Trial Outcomes & Findings for A Rheumatoid Arthritis Study in Participants on a Background Treatment of Methotrexate (NCT NCT01198002)

NCT ID: NCT01198002

Last Updated: 2018-05-08

Results Overview

ACR Responder Index: Composite of clinical, laboratory, and functional measures of rheumatoid arthritis (RA). ACR20 Responder: had ≥20% improvement from baseline in both 68 tender and 66 swollen joint counts and ≥20% improvement in at least 3 of 5 criteria: participant's and physician's global assessment of disease activity, Health Assessment Questionnaire-Disability Index (HAQ-DI) (which measured participants' perceived degree of difficulty performing daily activities), joint pain, and C-reactive protein (CRP). Percentage of participants achieving ACR20 response=(number of ACR20 responders) / (number of participants treated) \* 100. All NR at Week 16 as well as all participants who discontinued study treatment at any time for any reason were defined as NR starting at that time-point and going forward, including Week 24 endpoint.

• Recruitment status: TERMINATED
• Study phase: PHASE3
• Target enrollment: 1041 participants
• Primary outcome timeframe: Baseline through 24 weeks
• Results posted on: 2018-05-08

Participant Flow

Study had a blinded Treatment Period 1 (Weeks 0-52), a non-blinded Treatment Period 2 (Weeks 52-100) and a post-treatment follow-up (24-48 weeks in length). All participants were assessed for nonresponse at Week 16 with non-responders (NR) defined as participants with <20% improvement from baseline in both tender and swollen joint counts.

Participant milestones

Measure	120 mg LY2127399 Treatment Period 1 (Weeks 0-52): A loading dose of 240 milligrams (mg) (2 injections of 120 mg) of LY2127399, followed by maintenance dosing of 120 mg of LY2127399 administered subcutaneously (SC) every 4 weeks (Q4W). For blinding purposes, participants alternated injections of LY2127399 and injections of placebo every 2 weeks (Q2W). At Week 16, responders received 1 injection of 120 mg of LY2127399 and 1 injection of placebo, followed by 120 mg of LY2127399 Q4W for the rest of the Treatment Period 1. Treatment Period 2 (Weeks 52-100): At Week 52, Week 16 responders received 1 injection of 120 mg of LY2127399 and 1 injection of placebo, followed by 120 mg of LY2127399 Q4W for the rest of the Treatment Period 2. At Week 16, NR received 1 injection of 90 mg of LY2127399 and 1 injection of placebo, followed by 90 mg of LY2127399 Q2W for the rest of the 100-week treatment period.	90 mg LY2127399 Treatment Period 1 (Weeks 0-52): A loading dose of 180 mg of LY2127399 (2 injections of 90 mg), followed by maintenance dosing of 90 mg of LY2127399 administered SC Q2W. At Week 16, responders received 1 injection of 90 mg of LY2127399 and 1 injection of placebo, followed by 90 mg of LY2127399 Q2W for the rest of the Treatment Period 1. Treatment Period 2 (Weeks 52-100): At Week 52, Week 16 responders received 1 injection of 90 mg of LY2127399 and 1 injection of placebo, followed by 90 mg of LY2127399 Q2W for the rest of the Treatment Period 2. At Week 16, NR received 1 injection of 90 mg of LY2127399 and 1 injection of placebo, followed by 90 mg of LY2127399 Q2W for the rest of the 100-week treatment period.	Placebo Treatment Period 1 (Weeks 0-52): A loading dose of 2 injections of placebo, followed by maintenance dosing of 1 injection of placebo administered SC Q2W. At Week 16, responders received 2 injections of placebo, followed by 1 injection of placebo Q2W for the rest of the Treatment Period 1. Treatment Period 2 (Weeks 52-100): At Week 52, responders were randomized to receive either 2 injections of 120 mg of LY2127399, followed by 120 mg of LY2127399 Q4W for the rest of the Treatment Period 2 or 2 injections of 90 mg of LY2127399, followed by 90 mg of LY2127399 Q2W for the rest of the Treatment Period 2. At Week 16, NR received a loading dose of 180 mg of LY2127399 (2 injections of 90 mg), followed by 90 mg of LY2127399 Q2W for the rest of the 100-week treatment period.
Treatment Period 1 (Weeks 0-52) STARTED	345	347	349
Treatment Period 1 (Weeks 0-52) Received at Least 1 Dose of Study Drug	345	345	348
Treatment Period 1 (Weeks 0-52) Week 16 NR	58	62	90
Treatment Period 1 (Weeks 0-52) Post-Treatment Follow-Up Population	293	303	307
Treatment Period 1 (Weeks 0-52) COMPLETED	70	73	80
Treatment Period 1 (Weeks 0-52) NOT COMPLETED	275	274	269
Treatment Period 2 (Weeks 52-100) STARTED	70	73	80
Treatment Period 2 (Weeks 52-100) COMPLETED	1	0	2
Treatment Period 2 (Weeks 52-100) NOT COMPLETED	69	73	78

Reasons for withdrawal

Measure	120 mg LY2127399 Treatment Period 1 (Weeks 0-52): A loading dose of 240 milligrams (mg) (2 injections of 120 mg) of LY2127399, followed by maintenance dosing of 120 mg of LY2127399 administered subcutaneously (SC) every 4 weeks (Q4W). For blinding purposes, participants alternated injections of LY2127399 and injections of placebo every 2 weeks (Q2W). At Week 16, responders received 1 injection of 120 mg of LY2127399 and 1 injection of placebo, followed by 120 mg of LY2127399 Q4W for the rest of the Treatment Period 1. Treatment Period 2 (Weeks 52-100): At Week 52, Week 16 responders received 1 injection of 120 mg of LY2127399 and 1 injection of placebo, followed by 120 mg of LY2127399 Q4W for the rest of the Treatment Period 2. At Week 16, NR received 1 injection of 90 mg of LY2127399 and 1 injection of placebo, followed by 90 mg of LY2127399 Q2W for the rest of the 100-week treatment period.	90 mg LY2127399 Treatment Period 1 (Weeks 0-52): A loading dose of 180 mg of LY2127399 (2 injections of 90 mg), followed by maintenance dosing of 90 mg of LY2127399 administered SC Q2W. At Week 16, responders received 1 injection of 90 mg of LY2127399 and 1 injection of placebo, followed by 90 mg of LY2127399 Q2W for the rest of the Treatment Period 1. Treatment Period 2 (Weeks 52-100): At Week 52, Week 16 responders received 1 injection of 90 mg of LY2127399 and 1 injection of placebo, followed by 90 mg of LY2127399 Q2W for the rest of the Treatment Period 2. At Week 16, NR received 1 injection of 90 mg of LY2127399 and 1 injection of placebo, followed by 90 mg of LY2127399 Q2W for the rest of the 100-week treatment period.	Placebo Treatment Period 1 (Weeks 0-52): A loading dose of 2 injections of placebo, followed by maintenance dosing of 1 injection of placebo administered SC Q2W. At Week 16, responders received 2 injections of placebo, followed by 1 injection of placebo Q2W for the rest of the Treatment Period 1. Treatment Period 2 (Weeks 52-100): At Week 52, responders were randomized to receive either 2 injections of 120 mg of LY2127399, followed by 120 mg of LY2127399 Q4W for the rest of the Treatment Period 2 or 2 injections of 90 mg of LY2127399, followed by 90 mg of LY2127399 Q2W for the rest of the Treatment Period 2. At Week 16, NR received a loading dose of 180 mg of LY2127399 (2 injections of 90 mg), followed by 90 mg of LY2127399 Q2W for the rest of the 100-week treatment period.
Treatment Period 1 (Weeks 0-52) Adverse Event	18	11	11
Treatment Period 1 (Weeks 0-52) Death	2	0	1
Treatment Period 1 (Weeks 0-52) Lack of Efficacy	10	9	6
Treatment Period 1 (Weeks 0-52) Entry Criteria Not Met	1	3	3
Treatment Period 1 (Weeks 0-52) Lost to Follow-up	0	2	0
Treatment Period 1 (Weeks 0-52) Withdrawal by Subject	16	21	12
Treatment Period 1 (Weeks 0-52) Physician Decision	1	2	2
Treatment Period 1 (Weeks 0-52) Protocol Violation	14	10	10
Treatment Period 1 (Weeks 0-52) Sponsor Decision	213	216	224
Treatment Period 2 (Weeks 52-100) Adverse Event	2	0	1
Treatment Period 2 (Weeks 52-100) Lack of Efficacy	3	1	1
Treatment Period 2 (Weeks 52-100) Entry Criteria Not Met	1	0	0
Treatment Period 2 (Weeks 52-100) Lost to Follow-up	0	2	0
Treatment Period 2 (Weeks 52-100) Physician Decision	1	0	1
Treatment Period 2 (Weeks 52-100) Sponsor Decision	62	70	75

Baseline Characteristics

A Rheumatoid Arthritis Study in Participants on a Background Treatment of Methotrexate

Baseline characteristics by cohort

Measure	90 mg LY2127399 n=347 Participants Treatment Period 1 (Weeks 0-52): A loading dose of 180 mg of LY2127399 (2 injections of 90 mg), followed by maintenance dosing of 90 mg of LY2127399 administered SC Q2W. At Week 16, responders received 1 injection of 90 mg of LY2127399 and 1 injection of placebo, followed by 90 mg of LY2127399 Q2W for the rest of the Treatment Period 1. Treatment Period 2 (Weeks 52-100): At Week 52, Week 16 responders received 1 injection of 90 mg of LY2127399 and 1 injection of placebo, followed by 90 mg of LY2127399 Q2W for the rest of the Treatment Period 2. At Week 16, NR received 1 injection of 90 mg of LY2127399 and 1 injection of placebo, followed by 90 mg of LY2127399 Q2W for the rest of the 100-week treatment period.	Placebo n=349 Participants Treatment Period 1 (Weeks 0-52): A loading dose of 2 injections of placebo, followed by maintenance dosing of 1 injection of placebo administered SC Q2W. At Week 16, responders received 2 injections of placebo, followed by 1 injection of placebo Q2W for the rest of the Treatment Period 1. Treatment Period 2 (Weeks 52-100): At Week 52, responders were randomized to receive either 2 injections of 120 mg of LY2127399, followed by 120 mg of LY2127399 Q4W for the rest of the Treatment Period 2 or 2 injections of 90 mg of LY2127399, followed by 90 mg of LY2127399 Q2W for the rest of the Treatment Period 2. At Week 16, NR received a loading dose of 180 mg of LY2127399 (2 injections of 90 mg), followed by 90 mg of LY2127399 Q2W for the rest of the 100-week treatment period.	Total n=1041 Participants Total of all reporting groups	120 mg LY2127399 n=345 Participants Treatment Period 1 (Weeks 0-52): A loading dose of 240 mg (2 injections of 120 mg) of LY2127399, followed by maintenance dosing of 120 mg of LY2127399 administered SC Q4W. For blinding purposes, participants alternated injections of LY2127399 and injections of placebo Q2W. At Week 16, responders received 1 injection of 120 mg of LY2127399 and 1 injection of placebo, followed by 120 mg of LY2127399 Q4W for the rest of the Treatment Period 1. Treatment Period 2 (Weeks 52-100): At Week 52, Week 16 responders received 1 injection of 120 mg of LY2127399 and 1 injection of placebo, followed by 120 mg of LY2127399 Q4W for the rest of the Treatment Period 2. At Week 16, NR received 1 injection of 90 mg of LY2127399 and 1 injection of placebo, followed by 90 mg of LY2127399 Q2W for the rest of the 100-week treatment period.
Age, Continuous	52.8 years STANDARD_DEVIATION 10.9 • n=7 Participants	52.9 years STANDARD_DEVIATION 11.5 • n=5 Participants	53.2 years STANDARD_DEVIATION 11.4 • n=4 Participants	53.7 years STANDARD_DEVIATION 11.8 • n=5 Participants
Sex: Female, Male Female	291 Participants n=7 Participants	292 Participants n=5 Participants	877 Participants n=4 Participants	294 Participants n=5 Participants
Sex: Female, Male Male	56 Participants n=7 Participants	57 Participants n=5 Participants	164 Participants n=4 Participants	51 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	67 Participants n=7 Participants	61 Participants n=5 Participants	191 Participants n=4 Participants	63 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	131 Participants n=7 Participants	140 Participants n=5 Participants	411 Participants n=4 Participants	140 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	149 Participants n=7 Participants	148 Participants n=5 Participants	439 Participants n=4 Participants	142 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	18 Participants n=7 Participants	15 Participants n=5 Participants	53 Participants n=4 Participants	20 Participants n=5 Participants
Race (NIH/OMB) Asian	102 Participants n=7 Participants	101 Participants n=5 Participants	303 Participants n=4 Participants	100 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	1 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	19 Participants n=7 Participants	22 Participants n=5 Participants	63 Participants n=4 Participants	22 Participants n=5 Participants
Race (NIH/OMB) White	197 Participants n=7 Participants	200 Participants n=5 Participants	588 Participants n=4 Participants	191 Participants n=5 Participants
Race (NIH/OMB) More than one race	7 Participants n=7 Participants	7 Participants n=5 Participants	23 Participants n=4 Participants	9 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	3 Participants n=7 Participants	4 Participants n=5 Participants	10 Participants n=4 Participants	3 Participants n=5 Participants
Region of Enrollment United States	55 Participants n=7 Participants	56 Participants n=5 Participants	167 Participants n=4 Participants	56 Participants n=5 Participants
Region of Enrollment Taiwan	11 Participants n=7 Participants	10 Participants n=5 Participants	31 Participants n=4 Participants	10 Participants n=5 Participants
Region of Enrollment Slovakia	3 Participants n=7 Participants	4 Participants n=5 Participants	11 Participants n=4 Participants	4 Participants n=5 Participants
Region of Enrollment Ukraine	22 Participants n=7 Participants	23 Participants n=5 Participants	68 Participants n=4 Participants	23 Participants n=5 Participants
Region of Enrollment Lithuania	6 Participants n=7 Participants	8 Participants n=5 Participants	20 Participants n=4 Participants	6 Participants n=5 Participants
Region of Enrollment Russia	25 Participants n=7 Participants	24 Participants n=5 Participants	72 Participants n=4 Participants	23 Participants n=5 Participants
Region of Enrollment Colombia	21 Participants n=7 Participants	11 Participants n=5 Participants	51 Participants n=4 Participants	19 Participants n=5 Participants
Region of Enrollment Sri Lanka	2 Participants n=7 Participants	2 Participants n=5 Participants	5 Participants n=4 Participants	1 Participants n=5 Participants
Region of Enrollment India	5 Participants n=7 Participants	4 Participants n=5 Participants	14 Participants n=4 Participants	5 Participants n=5 Participants
Region of Enrollment Hungary	9 Participants n=7 Participants	8 Participants n=5 Participants	25 Participants n=4 Participants	8 Participants n=5 Participants
Region of Enrollment Mexico	16 Participants n=7 Participants	28 Participants n=5 Participants	64 Participants n=4 Participants	20 Participants n=5 Participants
Region of Enrollment Argentina	17 Participants n=7 Participants	16 Participants n=5 Participants	50 Participants n=4 Participants	17 Participants n=5 Participants
Region of Enrollment Malaysia	3 Participants n=7 Participants	3 Participants n=5 Participants	8 Participants n=4 Participants	2 Participants n=5 Participants
Region of Enrollment Brazil	14 Participants n=7 Participants	13 Participants n=5 Participants	41 Participants n=4 Participants	14 Participants n=5 Participants
Region of Enrollment Poland	34 Participants n=7 Participants	33 Participants n=5 Participants	100 Participants n=4 Participants	33 Participants n=5 Participants
Region of Enrollment Croatia	0 Participants n=7 Participants	1 Participants n=5 Participants	2 Participants n=4 Participants	1 Participants n=5 Participants
Region of Enrollment Romania	2 Participants n=7 Participants	2 Participants n=5 Participants	4 Participants n=4 Participants	0 Participants n=5 Participants
Region of Enrollment South Africa	16 Participants n=7 Participants	16 Participants n=5 Participants	48 Participants n=4 Participants	16 Participants n=5 Participants
Region of Enrollment Bulgaria	11 Participants n=7 Participants	10 Participants n=5 Participants	32 Participants n=4 Participants	11 Participants n=5 Participants
Region of Enrollment Japan	53 Participants n=7 Participants	53 Participants n=5 Participants	158 Participants n=4 Participants	52 Participants n=5 Participants
Region of Enrollment New Zealand	0 Participants n=7 Participants	1 Participants n=5 Participants	2 Participants n=4 Participants	1 Participants n=5 Participants
Region of Enrollment South Korea	22 Participants n=7 Participants	23 Participants n=5 Participants	68 Participants n=4 Participants	23 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline through 24 weeks

Population: All randomized participants with evaluable ACR20 responder data. If participant's CRP was missing, last post-baseline value was used. If ACR was missing after carrying forward CRP, last post-baseline ACR response was used. Data after Week 16 for Week 16 NR were not included.

ACR Responder Index: Composite of clinical, laboratory, and functional measures of rheumatoid arthritis (RA). ACR20 Responder: had ≥20% improvement from baseline in both 68 tender and 66 swollen joint counts and ≥20% improvement in at least 3 of 5 criteria: participant's and physician's global assessment of disease activity, Health Assessment Questionnaire-Disability Index (HAQ-DI) (which measured participants' perceived degree of difficulty performing daily activities), joint pain, and C-reactive protein (CRP). Percentage of participants achieving ACR20 response=(number of ACR20 responders) / (number of participants treated) * 100. All NR at Week 16 as well as all participants who discontinued study treatment at any time for any reason were defined as NR starting at that time-point and going forward, including Week 24 endpoint.

Outcome measures

Measure	120 mg LY2127399 n=330 Participants Treatment Period 1 (Weeks 0-52): A loading dose of 240 mg (2 injections of 120 mg) of LY2127399, followed by maintenance dosing of 120 mg of LY2127399 administered SC Q4W. For blinding purposes, participants alternated injections of LY2127399 and injections of placebo Q2W. At Week 16, responders received 1 injection of 120 mg of LY2127399 and 1 injection of placebo, followed by 120 mg of LY2127399 Q4W for the rest of the Treatment Period 1. Treatment Period 2 (Weeks 52-100): At Week 52, Week 16 responders received 1 injection of 120 mg of LY2127399 and 1 injection of placebo, followed by 120 mg of LY2127399 Q4W for the rest of the Treatment Period 2.	90 mg LY2127399 n=332 Participants Treatment Period 1 (Weeks 0-52): A loading dose of 180 mg of LY2127399 (2 injections of 90 mg), followed by maintenance dosing of 90 mg of LY2127399 administered SC Q2W. At Week 16, responders received 1 injection of 90 mg of LY2127399 and 1 injection of placebo, followed by 90 mg of LY2127399 Q2W for the rest of the Treatment Period 1. Treatment Period 2 (Weeks 52-100): At Week 52, Week 16 responders received 1 injection of 90 mg of LY2127399 and 1 injection of placebo, followed by 90 mg of LY2127399 Q2W for the rest of the Treatment Period 2.	Placebo n=335 Participants Placebo Treatment Period 1 (Weeks 0-52): A loading dose of 2 injections of placebo, followed by maintenance dosing of 1 injection of placebo administered SC Q2W. At Week 16, responders received 2 injections of placebo, followed by 1 injection of placebo Q2W for the rest of the Treatment Period 1. Treatment Period 2 (Weeks 52-100): At Week 52, responders were randomized to receive either 2 injections of 120 mg of LY2127399, followed by 120 mg of LY2127399 Q4W for the rest of the Treatment Period 2 or 2 injections of 90 mg of LY2127399, followed by 90 mg of LY2127399 Q2W for the rest of the Treatment Period 2.
Percentage of Participants With American College of Rheumatology 20% Response (ACR20) at Week 24	29.7 percentage of participants	32.8 percentage of participants	25.1 percentage of participants

PRIMARY outcome

Timeframe: Baseline, 52 Weeks

Population: All randomized participants with evaluable mTSS data. A linear extrapolation method was used to impute missing post-baseline values. Data after Week 16 for Week 16 NR were included.

The mTSS quantifies the extent of bone erosions and joint space narrowing for 44 and 42 joints. X-rays of the hands/wrists and feet are scored for erosions on a scale from 0 (no damage) to 5 (complete collapse) and joint space narrowing on a scale from 0 (no damage) to 4 (ankylosis or complete dislocation). Erosions scores (range = 0 to 220 for 44 joints) and narrowing scores (range = 0 to 168 for 42 joints) were added to obtain the mTSS (range = 0 [normal] to 388 [maximal disease]). Least Squares (LS) means were calculated using analysis of covariance (ANCOVA) with treatment and region as fixed factors and baseline as a covariate.

Outcome measures

Measure	120 mg LY2127399 n=295 Participants Treatment Period 1 (Weeks 0-52): A loading dose of 240 mg (2 injections of 120 mg) of LY2127399, followed by maintenance dosing of 120 mg of LY2127399 administered SC Q4W. For blinding purposes, participants alternated injections of LY2127399 and injections of placebo Q2W. At Week 16, responders received 1 injection of 120 mg of LY2127399 and 1 injection of placebo, followed by 120 mg of LY2127399 Q4W for the rest of the Treatment Period 1. Treatment Period 2 (Weeks 52-100): At Week 52, Week 16 responders received 1 injection of 120 mg of LY2127399 and 1 injection of placebo, followed by 120 mg of LY2127399 Q4W for the rest of the Treatment Period 2.	90 mg LY2127399 n=304 Participants Treatment Period 1 (Weeks 0-52): A loading dose of 180 mg of LY2127399 (2 injections of 90 mg), followed by maintenance dosing of 90 mg of LY2127399 administered SC Q2W. At Week 16, responders received 1 injection of 90 mg of LY2127399 and 1 injection of placebo, followed by 90 mg of LY2127399 Q2W for the rest of the Treatment Period 1. Treatment Period 2 (Weeks 52-100): At Week 52, Week 16 responders received 1 injection of 90 mg of LY2127399 and 1 injection of placebo, followed by 90 mg of LY2127399 Q2W for the rest of the Treatment Period 2.	Placebo n=306 Participants Placebo Treatment Period 1 (Weeks 0-52): A loading dose of 2 injections of placebo, followed by maintenance dosing of 1 injection of placebo administered SC Q2W. At Week 16, responders received 2 injections of placebo, followed by 1 injection of placebo Q2W for the rest of the Treatment Period 1. Treatment Period 2 (Weeks 52-100): At Week 52, responders were randomized to receive either 2 injections of 120 mg of LY2127399, followed by 120 mg of LY2127399 Q4W for the rest of the Treatment Period 2 or 2 injections of 90 mg of LY2127399, followed by 90 mg of LY2127399 Q2W for the rest of the Treatment Period 2.
Change From Baseline to Week 52 in Van Der Heijde Modified Total Sharp Score (mTSS)	1.43 units on a scale Standard Error 0.27	0.84 units on a scale Standard Error 0.27	1.57 units on a scale Standard Error 0.27

PRIMARY outcome

Timeframe: Baseline, 24 weeks

Population: All randomized participants with evaluable HAQ-DI data. Modified Baseline Observation Carried Forward (mBOCF) was used to impute missing post-baseline values. Data after Week 16 for Week 16 NR were not included.

