity	0.00% 0/550 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for approximately 52 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of 52 weeks	0.18% 1/552 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for approximately 52 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of 52 weeks	0.09% 1/1102 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for approximately 52 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of 52 weeks
Infections and infestations Bronchitis	0.18% 1/550 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for approximately 52 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of 52 weeks	0.00% 0/552 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for approximately 52 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of 52 weeks	0.09% 1/1102 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for approximately 52 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of 52 weeks
Infections and infestations Cellulitis	0.18% 1/550 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for approximately 52 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of 52 weeks	0.36% 2/552 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for approximately 52 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of 52 weeks	0.27% 3/1102 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for approximately 52 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of 52 weeks
Infections and infestations Clostridium difficile colitis	0.18% 1/550 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for approximately 52 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of 52 weeks	0.00% 0/552 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for approximately 52 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of 52 weeks	0.09% 1/1102 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for approximately 52 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of 52 weeks
Infections and infestations Dengue fever	0.36% 2/550 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for approximately 52 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of 52 weeks	0.00% 0/552 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for approximately 52 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of 52 weeks	0.18% 2/1102 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for approximately 52 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of 52 weeks
Infections and infestations Diverticulitis	0.18% 1/550 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for approximately 52 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of 52 weeks	0.00% 0/552 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for approximately 52 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of 52 weeks	0.09% 1/1102 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for approximately 52 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of 52 weeks
Infections and infestations Endocarditis	0.00% 0/550 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for approximately 52 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of 52 weeks	0.18% 1/552 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for approximately 52 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of 52 weeks	0.09% 1/1102 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for approximately 52 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of 52 weeks
Infections and infestations Peritonitis	0.18% 1/550 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for approximately 52 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of 52 weeks	0.00% 0/552 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for approximately 52 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of 52 weeks	0.09% 1/1102 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for approximately 52 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of 52 weeks
Infections and infestations Pharyngitis	0.18% 1/550 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for approximately 52 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of 52 weeks	0.00% 0/552 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for approximately 52 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of 52 weeks	0.09% 1/1102 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for approximately 52 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of 52 weeks
Infections and infestations Pneumonia streptococcal	0.18% 1/550 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for approximately 52 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of 52 weeks	0.00% 0/552 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for approximately 52 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of 52 weeks	0.09% 1/1102 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for approximately 52 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of 52 weeks
Infections and infestations Pyelonephritis acute	0.00% 0/550 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for approximately 52 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of 52 weeks	0.18% 1/552 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for approximately 52 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of 52 weeks	0.09% 1/1102 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for approximately 52 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of 52 weeks
Infections and infestations Sepsis	0.18% 1/550 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for approximately 52 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of 52 weeks	0.00% 0/552 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for approximately 52 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of 52 weeks	0.09% 1/1102 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for approximately 52 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of 52 weeks
Infections and infestations Skin candida	0.18% 1/550 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for approximately 52 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of 52 weeks	0.00% 0/552 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for approximately 52 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of 52 weeks	0.09% 1/1102 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for approximately 52 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of 52 weeks
Infections and infestations Tonsillitis	0.18% 1/550 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for approximately 52 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of 52 weeks	0.00% 0/552 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for approximately 52 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of 52 weeks	0.09% 1/1102 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for approximately 52 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of 52 weeks
Infections and infestations Urinary tract infection	0.00% 0/550 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for approximately 52 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of 52 weeks	0.18% 1/552 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for approximately 52 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of 52 weeks	0.09% 1/1102 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for approximately 52 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of 52 weeks
Injury, poisoning and procedural complications Comminuted fracture	0.00% 0/550 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for approximately 52 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of 52 weeks	0.18% 1/552 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for approximately 52 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of 52 weeks	0.09% 1/1102 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for approximately 52 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of 52 weeks
Injury, poisoning and procedural complications Fall	0.00% 0/550 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for approximately 52 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of 52 weeks	0.18% 1/552 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for approximately 52 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of 52 weeks	0.09% 1/1102 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for approximately 52 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of 52 weeks
Injury, poisoning and procedural complications Gun shot wound	0.00% 0/550 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for approximately 52 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of 52 weeks	0.18% 1/552 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for approximately 52 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of 52 weeks	0.09% 1/1102 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for approximately 52 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of 52 weeks
Injury, poisoning and procedural complications Incisional hernia	0.18% 1/550 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for approximately 52 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of 52 weeks	0.00% 0/552 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for approximately 52 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of 52 weeks	0.09% 1/1102 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for approximately 52 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of 52 weeks
Injury, poisoning and procedural complications Postoperative ileus	0.18% 1/550 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for approximately 52 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of 52 weeks	0.00% 0/552 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for approximately 52 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of 52 weeks	0.09% 1/1102 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for approximately 52 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of 52 weeks
Injury, poisoning and procedural complications Toxicity to various agents	0.18% 1/550 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for approximately 52 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of 52 weeks	0.00% 0/552 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for approximately 52 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of 52 weeks	0.09% 1/1102 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for approximately 52 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of 52 weeks
Injury, poisoning and procedural complications Wrist fracture	0.00% 0/550 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for approximately 52 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of 52 weeks	0.18% 1/552 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for approximately 52 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of 52 weeks	0.09% 1/1102 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for approximately 52 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of 52 weeks