The HAQ-DI questionnaire assesses the participant's self-perception on the degree of difficulty [0 (without any difficulty), 1 (with some difficulty), 2 (with much difficulty), and 3 (unable to do)] when dressing and grooming, arising, eating, walking, hygiene, reaching, gripping, and performing other daily activities. Scores for each functional area were averaged to calculate HAQ-DI scores, which ranged from 0 (no disability) to 3 (severe disability). A decrease in HAQ-DI score indicated an improvement in the participant's condition. LS means were calculated using ANCOVA with treatment and region as fixed factors and baseline as a covariate.

Outcome measures

Measure	120 mg LY2127399 n=329 Participants Treatment Period 1 (Weeks 0-52): A loading dose of 240 mg (2 injections of 120 mg) of LY2127399, followed by maintenance dosing of 120 mg of LY2127399 administered SC Q4W. For blinding purposes, participants alternated injections of LY2127399 and injections of placebo Q2W. At Week 16, responders received 1 injection of 120 mg of LY2127399 and 1 injection of placebo, followed by 120 mg of LY2127399 Q4W for the rest of the Treatment Period 1. Treatment Period 2 (Weeks 52-100): At Week 52, Week 16 responders received 1 injection of 120 mg of LY2127399 and 1 injection of placebo, followed by 120 mg of LY2127399 Q4W for the rest of the Treatment Period 2.	90 mg LY2127399 n=327 Participants Treatment Period 1 (Weeks 0-52): A loading dose of 180 mg of LY2127399 (2 injections of 90 mg), followed by maintenance dosing of 90 mg of LY2127399 administered SC Q2W. At Week 16, responders received 1 injection of 90 mg of LY2127399 and 1 injection of placebo, followed by 90 mg of LY2127399 Q2W for the rest of the Treatment Period 1. Treatment Period 2 (Weeks 52-100): At Week 52, Week 16 responders received 1 injection of 90 mg of LY2127399 and 1 injection of placebo, followed by 90 mg of LY2127399 Q2W for the rest of the Treatment Period 2.	Placebo n=328 Participants Placebo Treatment Period 1 (Weeks 0-52): A loading dose of 2 injections of placebo, followed by maintenance dosing of 1 injection of placebo administered SC Q2W. At Week 16, responders received 2 injections of placebo, followed by 1 injection of placebo Q2W for the rest of the Treatment Period 1. Treatment Period 2 (Weeks 52-100): At Week 52, responders were randomized to receive either 2 injections of 120 mg of LY2127399, followed by 120 mg of LY2127399 Q4W for the rest of the Treatment Period 2 or 2 injections of 90 mg of LY2127399, followed by 90 mg of LY2127399 Q2W for the rest of the Treatment Period 2.
Change From Baseline to Week 24 in Health Assessment Questionnaire-Disability Index (HAQ-DI)	-0.26 units on a scale Standard Error 0.03	-0.30 units on a scale Standard Error 0.03	-0.20 units on a scale Standard Error 0.03

SECONDARY outcome

Timeframe: Baseline through 24 weeks and 52 weeks

Population: All randomized participants with evaluable ACR50 or ACR70 responder data. If participant's CRP was missing, last post-baseline value was used. If ACR was missing after carrying forward CRP, last post-baseline ACR response was used. Data after Week 16 for Week 16 NR were not included.

ACR Responder Index: Composite of clinical, laboratory, and functional measures of RA. ACR50 Responder: had ≥50% improvement from baseline in both 68 tender joint (TJ) and 66 swollen joint (SJ) counts and ≥50% improvement in at least 3 of 5 criteria: participant's (Pt's) and physician's global assessment of disease activity, HAQ-DI (measured Pts' perceived degree of difficulty performing daily activities), joint pain, and CRP. Percentage of Pt achieving ACR50 response=(number (No.) of ACR50 responders) / (No. of Pts treated) * 100. ACR70 Responder: had ≥70% improvement from baseline in both TJ and SJ counts and ≥70% improvement in at least 3 of same 5 criteria for ACR50. Percentage of Pts achieving ACR70 response= (No. of ACR70 responders) / (No. of Pts treated) * 100. All NR at Week 16 as well as all Pts who discontinued study treatment at any time for any reason were defined as NR starting at that time-point and going forward, including Weeks 24 and 52 endpoints.

Outcome measures

Measure	120 mg LY2127399 n=330 Participants Treatment Period 1 (Weeks 0-52): A loading dose of 240 mg (2 injections of 120 mg) of LY2127399, followed by maintenance dosing of 120 mg of LY2127399 administered SC Q4W. For blinding purposes, participants alternated injections of LY2127399 and injections of placebo Q2W. At Week 16, responders received 1 injection of 120 mg of LY2127399 and 1 injection of placebo, followed by 120 mg of LY2127399 Q4W for the rest of the Treatment Period 1. Treatment Period 2 (Weeks 52-100): At Week 52, Week 16 responders received 1 injection of 120 mg of LY2127399 and 1 injection of placebo, followed by 120 mg of LY2127399 Q4W for the rest of the Treatment Period 2.	90 mg LY2127399 n=332 Participants Treatment Period 1 (Weeks 0-52): A loading dose of 180 mg of LY2127399 (2 injections of 90 mg), followed by maintenance dosing of 90 mg of LY2127399 administered SC Q2W. At Week 16, responders received 1 injection of 90 mg of LY2127399 and 1 injection of placebo, followed by 90 mg of LY2127399 Q2W for the rest of the Treatment Period 1. Treatment Period 2 (Weeks 52-100): At Week 52, Week 16 responders received 1 injection of 90 mg of LY2127399 and 1 injection of placebo, followed by 90 mg of LY2127399 Q2W for the rest of the Treatment Period 2.	Placebo n=335 Participants Placebo Treatment Period 1 (Weeks 0-52): A loading dose of 2 injections of placebo, followed by maintenance dosing of 1 injection of placebo administered SC Q2W. At Week 16, responders received 2 injections of placebo, followed by 1 injection of placebo Q2W for the rest of the Treatment Period 1. Treatment Period 2 (Weeks 52-100): At Week 52, responders were randomized to receive either 2 injections of 120 mg of LY2127399, followed by 120 mg of LY2127399 Q4W for the rest of the Treatment Period 2 or 2 injections of 90 mg of LY2127399, followed by 90 mg of LY2127399 Q2W for the rest of the Treatment Period 2.
Percentage of Participants With American College of Rheumatology 50% (ACR50) and 70% (ACR70) Response ACR50 - Week 24	10.6 percentage of participants	11.1 percentage of participants	10.1 percentage of participants
Percentage of Participants With American College of Rheumatology 50% (ACR50) and 70% (ACR70) Response ACR50 - Week 52	4.2 percentage of participants	3.0 percentage of participants	4.8 percentage of participants
Percentage of Participants With American College of Rheumatology 50% (ACR50) and 70% (ACR70) Response ACR70 - Week 24	3.9 percentage of participants	3.0 percentage of participants	3.0 percentage of participants
Percentage of Participants With American College of Rheumatology 50% (ACR50) and 70% (ACR70) Response ACR70 - Week 52	1.5 percentage of participants	1.2 percentage of participants	1.8 percentage of participants

SECONDARY outcome

Timeframe: Baseline, 24 weeks and 52 weeks

Population: All randomized participants with evaluable DAS28-CRP data. mBOCF was used to impute missing post-baseline values. Data after Week 16 for Week 16 NR were not included.

Disease Activity Score (DAS) modified to include 28 joint count (DAS28) consisted of composite score of following variables: tender joint count (TJC28), swollen joint count (SJC28), CRP [milligrams per liter (mg/L)], and participant's global assessment of disease activity using visual analog scale (VAS) (participant global VAS). DAS28-CRP=0.56*square root (sqrt)(TJC28)+0.28*sqrt(SJC28)+0.36*natural log(CRP+1)+0.014*participant global VAS+0.96. Scores ranged from 1.0-9.4, where lower scores indicated less disease activity and remission is DAS28-CRP <2.6. A decrease in DAS28-CRP indicated an improvement in participant's condition. LS means were calculated using ANCOVA with treatment and region as fixed factors and baseline as a covariate.

Outcome measures

Measure	120 mg LY2127399 n=328 Participants Treatment Period 1 (Weeks 0-52): A loading dose of 240 mg (2 injections of 120 mg) of LY2127399, followed by maintenance dosing of 120 mg of LY2127399 administered SC Q4W. For blinding purposes, participants alternated injections of LY2127399 and injections of placebo Q2W. At Week 16, responders received 1 injection of 120 mg of LY2127399 and 1 injection of placebo, followed by 120 mg of LY2127399 Q4W for the rest of the Treatment Period 1. Treatment Period 2 (Weeks 52-100): At Week 52, Week 16 responders received 1 injection of 120 mg of LY2127399 and 1 injection of placebo, followed by 120 mg of LY2127399 Q4W for the rest of the Treatment Period 2.	90 mg LY2127399 n=327 Participants Treatment Period 1 (Weeks 0-52): A loading dose of 180 mg of LY2127399 (2 injections of 90 mg), followed by maintenance dosing of 90 mg of LY2127399 administered SC Q2W. At Week 16, responders received 1 injection of 90 mg of LY2127399 and 1 injection of placebo, followed by 90 mg of LY2127399 Q2W for the rest of the Treatment Period 1. Treatment Period 2 (Weeks 52-100): At Week 52, Week 16 responders received 1 injection of 90 mg of LY2127399 and 1 injection of placebo, followed by 90 mg of LY2127399 Q2W for the rest of the Treatment Period 2.	Placebo n=328 Participants Placebo Treatment Period 1 (Weeks 0-52): A loading dose of 2 injections of placebo, followed by maintenance dosing of 1 injection of placebo administered SC Q2W. At Week 16, responders received 2 injections of placebo, followed by 1 injection of placebo Q2W for the rest of the Treatment Period 1. Treatment Period 2 (Weeks 52-100): At Week 52, responders were randomized to receive either 2 injections of 120 mg of LY2127399, followed by 120 mg of LY2127399 Q4W for the rest of the Treatment Period 2 or 2 injections of 90 mg of LY2127399, followed by 90 mg of LY2127399 Q2W for the rest of the Treatment Period 2.
Change From Baseline in Disease Activity Score Based on 28 Joint Count and C-Reactive Protein Level (DAS28-CRP) Week 24	-1.02 units on a scale Standard Error 0.07	-1.00 units on a scale Standard Error 0.07	-0.78 units on a scale Standard Error 0.07
Change From Baseline in Disease Activity Score Based on 28 Joint Count and C-Reactive Protein Level (DAS28-CRP) Week 52	-1.07 units on a scale Standard Error 0.07	-1.00 units on a scale Standard Error 0.07	-0.80 units on a scale Standard Error 0.07

SECONDARY outcome

Timeframe: Baseline through 24 weeks and 52 weeks

Population: All randomized participants with evaluable EULAR response data. Modified last observation carried forward (mLOCF) was used to impute missing post-baseline values. Data after Week 16 for Week 16 NR were not included.

EULAR Responder index based on 28 joint counts categorizes clinical response based on improvement since baseline in DAS28-CRP. DAS28-CRP scores range from 1.0-9.4, where lower scores indicated less disease activity. High disease activity: DAS28-CRP >5.1, low disease activity: DAS28-CRP <3.2, and remission: DAS28-CRP <2.6. Participants are categorized as EULAR responders or NR based on improvement of DAS28-CRP scores from baseline. EULAR DAS28-CRP responder index defines a good (absolute: <3.2 or >1.2 improvement from baseline), moderate (absolute: 3.2-5.1 or 0.6-1.2 improvement from baseline), or no response (absolute: >5.1 or <0.6 improvement from baseline). Percentage of participants with DAS28-CRP based EULAR response =(number of participants with specific response) / (number of participants analyzed in the group) * 100.

Outcome measures

Measure	120 mg LY2127399 n=328 Participants Treatment Period 1 (Weeks 0-52): A loading dose of 240 mg (2 injections of 120 mg) of LY2127399, followed by maintenance dosing of 120 mg of LY2127399 administered SC Q4W. For blinding purposes, participants alternated injections of LY2127399 and injections of placebo Q2W. At Week 16, responders received 1 injection of 120 mg of LY2127399 and 1 injection of placebo, followed by 120 mg of LY2127399 Q4W for the rest of the Treatment Period 1. Treatment Period 2 (Weeks 52-100): At Week 52, Week 16 responders received 1 injection of 120 mg of LY2127399 and 1 injection of placebo, followed by 120 mg of LY2127399 Q4W for the rest of the Treatment Period 2.	90 mg LY2127399 n=327 Participants Treatment Period 1 (Weeks 0-52): A loading dose of 180 mg of LY2127399 (2 injections of 90 mg), followed by maintenance dosing of 90 mg of LY2127399 administered SC Q2W. At Week 16, responders received 1 injection of 90 mg of LY2127399 and 1 injection of placebo, followed by 90 mg of LY2127399 Q2W for the rest of the Treatment Period 1. Treatment Period 2 (Weeks 52-100): At Week 52, Week 16 responders received 1 injection of 90 mg of LY2127399 and 1 injection of placebo, followed by 90 mg of LY2127399 Q2W for the rest of the Treatment Period 2.	Placebo n=328 Participants Placebo Treatment Period 1 (Weeks 0-52): A loading dose of 2 injections of placebo, followed by maintenance dosing of 1 injection of placebo administered SC Q2W. At Week 16, responders received 2 injections of placebo, followed by 1 injection of placebo Q2W for the rest of the Treatment Period 1. Treatment Period 2 (Weeks 52-100): At Week 52, responders were randomized to receive either 2 injections of 120 mg of LY2127399, followed by 120 mg of LY2127399 Q4W for the rest of the Treatment Period 2 or 2 injections of 90 mg of LY2127399, followed by 90 mg of LY2127399 Q2W for the rest of the Treatment Period 2.
Percentage of Participants With DAS28-CRP Based European League Against Rheumatism (EULAR) Response Week 24 - Moderate	41.5 percentage of participants	38.5 percentage of participants	30.8 percentage of participants
Percentage of Participants With DAS28-CRP Based European League Against Rheumatism (EULAR) Response Week 24- Good	17.7 percentage of participants	16.2 percentage of participants	14.3 percentage of participants
Percentage of Participants With DAS28-CRP Based European League Against Rheumatism (EULAR) Response Week 24 - No Response	40.9 percentage of participants	45.3 percentage of participants	54.9 percentage of participants
Percentage of Participants With DAS28-CRP Based European League Against Rheumatism (EULAR) Response Week 52 - Moderate	37.5 percentage of participants	39.1 percentage of participants	29.0 percentage of participants
Percentage of Participants With DAS28-CRP Based European League Against Rheumatism (EULAR) Response Week 52 - No Response	43.9 percentage of participants	46.2 percentage of participants	55.2 percentage of participants
Percentage of Participants With DAS28-CRP Based European League Against Rheumatism (EULAR) Response Week 52 - Good	18.6 percentage of participants	14.7 percentage of participants	15.9 percentage of participants

SECONDARY outcome

Timeframe: Baseline, 24 weeks and 52 weeks

Population: All randomized participants with evaluable SF-36 domain and summary scores. mBOCF was used to impute missing post-baseline values. Data after Week 16 for Week 16 NR were not included.

SF-36 is a health-related survey that assesses participant's quality of life and consists of 36 questions covering 8 health domains: physical functioning, bodily pain, role limitations due to physical problems and emotional problems, general health, mental health, social functioning, vitality, 2 component scores (CS), physical CS (PCS) and mental CS (MCS). Domain scores were calculated by summing each item for each domain and transforming scores into a 0-100 scale. Higher scores indicated better health status. If < 50% of the questions within a domain were answered, raw scores were not calculated. PCS score consisted of physical functioning, bodily pain, role-physical, and general health scales. MCS score consisted of social functioning, vitality, mental health, and role-emotional scales. Both PCS and MCS range from 0-100. Higher score indicated better mental or physical health. LS means were calculated using ANCOVA with treatment, region as fixed factors and baseline as a covariate.

Outcome measures

Measure	120 mg LY2127399 n=320 Participants Treatment Period 1 (Weeks 0-52): A loading dose of 240 mg (2 injections of 120 mg) of LY2127399, followed by maintenance dosing of 120 mg of LY2127399 administered SC Q4W. For blinding purposes, participants alternated injections of LY2127399 and injections of placebo Q2W. At Week 16, responders received 1 injection of 120 mg of LY2127399 and 1 injection of placebo, followed by 120 mg of LY2127399 Q4W for the rest of the Treatment Period 1. Treatment Period 2 (Weeks 52-100): At Week 52, Week 16 responders received 1 injection of 120 mg of LY2127399 and 1 injection of placebo, followed by 120 mg of LY2127399 Q4W for the rest of the Treatment Period 2.	90 mg LY2127399 n=322 Participants Treatment Period 1 (Weeks 0-52): A loading dose of 180 mg of LY2127399 (2 injections of 90 mg), followed by maintenance dosing of 90 mg of LY2127399 administered SC Q2W. At Week 16, responders received 1 injection of 90 mg of LY2127399 and 1 injection of placebo, followed by 90 mg of LY2127399 Q2W for the rest of the Treatment Period 1. Treatment Period 2 (Weeks 52-100): At Week 52, Week 16 responders received 1 injection of 90 mg of LY2127399 and 1 injection of placebo, followed by 90 mg of LY2127399 Q2W for the rest of the Treatment Period 2.	Placebo n=323 Participants Placebo Treatment Period 1 (Weeks 0-52): A loading dose of 2 injections of placebo, followed by maintenance dosing of 1 injection of placebo administered SC Q2W. At Week 16, responders received 2 injections of placebo, followed by 1 injection of placebo Q2W for the rest of the Treatment Period 1. Treatment Period 2 (Weeks 52-100): At Week 52, responders were randomized to receive either 2 injections of 120 mg of LY2127399, followed by 120 mg of LY2127399 Q4W for the rest of the Treatment Period 2 or 2 injections of 90 mg of LY2127399, followed by 90 mg of LY2127399 Q2W for the rest of the Treatment Period 2.
Change From Baseline in Medical Outcomes Study 36-Item Short Form (SF-36) Health Survey Domain Scores and Summary Scores Physical functioning - Week 24	2.70 units on a scale Standard Error 0.48	3.16 units on a scale Standard Error 0.47	2.06 units on a scale Standard Error 0.47
Change From Baseline in Medical Outcomes Study 36-Item Short Form (SF-36) Health Survey Domain Scores and Summary Scores Physical functioning - Week 52	2.15 units on a scale Standard Error 0.50	3.22 units on a scale Standard Error 0.49	1.82 units on a scale Standard Error 0.49
Change From Baseline in Medical Outcomes Study 36-Item Short Form (SF-36) Health Survey Domain Scores and Summary Scores Bodily pain - Week 52	3.77 units on a scale Standard Error 0.47	4.48 units on a scale Standard Error 0.46	2.32 units on a scale Standard Error 0.46
Change From Baseline in Medical Outcomes Study 36-Item Short Form (SF-36) Health Survey Domain Scores and Summary Scores RL - physical problems - Week 24	2.77 units on a scale Standard Error 0.46	3.64 units on a scale Standard Error 0.46	1.99 units on a scale Standard Error 0.45
Change From Baseline in Medical Outcomes Study 36-Item Short Form (SF-36) Health Survey Domain Scores and Summary Scores RL - physical problems - Week 52	3.01 units on a scale Standard Error 0.47	3.79 units on a scale Standard Error 0.46	1.82 units on a scale Standard Error 0.46
Change From Baseline in Medical Outcomes Study 36-Item Short Form (SF-36) Health Survey Domain Scores and Summary Scores RL - emotional problems- Week 24	3.20 units on a scale Standard Error 0.60	4.81 units on a scale Standard Error 0.59	2.91 units on a scale Standard Error 0.59
Change From Baseline in Medical Outcomes Study 36-Item Short Form (SF-36) Health Survey Domain Scores and Summary Scores RL - emotional problems- Week 52	2.84 units on a scale Standard Error 0.61	4.34 units on a scale Standard Error 0.59	2.56 units on a scale Standard Error 0.59
Change From Baseline in Medical Outcomes Study 36-Item Short Form (SF-36) Health Survey Domain Scores and Summary Scores GH Perception - Week 24	2.60 units on a scale Standard Error 0.41	3.72 units on a scale Standard Error 0.40	2.54 units on a scale Standard Error 0.40
Change From Baseline in Medical Outcomes Study 36-Item Short Form (SF-36) Health Survey Domain Scores and Summary Scores GH Perception - Week 52	2.89 units on a scale Standard Error 0.42	3.41 units on a scale Standard Error 0.41	2.18 units on a scale Standard Error 0.41
Change From Baseline in Medical Outcomes Study 36-Item Short Form (SF-36) Health Survey Domain Scores and Summary Scores Mental Health - Week 24	3.39 units on a scale Standard Error 0.53	4.47 units on a scale Standard Error 0.53	3.28 units on a scale Standard Error 0.52
Change From Baseline in Medical Outcomes Study 36-Item Short Form (SF-36) Health Survey Domain Scores and Summary Scores Mental Health - Week 52	3.01 units on a scale Standard Error 0.55	4.37 units on a scale Standard Error 0.54	3.10 units on a scale Standard Error 0.54
Change From Baseline in Medical Outcomes Study 36-Item Short Form (SF-36) Health Survey Domain Scores and Summary Scores Social function - Week 24	3.25 units on a scale Standard Error 0.53	4.18 units on a scale Standard Error 0.52	2.79 units on a scale Standard Error 0.52
Change From Baseline in Medical Outcomes Study 36-Item Short Form (SF-36) Health Survey Domain Scores and Summary Scores Social function - Week 52	3.04 units on a scale Standard Error 0.53	3.99 units on a scale Standard Error 0.52	2.87 units on a scale Standard Error 0.52
Change From Baseline in Medical Outcomes Study 36-Item Short Form (SF-36) Health Survey Domain Scores and Summary Scores Vitality - Week 24	3.43 units on a scale Standard Error 0.50	4.41 units on a scale Standard Error 0.49	2.99 units on a scale Standard Error 0.48
Change From Baseline in Medical Outcomes Study 36-Item Short Form (SF-36) Health Survey Domain Scores and Summary Scores Vitality - Week 52	3.10 units on a scale Standard Error 0.51	3.96 units on a scale Standard Error 0.50	3.02 units on a scale Standard Error 0.49
Change From Baseline in Medical Outcomes Study 36-Item Short Form (SF-36) Health Survey Domain Scores and Summary Scores PCS - Week 24	2.80 units on a scale Standard Error 0.43	3.08 units on a scale Standard Error 0.43	1.76 units on a scale Standard Error 0.42
Change From Baseline in Medical Outcomes Study 36-Item Short Form (SF-36) Health Survey Domain Scores and Summary Scores PCS - Week 52	2.79 units on a scale Standard Error 0.44	3.30 units on a scale Standard Error 0.43	1.55 units on a scale Standard Error 0.43
Change From Baseline in Medical Outcomes Study 36-Item Short Form (SF-36) Health Survey Domain Scores and Summary Scores MCS - Week 24	3.34 units on a scale Standard Error 0.56	4.74 units on a scale Standard Error 0.55	3.33 units on a scale Standard Error 0.55
Change From Baseline in Medical Outcomes Study 36-Item Short Form (SF-36) Health Survey Domain Scores and Summary Scores MCS - Week 52	2.98 units on a scale Standard Error 0.57	4.27 units on a scale Standard Error 0.56	3.22 units on a scale Standard Error 0.56
Change From Baseline in Medical Outcomes Study 36-Item Short Form (SF-36) Health Survey Domain Scores and Summary Scores Bodily pain - Week 24	4.07 units on a scale Standard Error 0.46	4.08 units on a scale Standard Error 0.45	2.52 units on a scale Standard Error 0.45

SECONDARY outcome

Timeframe: Baseline, 24 weeks and 52 weeks

Population: All randomized participants with evaluable BFI data. mBOCF was used to impute missing post-baseline values. Data after Week 16 for Week 16 NR were not included.

The BFI is a brief participant-reported questionnaire for the rapid assessment of fatigue severity and the impact of fatigue on daily functioning in the past 24 hours. The BFI contains 10 items; however, Item 1 is not included in the scoring of the scale as it asks about usual fatigue over the past week with the participant answering 'yes' or 'no'. The remaining 9 items assess fatigue severity (3 items) and impact of fatigue on daily functioning (6 items) using an 11-point numeric scale, with 0=no fatigue and 10=fatigue as bad as you can imagine. The fatigue impact subscale score is the average of the non-missing responses to 6 items: general activity, mood, walking ability, normal work, relations with other people, and enjoyment of life. If more than 3 items within the fatigue impact subscale were not answered by a participant, the subscale is set to missing. LS means were calculated using ANCOVA with treatment and region as fixed factors and baseline as a covariate.

Outcome measures

Measure	120 mg LY2127399 n=320 Participants Treatment Period 1 (Weeks 0-52): A loading dose of 240 mg (2 injections of 120 mg) of LY2127399, followed by maintenance dosing of 120 mg of LY2127399 administered SC Q4W. For blinding purposes, participants alternated injections of LY2127399 and injections of placebo Q2W. At Week 16, responders received 1 injection of 120 mg of LY2127399 and 1 injection of placebo, followed by 120 mg of LY2127399 Q4W for the rest of the Treatment Period 1. Treatment Period 2 (Weeks 52-100): At Week 52, Week 16 responders received 1 injection of 120 mg of LY2127399 and 1 injection of placebo, followed by 120 mg of LY2127399 Q4W for the rest of the Treatment Period 2.	90 mg LY2127399 n=322 Participants Treatment Period 1 (Weeks 0-52): A loading dose of 180 mg of LY2127399 (2 injections of 90 mg), followed by maintenance dosing of 90 mg of LY2127399 administered SC Q2W. At Week 16, responders received 1 injection of 90 mg of LY2127399 and 1 injection of placebo, followed by 90 mg of LY2127399 Q2W for the rest of the Treatment Period 1. Treatment Period 2 (Weeks 52-100): At Week 52, Week 16 responders received 1 injection of 90 mg of LY2127399 and 1 injection of placebo, followed by 90 mg of LY2127399 Q2W for the rest of the Treatment Period 2.	Placebo n=323 Participants Placebo Treatment Period 1 (Weeks 0-52): A loading dose of 2 injections of placebo, followed by maintenance dosing of 1 injection of placebo administered SC Q2W. At Week 16, responders received 2 injections of placebo, followed by 1 injection of placebo Q2W for the rest of the Treatment Period 1. Treatment Period 2 (Weeks 52-100): At Week 52, responders were randomized to receive either 2 injections of 120 mg of LY2127399, followed by 120 mg of LY2127399 Q4W for the rest of the Treatment Period 2 or 2 injections of 90 mg of LY2127399, followed by 90 mg of LY2127399 Q2W for the rest of the Treatment Period 2.
Change From Baseline in Brief Fatigue Inventory (BFI) Individual Items and Impact Score Fatigue-Now - Week 24	-0.86 units on a scale Standard Error 0.14	-1.12 units on a scale Standard Error 0.13	-0.61 units on a scale Standard Error 0.13
Change From Baseline in Brief Fatigue Inventory (BFI) Individual Items and Impact Score Fatigue-Now - Week 52	-0.79 units on a scale Standard Error 0.14	-1.01 units on a scale Standard Error 0.13	-0.56 units on a scale Standard Error 0.13
Change From Baseline in Brief Fatigue Inventory (BFI) Individual Items and Impact Score Fatigue-Worst - Week 52	-1.22 units on a scale Standard Error 0.15	-1.19 units on a scale Standard Error 0.14	-0.81 units on a scale Standard Error 0.14
Change From Baseline in Brief Fatigue Inventory (BFI) Individual Items and Impact Score Normal Work - Week 24	-0.78 units on a scale Standard Error 0.14	-1.07 units on a scale Standard Error 0.14	-0.48 units on a scale Standard Error 0.14
Change From Baseline in Brief Fatigue Inventory (BFI) Individual Items and Impact Score Fatigue Impact Subscale- Week 52	-0.80 units on a scale Standard Error 0.13	-0.83 units on a scale Standard Error 0.13	-0.46 units on a scale Standard Error 0.13
Change From Baseline in Brief Fatigue Inventory (BFI) Individual Items and Impact Score Fatigue-Usual - Week 24	-0.93 units on a scale Standard Error 0.13	-1.06 units on a scale Standard Error 0.13	-0.61 units on a scale Standard Error 0.13
Change From Baseline in Brief Fatigue Inventory (BFI) Individual Items and Impact Score Fatigue-Usual - Week 52	-0.91 units on a scale Standard Error 0.14	-0.97 units on a scale Standard Error 0.13	-0.66 units on a scale Standard Error 0.13
Change From Baseline in Brief Fatigue Inventory (BFI) Individual Items and Impact Score Fatigue-Worst - Week 24	-0.98 units on a scale Standard Error 0.14	-1.22 units on a scale Standard Error 0.14	-0.71 units on a scale Standard Error 0.14
Change From Baseline in Brief Fatigue Inventory (BFI) Individual Items and Impact Score General Activity - Week 24	-0.93 units on a scale Standard Error 0.14	-1.09 units on a scale Standard Error 0.13	-0.61 units on a scale Standard Error 0.13
Change From Baseline in Brief Fatigue Inventory (BFI) Individual Items and Impact Score General Activity - Week 52	-1.03 units on a scale Standard Error 0.14	-1.07 units on a scale Standard Error 0.13	-0.61 units on a scale Standard Error 0.13
Change From Baseline in Brief Fatigue Inventory (BFI) Individual Items and Impact Score Mood - Week 24	-0.67 units on a scale Standard Error 0.14	-1.01 units on a scale Standard Error 0.14	-0.47 units on a scale Standard Error 0.14
Change From Baseline in Brief Fatigue Inventory (BFI) Individual Items and Impact Score Mood - Week 52	-0.86 units on a scale Standard Error 0.14	-0.82 units on a scale Standard Error 0.14	-0.53 units on a scale Standard Error 0.14
Change From Baseline in Brief Fatigue Inventory (BFI) Individual Items and Impact Score Walking Ability - Week 24	-0.92 units on a scale Standard Error 0.15	-1.02 units on a scale Standard Error 0.14	-0.44 units on a scale Standard Error 0.14
Change From Baseline in Brief Fatigue Inventory (BFI) Individual Items and Impact Score Walking Ability - Week 52	-0.88 units on a scale Standard Error 0.14	-0.98 units on a scale Standard Error 0.14	-0.45 units on a scale Standard Error 0.14
Change From Baseline in Brief Fatigue Inventory (BFI) Individual Items and Impact Score Normal Work - Week 52	-0.88 units on a scale Standard Error 0.14	-1.00 units on a scale Standard Error 0.14	-0.52 units on a scale Standard Error 0.14
Change From Baseline in Brief Fatigue Inventory (BFI) Individual Items and Impact Score Relations with Other - Week 24	-0.39 units on a scale Standard Error 0.14	-0.64 units on a scale Standard Error 0.14	-0.13 units on a scale Standard Error 0.14
Change From Baseline in Brief Fatigue Inventory (BFI) Individual Items and Impact Score Relations with Other - Week 52	-0.47 units on a scale Standard Error 0.14	-0.46 units on a scale Standard Error 0.14	-0.16 units on a scale Standard Error 0.14
Change From Baseline in Brief Fatigue Inventory (BFI) Individual Items and Impact Score Enjoyment of Life - Week 24	-0.58 units on a scale Standard Error 0.15	-0.82 units on a scale Standard Error 0.15	-0.36 units on a scale Standard Error 0.14
Change From Baseline in Brief Fatigue Inventory (BFI) Individual Items and Impact Score Enjoyment of Life - Week 52	-0.66 units on a scale Standard Error 0.15	-0.74 units on a scale Standard Error 0.14	-0.46 units on a scale Standard Error 0.14
Change From Baseline in Brief Fatigue Inventory (BFI) Individual Items and Impact Score Fatigue Impact Subscale- Week 24	-0.71 units on a scale Standard Error 0.13	-0.93 units on a scale Standard Error 0.13	-0.42 units on a scale Standard Error 0.13

SECONDARY outcome

Timeframe: Baseline, 24 weeks and 52 weeks

Population: All randomized participants with evaluable morning stiffness data; mBOCF was used to impute missing post-baseline values. Data after Week 16 for Week 16 NR were not included.

The Investigator asks participants about the duration of their morning stiffness (in minutes) in and around the joints and records the duration. The Investigator should ask the participants about duration of morning stiffness on the day prior to the study visit to capture actual symptoms. If morning stiffness duration is longer than 12 hours (720 minutes), it was truncated to 720 minutes for statistical presentations and analyses. LS means were calculated using ANCOVA with treatment and region as fixed factors and baseline as a covariate.

Outcome measures

Measure	120 mg LY2127399 n=307 Participants Treatment Period 1 (Weeks 0-52): A loading dose of 240 mg (2 injections of 120 mg) of LY2127399, followed by maintenance dosing of 120 mg of LY2127399 administered SC Q4W. For blinding purposes, participants alternated injections of LY2127399 and injections of placebo Q2W. At Week 16, responders received 1 injection of 120 mg of LY2127399 and 1 injection of placebo, followed by 120 mg of LY2127399 Q4W for the rest of the Treatment Period 1. Treatment Period 2 (Weeks 52-100): At Week 52, Week 16 responders received 1 injection of 120 mg of LY2127399 and 1 injection of placebo, followed by 120 mg of LY2127399 Q4W for the rest of the Treatment Period 2.	90 mg LY2127399 n=319 Participants Treatment Period 1 (Weeks 0-52): A loading dose of 180 mg of LY2127399 (2 injections of 90 mg), followed by maintenance dosing of 90 mg of LY2127399 administered SC Q2W. At Week 16, responders received 1 injection of 90 mg of LY2127399 and 1 injection of placebo, followed by 90 mg of LY2127399 Q2W for the rest of the Treatment Period 1. Treatment Period 2 (Weeks 52-100): At Week 52, Week 16 responders received 1 injection of 90 mg of LY2127399 and 1 injection of placebo, followed by 90 mg of LY2127399 Q2W for the rest of the Treatment Period 2.	Placebo n=314 Participants Placebo Treatment Period 1 (Weeks 0-52): A loading dose of 2 injections of placebo, followed by maintenance dosing of 1 injection of placebo administered SC Q2W. At Week 16, responders received 2 injections of placebo, followed by 1 injection of placebo Q2W for the rest of the Treatment Period 1. Treatment Period 2 (Weeks 52-100): At Week 52, responders were randomized to receive either 2 injections of 120 mg of LY2127399, followed by 120 mg of LY2127399 Q4W for the rest of the Treatment Period 2 or 2 injections of 90 mg of LY2127399, followed by 90 mg of LY2127399 Q2W for the rest of the Treatment Period 2.
Change From Baseline in Duration of Morning Stiffness (Minutes) Week 24	-41.2 minutes Standard Error 5.0	-32.0 minutes Standard Error 4.8	-34.5 minutes Standard Error 4.9
Change From Baseline in Duration of Morning Stiffness (Minutes) Week 52	-41.4 minutes Standard Error 5.2	-31.2 minutes Standard Error 5.0	-37.3 minutes Standard Error 5.1

SECONDARY outcome

Timeframe: Baseline, 24 weeks and 52 weeks

Population: All randomized participants with evaluable BPI-SF scores. mBOCF was used to impute missing post-baseline values. Data after Week 16 for Week 16 NR were not included.

The BPI-SF is a self-reported scale that measures the severity of pain based on the worst pain, least pain, average pain experienced during the past 24-hours and pain based on the pain right now with scores ranging from 0 (no pain) to 10 (pain as severe as you can imagine). Pain interference score is the average of the responses in past 24-hours to 7 items: general activity, mood, walking ability, normal work, relations with other people, sleep, and enjoyment of life [each item scored from 0 (does not interfere) to 10 (completely interferes)]. If more than 3 items of the Pain Interference Score are not answered by a participant, the score were set to missing. LS means were calculated using ANCOVA with treatment and region as fixed factors and baseline as a covariate.

Outcome measures

Measure	120 mg LY2127399 n=320 Participants Treatment Period 1 (Weeks 0-52): A loading dose of 240 mg (2 injections of 120 mg) of LY2127399, followed by maintenance dosing of 120 mg of LY2127399 administered SC Q4W. For blinding purposes, participants alternated injections of LY2127399 and injections of placebo Q2W. At Week 16, responders received 1 injection of 120 mg of LY2127399 and 1 injection of placebo, followed by 120 mg of LY2127399 Q4W for the rest of the Treatment Period 1. Treatment Period 2 (Weeks 52-100): At Week 52, Week 16 responders received 1 injection of 120 mg of LY2127399 and 1 injection of placebo, followed by 120 mg of LY2127399 Q4W for the rest of the Treatment Period 2.	90 mg LY2127399 n=322 Participants Treatment Period 1 (Weeks 0-52): A loading dose of 180 mg of LY2127399 (2 injections of 90 mg), followed by maintenance dosing of 90 mg of LY2127399 administered SC Q2W. At Week 16, responders received 1 injection of 90 mg of LY2127399 and 1 injection of placebo, followed by 90 mg of LY2127399 Q2W for the rest of the Treatment Period 1. Treatment Period 2 (Weeks 52-100): At Week 52, Week 16 responders received 1 injection of 90 mg of LY2127399 and 1 injection of placebo, followed by 90 mg of LY2127399 Q2W for the rest of the Treatment Period 2.	Placebo n=323 Participants Placebo Treatment Period 1 (Weeks 0-52): A loading dose of 2 injections of placebo, followed by maintenance dosing of 1 injection of placebo administered SC Q2W. At Week 16, responders received 2 injections of placebo, followed by 1 injection of placebo Q2W for the rest of the Treatment Period 1. Treatment Period 2 (Weeks 52-100): At Week 52, responders were randomized to receive either 2 injections of 120 mg of LY2127399, followed by 120 mg of LY2127399 Q4W for the rest of the Treatment Period 2 or 2 injections of 90 mg of LY2127399, followed by 90 mg of LY2127399 Q2W for the rest of the Treatment Period 2.
Change From Baseline in Brief Pain Inventory Short Form (BPI-SF) Individual Items and Interference Scores Pain-Worst - Week 24	-1.1 units on a scale Standard Error 0.1	-1.1 units on a scale Standard Error 0.1	-0.7 units on a scale Standard Error 0.1
Change From Baseline in Brief Pain Inventory Short Form (BPI-SF) Individual Items and Interference Scores Pain-Now - Week 24	-1.1 units on a scale Standard Error 0.1	-1.2 units on a scale Standard Error 0.1	-0.5 units on a scale Standard Error 0.1
Change From Baseline in Brief Pain Inventory Short Form (BPI-SF) Individual Items and Interference Scores Pain-Now - Week 52	-1.0 units on a scale Standard Error 0.1	-1.3 units on a scale Standard Error 0.1	-0.5 units on a scale Standard Error 0.1
Change From Baseline in Brief Pain Inventory Short Form (BPI-SF) Individual Items and Interference Scores General Activity - Week 24	-1.0 units on a scale Standard Error 0.1	-1.0 units on a scale Standard Error 0.1	-0.6 units on a scale Standard Error 0.1
Change From Baseline in Brief Pain Inventory Short Form (BPI-SF) Individual Items and Interference Scores Pain-Average - Week 52	-0.7 units on a scale Standard Error 0.1	-1.0 units on a scale Standard Error 0.1	-0.3 units on a scale Standard Error 0.1
Change From Baseline in Brief Pain Inventory Short Form (BPI-SF) Individual Items and Interference Scores Pain-Worst - Week 52	-1.1 units on a scale Standard Error 0.1	-1.3 units on a scale Standard Error 0.1	-0.8 units on a scale Standard Error 0.1
Change From Baseline in Brief Pain Inventory Short Form (BPI-SF) Individual Items and Interference Scores Pain-Least - Week 24	-0.3 units on a scale Standard Error 0.1	-0.6 units on a scale Standard Error 0.1	-0.1 units on a scale Standard Error 0.1
Change From Baseline in Brief Pain Inventory Short Form (BPI-SF) Individual Items and Interference Scores Pain-Least - Week 52	-0.3 units on a scale Standard Error 0.1	-0.6 units on a scale Standard Error 0.1	-0.1 units on a scale Standard Error 0.1
Change From Baseline in Brief Pain Inventory Short Form (BPI-SF) Individual Items and Interference Scores Pain-Average - Week 24	-0.8 units on a scale Standard Error 0.1	-0.9 units on a scale Standard Error 0.1	-0.3 units on a scale Standard Error 0.1
Change From Baseline in Brief Pain Inventory Short Form (BPI-SF) Individual Items and Interference Scores General Activity - Week 52	-1.0 units on a scale Standard Error 0.1	-1.2 units on a scale Standard Error 0.1	-0.8 units on a scale Standard Error 0.1
Change From Baseline in Brief Pain Inventory Short Form (BPI-SF) Individual Items and Interference Scores Mood - Week 24	-0.9 units on a scale Standard Error 0.1	-1.0 units on a scale Standard Error 0.1	-0.6 units on a scale Standard Error 0.1
Change From Baseline in Brief Pain Inventory Short Form (BPI-SF) Individual Items and Interference Scores Mood - Week 52	-1.0 units on a scale Standard Error 0.1	-1.1 units on a scale Standard Error 0.1	-0.7 units on a scale Standard Error 0.1
Change From Baseline in Brief Pain Inventory Short Form (BPI-SF) Individual Items and Interference Scores Walking Ability - Week 24	-0.9 units on a scale Standard Error 0.1	-1.2 units on a scale Standard Error 0.1	-0.5 units on a scale Standard Error 0.1
Change From Baseline in Brief Pain Inventory Short Form (BPI-SF) Individual Items and Interference Scores Walking Ability - Week 52	-0.8 units on a scale Standard Error 0.1	-1.1 units on a scale Standard Error 0.1	-0.6 units on a scale Standard Error 0.1
Change From Baseline in Brief Pain Inventory Short Form (BPI-SF) Individual Items and Interference Scores Normal Work - Week 24	-1.0 units on a scale Standard Error 0.1	-1.0 units on a scale Standard Error 0.1	-0.6 units on a scale Standard Error 0.1
Change From Baseline in Brief Pain Inventory Short Form (BPI-SF) Individual Items and Interference Scores Normal Work - Week 52	-0.9 units on a scale Standard Error 0.1	-1.1 units on a scale Standard Error 0.1	-0.6 units on a scale Standard Error 0.1
Change From Baseline in Brief Pain Inventory Short Form (BPI-SF) Individual Items and Interference Scores Relations with Other - Week 24	-0.5 units on a scale Standard Error 0.1	-0.6 units on a scale Standard Error 0.1	-0.3 units on a scale Standard Error 0.1
Change From Baseline in Brief Pain Inventory Short Form (BPI-SF) Individual Items and Interference Scores Relations with Other - Week 52	-0.5 units on a scale Standard Error 0.1	-0.5 units on a scale Standard Error 0.1	-0.3 units on a scale Standard Error 0.1
Change From Baseline in Brief Pain Inventory Short Form (BPI-SF) Individual Items and Interference Scores Sleep - Week 24	-1.0 units on a scale Standard Error 0.1	-1.1 units on a scale Standard Error 0.1	-0.4 units on a scale Standard Error 0.1
Change From Baseline in Brief Pain Inventory Short Form (BPI-SF) Individual Items and Interference Scores Sleep - Week 52	-0.9 units on a scale Standard Error 0.1	-1.0 units on a scale Standard Error 0.1	-0.5 units on a scale Standard Error 0.1
Change From Baseline in Brief Pain Inventory Short Form (BPI-SF) Individual Items and Interference Scores Enjoyment of Life - Week 24	-0.8 units on a scale Standard Error 0.1	-1.2 units on a scale Standard Error 0.1	-0.5 units on a scale Standard Error 0.1
Change From Baseline in Brief Pain Inventory Short Form (BPI-SF) Individual Items and Interference Scores Enjoyment of Life - Week 52	-0.9 units on a scale Standard Error 0.1	-1.1 units on a scale Standard Error 0.1	-0.5 units on a scale Standard Error 0.1
Change From Baseline in Brief Pain Inventory Short Form (BPI-SF) Individual Items and Interference Scores Pain Interference Score - Week 24	-0.89 units on a scale Standard Error 0.12	-1.02 units on a scale Standard Error 0.12	-0.50 units on a scale Standard Error 0.12
Change From Baseline in Brief Pain Inventory Short Form (BPI-SF) Individual Items and Interference Scores Pain Interference Score - Week 52	-0.85 units on a scale Standard Error 0.12	-1.00 units on a scale Standard Error 0.12	-0.58 units on a scale Standard Error 0.12

SECONDARY outcome

Timeframe: Baseline through 52 weeks

Population: Zero participants analyzed. Per protocol and statistical analysis plan (SAP) amendments, the major clinical response classification was not collected for analysis.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline through 24 weeks

Population: All randomized participants with evaluable mTSS data. A linear extrapolation method was used to impute missing post-baseline values. Data after Week 16 for Week 16 NR were included.

The mTSS quantifies the extent of bone erosions and joint space narrowing for 44 and 42 joints. X-rays of the hands/wrists and feet are scored for erosions on a scale from 0 (no damage) to 5 (complete collapse) and joint space narrowing on a scale from 0 (no damage) to 4 (ankylosis or complete dislocation). Erosions scores (range=0 to 220 for 44 joints) and narrowing scores (range=0 to 168 for 42 joints) were added to obtain the mTSS (range = 0 [normal] to 388 [maximal disease]). Percentage of participants = (number of participants with mTSS ≤0 at Week 24) / (total number of participants analyzed in the group) * 100.