Investigations Haemoglobin decreased	0.00% 0/550 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for approximately 52 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of 52 weeks	0.18% 1/552 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for approximately 52 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of 52 weeks	0.09% 1/1102 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for approximately 52 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of 52 weeks
Metabolism and nutrition disorders Dehydration	0.00% 0/550 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for approximately 52 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of 52 weeks	0.18% 1/552 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for approximately 52 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of 52 weeks	0.09% 1/1102 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for approximately 52 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of 52 weeks
Metabolism and nutrition disorders Hyperglycaemia	0.00% 0/550 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for approximately 52 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of 52 weeks	0.18% 1/552 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for approximately 52 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of 52 weeks	0.09% 1/1102 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for approximately 52 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of 52 weeks
Musculoskeletal and connective tissue disorders Bursitis	0.00% 0/550 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for approximately 52 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of 52 weeks	0.18% 1/552 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for approximately 52 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of 52 weeks	0.09% 1/1102 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for approximately 52 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of 52 weeks
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Adenocarcinoma	0.00% 0/550 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for approximately 52 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of 52 weeks	0.18% 1/552 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for approximately 52 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of 52 weeks	0.09% 1/1102 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for approximately 52 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of 52 weeks

Other adverse events
Measure	AIN457 300 mg n=550 participants at risk Secukinumab 300mg s.c. injection in 2 150mg pre-fiilled syringes	UST 45/90 mg n=552 participants at risk Ustekinumab s.c. 45mg or 90 mg (depending on body weight) (using 45mg pre-filled syringes)	All Patients n=1102 participants at risk All Patients from both arms
Gastrointestinal disorders Diarrhoea	4.7% 26/550 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for approximately 52 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of 52 weeks	4.3% 24/552 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for approximately 52 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of 52 weeks	4.5% 50/1102 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for approximately 52 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of 52 weeks
Gastrointestinal disorders Nausea	1.1% 6/550 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for approximately 52 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of 52 weeks	2.4% 13/552 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for approximately 52 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of 52 weeks	1.7% 19/1102 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for approximately 52 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of 52 weeks
Infections and infestations Bronchitis	1.5% 8/550 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for approximately 52 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of 52 weeks	3.3% 18/552 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for approximately 52 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of 52 weeks	2.4% 26/1102 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for approximately 52 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of 52 weeks
Infections and infestations Conjunctivitis	2.2% 12/550 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for approximately 52 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of 52 weeks	1.1% 6/552 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for approximately 52 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of 52 weeks	1.6% 18/1102 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for approximately 52 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of 52 weeks
Infections and infestations Nasopharyngitis	10.0% 55/550 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for approximately 52 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of 52 weeks	9.8% 54/552 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for approximately 52 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of 52 weeks	9.9% 109/1102 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for approximately 52 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of 52 weeks
Infections and infestations Sinusitis	4.5% 25/550 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for approximately 52 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of 52 weeks	3.3% 18/552 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for approximately 52 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of 52 weeks	3.9% 43/1102 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for approximately 52 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of 52 weeks
Infections and infestations Upper respiratory tract infection	8.9% 49/550 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for approximately 52 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of 52 weeks	11.1% 61/552 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for approximately 52 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of 52 weeks	10.0% 110/1102 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for approximately 52 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of 52 weeks
Infections and infestations Urinary tract infection	2.4% 13/550 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for approximately 52 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of 52 weeks	1.6% 9/552 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for approximately 52 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of 52 weeks	2.0% 22/1102 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for approximately 52 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of 52 weeks
Musculoskeletal and connective tissue disorders Arthralgia	1.6% 9/550 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for approximately 52 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of 52 weeks	2.5% 14/552 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for approximately 52 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of 52 weeks	2.1% 23/1102 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for approximately 52 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of 52 weeks
Musculoskeletal and connective tissue disorders Back pain	2.5% 14/550 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for approximately 52 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of 52 weeks	3.6% 20/552 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for approximately 52 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of 52 weeks	3.1% 34/1102 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for approximately 52 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of 52 weeks
Nervous system disorders Headache	4.7% 26/550 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for approximately 52 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of 52 weeks	4.5% 25/552 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for approximately 52 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of 52 weeks	4.6% 51/1102 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for approximately 52 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of 52 weeks
Respiratory, thoracic and mediastinal disorders Cough	3.1% 17/550 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for approximately 52 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of 52 weeks	2.9% 16/552 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for approximately 52 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of 52 weeks	3.0% 33/1102 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for approximately 52 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of 52 weeks
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	2.5% 14/550 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for approximately 52 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of 52 weeks	3.1% 17/552 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for approximately 52 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of 52 weeks	2.8% 31/1102 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for approximately 52 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of 52 weeks
Skin and subcutaneous tissue disorders Dermatitis contact	2.2% 12/550 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for approximately 52 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of 52 weeks	1.4% 8/552 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for approximately 52 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of 52 weeks	1.8% 20/1102 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for approximately 52 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of 52 weeks
Skin and subcutaneous tissue disorders Pruritus	2.2% 12/550 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for approximately 52 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of 52 weeks	3.3% 18/552 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for approximately 52 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of 52 weeks	2.7% 30/1102 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for approximately 52 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of 52 weeks
Vascular disorders Hypertension	3.1% 17/550 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for approximately 52 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of 52 weeks	4.0% 22/552 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for approximately 52 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of 52 weeks	3.5% 39/1102 • AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for approximately 52 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 52 weeks All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of 52 weeks