Outcome measures

Measure	120 mg LY2127399 n=295 Participants Treatment Period 1 (Weeks 0-52): A loading dose of 240 mg (2 injections of 120 mg) of LY2127399, followed by maintenance dosing of 120 mg of LY2127399 administered SC Q4W. For blinding purposes, participants alternated injections of LY2127399 and injections of placebo Q2W. At Week 16, responders received 1 injection of 120 mg of LY2127399 and 1 injection of placebo, followed by 120 mg of LY2127399 Q4W for the rest of the Treatment Period 1. Treatment Period 2 (Weeks 52-100): At Week 52, Week 16 responders received 1 injection of 120 mg of LY2127399 and 1 injection of placebo, followed by 120 mg of LY2127399 Q4W for the rest of the Treatment Period 2.	90 mg LY2127399 n=304 Participants Treatment Period 1 (Weeks 0-52): A loading dose of 180 mg of LY2127399 (2 injections of 90 mg), followed by maintenance dosing of 90 mg of LY2127399 administered SC Q2W. At Week 16, responders received 1 injection of 90 mg of LY2127399 and 1 injection of placebo, followed by 90 mg of LY2127399 Q2W for the rest of the Treatment Period 1. Treatment Period 2 (Weeks 52-100): At Week 52, Week 16 responders received 1 injection of 90 mg of LY2127399 and 1 injection of placebo, followed by 90 mg of LY2127399 Q2W for the rest of the Treatment Period 2.	Placebo n=306 Participants Placebo Treatment Period 1 (Weeks 0-52): A loading dose of 2 injections of placebo, followed by maintenance dosing of 1 injection of placebo administered SC Q2W. At Week 16, responders received 2 injections of placebo, followed by 1 injection of placebo Q2W for the rest of the Treatment Period 1. Treatment Period 2 (Weeks 52-100): At Week 52, responders were randomized to receive either 2 injections of 120 mg of LY2127399, followed by 120 mg of LY2127399 Q4W for the rest of the Treatment Period 2 or 2 injections of 90 mg of LY2127399, followed by 90 mg of LY2127399 Q2W for the rest of the Treatment Period 2.
Percentage of Participants With Change From Baseline in mTSS Less Than or Equal to (≤) 0	61.0 percentage of participants	61.8 percentage of participants	56.2 percentage of participants

SECONDARY outcome

Timeframe: Baseline, 52 weeks

Population: All randomized participants with evaluable B cell subset counts data. mLOCF was used to impute missing post-baseline values. Data after Week 16 for Week 16 NR were not included.

B cell subset counts are: cluster designation (CD)19+ B cell counts, Immature/transitional [CD19+immunoglobulin D (IgD)-CD27-], Mature naïve (CD19+IgD+CD27-), Non-switched memory (CD19+IgD+CD27+) and Memory (CD19+IgD-CD27+). A positive or negative change indicated an increase or decrease, respectively in B cell count. LS means were calculated using ANCOVA with treatment and region as fixed factors and baseline as a covariate.

Outcome measures

Measure	120 mg LY2127399 n=326 Participants Treatment Period 1 (Weeks 0-52): A loading dose of 240 mg (2 injections of 120 mg) of LY2127399, followed by maintenance dosing of 120 mg of LY2127399 administered SC Q4W. For blinding purposes, participants alternated injections of LY2127399 and injections of placebo Q2W. At Week 16, responders received 1 injection of 120 mg of LY2127399 and 1 injection of placebo, followed by 120 mg of LY2127399 Q4W for the rest of the Treatment Period 1. Treatment Period 2 (Weeks 52-100): At Week 52, Week 16 responders received 1 injection of 120 mg of LY2127399 and 1 injection of placebo, followed by 120 mg of LY2127399 Q4W for the rest of the Treatment Period 2.	90 mg LY2127399 n=333 Participants Treatment Period 1 (Weeks 0-52): A loading dose of 180 mg of LY2127399 (2 injections of 90 mg), followed by maintenance dosing of 90 mg of LY2127399 administered SC Q2W. At Week 16, responders received 1 injection of 90 mg of LY2127399 and 1 injection of placebo, followed by 90 mg of LY2127399 Q2W for the rest of the Treatment Period 1. Treatment Period 2 (Weeks 52-100): At Week 52, Week 16 responders received 1 injection of 90 mg of LY2127399 and 1 injection of placebo, followed by 90 mg of LY2127399 Q2W for the rest of the Treatment Period 2.	Placebo n=339 Participants Placebo Treatment Period 1 (Weeks 0-52): A loading dose of 2 injections of placebo, followed by maintenance dosing of 1 injection of placebo administered SC Q2W. At Week 16, responders received 2 injections of placebo, followed by 1 injection of placebo Q2W for the rest of the Treatment Period 1. Treatment Period 2 (Weeks 52-100): At Week 52, responders were randomized to receive either 2 injections of 120 mg of LY2127399, followed by 120 mg of LY2127399 Q4W for the rest of the Treatment Period 2 or 2 injections of 90 mg of LY2127399, followed by 90 mg of LY2127399 Q2W for the rest of the Treatment Period 2.
Change From Baseline to Week 52 in B Cell Subset Counts CD19+IgD-CD27-	-3.1 cells/microliter (cells/µL) Standard Error 0.7	-3.9 cells/microliter (cells/µL) Standard Error 0.7	0.2 cells/microliter (cells/µL) Standard Error 0.7
Change From Baseline to Week 52 in B Cell Subset Counts CD19+IgD-CD27+	19.7 cells/microliter (cells/µL) Standard Error 1.9	20.6 cells/microliter (cells/µL) Standard Error 1.8	3.2 cells/microliter (cells/µL) Standard Error 1.8
Change From Baseline to Week 52 in B Cell Subset Counts CD19+	-57.1 cells/microliter (cells/µL) Standard Error 4.9	-60.9 cells/microliter (cells/µL) Standard Error 4.9	0.7 cells/microliter (cells/µL) Standard Error 4.8
Change From Baseline to Week 52 in B Cell Subset Counts CD19+IgD+CD27-	-89.4 cells/microliter (cells/µL) Standard Error 3.3	-92.4 cells/microliter (cells/µL) Standard Error 3.3	-3.5 cells/microliter (cells/µL) Standard Error 3.2
Change From Baseline to Week 52 in B Cell Subset Counts CD19+IgD+CD27+	9.5 cells/microliter (cells/µL) Standard Error 1.0	8.9 cells/microliter (cells/µL) Standard Error 1.0	1.0 cells/microliter (cells/µL) Standard Error 1.0

SECONDARY outcome

Timeframe: Baseline through 52 weeks

Population: All randomized participants who received at least 1 dose of LY2127399 with evaluable LY2127399 PK data.

Population estimate of constant clearance as determined by population PK analysis. A 2-compartment model was used in PK modeling. Constant clearance is the PK parameter which describes the linear elimination of LY2127399 from serum.

Outcome measures

Measure	120 mg LY2127399 n=825 Participants Treatment Period 1 (Weeks 0-52): A loading dose of 240 mg (2 injections of 120 mg) of LY2127399, followed by maintenance dosing of 120 mg of LY2127399 administered SC Q4W. For blinding purposes, participants alternated injections of LY2127399 and injections of placebo Q2W. At Week 16, responders received 1 injection of 120 mg of LY2127399 and 1 injection of placebo, followed by 120 mg of LY2127399 Q4W for the rest of the Treatment Period 1. Treatment Period 2 (Weeks 52-100): At Week 52, Week 16 responders received 1 injection of 120 mg of LY2127399 and 1 injection of placebo, followed by 120 mg of LY2127399 Q4W for the rest of the Treatment Period 2.	90 mg LY2127399 Treatment Period 1 (Weeks 0-52): A loading dose of 180 mg of LY2127399 (2 injections of 90 mg), followed by maintenance dosing of 90 mg of LY2127399 administered SC Q2W. At Week 16, responders received 1 injection of 90 mg of LY2127399 and 1 injection of placebo, followed by 90 mg of LY2127399 Q2W for the rest of the Treatment Period 1. Treatment Period 2 (Weeks 52-100): At Week 52, Week 16 responders received 1 injection of 90 mg of LY2127399 and 1 injection of placebo, followed by 90 mg of LY2127399 Q2W for the rest of the Treatment Period 2.	Placebo Placebo Treatment Period 1 (Weeks 0-52): A loading dose of 2 injections of placebo, followed by maintenance dosing of 1 injection of placebo administered SC Q2W. At Week 16, responders received 2 injections of placebo, followed by 1 injection of placebo Q2W for the rest of the Treatment Period 1. Treatment Period 2 (Weeks 52-100): At Week 52, responders were randomized to receive either 2 injections of 120 mg of LY2127399, followed by 120 mg of LY2127399 Q4W for the rest of the Treatment Period 2 or 2 injections of 90 mg of LY2127399, followed by 90 mg of LY2127399 Q2W for the rest of the Treatment Period 2.
Population Pharmacokinetics (PK): Constant Clearance	3.60 milliliter per hour (mL/h) Interval 3.46 to 3.73	—	—

SECONDARY outcome

Timeframe: Baseline through 52 weeks

Population: All randomized participants who received at least 1 dose of study drug with an evaluable baseline ADA result and a post-baseline ADA result. Participants missing an evaluable baseline result with all negative post-baseline results were included. Data after Week 16 for Week 16 NR were not included.

Participants with treatment-emergent anti-drug antibodies (ADA) were participants who had any sample from baseline up to and through Week 24 that was a 4-fold increase (2-dilution increase) in immunogenicity titer over baseline titer, or participants who tested negative at baseline and positive post-baseline (at titer of ≥1:20). Percentage of participants with ADA=(number of participants with treatment-emergent ADA) / (number of participants assessed) * 100.

Outcome measures

Measure	120 mg LY2127399 n=344 Participants Treatment Period 1 (Weeks 0-52): A loading dose of 240 mg (2 injections of 120 mg) of LY2127399, followed by maintenance dosing of 120 mg of LY2127399 administered SC Q4W. For blinding purposes, participants alternated injections of LY2127399 and injections of placebo Q2W. At Week 16, responders received 1 injection of 120 mg of LY2127399 and 1 injection of placebo, followed by 120 mg of LY2127399 Q4W for the rest of the Treatment Period 1. Treatment Period 2 (Weeks 52-100): At Week 52, Week 16 responders received 1 injection of 120 mg of LY2127399 and 1 injection of placebo, followed by 120 mg of LY2127399 Q4W for the rest of the Treatment Period 2.	90 mg LY2127399 n=344 Participants Treatment Period 1 (Weeks 0-52): A loading dose of 180 mg of LY2127399 (2 injections of 90 mg), followed by maintenance dosing of 90 mg of LY2127399 administered SC Q2W. At Week 16, responders received 1 injection of 90 mg of LY2127399 and 1 injection of placebo, followed by 90 mg of LY2127399 Q2W for the rest of the Treatment Period 1. Treatment Period 2 (Weeks 52-100): At Week 52, Week 16 responders received 1 injection of 90 mg of LY2127399 and 1 injection of placebo, followed by 90 mg of LY2127399 Q2W for the rest of the Treatment Period 2.	Placebo n=347 Participants Placebo Treatment Period 1 (Weeks 0-52): A loading dose of 2 injections of placebo, followed by maintenance dosing of 1 injection of placebo administered SC Q2W. At Week 16, responders received 2 injections of placebo, followed by 1 injection of placebo Q2W for the rest of the Treatment Period 1. Treatment Period 2 (Weeks 52-100): At Week 52, responders were randomized to receive either 2 injections of 120 mg of LY2127399, followed by 120 mg of LY2127399 Q4W for the rest of the Treatment Period 2 or 2 injections of 90 mg of LY2127399, followed by 90 mg of LY2127399 Q2W for the rest of the Treatment Period 2.
Percentage of Participants Developing Anti-LY2127399 Antibodies	3.8 percentage of participants	1.5 percentage of participants	4.9 percentage of participants

SECONDARY outcome

Timeframe: Baseline through 52 weeks

Population: All randomized participants with evaluable mTSS data. A linear extrapolation method was used to impute missing post-baseline values. Data after Week 16 for Week 16 NR were included.

No structural progression is defined as the change in mTSS from baseline ≤0. The mTSS quantifies the extent of bone erosions and joint space narrowing for 44 and 42 joints. X-rays of the hands/wrists and feet are scored for erosions on a scale from 0 (no damage) to 5 (complete collapse) and joint space narrowing on a scale from 0 (no damage) to 4 (ankylosis or complete dislocation). Erosions scores (range=0 to 220 for 44 joints) and narrowing scores (range=0 to 168 for 42 joints) were added to obtain the mTSS (range=0 [normal] to 388 [maximal disease]). Percentage of participants=(number of participants with mTSS ≤0 at Week 52) / (total number of participants analyzed in the group) * 100.

Outcome measures

Measure	120 mg LY2127399 n=295 Participants Treatment Period 1 (Weeks 0-52): A loading dose of 240 mg (2 injections of 120 mg) of LY2127399, followed by maintenance dosing of 120 mg of LY2127399 administered SC Q4W. For blinding purposes, participants alternated injections of LY2127399 and injections of placebo Q2W. At Week 16, responders received 1 injection of 120 mg of LY2127399 and 1 injection of placebo, followed by 120 mg of LY2127399 Q4W for the rest of the Treatment Period 1. Treatment Period 2 (Weeks 52-100): At Week 52, Week 16 responders received 1 injection of 120 mg of LY2127399 and 1 injection of placebo, followed by 120 mg of LY2127399 Q4W for the rest of the Treatment Period 2.	90 mg LY2127399 n=304 Participants Treatment Period 1 (Weeks 0-52): A loading dose of 180 mg of LY2127399 (2 injections of 90 mg), followed by maintenance dosing of 90 mg of LY2127399 administered SC Q2W. At Week 16, responders received 1 injection of 90 mg of LY2127399 and 1 injection of placebo, followed by 90 mg of LY2127399 Q2W for the rest of the Treatment Period 1. Treatment Period 2 (Weeks 52-100): At Week 52, Week 16 responders received 1 injection of 90 mg of LY2127399 and 1 injection of placebo, followed by 90 mg of LY2127399 Q2W for the rest of the Treatment Period 2.	Placebo n=306 Participants Placebo Treatment Period 1 (Weeks 0-52): A loading dose of 2 injections of placebo, followed by maintenance dosing of 1 injection of placebo administered SC Q2W. At Week 16, responders received 2 injections of placebo, followed by 1 injection of placebo Q2W for the rest of the Treatment Period 1. Treatment Period 2 (Weeks 52-100): At Week 52, responders were randomized to receive either 2 injections of 120 mg of LY2127399, followed by 120 mg of LY2127399 Q4W for the rest of the Treatment Period 2 or 2 injections of 90 mg of LY2127399, followed by 90 mg of LY2127399 Q2W for the rest of the Treatment Period 2.
Percentage of Participants With No Structural Progression at Week 52	55.6 percentage of participants	57.6 percentage of participants	53.9 percentage of participants

SECONDARY outcome

Timeframe: Baseline, 24 weeks

Population: All randomized participants with evaluable mTSS data. A linear extrapolation method was used to impute missing post-baseline values. Data after Week 16 for Week 16 NR were included.

The mTSS quantifies the extent of bone erosions and joint space narrowing for 44 and 42 joints. X-rays of the hands/wrists and feet are scored for erosions on a scale from 0 (no damage) to 5 (complete collapse) and joint space narrowing on a scale from 0 (no damage) to 4 (ankylosis or complete dislocation). Erosions scores (range=0 to 220 for 44 joints) and narrowing scores (range=0 to 168 for 42 joints) were added to obtain the mTSS (range=0 [normal] to 388 [maximal disease]). LS means were calculated using ANCOVA with treatment and region as fixed factors and baseline as a covariate.

Outcome measures

Measure	120 mg LY2127399 n=295 Participants Treatment Period 1 (Weeks 0-52): A loading dose of 240 mg (2 injections of 120 mg) of LY2127399, followed by maintenance dosing of 120 mg of LY2127399 administered SC Q4W. For blinding purposes, participants alternated injections of LY2127399 and injections of placebo Q2W. At Week 16, responders received 1 injection of 120 mg of LY2127399 and 1 injection of placebo, followed by 120 mg of LY2127399 Q4W for the rest of the Treatment Period 1. Treatment Period 2 (Weeks 52-100): At Week 52, Week 16 responders received 1 injection of 120 mg of LY2127399 and 1 injection of placebo, followed by 120 mg of LY2127399 Q4W for the rest of the Treatment Period 2.	90 mg LY2127399 n=304 Participants Treatment Period 1 (Weeks 0-52): A loading dose of 180 mg of LY2127399 (2 injections of 90 mg), followed by maintenance dosing of 90 mg of LY2127399 administered SC Q2W. At Week 16, responders received 1 injection of 90 mg of LY2127399 and 1 injection of placebo, followed by 90 mg of LY2127399 Q2W for the rest of the Treatment Period 1. Treatment Period 2 (Weeks 52-100): At Week 52, Week 16 responders received 1 injection of 90 mg of LY2127399 and 1 injection of placebo, followed by 90 mg of LY2127399 Q2W for the rest of the Treatment Period 2.	Placebo n=306 Participants Placebo Treatment Period 1 (Weeks 0-52): A loading dose of 2 injections of placebo, followed by maintenance dosing of 1 injection of placebo administered SC Q2W. At Week 16, responders received 2 injections of placebo, followed by 1 injection of placebo Q2W for the rest of the Treatment Period 1. Treatment Period 2 (Weeks 52-100): At Week 52, responders were randomized to receive either 2 injections of 120 mg of LY2127399, followed by 120 mg of LY2127399 Q4W for the rest of the Treatment Period 2 or 2 injections of 90 mg of LY2127399, followed by 90 mg of LY2127399 Q2W for the rest of the Treatment Period 2.
Change From Baseline to Week 24 in mTSS	0.63 units on a scale Standard Error 0.14	0.45 units on a scale Standard Error 0.14	0.82 units on a scale Standard Error 0.14

SECONDARY outcome

Timeframe: Baseline, 52 weeks

Population: All randomized participants with evaluable serum Ig data. mLOCF was used to impute missing post-baseline values. Data after Week 16 for Week 16 NR were not included.

Immunoglobulins (Ig), or antibodies, are large proteins used by the immune system to identify and neutralize foreign particles such as bacteria and viruses. Their normal blood levels indicate proper immune status. Change from baseline serum immunoglobulin G (IgG), immunoglobulin A (IgA), and immunoglobulin M (IgM) levels are reported. A negative change indicated a decrease in Ig levels. LS means were calculated using ANCOVA with treatment and region as fixed factors and baseline as a covariate.

Outcome measures

Measure	120 mg LY2127399 n=342 Participants Treatment Period 1 (Weeks 0-52): A loading dose of 240 mg (2 injections of 120 mg) of LY2127399, followed by maintenance dosing of 120 mg of LY2127399 administered SC Q4W. For blinding purposes, participants alternated injections of LY2127399 and injections of placebo Q2W. At Week 16, responders received 1 injection of 120 mg of LY2127399 and 1 injection of placebo, followed by 120 mg of LY2127399 Q4W for the rest of the Treatment Period 1. Treatment Period 2 (Weeks 52-100): At Week 52, Week 16 responders received 1 injection of 120 mg of LY2127399 and 1 injection of placebo, followed by 120 mg of LY2127399 Q4W for the rest of the Treatment Period 2.	90 mg LY2127399 n=342 Participants Treatment Period 1 (Weeks 0-52): A loading dose of 180 mg of LY2127399 (2 injections of 90 mg), followed by maintenance dosing of 90 mg of LY2127399 administered SC Q2W. At Week 16, responders received 1 injection of 90 mg of LY2127399 and 1 injection of placebo, followed by 90 mg of LY2127399 Q2W for the rest of the Treatment Period 1. Treatment Period 2 (Weeks 52-100): At Week 52, Week 16 responders received 1 injection of 90 mg of LY2127399 and 1 injection of placebo, followed by 90 mg of LY2127399 Q2W for the rest of the Treatment Period 2.	Placebo n=347 Participants Placebo Treatment Period 1 (Weeks 0-52): A loading dose of 2 injections of placebo, followed by maintenance dosing of 1 injection of placebo administered SC Q2W. At Week 16, responders received 2 injections of placebo, followed by 1 injection of placebo Q2W for the rest of the Treatment Period 1. Treatment Period 2 (Weeks 52-100): At Week 52, responders were randomized to receive either 2 injections of 120 mg of LY2127399, followed by 120 mg of LY2127399 Q4W for the rest of the Treatment Period 2 or 2 injections of 90 mg of LY2127399, followed by 90 mg of LY2127399 Q2W for the rest of the Treatment Period 2.
Change From Baseline in Serum Immunoglobulin (Ig) Levels IgA	-0.380 grams/liter (g/L) Standard Error 0.028	-0.382 grams/liter (g/L) Standard Error 0.028	-0.009 grams/liter (g/L) Standard Error 0.028
Change From Baseline in Serum Immunoglobulin (Ig) Levels IgG	-1.375 grams/liter (g/L) Standard Error 0.096	-1.235 grams/liter (g/L) Standard Error 0.097	-0.176 grams/liter (g/L) Standard Error 0.096
Change From Baseline in Serum Immunoglobulin (Ig) Levels IgM	-0.235 grams/liter (g/L) Standard Error 0.016	-0.274 grams/liter (g/L) Standard Error 0.016	-0.032 grams/liter (g/L) Standard Error 0.016

SECONDARY outcome

Timeframe: Baseline, 24 weeks and 52 weeks

Population: All randomized participants with evaluable mTSS data. A linear extrapolation method was used to impute missing post-baseline values. Data after Week 16 for Week 16 NR were included.

The mTSS quantifies the extent of bone erosions and joint space narrowing for 44 and 42 joints. X-rays of the hands/wrists and feet are scored for erosions on a scale from 0 (no damage) to 5 (complete collapse) and joint space narrowing on a scale from 0 (no damage) to 4 (ankylosis or complete dislocation). Erosions scores (range=0 to 220 for 44 joints) and narrowing scores (range=0 to 168 for 42 joints) were added to obtain the mTSS (range=0 [normal] to 388 [maximal disease]). LS means were calculated using ANCOVA with treatment and region as fixed factors and baseline as a covariate.

Outcome measures

Measure	120 mg LY2127399 n=295 Participants Treatment Period 1 (Weeks 0-52): A loading dose of 240 mg (2 injections of 120 mg) of LY2127399, followed by maintenance dosing of 120 mg of LY2127399 administered SC Q4W. For blinding purposes, participants alternated injections of LY2127399 and injections of placebo Q2W. At Week 16, responders received 1 injection of 120 mg of LY2127399 and 1 injection of placebo, followed by 120 mg of LY2127399 Q4W for the rest of the Treatment Period 1. Treatment Period 2 (Weeks 52-100): At Week 52, Week 16 responders received 1 injection of 120 mg of LY2127399 and 1 injection of placebo, followed by 120 mg of LY2127399 Q4W for the rest of the Treatment Period 2.	90 mg LY2127399 n=304 Participants Treatment Period 1 (Weeks 0-52): A loading dose of 180 mg of LY2127399 (2 injections of 90 mg), followed by maintenance dosing of 90 mg of LY2127399 administered SC Q2W. At Week 16, responders received 1 injection of 90 mg of LY2127399 and 1 injection of placebo, followed by 90 mg of LY2127399 Q2W for the rest of the Treatment Period 1. Treatment Period 2 (Weeks 52-100): At Week 52, Week 16 responders received 1 injection of 90 mg of LY2127399 and 1 injection of placebo, followed by 90 mg of LY2127399 Q2W for the rest of the Treatment Period 2.	Placebo n=306 Participants Placebo Treatment Period 1 (Weeks 0-52): A loading dose of 2 injections of placebo, followed by maintenance dosing of 1 injection of placebo administered SC Q2W. At Week 16, responders received 2 injections of placebo, followed by 1 injection of placebo Q2W for the rest of the Treatment Period 1. Treatment Period 2 (Weeks 52-100): At Week 52, responders were randomized to receive either 2 injections of 120 mg of LY2127399, followed by 120 mg of LY2127399 Q4W for the rest of the Treatment Period 2 or 2 injections of 90 mg of LY2127399, followed by 90 mg of LY2127399 Q2W for the rest of the Treatment Period 2.
Change From Baseline in Joint Space Narrowing Score and Bone Erosions Score (Components of mTSS) Joint Space Narrowing - Week 24	0.22 units on a scale Standard Error 0.09	0.19 units on a scale Standard Error 0.09	0.34 units on a scale Standard Error 0.09
Change From Baseline in Joint Space Narrowing Score and Bone Erosions Score (Components of mTSS) Joint Space Narrowing - Week 52	0.56 units on a scale Standard Error 0.16	0.35 units on a scale Standard Error 0.16	0.61 units on a scale Standard Error 0.16
Change From Baseline in Joint Space Narrowing Score and Bone Erosions Score (Components of mTSS) Bone Erosions - Week 24	0.40 units on a scale Standard Error 0.09	0.26 units on a scale Standard Error 0.08	0.48 units on a scale Standard Error 0.08
Change From Baseline in Joint Space Narrowing Score and Bone Erosions Score (Components of mTSS) Bone Erosions - Week 52	0.86 units on a scale Standard Error 0.17	0.49 units on a scale Standard Error 0.17	0.96 units on a scale Standard Error 0.17

SECONDARY outcome

Timeframe: Baseline through 24 weeks and 52 weeks

Population: All randomized participants with evaluable ACR-N data. mBOCF was used to impute missing post-baseline values. Data after Week 16 for Week 16 NR were not included.

ACR-N is a continuous measure of clinical, laboratory, and functional outcomes in RA that characterizes percentage (%) of improvement in disease activity from baseline based on ACR core set. This index was calculated as minimum of either a) % change in TJ count, b) % change in SJ count, or c) the median % change of remaining 5 ACR core criteria: If ≥3 components of the 5 ACR core criteria were missing, then c) was set to missing; if any of 3 components a), b), or c) were missing, then ACR-N was set to missing. Percentage of improvement was truncated to range of -100 to 100 to minimize impact of outliers (greater values indicate greater % improvement) and negative scores indicate a decline. LS means were calculated using ANCOVA with treatment and region as fixed factors and baseline DAS28-CRP as a covariate.

Outcome measures

Measure	120 mg LY2127399 n=329 Participants Treatment Period 1 (Weeks 0-52): A loading dose of 240 mg (2 injections of 120 mg) of LY2127399, followed by maintenance dosing of 120 mg of LY2127399 administered SC Q4W. For blinding purposes, participants alternated injections of LY2127399 and injections of placebo Q2W. At Week 16, responders received 1 injection of 120 mg of LY2127399 and 1 injection of placebo, followed by 120 mg of LY2127399 Q4W for the rest of the Treatment Period 1. Treatment Period 2 (Weeks 52-100): At Week 52, Week 16 responders received 1 injection of 120 mg of LY2127399 and 1 injection of placebo, followed by 120 mg of LY2127399 Q4W for the rest of the Treatment Period 2.	90 mg LY2127399 n=326 Participants Treatment Period 1 (Weeks 0-52): A loading dose of 180 mg of LY2127399 (2 injections of 90 mg), followed by maintenance dosing of 90 mg of LY2127399 administered SC Q2W. At Week 16, responders received 1 injection of 90 mg of LY2127399 and 1 injection of placebo, followed by 90 mg of LY2127399 Q2W for the rest of the Treatment Period 1. Treatment Period 2 (Weeks 52-100): At Week 52, Week 16 responders received 1 injection of 90 mg of LY2127399 and 1 injection of placebo, followed by 90 mg of LY2127399 Q2W for the rest of the Treatment Period 2.	Placebo n=327 Participants Placebo Treatment Period 1 (Weeks 0-52): A loading dose of 2 injections of placebo, followed by maintenance dosing of 1 injection of placebo administered SC Q2W. At Week 16, responders received 2 injections of placebo, followed by 1 injection of placebo Q2W for the rest of the Treatment Period 1. Treatment Period 2 (Weeks 52-100): At Week 52, responders were randomized to receive either 2 injections of 120 mg of LY2127399, followed by 120 mg of LY2127399 Q4W for the rest of the Treatment Period 2 or 2 injections of 90 mg of LY2127399, followed by 90 mg of LY2127399 Q2W for the rest of the Treatment Period 2.
American College of Rheumatology Percent Improvement (ACR-N) Week 24	2.0 percentage of improvement Standard Error 2.5	2.1 percentage of improvement Standard Error 2.5	-6.9 percentage of improvement Standard Error 2.5
American College of Rheumatology Percent Improvement (ACR-N) Week 52	2.9 percentage of improvement Standard Error 2.5	0.3 percentage of improvement Standard Error 2.5	-7.3 percentage of improvement Standard Error 2.5

SECONDARY outcome

Timeframe: Baseline, 24 weeks and 52 weeks

Population: All randomized participants with evaluable tender joint count data. mBOCF was used to impute missing post-baseline values. Data after Week 16 for Week 16 NR were not included.

Tender joint count is the number of tender and painful joints determined for each participant by examination of 68 joints. Joints were assessed by pressure and joint manipulation on physical examination. Participants were asked for pain sensations on these manipulations and watched for spontaneous pain reactions. Any positive response on pressure, movement, or both was translated into a single tender-versus-nontender dichotomy. LS means were calculated using ANCOVA with treatment and region as fixed factors and baseline as a covariate.

Outcome measures

Measure	120 mg LY2127399 n=329 Participants Treatment Period 1 (Weeks 0-52): A loading dose of 240 mg (2 injections of 120 mg) of LY2127399, followed by maintenance dosing of 120 mg of LY2127399 administered SC Q4W. For blinding purposes, participants alternated injections of LY2127399 and injections of placebo Q2W. At Week 16, responders received 1 injection of 120 mg of LY2127399 and 1 injection of placebo, followed by 120 mg of LY2127399 Q4W for the rest of the Treatment Period 1. Treatment Period 2 (Weeks 52-100): At Week 52, Week 16 responders received 1 injection of 120 mg of LY2127399 and 1 injection of placebo, followed by 120 mg of LY2127399 Q4W for the rest of the Treatment Period 2.	90 mg LY2127399 n=329 Participants Treatment Period 1 (Weeks 0-52): A loading dose of 180 mg of LY2127399 (2 injections of 90 mg), followed by maintenance dosing of 90 mg of LY2127399 administered SC Q2W. At Week 16, responders received 1 injection of 90 mg of LY2127399 and 1 injection of placebo, followed by 90 mg of LY2127399 Q2W for the rest of the Treatment Period 1. Treatment Period 2 (Weeks 52-100): At Week 52, Week 16 responders received 1 injection of 90 mg of LY2127399 and 1 injection of placebo, followed by 90 mg of LY2127399 Q2W for the rest of the Treatment Period 2.	Placebo n=334 Participants Placebo Treatment Period 1 (Weeks 0-52): A loading dose of 2 injections of placebo, followed by maintenance dosing of 1 injection of placebo administered SC Q2W. At Week 16, responders received 2 injections of placebo, followed by 1 injection of placebo Q2W for the rest of the Treatment Period 1. Treatment Period 2 (Weeks 52-100): At Week 52, responders were randomized to receive either 2 injections of 120 mg of LY2127399, followed by 120 mg of LY2127399 Q4W for the rest of the Treatment Period 2 or 2 injections of 90 mg of LY2127399, followed by 90 mg of LY2127399 Q2W for the rest of the Treatment Period 2.
Change From Baseline in Tender Joint Count (68 Joint Count) Week 24	-7.41 joint counts Standard Error 0.72	-7.88 joint counts Standard Error 0.72	-6.40 joint counts Standard Error 0.72
Change From Baseline in Tender Joint Count (68 Joint Count) Week 52	-7.88 joint counts Standard Error 0.73	-8.09 joint counts Standard Error 0.73	-5.72 joint counts Standard Error 0.73

SECONDARY outcome

Timeframe: Baseline, 24 weeks and 52 weeks

Population: All randomized participants with evaluable swollen joint count data. mBOCF was used to impute missing post-baseline values. Data after Week 16 for Week 16 NR were not included.

Swollen joint count is the number of swollen joints determined for each participant by examination of 66 joints. Joints were classified as either swollen or not swollen. Swelling was defined as palpable fluctuating synovitis of the joint. LS means were calculated using ANCOVA with treatment and region as fixed factors and baseline as a covariate.

Outcome measures

Measure	120 mg LY2127399 n=329 Participants Treatment Period 1 (Weeks 0-52): A loading dose of 240 mg (2 injections of 120 mg) of LY2127399, followed by maintenance dosing of 120 mg of LY2127399 administered SC Q4W. For blinding purposes, participants alternated injections of LY2127399 and injections of placebo Q2W. At Week 16, responders received 1 injection of 120 mg of LY2127399 and 1 injection of placebo, followed by 120 mg of LY2127399 Q4W for the rest of the Treatment Period 1. Treatment Period 2 (Weeks 52-100): At Week 52, Week 16 responders received 1 injection of 120 mg of LY2127399 and 1 injection of placebo, followed by 120 mg of LY2127399 Q4W for the rest of the Treatment Period 2.	90 mg LY2127399 n=329 Participants Treatment Period 1 (Weeks 0-52): A loading dose of 180 mg of LY2127399 (2 injections of 90 mg), followed by maintenance dosing of 90 mg of LY2127399 administered SC Q2W. At Week 16, responders received 1 injection of 90 mg of LY2127399 and 1 injection of placebo, followed by 90 mg of LY2127399 Q2W for the rest of the Treatment Period 1. Treatment Period 2 (Weeks 52-100): At Week 52, Week 16 responders received 1 injection of 90 mg of LY2127399 and 1 injection of placebo, followed by 90 mg of LY2127399 Q2W for the rest of the Treatment Period 2.	Placebo n=334 Participants Placebo Treatment Period 1 (Weeks 0-52): A loading dose of 2 injections of placebo, followed by maintenance dosing of 1 injection of placebo administered SC Q2W. At Week 16, responders received 2 injections of placebo, followed by 1 injection of placebo Q2W for the rest of the Treatment Period 1. Treatment Period 2 (Weeks 52-100): At Week 52, responders were randomized to receive either 2 injections of 120 mg of LY2127399, followed by 120 mg of LY2127399 Q4W for the rest of the Treatment Period 2 or 2 injections of 90 mg of LY2127399, followed by 90 mg of LY2127399 Q2W for the rest of the Treatment Period 2.
Change From Baseline in Swollen Joint Count (66 Joint Count) Week 24	-5.38 joint counts Standard Error 0.49	-5.64 joint counts Standard Error 0.49	-4.67 joint counts Standard Error 0.49
Change From Baseline in Swollen Joint Count (66 Joint Count) Week 52	-6.10 joint counts Standard Error 0.49	-5.53 joint counts Standard Error 0.49	-4.61 joint counts Standard Error 0.49

SECONDARY outcome

Timeframe: Baseline, 24 weeks and 52 weeks

Population: All randomized participants with evaluable participant's assessment of pain data. mBOCF was used to impute missing post-baseline values. Data after Week 16 for Week 16 NR were not included.

Participant's assessment of their current arthritis pain using VAS ranged from 0 millimeters (mm) (no pain) to 100 mm (worst possible pain). A decrease in pain score indicated an improvement in the participant's condition. LS means were calculated using ANCOVA with treatment and region as fixed factors and baseline as a covariate.

Outcome measures

Measure	120 mg LY2127399 n=329 Participants Treatment Period 1 (Weeks 0-52): A loading dose of 240 mg (2 injections of 120 mg) of LY2127399, followed by maintenance dosing of 120 mg of LY2127399 administered SC Q4W. For blinding purposes, participants alternated injections of LY2127399 and injections of placebo Q2W. At Week 16, responders received 1 injection of 120 mg of LY2127399 and 1 injection of placebo, followed by 120 mg of LY2127399 Q4W for the rest of the Treatment Period 1. Treatment Period 2 (Weeks 52-100): At Week 52, Week 16 responders received 1 injection of 120 mg of LY2127399 and 1 injection of placebo, followed by 120 mg of LY2127399 Q4W for the rest of the Treatment Period 2.	90 mg LY2127399 n=327 Participants Treatment Period 1 (Weeks 0-52): A loading dose of 180 mg of LY2127399 (2 injections of 90 mg), followed by maintenance dosing of 90 mg of LY2127399 administered SC Q2W. At Week 16, responders received 1 injection of 90 mg of LY2127399 and 1 injection of placebo, followed by 90 mg of LY2127399 Q2W for the rest of the Treatment Period 1. Treatment Period 2 (Weeks 52-100): At Week 52, Week 16 responders received 1 injection of 90 mg of LY2127399 and 1 injection of placebo, followed by 90 mg of LY2127399 Q2W for the rest of the Treatment Period 2.	Placebo n=328 Participants Placebo Treatment Period 1 (Weeks 0-52): A loading dose of 2 injections of placebo, followed by maintenance dosing of 1 injection of placebo administered SC Q2W. At Week 16, responders received 2 injections of placebo, followed by 1 injection of placebo Q2W for the rest of the Treatment Period 1. Treatment Period 2 (Weeks 52-100): At Week 52, responders were randomized to receive either 2 injections of 120 mg of LY2127399, followed by 120 mg of LY2127399 Q4W for the rest of the Treatment Period 2 or 2 injections of 90 mg of LY2127399, followed by 90 mg of LY2127399 Q2W for the rest of the Treatment Period 2.
Change From Baseline in Participant's Assessment of Pain [Visual Analog Scale (VAS)] Week 24	-13.6 units on a scale Standard Error 1.2	-14.6 units on a scale Standard Error 1.2	-9.0 units on a scale Standard Error 1.2
Change From Baseline in Participant's Assessment of Pain [Visual Analog Scale (VAS)] Week 52	-13.2 units on a scale Standard Error 1.2	-14.6 units on a scale Standard Error 1.2	-8.7 units on a scale Standard Error 1.2

SECONDARY outcome

Timeframe: Baseline, 24 weeks and 52 weeks

Population: All randomized participants with evaluable participant's global assessment of disease activity data. mBOCF was used to impute missing post-baseline values. Data after Week 16 for Week 16 NR were not included.

Participant's assessment of their current arthritis disease activity using VAS ranged from 0 mm (no arthritis activity) to 100 mm (extremely active arthritis). A decrease in disease activity score indicated an improvement in the participant's condition. LS means were calculated using ANCOVA with treatment and region as fixed factors and baseline as a covariate.

Outcome measures

Measure	120 mg LY2127399 n=329 Participants Treatment Period 1 (Weeks 0-52): A loading dose of 240 mg (2 injections of 120 mg) of LY2127399, followed by maintenance dosing of 120 mg of LY2127399 administered SC Q4W. For blinding purposes, participants alternated injections of LY2127399 and injections of placebo Q2W. At Week 16, responders received 1 injection of 120 mg of LY2127399 and 1 injection of placebo, followed by 120 mg of LY2127399 Q4W for the rest of the Treatment Period 1. Treatment Period 2 (Weeks 52-100): At Week 52, Week 16 responders received 1 injection of 120 mg of LY2127399 and 1 injection of placebo, followed by 120 mg of LY2127399 Q4W for the rest of the Treatment Period 2.	90 mg LY2127399 n=327 Participants Treatment Period 1 (Weeks 0-52): A loading dose of 180 mg of LY2127399 (2 injections of 90 mg), followed by maintenance dosing of 90 mg of LY2127399 administered SC Q2W. At Week 16, responders received 1 injection of 90 mg of LY2127399 and 1 injection of placebo, followed by 90 mg of LY2127399 Q2W for the rest of the Treatment Period 1. Treatment Period 2 (Weeks 52-100): At Week 52, Week 16 responders received 1 injection of 90 mg of LY2127399 and 1 injection of placebo, followed by 90 mg of LY2127399 Q2W for the rest of the Treatment Period 2.	Placebo n=328 Participants Placebo Treatment Period 1 (Weeks 0-52): A loading dose of 2 injections of placebo, followed by maintenance dosing of 1 injection of placebo administered SC Q2W. At Week 16, responders received 2 injections of placebo, followed by 1 injection of placebo Q2W for the rest of the Treatment Period 1. Treatment Period 2 (Weeks 52-100): At Week 52, responders were randomized to receive either 2 injections of 120 mg of LY2127399, followed by 120 mg of LY2127399 Q4W for the rest of the Treatment Period 2 or 2 injections of 90 mg of LY2127399, followed by 90 mg of LY2127399 Q2W for the rest of the Treatment Period 2.
Change From Baseline in Participant's Global Assessment of Disease Activity (VAS) Week 24	-13.2 mm Standard Error 1.2	-15.1 mm Standard Error 1.2	-11.0 mm Standard Error 1.2
Change From Baseline in Participant's Global Assessment of Disease Activity (VAS) Week 52	-13.1 mm Standard Error 1.2	-15.2 mm Standard Error 1.2	-10.8 mm Standard Error 1.2

SECONDARY outcome

Timeframe: Baseline, 24 weeks and 52 weeks

Population: All randomized participants with evaluable physician's global assessment of disease activity data. mBOCF was used to impute missing post-baseline values. Data after Week 16 for Week 16 NR were not included.

Physician's assessment of the participant's current arthritis disease activity using VAS ranged from 0 mm (no arthritis activity) to 100 mm (extremely active arthritis). A decrease in disease activity score indicated an improvement in the participant's condition. LS means were calculated using ANCOVA with treatment and region as fixed factors and baseline as a covariate.

Outcome measures

Measure	120 mg LY2127399 n=321 Participants Treatment Period 1 (Weeks 0-52): A loading dose of 240 mg (2 injections of 120 mg) of LY2127399, followed by maintenance dosing of 120 mg of LY2127399 administered SC Q4W. For blinding purposes, participants alternated injections of LY2127399 and injections of placebo Q2W. At Week 16, responders received 1 injection of 120 mg of LY2127399 and 1 injection of placebo, followed by 120 mg of LY2127399 Q4W for the rest of the Treatment Period 1. Treatment Period 2 (Weeks 52-100): At Week 52, Week 16 responders received 1 injection of 120 mg of LY2127399 and 1 injection of placebo, followed by 120 mg of LY2127399 Q4W for the rest of the Treatment Period 2.	90 mg LY2127399 n=315 Participants Treatment Period 1 (Weeks 0-52): A loading dose of 180 mg of LY2127399 (2 injections of 90 mg), followed by maintenance dosing of 90 mg of LY2127399 administered SC Q2W. At Week 16, responders received 1 injection of 90 mg of LY2127399 and 1 injection of placebo, followed by 90 mg of LY2127399 Q2W for the rest of the Treatment Period 1. Treatment Period 2 (Weeks 52-100): At Week 52, Week 16 responders received 1 injection of 90 mg of LY2127399 and 1 injection of placebo, followed by 90 mg of LY2127399 Q2W for the rest of the Treatment Period 2.	Placebo n=314 Participants Placebo Treatment Period 1 (Weeks 0-52): A loading dose of 2 injections of placebo, followed by maintenance dosing of 1 injection of placebo administered SC Q2W. At Week 16, responders received 2 injections of placebo, followed by 1 injection of placebo Q2W for the rest of the Treatment Period 1. Treatment Period 2 (Weeks 52-100): At Week 52, responders were randomized to receive either 2 injections of 120 mg of LY2127399, followed by 120 mg of LY2127399 Q4W for the rest of the Treatment Period 2 or 2 injections of 90 mg of LY2127399, followed by 90 mg of LY2127399 Q2W for the rest of the Treatment Period 2.
Change From Baseline in Physician's Global Assessment of Disease Activity (VAS) Week 24	-20.7 mm Standard Error 1.3	-22.0 mm Standard Error 1.3	-17.2 mm Standard Error 1.3
Change From Baseline in Physician's Global Assessment of Disease Activity (VAS) Week 52	-20.4 mm Standard Error 1.3	-20.6 mm Standard Error 1.3	-17.8 mm Standard Error 1.3

SECONDARY outcome

Timeframe: Baseline, 52 weeks

Population: All randomized participants with evaluable HAQ-DI data. mBOCF was used to impute missing post-baseline values. Data after Week 16 for Week 16 NR were not included.

The HAQ-DI questionnaire assesses the participant's self-perception on the degree of difficulty [0 (without any difficulty), 1 (with some difficulty), 2 (with much difficulty), and 3 (unable to do)] when dressing and grooming, arising, eating, walking, hygiene, reaching, gripping, and performing other daily activities. Scores for each functional area were averaged to calculate HAQ-DI scores, which ranged from 0 (no disability) to 3 (severe disability). A decrease in HAQ-DI score indicated an improvement in the participant's condition. LS means were calculated using ANCOVA with treatment and region as fixed factors and baseline as a covariate.

Outcome measures

Measure	120 mg LY2127399 n=329 Participants Treatment Period 1 (Weeks 0-52): A loading dose of 240 mg (2 injections of 120 mg) of LY2127399, followed by maintenance dosing of 120 mg of LY2127399 administered SC Q4W. For blinding purposes, participants alternated injections of LY2127399 and injections of placebo Q2W. At Week 16, responders received 1 injection of 120 mg of LY2127399 and 1 injection of placebo, followed by 120 mg of LY2127399 Q4W for the rest of the Treatment Period 1. Treatment Period 2 (Weeks 52-100): At Week 52, Week 16 responders received 1 injection of 120 mg of LY2127399 and 1 injection of placebo, followed by 120 mg of LY2127399 Q4W for the rest of the Treatment Period 2.	90 mg LY2127399 n=327 Participants Treatment Period 1 (Weeks 0-52): A loading dose of 180 mg of LY2127399 (2 injections of 90 mg), followed by maintenance dosing of 90 mg of LY2127399 administered SC Q2W. At Week 16, responders received 1 injection of 90 mg of LY2127399 and 1 injection of placebo, followed by 90 mg of LY2127399 Q2W for the rest of the Treatment Period 1. Treatment Period 2 (Weeks 52-100): At Week 52, Week 16 responders received 1 injection of 90 mg of LY2127399 and 1 injection of placebo, followed by 90 mg of LY2127399 Q2W for the rest of the Treatment Period 2.	Placebo n=328 Participants Placebo Treatment Period 1 (Weeks 0-52): A loading dose of 2 injections of placebo, followed by maintenance dosing of 1 injection of placebo administered SC Q2W. At Week 16, responders received 2 injections of placebo, followed by 1 injection of placebo Q2W for the rest of the Treatment Period 1. Treatment Period 2 (Weeks 52-100): At Week 52, responders were randomized to receive either 2 injections of 120 mg of LY2127399, followed by 120 mg of LY2127399 Q4W for the rest of the Treatment Period 2 or 2 injections of 90 mg of LY2127399, followed by 90 mg of LY2127399 Q2W for the rest of the Treatment Period 2.
Change From Baseline to Week 52 in HAQ-DI	-0.24 units on a scale Standard Error 0.03	-0.30 units on a scale Standard Error 0.03	-0.18 units on a scale Standard Error 0.03

SECONDARY outcome

Timeframe: Baseline, 52 weeks

Population: All randomized participants with evaluable CD3-CD20+ B cell counts. mLOCF was used to impute missing post-baseline values. Data after Week 16 for Week 16 NR were not included.

Cell-surface marker cluster designation (CD) 3 negative, CD20 positive (CD3-CD20+) defines total mature B cells. B-lymphocyte antigen CD20 is an activated-glycosylated phosphoprotein expressed on the surface of all mature B cells. A positive or negative change indicated an increase or decrease, respectively in B cell count. LS means were calculated using ANCOVA with treatment and region as fixed factors and baseline as a covariate.

Outcome measures

Measure	120 mg LY2127399 n=343 Participants Treatment Period 1 (Weeks 0-52): A loading dose of 240 mg (2 injections of 120 mg) of LY2127399, followed by maintenance dosing of 120 mg of LY2127399 administered SC Q4W. For blinding purposes, participants alternated injections of LY2127399 and injections of placebo Q2W. At Week 16, responders received 1 injection of 120 mg of LY2127399 and 1 injection of placebo, followed by 120 mg of LY2127399 Q4W for the rest of the Treatment Period 1. Treatment Period 2 (Weeks 52-100): At Week 52, Week 16 responders received 1 injection of 120 mg of LY2127399 and 1 injection of placebo, followed by 120 mg of LY2127399 Q4W for the rest of the Treatment Period 2.	90 mg LY2127399 n=344 Participants Treatment Period 1 (Weeks 0-52): A loading dose of 180 mg of LY2127399 (2 injections of 90 mg), followed by maintenance dosing of 90 mg of LY2127399 administered SC Q2W. At Week 16, responders received 1 injection of 90 mg of LY2127399 and 1 injection of placebo, followed by 90 mg of LY2127399 Q2W for the rest of the Treatment Period 1. Treatment Period 2 (Weeks 52-100): At Week 52, Week 16 responders received 1 injection of 90 mg of LY2127399 and 1 injection of placebo, followed by 90 mg of LY2127399 Q2W for the rest of the Treatment Period 2.	Placebo n=348 Participants Placebo Treatment Period 1 (Weeks 0-52): A loading dose of 2 injections of placebo, followed by maintenance dosing of 1 injection of placebo administered SC Q2W. At Week 16, responders received 2 injections of placebo, followed by 1 injection of placebo Q2W for the rest of the Treatment Period 1. Treatment Period 2 (Weeks 52-100): At Week 52, responders were randomized to receive either 2 injections of 120 mg of LY2127399, followed by 120 mg of LY2127399 Q4W for the rest of the Treatment Period 2 or 2 injections of 90 mg of LY2127399, followed by 90 mg of LY2127399 Q2W for the rest of the Treatment Period 2.
Change From Baseline to Week 52 in Absolute B Cell Counts	-56.5 cells/microliter (cells/µL) Standard Error 4.5	-58.6 cells/microliter (cells/µL) Standard Error 4.5	-6.8 cells/microliter (cells/µL) Standard Error 4.5

SECONDARY outcome

Timeframe: Baseline through 52 weeks

Population: All randomized participants with evaluable ACR20 responder data. If participant's CRP was missing, last post-baseline value was used. If ACR was missing after carrying forward CRP, last post-baseline ACR response was used. Data after Week 16 for Week 16 NR were not included.

ACR Responder Index: Composite of clinical, laboratory, and functional measures of rheumatoid arthritis (RA). ACR20 Responder: had ≥20% improvement from baseline in both 68 tender and 66 swollen joint counts and ≥20% improvement in at least 3 of 5 criteria: participant's and physician's global assessment of disease activity, HAQ-DI (which measured participants' perceived degree of difficulty performing daily activities), joint pain, and CRP. Percentage of participants achieving ACR20 response=(number of ACR20 responders) /( number of participants treated) * 100. All NR at Week 16 as well as all participants who discontinued study treatment at any time for any reason were defined as NR starting at that time-point and going forward, including Week 52 endpoint.

Outcome measures

Measure	120 mg LY2127399 n=330 Participants Treatment Period 1 (Weeks 0-52): A loading dose of 240 mg (2 injections of 120 mg) of LY2127399, followed by maintenance dosing of 120 mg of LY2127399 administered SC Q4W. For blinding purposes, participants alternated injections of LY2127399 and injections of placebo Q2W. At Week 16, responders received 1 injection of 120 mg of LY2127399 and 1 injection of placebo, followed by 120 mg of LY2127399 Q4W for the rest of the Treatment Period 1. Treatment Period 2 (Weeks 52-100): At Week 52, Week 16 responders received 1 injection of 120 mg of LY2127399 and 1 injection of placebo, followed by 120 mg of LY2127399 Q4W for the rest of the Treatment Period 2.	90 mg LY2127399 n=332 Participants Treatment Period 1 (Weeks 0-52): A loading dose of 180 mg of LY2127399 (2 injections of 90 mg), followed by maintenance dosing of 90 mg of LY2127399 administered SC Q2W. At Week 16, responders received 1 injection of 90 mg of LY2127399 and 1 injection of placebo, followed by 90 mg of LY2127399 Q2W for the rest of the Treatment Period 1. Treatment Period 2 (Weeks 52-100): At Week 52, Week 16 responders received 1 injection of 90 mg of LY2127399 and 1 injection of placebo, followed by 90 mg of LY2127399 Q2W for the rest of the Treatment Period 2.	Placebo n=335 Participants Placebo Treatment Period 1 (Weeks 0-52): A loading dose of 2 injections of placebo, followed by maintenance dosing of 1 injection of placebo administered SC Q2W. At Week 16, responders received 2 injections of placebo, followed by 1 injection of placebo Q2W for the rest of the Treatment Period 1. Treatment Period 2 (Weeks 52-100): At Week 52, responders were randomized to receive either 2 injections of 120 mg of LY2127399, followed by 120 mg of LY2127399 Q4W for the rest of the Treatment Period 2 or 2 injections of 90 mg of LY2127399, followed by 90 mg of LY2127399 Q2W for the rest of the Treatment Period 2.
Percentage of Participants With ACR20 at Week 52	7.9 percentage of participants	9.6 percentage of participants	10.7 percentage of participants

SECONDARY outcome

Timeframe: Baseline through 52 weeks

Population: All randomized participants with evaluable ACR20 responder data. The number of participants censored are 128 (120 mg LY2127399), 123 (90 mg LY2127399) and 162 (placebo).

ACR Responder Index: Composite of clinical, laboratory, and functional measures of rheumatoid arthritis (RA). ACR20 Responder: had ≥20% improvement from baseline in both 68 tender and 66 swollen joint counts and ≥20% improvement in at least 3 of 5 criteria: participant's and physician's global assessment of disease activity, HAQ-DI (which measured participants' perceived degree of difficulty performing daily activities), joint pain, and CRP. The Kaplan-Meier was used to estimate time to ACR20 response over the Treatment Period (52 weeks). Time to ACR20 response = (Date of the first post-baseline visit during the Treatment Period meeting ACR20 response criteria - Date of first injection of study treatment + 1) / 7. Week 16 NR are counted as responders if they responded prior to Week 16. Otherwise, they are censored at the date of the Week 16 injection. All participants ongoing at Week 52 and had not yet responded are censored at the date of the Week 52 visit.

Outcome measures

Measure	120 mg LY2127399 n=327 Participants Treatment Period 1 (Weeks 0-52): A loading dose of 240 mg (2 injections of 120 mg) of LY2127399, followed by maintenance dosing of 120 mg of LY2127399 administered SC Q4W. For blinding purposes, participants alternated injections of LY2127399 and injections of placebo Q2W. At Week 16, responders received 1 injection of 120 mg of LY2127399 and 1 injection of placebo, followed by 120 mg of LY2127399 Q4W for the rest of the Treatment Period 1. Treatment Period 2 (Weeks 52-100): At Week 52, Week 16 responders received 1 injection of 120 mg of LY2127399 and 1 injection of placebo, followed by 120 mg of LY2127399 Q4W for the rest of the Treatment Period 2.	90 mg LY2127399 n=327 Participants Treatment Period 1 (Weeks 0-52): A loading dose of 180 mg of LY2127399 (2 injections of 90 mg), followed by maintenance dosing of 90 mg of LY2127399 administered SC Q2W. At Week 16, responders received 1 injection of 90 mg of LY2127399 and 1 injection of placebo, followed by 90 mg of LY2127399 Q2W for the rest of the Treatment Period 1. Treatment Period 2 (Weeks 52-100): At Week 52, Week 16 responders received 1 injection of 90 mg of LY2127399 and 1 injection of placebo, followed by 90 mg of LY2127399 Q2W for the rest of the Treatment Period 2.	Placebo n=329 Participants Placebo Treatment Period 1 (Weeks 0-52): A loading dose of 2 injections of placebo, followed by maintenance dosing of 1 injection of placebo administered SC Q2W. At Week 16, responders received 2 injections of placebo, followed by 1 injection of placebo Q2W for the rest of the Treatment Period 1. Treatment Period 2 (Weeks 52-100): At Week 52, responders were randomized to receive either 2 injections of 120 mg of LY2127399, followed by 120 mg of LY2127399 Q4W for the rest of the Treatment Period 2 or 2 injections of 90 mg of LY2127399, followed by 90 mg of LY2127399 Q2W for the rest of the Treatment Period 2.
Time to ACR20 Response	16.1 weeks Interval 12.1 to 16.4	16.1 weeks Interval 12.3 to 20.0	20.1 weeks Interval 16.4 to 24.7

SECONDARY outcome

Timeframe: Baseline, 24 weeks and 52 weeks

Population: All randomized participants with evaluable CRP data. mBOCF was used to impute missing post-baseline values. Data after Week 16 for Week 16 NR were not included.

CRP is an indicator of inflammation. A negative change indicated an improvement in the participant's condition. LS means were calculated using ANCOVA with treatment and region as fixed factors and baseline as a covariate.

Outcome measures

Measure	120 mg LY2127399 n=329 Participants Treatment Period 1 (Weeks 0-52): A loading dose of 240 mg (2 injections of 120 mg) of LY2127399, followed by maintenance dosing of 120 mg of LY2127399 administered SC Q4W. For blinding purposes, participants alternated injections of LY2127399 and injections of placebo Q2W. At Week 16, responders received 1 injection of 120 mg of LY2127399 and 1 injection of placebo, followed by 120 mg of LY2127399 Q4W for the rest of the Treatment Period 1. Treatment Period 2 (Weeks 52-100): At Week 52, Week 16 responders received 1 injection of 120 mg of LY2127399 and 1 injection of placebo, followed by 120 mg of LY2127399 Q4W for the rest of the Treatment Period 2.	90 mg LY2127399 n=328 Participants Treatment Period 1 (Weeks 0-52): A loading dose of 180 mg of LY2127399 (2 injections of 90 mg), followed by maintenance dosing of 90 mg of LY2127399 administered SC Q2W. At Week 16, responders received 1 injection of 90 mg of LY2127399 and 1 injection of placebo, followed by 90 mg of LY2127399 Q2W for the rest of the Treatment Period 1. Treatment Period 2 (Weeks 52-100): At Week 52, Week 16 responders received 1 injection of 90 mg of LY2127399 and 1 injection of placebo, followed by 90 mg of LY2127399 Q2W for the rest of the Treatment Period 2.	Placebo n=334 Participants Placebo Treatment Period 1 (Weeks 0-52): A loading dose of 2 injections of placebo, followed by maintenance dosing of 1 injection of placebo administered SC Q2W. At Week 16, responders received 2 injections of placebo, followed by 1 injection of placebo Q2W for the rest of the Treatment Period 1. Treatment Period 2 (Weeks 52-100): At Week 52, responders were randomized to receive either 2 injections of 120 mg of LY2127399, followed by 120 mg of LY2127399 Q4W for the rest of the Treatment Period 2 or 2 injections of 90 mg of LY2127399, followed by 90 mg of LY2127399 Q2W for the rest of the Treatment Period 2.
Change From Baseline in CRP Week 24	-3.30 milligrams/liter (mg/L) Standard Error 0.83	-2.03 milligrams/liter (mg/L) Standard Error 0.84	-0.54 milligrams/liter (mg/L) Standard Error 0.83
Change From Baseline in CRP Week 52	-1.72 milligrams/liter (mg/L) Standard Error 0.96	-2.04 milligrams/liter (mg/L) Standard Error 0.97	-0.40 milligrams/liter (mg/L) Standard Error 0.96

OTHER_PRE_SPECIFIED outcome

Timeframe: Discontinuation from study treatment up to 48 weeks during follow-up period

Population: All randomized participants who received at least 1 dose of study drug and entered post-treatment follow-up period.

Outcome measures

Measure	120 mg LY2127399 n=293 Participants Treatment Period 1 (Weeks 0-52): A loading dose of 240 mg (2 injections of 120 mg) of LY2127399, followed by maintenance dosing of 120 mg of LY2127399 administered SC Q4W. For blinding purposes, participants alternated injections of LY2127399 and injections of placebo Q2W. At Week 16, responders received 1 injection of 120 mg of LY2127399 and 1 injection of placebo, followed by 120 mg of LY2127399 Q4W for the rest of the Treatment Period 1. Treatment Period 2 (Weeks 52-100): At Week 52, Week 16 responders received 1 injection of 120 mg of LY2127399 and 1 injection of placebo, followed by 120 mg of LY2127399 Q4W for the rest of the Treatment Period 2.	90 mg LY2127399 n=303 Participants Treatment Period 1 (Weeks 0-52): A loading dose of 180 mg of LY2127399 (2 injections of 90 mg), followed by maintenance dosing of 90 mg of LY2127399 administered SC Q2W. At Week 16, responders received 1 injection of 90 mg of LY2127399 and 1 injection of placebo, followed by 90 mg of LY2127399 Q2W for the rest of the Treatment Period 1. Treatment Period 2 (Weeks 52-100): At Week 52, Week 16 responders received 1 injection of 90 mg of LY2127399 and 1 injection of placebo, followed by 90 mg of LY2127399 Q2W for the rest of the Treatment Period 2.	Placebo n=307 Participants Placebo Treatment Period 1 (Weeks 0-52): A loading dose of 2 injections of placebo, followed by maintenance dosing of 1 injection of placebo administered SC Q2W. At Week 16, responders received 2 injections of placebo, followed by 1 injection of placebo Q2W for the rest of the Treatment Period 1. Treatment Period 2 (Weeks 52-100): At Week 52, responders were randomized to receive either 2 injections of 120 mg of LY2127399, followed by 120 mg of LY2127399 Q4W for the rest of the Treatment Period 2 or 2 injections of 90 mg of LY2127399, followed by 90 mg of LY2127399 Q2W for the rest of the Treatment Period 2.
Number of Participants Who Died During Post-Treatment Follow-Up Period	0 Participants	1 Participants	2 Participants

Adverse Events

LY 120 mg Q4W, Randomized Treatment Period 1

Serious events: 19 serious events

Other events: 137 other events

Deaths: 0 deaths

LY 90 mg Q2W, Randomized Treatment Period 1

Serious events: 17 serious events

Other events: 117 other events

Deaths: 0 deaths

Placebo, Randomized Treatment Period 1

Serious events: 17 serious events

Other events: 129 other events

Deaths: 0 deaths

LY 120 mg Q4W to LY 90 mg Q2W (Week 16), Rescue Period

Serious events: 3 serious events

Other events: 22 other events

Deaths: 0 deaths

LY 90 mg Q2W, Rescue Period

Serious events: 3 serious events

Other events: 25 other events

Deaths: 0 deaths

Placebo to LY 90 mg Q2W (Week 16), Rescue Period

Serious events: 2 serious events

Other events: 20 other events

Deaths: 0 deaths

LY 120 mg Q4W, Treatment Period 2

Serious events: 1 serious events

Other events: 22 other events

Deaths: 0 deaths

LY 90 mg Q2W, Treatment Period 2

Serious events: 1 serious events

Other events: 20 other events

Deaths: 0 deaths

Placebo to LY 120 mg Q4W (Week 52), Treatment Period 2

Serious events: 2 serious events

Other events: 7 other events

Deaths: 0 deaths

Placebo to LY 90 mg Q2W (Week 52), Treatment Period 2

Serious events: 1 serious events

Other events: 4 other events

Deaths: 0 deaths

LY 120 mg Q4W to LY 90 mg Q2W (Week 16), Treatment Period 2

Serious events: 0 serious events

Other events: 7 other events

Deaths: 0 deaths

Placebo to LY 90 mg Q2W (Week 16), Treatment Period 2

Serious events: 0 serious events

Other events: 9 other events

Deaths: 0 deaths

LY 120 mg Q4W, Follow-up Period

Serious events: 9 serious events

Other events: 43 other events

Deaths: 0 deaths

LY 90 mg Q2W, Follow-up Period

Serious events: 14 serious events

Other events: 39 other events

Deaths: 0 deaths

Placebo to LY 120 mg Q4W (Week 52), Follow-up Period

Serious events: 1 serious events

Other events: 6 other events

Deaths: 0 deaths

Placebo to LY 90 mg Q2W (Week 52), Follow-up Period

Serious events: 1 serious events

Other events: 9 other events

Deaths: 0 deaths

LY 120 mg Q4W to LY 90 mg Q2W (Week 16), Follow-up Period

Serious events: 5 serious events

Other events: 10 other events

Deaths: 0 deaths

Placebo to LY 90 mg Q2W (Week 16), Follow-up Period

Serious events: 4 serious events

Other events: 10 other events

Deaths: 0 deaths

Placebo, Follow-up Period

Serious events: 14 serious events

Other events: 26 other events

Deaths: 0 deaths

Serious adverse events

Measure	LY 120 mg Q4W, Randomized Treatment Period 1 n=345 participants at risk A loading dose of 240 mg of LY2127399 (2 injections of 120 mg) followed by maintenance dosing of 120 mg of LY2127399 administered SC Q4W for 52 weeks during Treatment Period 1. At Week 16, responders received 1 injection of 120 mg of LY2127399 and 1 injection of placebo, followed by 120 mg of LY2127399 Q4W for the rest of the 52-week Treatment Period 1. For blinding purposes, participants alternated injections of LY2127399 and injections of placebo Q2W. The Randomized Treatment Period 1 was defined as the time all data was collected during the Treatment Period 1, excluding the data collected after the date of the Week 16 injection for the Week 16 NR.	LY 90 mg Q2W, Randomized Treatment Period 1 n=345 participants at risk A loading dose of 180 mg of LY2127399 (2 injections of 90 mg) followed by maintenance dosing of 90 mg of LY2127399 administered SC Q2W for 52 weeks during Treatment Period 1. At Week 16, responders received 1 injection of 90 mg of LY2127399 and 1 injection of placebo, followed by 90 mg of LY2127399 Q2W for the rest of the Treatment Period 1. The Randomized Treatment Period 1 was defined as the time all data was collected during the Treatment Period 1, excluding the data collected after the date of the Week 16 injection for the Week 16 NR.	Placebo, Randomized Treatment Period 1 n=348 participants at risk A loading dose of 2 injections of placebo followed by maintenance dosing of placebo administered SC Q2W for 52 weeks during Treatment Period 1. At Week 16, responders received 2 injections of placebo, followed by 1 injection of placebo Q2W for the rest of the Treatment Period 1. The Randomized Treatment Period 1 was defined as the time all data was collected during the Treatment Period 1, excluding the data collected after the date of the Week 16 injection for the Week 16 NR.	LY 120 mg Q4W to LY 90 mg Q2W (Week 16), Rescue Period n=58 participants at risk A loading dose of 240 mg of LY2127399 (2 injections of 120 mg) followed by maintenance dosing of 120 mg of LY2127399 administered SC Q4W for 16 weeks during Treatment Period 1. For blinding purposes, participants alternated injections of LY2127399 and injections of placebo Q2W. At Week 16, NR received 1 injection of 90 mg of LY2127399 and 1 injection of placebo, followed by 90 mg of LY2127399 Q2W for the rest of the 52-week Treatment Period 1. The Rescue Treatment Period was defined as all data collected after the date of the Week 16 injection during the Treatment Period 1 for Week 16 NR.	LY 90 mg Q2W, Rescue Period n=62 participants at risk A loading dose of 180 mg of LY2127399 (2 injections of 90 mg) followed by maintenance dosing of 90 mg of LY2127399 administered SC Q2W for 16 weeks during Treatment Period 1. At Week 16, NR received 1 injection of 90 mg of LY2127399 and 1 injection of placebo, followed by 90 mg of LY2127399 Q2W for the rest of the 52-week Treatment Period 1. The Rescue Treatment Period was defined as all data collected after the date of the Week 16 injection during the Treatment Period 1 for Week 16 NR.	Placebo to LY 90 mg Q2W (Week 16), Rescue Period n=90 participants at risk A loading dose of 2 injections of placebo followed by maintenance dosing of placebo administered SC Q2W for 16 weeks during Treatment Period 1. At Week 16, NR received a loading dose of 180 mg of LY2127399 (2 injections of 90 mg), followed by 90 mg of LY2127399 Q2W for the rest of the 52-week Treatment Period 1. The Rescue Treatment Period was defined as all data collected after the date of the Week 16 injection during the Treatment Period 1 for Week 16 NR.	LY 120 mg Q4W, Treatment Period 2 n=57 participants at risk A loading dose of 240 mg of LY2127399 (2 injections of 120 mg) followed by maintenance dosing of 120 mg of LY2127399 administered SC Q4W for 52 weeks during Treatment Period 1. At Week 16, Week 16 responders received 1 injection of 120 mg of LY2127399 and 1 injection of placebo, followed by 120 mg of LY2127399 Q4W for the rest of the 52-week Treatment Period 1. For blinding purposes, participants alternated injections of LY2127399 and injections of placebo Q2W. At Week 52, Week 16 responders received 1 injection of 120 mg of LY2127399 and 1 injection of placebo, followed by 120 mg of LY2127399 Q4W for the rest of the Treatment Period 2. Treatment Period 2 was defined as all data collected from Week 52 to Week 100 during non-blinded Treatment Period 2.	LY 90 mg Q2W, Treatment Period 2 n=73 participants at risk A loading dose of 180 mg of LY2127399 (2 injections of 90 mg) followed by maintenance dosing of 90 mg of LY2127399 administered SC Q2W for 52 weeks during Treatment Period 1. At Week 16, both Week 16 responders and NR received 1 injection of 90 mg of LY2127399 and 1 injection of placebo, followed by 90 mg of LY2127399 Q2W for the rest of the Treatment Period 1. At Week 52, both Week 16 responders and NR received 1 injection of 90 mg of LY2127399 and 1 injection of placebo, followed by 90 mg of LY2127399 Q2W for the rest of the Treatment Period 2. Treatment Period 2 was defined as all data collected from Week 52 to Week 100 during non-blinded Treatment Period 2.	Placebo to LY 120 mg Q4W (Week 52), Treatment Period 2 n=27 participants at risk A loading dose of 2 injections of placebo followed by maintenance dosing of placebo administered SC Q2W for 52 weeks during Treatment Period 1. At Week 16, Week 16 responders received 2 injections of placebo, followed by 1 injection of placebo Q2W for the rest of the Treatment Period 1. At Week 52, Week 16 responders were randomized to receive 2 injections of 120 mg of LY2127399, followed by 120 mg of LY2127399 Q4W for the rest of the Treatment Period 2 Treatment Period 2 was defined as all data collected from Week 52 to Week 100 during non-blinded Treatment Period 2.	Placebo to LY 90 mg Q2W (Week 52), Treatment Period 2 n=31 participants at risk A loading dose of 2 injections of placebo followed by maintenance dosing of placebo administered SC Q2W for 52 weeks during Treatment Period 1. At Week 16, Week 16 responders received 2 injections of placebo, followed by 1 injection of placebo Q2W for the rest of the Treatment Period 1. At Week 52, Week 16 responders were randomized to receive 2 injections of 90 mg of LY2127399, followed by 90 mg of LY2127399 Q4W for the rest of the Treatment Period 2 Treatment Period 2 was defined as all data collected from Week 52 to Week 100 during non-blinded Treatment Period 2.	LY 120 mg Q4W to LY 90 mg Q2W (Week 16), Treatment Period 2 n=13 participants at risk A loading dose of 240 mg of LY2127399 (2 injections of 120 mg) followed by maintenance dosing of 120 mg of LY2127399 administered SC Q4W for 16 weeks during Treatment Period 1. For blinding purposes, participants alternated injections of LY2127399 and injections of placebo Q2W. At Week 16, Week 16 NR received 1 injection of 90 mg of LY2127399 and 1 injection of placebo, followed by 90 mg of LY2127399 Q2W for the rest of the 52-week Treatment Period 1. During non-blinded Treatment Period 2, Week 16 NR received 1 injection of 90 mg of LY2127399. Treatment Period 2 was defined as all data collected from Week 52 to Week 100 during non-blinded Treatment Period 2.	Placebo to LY 90 mg Q2W (Week 16), Treatment Period 2 n=22 participants at risk A loading dose of 2 injections of placebo followed by maintenance dosing of placebo administered SC Q2W for 16 weeks during Treatment Period 1. At Week 16, Week 16 NR received a loading dose of 180 mg of LY2127399 (2 injections of 90 mg), followed by 90 mg of LY2127399 Q2W for the rest of the 52-week Treatment Period 1. During non-blinded Treatment Period 2, Week 16 NR received 1 injection of 90 mg of LY2127399. Treatment Period 2 was defined as all data collected from Week 52 to Week 100 during non-blinded Treatment Period 2.	LY 120 mg Q4W, Follow-up Period n=241 participants at risk A loading dose of 240 mg of LY2127399 (2 injections of 120 mg) followed by maintenance dosing of 120 mg of LY2127399 administered SC Q4W for 52 weeks during Treatment Period 1. At Week 16, Week 16 responders received 1 injection of 120 mg of LY2127399 and 1 injection of placebo, followed by 120 mg of LY2127399 Q4W for the rest of the 52-week Treatment Period 1. For blinding purposes, participants alternated injections of LY2127399 and injections of placebo Q2W. At Week 52, Week 16 responders received 1 injection of 120 mg of LY2127399 and 1 injection of placebo, followed by 120 mg of LY2127399 Q4W for the rest of the Treatment Period 2. The Post-Treatment Follow-Up Period started after Week 100 or the early discontinuation visit and lasted up to 48 weeks following the last injection of study treatment.	LY 90 mg Q2W, Follow-up Period n=303 participants at risk A loading dose of 180 mg of LY2127399 (2 injections of 90 mg) followed by maintenance dosing of 90 mg of LY2127399 administered SC Q2W for 52 weeks during Treatment Period 1. At Week 16, both Week 16 responders and NR received 1 injection of 90 mg of LY2127399 and 1 injection of placebo, followed by 90 mg of LY2127399 Q2W for the rest of the Treatment Period 1. At Week 52, both Week 16 responders and NR received 1 injection of 90 mg of LY2127399 and 1 injection of placebo, followed by 90 mg of LY2127399 Q2W for the rest of the Treatment Period 2. The Post-Treatment Follow-Up Period started after Week 100 or the early discontinuation visit and lasted up to 48 weeks following the last injection of study treatment.	Placebo to LY 120 mg Q4W (Week 52), Follow-up Period n=27 participants at risk A loading dose of 2 injections of placebo followed by maintenance dosing of placebo administered SC Q2W for 52 weeks during Treatment Period 1. At Week 16, Week 16 responders received 2 injections of placebo, followed by 1 injection of placebo Q2W for the rest of the Treatment Period 1. At Week 52, Week 16 responders were randomized to receive 2 injections of 120 mg of LY2127399, followed by 120 mg of LY2127399 Q4W for the rest of the Treatment Period 2 The Post-Treatment Follow-Up Period started after Week 100 or the early discontinuation visit and lasted up to 48 weeks following the last injection of study treatment.	Placebo to LY 90 mg Q2W (Week 52), Follow-up Period n=27 participants at risk A loading dose of 2 injections of placebo followed by maintenance dosing of placebo administered SC Q2W for 52 weeks during Treatment Period 1. At Week 16, Week 16 responders received 2 injections of placebo, followed by 1 injection of placebo Q2W for the rest of the Treatment Period 1. At Week 52, Week 16 responders were randomized to receive 2 injections of 90 mg of LY2127399, followed by 90 mg of LY2127399 Q4W for the rest of the Treatment Period 2 The Post-Treatment Follow-Up Period started after Week 100 or the early discontinuation visit and lasted up to 48 weeks following the last injection of study treatment.	LY 120 mg Q4W to LY 90 mg Q2W (Week 16), Follow-up Period n=52 participants at risk A loading dose of 240 mg of LY2127399 (2 injections of 120 mg) followed by maintenance dosing of 120 mg of LY2127399 administered SC Q4W for 16 weeks during Treatment Period 1. For blinding purposes, participants alternated injections of LY2127399 and injections of placebo Q2W. At Week 16, Week 16 NR received 1 injection of 90 mg of LY2127399 and 1 injection of placebo, followed by 90 mg of LY2127399 Q2W for the rest of the 52-week Treatment Period 1. During non-blinded Treatment Period 2, Week 16 NR received 1 injection of 90 mg of LY2127399. The Post-Treatment Follow-Up Period started after Week 100 or the early discontinuation visit and lasted up to 48 weeks following the last injection of study treatment.	Placebo to LY 90 mg Q2W (Week 16), Follow-up Period n=85 participants at risk A loading dose of 2 injections of placebo followed by maintenance dosing of placebo administered SC Q2W for 16 weeks during Treatment Period 1. At Week 16, Week 16 NR received a loading dose of 180 mg of LY2127399 (2 injections of 90 mg), followed by 90 mg of LY2127399 Q2W for the rest of the 52-week Treatment Period 1. During non-blinded Treatment Period 2, Week 16 NR received 1 injection of 90 mg of LY2127399. The Post-Treatment Follow-Up Period started after Week 100 or the early discontinuation visit and lasted up to 48 weeks following the last injection of study treatment.	Placebo, Follow-up Period n=168 participants at risk A loading dose of 2 injections of placebo followed by maintenance dosing of placebo administered SC Q2W for 52 weeks during Treatment Period 1. At Week 16, responders received 2 injections of placebo, followed by 1 injection of placebo Q2W for the rest of the Treatment Period 1. The Post-Treatment Follow-Up Period started after Week 52 or the early discontinuation visit and lasted up to 48 weeks following the last injection of study treatment.
Injury, poisoning and procedural complications Femur fracture	0.29% 1/345 • Number of events 1	0.29% 1/345 • Number of events 1	0.00% 0/348	0.00% 0/58	0.00% 0/62	0.00% 0/90	0.00% 0/57	0.00% 0/73	7.4% 2/27 • Number of events 2	0.00% 0/31	0.00% 0/13	0.00% 0/22	0.00% 0/241	0.00% 0/303	0.00% 0/27	0.00% 0/27	0.00% 0/52	0.00% 0/85	0.00% 0/168
Blood and lymphatic system disorders Anaemia	0.29% 1/345 • Number of events 1	0.00% 0/345	0.00% 0/348	0.00% 0/58	0.00% 0/62	0.00% 0/90	0.00% 0/57	0.00% 0/73	0.00% 0/27	0.00% 0/31	0.00% 0/13	0.00% 0/22	0.00% 0/241	0.00% 0/303	0.00% 0/27	0.00% 0/27	0.00% 0/52	1.2% 1/85 • Number of events 1	0.00% 0/168
Blood and lymphatic system disorders Iron deficiency anaemia	0.00% 0/345	0.00% 0/345	0.00% 0/348	0.00% 0/58	0.00% 0/62	0.00% 0/90	0.00% 0/57	1.4% 1/73 • Number of events 1	0.00% 0/27	0.00% 0/31	0.00% 0/13	0.00% 0/22	0.00% 0/241	0.00% 0/303	0.00% 0/27	0.00% 0/27	0.00% 0/52	0.00% 0/85	0.00% 0/168
Blood and lymphatic system disorders Pancytopenia	0.00% 0/345	0.00% 0/345	0.00% 0/348	0.00% 0/58	0.00% 0/62	0.00% 0/90	0.00% 0/57	0.00% 0/73	0.00% 0/27	0.00% 0/31	0.00% 0/13	0.00% 0/22	0.41% 1/241 • Number of events 1	0.00% 0/303	0.00% 0/27	0.00% 0/27	0.00% 0/52	0.00% 0/85	0.00% 0/168
Cardiac disorders Acute myocardial infarction	0.00% 0/345	0.00% 0/345	0.00% 0/348	0.00% 0/58	0.00% 0/62	0.00% 0/90	0.00% 0/57	0.00% 0/73	0.00% 0/27	0.00% 0/31	0.00% 0/13	0.00% 0/22	0.00% 0/241	0.33% 1/303 • Number of events 1	0.00% 0/27	0.00% 0/27	0.00% 0/52	0.00% 0/85	0.60% 1/168 • Number of events 1
Cardiac disorders Arrhythmia	0.00% 0/345	0.00% 0/345	0.00% 0/348	0.00% 0/58	0.00% 0/62	0.00% 0/90	0.00% 0/57	0.00% 0/73	0.00% 0/27	0.00% 0/31	0.00% 0/13	0.00% 0/22	0.00% 0/241	0.33% 1/303 • Number of events 1	0.00% 0/27	0.00% 0/27	0.00% 0/52	0.00% 0/85	0.00% 0/168
Cardiac disorders Atrial fibrillation	0.00% 0/345	0.00% 0/345	0.00% 0/348	0.00% 0/58	0.00% 0/62	0.00% 0/90	0.00% 0/57	0.00% 0/73	0.00% 0/27	0.00% 0/31	0.00% 0/13	0.00% 0/22	0.00% 0/241	0.00% 0/303	0.00% 0/27	0.00% 0/27	0.00% 0/52	0.00% 0/85	0.60% 1/168 • Number of events 1
Cardiac disorders Cardiac failure chronic	0.00% 0/345	0.00% 0/345	0.29% 1/348 • Number of events 1	0.00% 0/58	0.00% 0/62	0.00% 0/90	0.00% 0/57	0.00% 0/73	0.00% 0/27	0.00% 0/31	0.00% 0/13	0.00% 0/22	0.00% 0/241	0.00% 0/303	0.00% 0/27	0.00% 0/27	0.00% 0/52	0.00% 0/85	0.00% 0/168
Cardiac disorders Cardiogenic shock	0.00% 0/345	0.00% 0/345	0.29% 1/348 • Number of events 1	0.00% 0/58	0.00% 0/62	0.00% 0/90	0.00% 0/57	0.00% 0/73	0.00% 0/27	0.00% 0/31	0.00% 0/13	0.00% 0/22	0.00% 0/241	0.00% 0/303	0.00% 0/27	0.00% 0/27	0.00% 0/52	0.00% 0/85	0.00% 0/168
Cardiac disorders Congestive cardiomyopathy	0.00% 0/345	0.00% 0/345	0.00% 0/348	0.00% 0/58	0.00% 0/62	0.00% 0/90	0.00% 0/57	0.00% 0/73	0.00% 0/27	0.00% 0/31	0.00% 0/13	0.00% 0/22	0.00% 0/241	0.00% 0/303	0.00% 0/27	0.00% 0/27	0.00% 0/52	0.00% 0/85	0.60% 1/168 • Number of events 1
Cardiac disorders Coronary artery insufficiency	0.00% 0/345	0.00% 0/345	0.29% 1/348 • Number of events 1	0.00% 0/58	0.00% 0/62	0.00% 0/90	0.00% 0/57	0.00% 0/73	0.00% 0/27	0.00% 0/31	0.00% 0/13	0.00% 0/22	0.00% 0/241	0.00% 0/303	0.00% 0/27	0.00% 0/27	0.00% 0/52	0.00% 0/85	0.00% 0/168
Cardiac disorders Myocardial infarction	0.29% 1/345 • Number of events 1	0.00% 0/345	0.57% 2/348 • Number of events 2	0.00% 0/58	0.00% 0/62	0.00% 0/90	0.00% 0/57	0.00% 0/73	0.00% 0/27	0.00% 0/31	0.00% 0/13	0.00% 0/22	0.00% 0/241	0.33% 1/303 • Number of events 1	0.00% 0/27	0.00% 0/27	0.00% 0/52	0.00% 0/85	0.00% 0/168
Cardiac disorders Sick sinus syndrome	0.00% 0/345	0.00% 0/345	0.00% 0/348	0.00% 0/58	1.6% 1/62 • Number of events 1	0.00% 0/90	0.00% 0/57	0.00% 0/73	0.00% 0/27	0.00% 0/31	0.00% 0/13	0.00% 0/22	0.00% 0/241	0.00% 0/303	0.00% 0/27	0.00% 0/27	0.00% 0/52	0.00% 0/85	0.00% 0/168
Eye disorders Ulcerative keratitis	0.29% 1/345 • Number of events 1	0.00% 0/345	0.00% 0/348	0.00% 0/58	0.00% 0/62	0.00% 0/90	0.00% 0/57	0.00% 0/73	0.00% 0/27	0.00% 0/31	0.00% 0/13	0.00% 0/22	0.00% 0/241	0.00% 0/303	0.00% 0/27	0.00% 0/27	0.00% 0/52	0.00% 0/85	0.00% 0/168
Gastrointestinal disorders Gastric haemorrhage	0.29% 1/345 • Number of events 1	0.00% 0/345	0.00% 0/348	0.00% 0/58	0.00% 0/62	0.00% 0/90	0.00% 0/57	0.00% 0/73	0.00% 0/27	0.00% 0/31	0.00% 0/13	0.00% 0/22	0.00% 0/241	0.00% 0/303	0.00% 0/27	0.00% 0/27	0.00% 0/52	0.00% 0/85	0.00% 0/168
Gastrointestinal disorders Gastric ulcer	0.00% 0/345	0.00% 0/345	0.29% 1/348 • Number of events 1	0.00% 0/58	0.00% 0/62	0.00% 0/90	0.00% 0/57	0.00% 0/73	0.00% 0/27	0.00% 0/31	0.00% 0/13	0.00% 0/22	0.00% 0/241	0.00% 0/303	0.00% 0/27	0.00% 0/27	0.00% 0/52	0.00% 0/85	0.00% 0/168
Gastrointestinal disorders Hiatus hernia	0.00% 0/345	0.00% 0/345	0.00% 0/348	0.00% 0/58	0.00% 0/62	0.00% 0/90	0.00% 0/57	0.00% 0/73	0.00% 0/27	0.00% 0/31	0.00% 0/13	0.00% 0/22	0.00% 0/241	0.33% 1/303 • Number of events 1	0.00% 0/27	0.00% 0/27	0.00% 0/52	0.00% 0/85	0.00% 0/168
Gastrointestinal disorders Mechanical ileus	0.00% 0/345	0.00% 0/345	0.00% 0/348	0.00% 0/58	0.00% 0/62	0.00% 0/90	0.00% 0/57	0.00% 0/73	0.00% 0/27	0.00% 0/31	0.00% 0/13	0.00% 0/22	0.41% 1/241 • Number of events 1	0.00% 0/303	0.00% 0/27	0.00% 0/27	0.00% 0/52	0.00% 0/85	0.00% 0/168
Gastrointestinal disorders Nausea	0.00% 0/345	0.29% 1/345 • Number of events 1	0.00% 0/348	0.00% 0/58	0.00% 0/62	0.00% 0/90	0.00% 0/57	0.00% 0/73	0.00% 0/27	0.00% 0/31	0.00% 0/13	0.00% 0/22	0.00% 0/241	0.00% 0/303	0.00% 0/27	0.00% 0/27	0.00% 0/52	0.00% 0/85	0.00% 0/168
Gastrointestinal disorders Pancreatitis acute	0.29% 1/345 • Number of events 1	0.29% 1/345 • Number of events 1	0.00% 0/348	0.00% 0/58	0.00% 0/62	0.00% 0/90	0.00% 0/57	0.00% 0/73	0.00% 0/27	0.00% 0/31	0.00% 0/13	0.00% 0/22	0.00% 0/241	0.00% 0/303	0.00% 0/27	0.00% 0/27	0.00% 0/52	0.00% 0/85	0.00% 0/168
Gastrointestinal disorders Pancreatitis chronic	0.00% 0/345	0.29% 1/345 • Number of events 1	0.00% 0/348	0.00% 0/58	0.00% 0/62	0.00% 0/90	0.00% 0/57	0.00% 0/73	0.00% 0/27	0.00% 0/31	0.00% 0/13	0.00% 0/22	0.00% 0/241	0.00% 0/303	0.00% 0/27	0.00% 0/27	0.00% 0/52	0.00% 0/85	0.00% 0/168
Gastrointestinal disorders Vomiting	0.00% 0/345	0.29% 1/345 • Number of events 1	0.00% 0/348	0.00% 0/58	0.00% 0/62	0.00% 0/90	0.00% 0/57	0.00% 0/73	0.00% 0/27	0.00% 0/31	0.00% 0/13	0.00% 0/22	0.00% 0/241	0.00% 0/303	0.00% 0/27	0.00% 0/27	0.00% 0/52	0.00% 0/85	0.00% 0/168
General disorders Death	0.00% 0/345	0.00% 0/345	0.00% 0/348	0.00% 0/58	0.00% 0/62	0.00% 0/90	0.00% 0/57	0.00% 0/73	0.00% 0/27	0.00% 0/31	0.00% 0/13	0.00% 0/22	0.00% 0/241	0.00% 0/303	0.00% 0/27	0.00% 0/27	0.00% 0/52	1.2% 1/85 • Number of events 1	0.00% 0/168
General disorders Device dislocation	0.00% 0/345	0.00% 0/345	0.00% 0/348	0.00% 0/58	0.00% 0/62	1.1% 1/90 • Number of events 1	0.00% 0/57	0.00% 0/73	0.00% 0/27	0.00% 0/31	0.00% 0/13	0.00% 0/22	0.00% 0/241	0.00% 0/303	0.00% 0/27	0.00% 0/27	0.00% 0/52	0.00% 0/85	0.00% 0/168
General disorders Non-cardiac chest pain	0.00% 0/345	0.00% 0/345	0.29% 1/348 • Number of events 1	0.00% 0/58	0.00% 0/62	0.00% 0/90	0.00% 0/57	0.00% 0/73	0.00% 0/27	0.00% 0/31	0.00% 0/13	0.00% 0/22	0.00% 0/241	0.00% 0/303	0.00% 0/27	0.00% 0/27	0.00% 0/52	0.00% 0/85	0.00% 0/168
General disorders Pyrexia	0.00% 0/345	0.00% 0/345	0.00% 0/348	0.00% 0/58	0.00% 0/62	0.00% 0/90	0.00% 0/57	0.00% 0/73	0.00% 0/27	0.00% 0/31	0.00% 0/13	0.00% 0/22	0.41% 1/241 • Number of events 1	0.00% 0/303	0.00% 0/27	0.00% 0/27	0.00% 0/52	0.00% 0/85	0.00% 0/168
Hepatobiliary disorders Cholecystitis	0.00% 0/345	0.00% 0/345	0.29% 1/348 • Number of events 1	0.00% 0/58	0.00% 0/62	0.00% 0/90	0.00% 0/57	0.00% 0/73	0.00% 0/27	0.00% 0/31	0.00% 0/13	0.00% 0/22	0.00% 0/241	0.00% 0/303	0.00% 0/27	0.00% 0/27	0.00% 0/52	0.00% 0/85	0.00% 0/168
Hepatobiliary disorders Cholelithiasis	0.00% 0/345	0.00% 0/345	0.29% 1/348 • Number of events 1	0.00% 0/58	0.00% 0/62	0.00% 0/90	0.00% 0/57	0.00% 0/73	0.00% 0/27	0.00% 0/31	0.00% 0/13	0.00% 0/22	0.00% 0/241	0.00% 0/303	0.00% 0/27	0.00% 0/27	0.00% 0/52	0.00% 0/85	0.00% 0/168
Immune system disorders Drug hypersensitivity	0.00% 0/345	0.29% 1/345 • Number of events 1	0.00% 0/348	0.00% 0/58	0.00% 0/62	0.00% 0/90	0.00% 0/57	0.00% 0/73	0.00% 0/27	0.00% 0/31	0.00% 0/13	0.00% 0/22	0.00% 0/241	0.00% 0/303	0.00% 0/27	0.00% 0/27	0.00% 0/52	0.00% 0/85	0.00% 0/168
Infections and infestations Bacterial infection	0.00% 0/345	0.00% 0/345	0.00% 0/348	0.00% 0/58	0.00% 0/62	0.00% 0/90	0.00% 0/57	0.00% 0/73	0.00% 0/27	0.00% 0/31	0.00% 0/13	0.00% 0/22	0.41% 1/241 • Number of events 1	0.00% 0/303	0.00% 0/27	0.00% 0/27	0.00% 0/52	0.00% 0/85	0.00% 0/168
Infections and infestations Bronchitis	0.29% 1/345 • Number of events 1	0.00% 0/345	0.00% 0/348	0.00% 0/58	0.00% 0/62	0.00% 0/90	0.00% 0/57	0.00% 0/73	0.00% 0/27	0.00% 0/31	0.00% 0/13	0.00% 0/22	0.00% 0/241	0.00% 0/303	0.00% 0/27	0.00% 0/27	0.00% 0/52	0.00% 0/85	0.00% 0/168
Infections and infestations Cellulitis	0.00% 0/345	0.00% 0/345	0.00% 0/348	0.00% 0/58	0.00% 0/62	0.00% 0/90	1.8% 1/57 • Number of events 1	0.00% 0/73	0.00% 0/27	0.00% 0/31	0.00% 0/13	0.00% 0/22	0.00% 0/241	0.00% 0/303	0.00% 0/27	0.00% 0/27	1.9% 1/52 • Number of events 1	0.00% 0/85	0.00% 0/168
Infections and infestations Device related infection	0.00% 0/345	0.00% 0/345	0.00% 0/348	0.00% 0/58	0.00% 0/62	0.00% 0/90	0.00% 0/57	0.00% 0/73	0.00% 0/27	0.00% 0/31	0.00% 0/13	0.00% 0/22	0.00% 0/241	0.00% 0/303	0.00% 0/27	0.00% 0/27	1.9% 1/52 • Number of events 1	0.00% 0/85	0.60% 1/168 • Number of events 1
Infections and infestations Diverticulitis	0.29% 1/345 • Number of events 1	0.00% 0/345	0.00% 0/348	0.00% 0/58	0.00% 0/62	0.00% 0/90	0.00% 0/57	0.00% 0/73	0.00% 0/27	0.00% 0/31	0.00% 0/13	0.00% 0/22	0.00% 0/241	0.00% 0/303	0.00% 0/27	0.00% 0/27	0.00% 0/52	0.00% 0/85	0.00% 0/168
Infections and infestations Enteritis infectious	0.29% 1/345 • Number of events 1	0.00% 0/345	0.00% 0/348	0.00% 0/58	0.00% 0/62	0.00% 0/90	0.00% 0/57	0.00% 0/73	0.00% 0/27	0.00% 0/31	0.00% 0/13	0.00% 0/22	0.00% 0/241	0.00% 0/303	0.00% 0/27	0.00% 0/27	0.00% 0/52	0.00% 0/85	0.00% 0/168
Infections and infestations Gastroenteritis	0.00% 0/345	0.00% 0/345	0.00% 0/348	0.00% 0/58	1.6% 1/62 • Number of events 1	0.00% 0/90	0.00% 0/57	0.00% 0/73	0.00% 0/27	0.00% 0/31	0.00% 0/13	0.00% 0/22	0.00% 0/241	0.00% 0/303	0.00% 0/27	0.00% 0/27	0.00% 0/52	0.00% 0/85	0.60% 1/168 • Number of events 1
Infections and infestations Herpes zoster	0.58% 2/345 • Number of events 2	0.29% 1/345 • Number of events 1	0.00% 0/348	0.00% 0/58	0.00% 0/62	0.00% 0/90	0.00% 0/57	0.00% 0/73	0.00% 0/27	0.00% 0/31	0.00% 0/13	0.00% 0/22	0.00% 0/241	0.00% 0/303	0.00% 0/27	0.00% 0/27	0.00% 0/52	0.00% 0/85	0.00% 0/168
Infections and infestations Infective tenosynovitis	0.00% 0/345	0.00% 0/345	0.00% 0/348	0.00% 0/58	0.00% 0/62	0.00% 0/90	0.00% 0/57	0.00% 0/73	0.00% 0/27	0.00% 0/31	0.00% 0/13	0.00% 0/22	0.00% 0/241	0.00% 0/303	0.00% 0/27	0.00% 0/27	0.00% 0/52	0.00% 0/85	0.60% 1/168 • Number of events 1
Infections and infestations Influenza	0.00% 0/345	0.00% 0/345	0.00% 0/348	0.00% 0/58	0.00% 0/62	0.00% 0/90	0.00% 0/57	0.00% 0/73	0.00% 0/27	0.00% 0/31	0.00% 0/13	0.00% 0/22	0.41% 1/241 • Number of events 1	0.00% 0/303	0.00% 0/27	0.00% 0/27	0.00% 0/52	0.00% 0/85	0.00% 0/168
Infections and infestations Peritonitis	0.29% 1/345 • Number of events 1	0.00% 0/345	0.00% 0/348	0.00% 0/58	0.00% 0/62	0.00% 0/90	0.00% 0/57	0.00% 0/73	0.00% 0/27	0.00% 0/31	0.00% 0/13	0.00% 0/22	0.00% 0/241	0.00% 0/303	0.00% 0/27	0.00% 0/27	0.00% 0/52	0.00% 0/85	0.00% 0/168
Infections and infestations Pneumonia	0.00% 0/345	0.00% 0/345	0.00% 0/348	0.00% 0/58	0.00% 0/62	1.1% 1/90 • Number of events 1	0.00% 0/57	0.00% 0/73	0.00% 0/27	0.00% 0/31	0.00% 0/13	0.00% 0/22	0.00% 0/241	0.33% 1/303 • Number of events 1	0.00% 0/27	0.00% 0/27	0.00% 0/52	1.2% 1/85 • Number of events 1	0.00% 0/168
Infections and infestations Post procedural infection	0.00% 0/345	0.00% 0/345	0.00% 0/348	0.00% 0/58	0.00% 0/62	0.00% 0/90	0.00% 0/57	0.00% 0/73	0.00% 0/27	0.00% 0/31	0.00% 0/13	0.00% 0/22	0.00% 0/241	0.00% 0/303	0.00% 0/27	0.00% 0/27	0.00% 0/52	1.2% 1/85 • Number of events 1	0.00% 0/168
Infections and infestations Pseudomembranous colitis	0.00% 0/345	0.00% 0/345	0.29% 1/348 • Number of events 1	0.00% 0/58	0.00% 0/62	0.00% 0/90	0.00% 0/57	0.00% 0/73	0.00% 0/27	0.00% 0/31	0.00% 0/13	0.00% 0/22	0.00% 0/241	0.00% 0/303	0.00% 0/27	0.00% 0/27	0.00% 0/52	0.00% 0/85	0.00% 0/168
Infections and infestations Pyelonephritis acute	0.00% 0/345	0.00% 0/345	0.00% 0/348	0.00% 0/58	0.00% 0/62	0.00% 0/90	0.00% 0/57	0.00% 0/73	0.00% 0/27	0.00% 0/31	0.00% 0/13	0.00% 0/22	0.41% 1/241 • Number of events 1	0.00% 0/303	0.00% 0/27	3.7% 1/27 • Number of events 1	0.00% 0/52	0.00% 0/85	0.00% 0/168
Infections and infestations Pyelonephritis chronic	0.00% 0/345	0.29% 1/345 • Number of events 1	0.00% 0/348	0.00% 0/58	0.00% 0/62	0.00% 0/90	0.00% 0/57	0.00% 0/73	0.00% 0/27	0.00% 0/31	0.00% 0/13	0.00% 0/22	0.00% 0/241	0.00% 0/303	0.00% 0/27	0.00% 0/27	0.00% 0/52	0.00% 0/85	0.00% 0/168
Infections and infestations Sepsis	0.29% 1/345 • Number of events 1	0.00% 0/345	0.29% 1/348 • Number of events 1	0.00% 0/58	0.00% 0/62	0.00% 0/90	0.00% 0/57	0.00% 0/73	0.00% 0/27	0.00% 0/31	0.00% 0/13	0.00% 0/22	0.00% 0/241	0.00% 0/303	0.00% 0/27	0.00% 0/27	0.00% 0/52	0.00% 0/85	0.00% 0/168
Infections and infestations Urinary tract infection	0.29% 1/345 • Number of events 1	0.00% 0/345	0.00% 0/348	0.00% 0/58	0.00% 0/62	0.00% 0/90	0.00% 0/57	0.00% 0/73	0.00% 0/27	0.00% 0/31	0.00% 0/13	0.00% 0/22	0.00% 0/241	0.00% 0/303	0.00% 0/27	0.00% 0/27	0.00% 0/52	0.00% 0/85	0.00% 0/168
Injury, poisoning and procedural complications Femoral neck fracture	0.00% 0/345	0.00% 0/345	0.00% 0/348	0.00% 0/58	0.00% 0/62	0.00% 0/90	0.00% 0/57	0.00% 0/73	0.00% 0/27	0.00% 0/31	0.00% 0/13	0.00% 0/22	0.41% 1/241 • Number of events 1	0.33% 1/303 • Number of events 1	0.00% 0/27	0.00% 0/27	0.00% 0/52	0.00% 0/85	0.00% 0/168
Injury, poisoning and procedural complications Foot fracture	0.00% 0/345	0.00% 0/345	0.00% 0/348	0.00% 0/58	0.00% 0/62	0.00% 0/90	0.00% 0/57	0.00% 0/73	0.00% 0/27	0.00% 0/31	0.00% 0/13	0.00% 0/22	0.00% 0/241	0.33% 1/303 • Number of events 1	0.00% 0/27	0.00% 0/27	0.00% 0/52	0.00% 0/85	0.00% 0/168
Injury, poisoning and procedural complications Head injury	0.00% 0/345	0.29% 1/345 • Number of events 1	0.00% 0/348	0.00% 0/58	0.00% 0/62	0.00% 0/90	0.00% 0/57	0.00% 0/73	0.00% 0/27	0.00% 0/31	0.00% 0/13	0.00% 0/22	0.00% 0/241	0.00% 0/303	0.00% 0/27	0.00% 0/27	0.00% 0/52	0.00% 0/85	0.00% 0/168
Injury, poisoning and procedural complications Joint dislocation	0.00% 0/345	0.29% 1/345 • Number of events 1	0.00% 0/348	0.00% 0/58	0.00% 0/62	0.00% 0/90	0.00% 0/57	0.00% 0/73	0.00% 0/27	0.00% 0/31	0.00% 0/13	0.00% 0/22	0.00% 0/241	0.00% 0/303	0.00% 0/27	0.00% 0/27	0.00% 0/52	0.00% 0/85	0.00% 0/168
Injury, poisoning and procedural complications Joint injury	0.00% 0/345	0.00% 0/345	0.00% 0/348	0.00% 0/58	1.6% 1/62 • Number of events 1	0.00% 0/90	0.00% 0/57	0.00% 0/73	0.00% 0/27	0.00% 0/31	0.00% 0/13	0.00% 0/22	0.00% 0/241	0.00% 0/303	0.00% 0/27	0.00% 0/27	0.00% 0/52	0.00% 0/85	0.00% 0/168
Injury, poisoning and procedural complications Multiple injuries	0.00% 0/345	0.29% 1/345 • Number of events 1	0.00% 0/348	0.00% 0/58	0.00% 0/62	0.00% 0/90	0.00% 0/57	0.00% 0/73	0.00% 0/27	0.00% 0/31	0.00% 0/13	0.00% 0/22	0.00% 0/241	0.00% 0/303	0.00% 0/27	0.00% 0/27	0.00% 0/52	0.00% 0/85	0.00% 0/168
Injury, poisoning and procedural complications Pubis fracture	0.00% 0/345	0.00% 0/345	0.29% 1/348 • Number of events 1	0.00% 0/58	0.00% 0/62	0.00% 0/90	0.00% 0/57	0.00% 0/73	0.00% 0/27	0.00% 0/31	0.00% 0/13	0.00% 0/22	0.00% 0/241	0.00% 0/303	0.00% 0/27	0.00% 0/27	0.00% 0/52	0.00% 0/85	0.00% 0/168
Injury, poisoning and procedural complications Radius fracture	0.00% 0/345	0.00% 0/345	0.29% 1/348 • Number of events 1	0.00% 0/58	0.00% 0/62	0.00% 0/90	0.00% 0/57	0.00% 0/73	0.00% 0/27	0.00% 0/31	0.00% 0/13	0.00% 0/22	0.00% 0/241	0.00% 0/303	0.00% 0/27	0.00% 0/27	0.00% 0/52	0.00% 0/85	0.00% 0/168
Injury, poisoning and procedural complications Spinal compression fracture	0.00% 0/345	0.29% 1/345 • Number of events 1	0.29% 1/348 • Number of events 1	1.7% 1/58 • Number of events 1	0.00% 0/62	0.00% 0/90	0.00% 0/57	0.00% 0/73	0.00% 0/27	0.00% 0/31	0.00% 0/13	0.00% 0/22	0.00% 0/241	0.00% 0/303	0.00% 0/27	0.00% 0/27	0.00% 0/52	0.00% 0/85	0.00% 0/168
Injury, poisoning and procedural complications Synovial rupture	0.00% 0/345	0.00% 0/345	0.00% 0/348	0.00% 0/58	0.00% 0/62	0.00% 0/90	0.00% 0/57	0.00% 0/73	0.00% 0/27	0.00% 0/31	0.00% 0/13	0.00% 0/22	0.00% 0/241	0.33% 1/303 • Number of events 1	0.00% 0/27	0.00% 0/27	0.00% 0/52	0.00% 0/85	0.00% 0/168
Injury, poisoning and procedural complications Tendon rupture	0.00% 0/345	0.58% 2/345 • Number of events 2	0.00% 0/348	0.00% 0/58	0.00% 0/62	0.00% 0/90	0.00% 0/57	0.00% 0/73	0.00% 0/27	0.00% 0/31	0.00% 0/13	0.00% 0/22	0.00% 0/241	0.33% 1/303 • Number of events 1	0.00% 0/27	0.00% 0/27	0.00% 0/52	0.00% 0/85	0.00% 0/168
Metabolism and nutrition disorders Diabetes mellitus inadequate control	0.29% 1/345 • Number of events 1	0.00% 0/345	0.00% 0/348	0.00% 0/58	0.00% 0/62	0.00% 0/90	0.00% 0/57	0.00% 0/73	0.00% 0/27	0.00% 0/31	0.00% 0/13	0.00% 0/22	0.00% 0/241	0.00% 0/303	0.00% 0/27	0.00% 0/27	0.00% 0/52	0.00% 0/85	0.00% 0/168
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/345	0.00% 0/345	0.00% 0/348	0.00% 0/58	0.00% 0/62	0.00% 0/90	0.00% 0/57	0.00% 0/73	0.00% 0/27	0.00% 0/31	0.00% 0/13	0.00% 0/22	0.00% 0/241	0.00% 0/303	0.00% 0/27	0.00% 0/27	0.00% 0/52	0.00% 0/85	0.60% 1/168 • Number of events 1
Musculoskeletal and connective tissue disorders Foot deformity	0.00% 0/345	0.29% 1/345 • Number of events 1	0.00% 0/348	0.00% 0/58	0.00% 0/62	0.00% 0/90	0.00% 0/57	0.00% 0/73	0.00% 0/27	0.00% 0/31	0.00% 0/13	0.00% 0/22	0.00% 0/241	0.00% 0/303	0.00% 0/27	0.00% 0/27	0.00% 0/52	0.00% 0/85	0.00% 0/168
Musculoskeletal and connective tissue disorders Intervertebral disc displacement	0.00% 0/345	0.00% 0/345	0.00% 0/348	0.00% 0/58	0.00% 0/62	0.00% 0/90	0.00% 0/57	0.00% 0/73	0.00% 0/27	0.00% 0/31	0.00% 0/13	0.00% 0/22	0.00% 0/241	0.00% 0/303	0.00% 0/27	0.00% 0/27	0.00% 0/52	0.00% 0/85	0.60% 1/168 • Number of events 1
Musculoskeletal and connective tissue disorders Intervertebral disc protrusion	0.29% 1/345 • Number of events 1	0.00% 0/345	0.00% 0/348	0.00% 0/58	0.00% 0/62	0.00% 0/90	0.00% 0/57	0.00% 0/73	0.00% 0/27	0.00% 0/31	0.00% 0/13	0.00% 0/22	0.00% 0/241	0.00% 0/303	0.00% 0/27	0.00% 0/27	0.00% 0/52	0.00% 0/85	0.00% 0/168
Musculoskeletal and connective tissue disorders Joint destruction	0.00% 0/345	0.00% 0/345	0.00% 0/348	0.00% 0/58	0.00% 0/62	0.00% 0/90	0.00% 0/57	0.00% 0/73	0.00% 0/27	0.00% 0/31	0.00% 0/13	0.00% 0/22	0.00% 0/241	0.33% 1/303 • Number of events 1	0.00% 0/27	0.00% 0/27	0.00% 0/52	0.00% 0/85	0.00% 0/168
Musculoskeletal and connective tissue disorders Monarthritis	0.00% 0/345	0.00% 0/345	0.29% 1/348 • Number of events 1	0.00% 0/58	0.00% 0/62	0.00% 0/90	0.00% 0/57	0.00% 0/73	0.00% 0/27	0.00% 0/31	0.00% 0/13	0.00% 0/22	0.00% 0/241	0.00% 0/303	0.00% 0/27	0.00% 0/27	0.00% 0/52	0.00% 0/85	0.00% 0/168
Musculoskeletal and connective tissue disorders Osteoarthritis	0.29% 1/345 • Number of events 1	0.29% 1/345 • Number of events 1	0.00% 0/348	0.00% 0/58	0.00% 0/62	0.00% 0/90	0.00% 0/57	0.00% 0/73	0.00% 0/27	0.00% 0/31	0.00% 0/13	0.00% 0/22	0.41% 1/241 • Number of events 1	0.33% 1/303 • Number of events 1	0.00% 0/27	0.00% 0/27	0.00% 0/52	1.2% 1/85 • Number of events 1	0.00% 0/168
Musculoskeletal and connective tissue disorders Rheumatoid arthritis	0.29% 1/345 • Number of events 1	0.29% 1/345 • Number of events 1	1.1% 4/348 • Number of events 4	1.7% 1/58 • Number of events 1	0.00% 0/62	0.00% 0/90	0.00% 0/57	0.00% 0/73	0.00% 0/27	0.00% 0/31	0.00% 0/13	0.00% 0/22	0.41% 1/241 • Number of events 1	0.66% 2/303 • Number of events 2	0.00% 0/27	0.00% 0/27	0.00% 0/52	0.00% 0/85	2.4% 4/168 • Number of events 4
Musculoskeletal and connective tissue disorders Spinal column stenosis	0.00% 0/345	0.00% 0/345	0.00% 0/348	0.00% 0/58	0.00% 0/62	0.00% 0/90	0.00% 0/57	0.00% 0/73	0.00% 0/27	0.00% 0/31	0.00% 0/13	0.00% 0/22	0.41% 1/241 • Number of events 1	0.00% 0/303	0.00% 0/27	0.00% 0/27	0.00% 0/52	0.00% 0/85	0.00% 0/168
Musculoskeletal and connective tissue disorders Spondylolisthesis	0.00% 0/345	0.00% 0/345	0.29% 1/348 • Number of events 1	0.00% 0/58	0.00% 0/62	0.00% 0/90	0.00% 0/57	0.00% 0/73	0.00% 0/27	0.00% 0/31	0.00% 0/13	0.00% 0/22	0.00% 0/241	0.00% 0/303	0.00% 0/27	0.00% 0/27	0.00% 0/52	0.00% 0/85	0.00% 0/168
Neoplasms benign, malignant and unspecified (incl cysts and polyps) B-cell lymphoma stage i	0.29% 1/345 • Number of events 1	0.00% 0/345	0.00% 0/348	0.00% 0/58	0.00% 0/62	0.00% 0/90	0.00% 0/57	0.00% 0/73	0.00% 0/27	0.00% 0/31	0.00% 0/13	0.00% 0/22	0.00% 0/241	0.00% 0/303	0.00% 0/27	0.00% 0/27	0.00% 0/52	0.00% 0/85	0.00% 0/168
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Basal cell carcinoma	0.00% 0/345	0.00% 0/345	0.00% 0/348	0.00% 0/58	0.00% 0/62	0.00% 0/90	0.00% 0/57	0.00% 0/73	0.00% 0/27	0.00% 0/31	0.00% 0/13	0.00% 0/22	0.00% 0/241	0.00% 0/303	0.00% 0/27	0.00% 0/27	1.9% 1/52 • Number of events 1	0.00% 0/85	0.00% 0/168
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Bladder transitional cell carcinoma stage iii	0.00% 0/345	0.00% 0/345	0.00% 0/348	0.00% 0/58	0.00% 0/62	0.00% 0/90	0.00% 0/57	0.00% 0/73	0.00% 0/27	3.2% 1/31 • Number of events 1	0.00% 0/13	0.00% 0/22	0.00% 0/241	0.00% 0/303	0.00% 0/27	0.00% 0/27	0.00% 0/52	0.00% 0/85	0.00% 0/168
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast cancer	0.00% 0/345	0.00% 0/345	0.00% 0/348	0.00% 0/58	0.00% 0/62	0.00% 0/90	0.00% 0/57	0.00% 0/73	0.00% 0/27	0.00% 0/31	0.00% 0/13	0.00% 0/22	0.00% 0/241	0.00% 0/303	0.00% 0/27	0.00% 0/27	0.00% 0/52	0.00% 0/85	0.60% 1/168 • Number of events 1
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Cervix carcinoma	0.00% 0/294	0.35% 1/289 • Number of events 1	0.00% 0/291	0.00% 0/44	0.00% 0/57	0.00% 0/69	0.00% 0/51	0.00% 0/62	0.00% 0/22	0.00% 0/27	0.00% 0/9	0.00% 0/19	0.00% 0/211	0.00% 0/255	0.00% 0/22	0.00% 0/24	0.00% 0/40	0.00% 0/66	0.00% 0/146
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Intraductal proliferative breast lesion	0.00% 0/345	0.00% 0/345	0.00% 0/348	0.00% 0/58	0.00% 0/62	0.00% 0/90	0.00% 0/57	0.00% 0/73	0.00% 0/27	0.00% 0/31	0.00% 0/13	0.00% 0/22	0.41% 1/241 • Number of events 1	0.00% 0/303	0.00% 0/27	0.00% 0/27	0.00% 0/52	0.00% 0/85	0.00% 0/168
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastatic gastric cancer	0.00% 0/345	0.00% 0/345	0.00% 0/348	0.00% 0/58	0.00% 0/62	0.00% 0/90	0.00% 0/57	0.00% 0/73	0.00% 0/27	0.00% 0/31	0.00% 0/13	0.00% 0/22	0.41% 1/241 • Number of events 1	0.00% 0/303	0.00% 0/27	0.00% 0/27	0.00% 0/52	0.00% 0/85	0.00% 0/168
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Ovarian cancer	0.00% 0/294	0.35% 1/289 • Number of events 1	0.00% 0/291	0.00% 0/44	0.00% 0/57	0.00% 0/69	0.00% 0/51	0.00% 0/62	0.00% 0/22	0.00% 0/27	0.00% 0/9	0.00% 0/19	0.00% 0/211	0.00% 0/255	0.00% 0/22	0.00% 0/24	0.00% 0/40	0.00% 0/66	0.00% 0/146
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Rectal adenocarcinoma	0.00% 0/345	0.00% 0/345	0.00% 0/348	0.00% 0/58	0.00% 0/62	0.00% 0/90	0.00% 0/57	0.00% 0/73	0.00% 0/27	0.00% 0/31	0.00% 0/13	0.00% 0/22	0.00% 0/241	0.00% 0/303	0.00% 0/27	0.00% 0/27	1.9% 1/52 • Number of events 1	0.00% 0/85	0.00% 0/168
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Squamous cell carcinoma	0.00% 0/345	0.00% 0/345	0.00% 0/348	0.00% 0/58	0.00% 0/62	0.00% 0/90	0.00% 0/57	0.00% 0/73	0.00% 0/27	0.00% 0/31	0.00% 0/13	0.00% 0/22	0.00% 0/241	0.00% 0/303	0.00% 0/27	0.00% 0/27	0.00% 0/52	0.00% 0/85	0.60% 1/168 • Number of events 1
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Uterine leiomyoma	0.34% 1/294 • Number of events 1	0.00% 0/289	0.00% 0/291	0.00% 0/44	0.00% 0/57	0.00% 0/69	0.00% 0/51	0.00% 0/62	0.00% 0/22	0.00% 0/27	0.00% 0/9	0.00% 0/19	0.00% 0/211	0.00% 0/255	0.00% 0/22	0.00% 0/24	0.00% 0/40	0.00% 0/66	0.00% 0/146
Nervous system disorders Cerebral atrophy	0.00% 0/345	0.00% 0/345	0.00% 0/348	0.00% 0/58	0.00% 0/62	0.00% 0/90	0.00% 0/57	0.00% 0/73	0.00% 0/27	0.00% 0/31	0.00% 0/13	0.00% 0/22	0.00% 0/241	0.00% 0/303	0.00% 0/27	0.00% 0/27	0.00% 0/52	1.2% 1/85 • Number of events 1	0.00% 0/168
Nervous system disorders Cerebral small vessel ischaemic disease	0.00% 0/345	0.00% 0/345	0.00% 0/348	0.00% 0/58	0.00% 0/62	0.00% 0/90	0.00% 0/57	0.00% 0/73	0.00% 0/27	0.00% 0/31	0.00% 0/13	0.00% 0/22	0.00% 0/241	0.00% 0/303	0.00% 0/27	0.00% 0/27	0.00% 0/52	1.2% 1/85 • Number of events 1	0.00% 0/168
Nervous system disorders Cerebrovascular accident	0.00% 0/345	0.00% 0/345	0.00% 0/348	0.00% 0/58	0.00% 0/62	0.00% 0/90	0.00% 0/57	0.00% 0/73	0.00% 0/27	0.00% 0/31	0.00% 0/13	0.00% 0/22	0.00% 0/241	0.00% 0/303	0.00% 0/27	0.00% 0/27	0.00% 0/52	1.2% 1/85 • Number of events 1	0.00% 0/168
Nervous system disorders Convulsion	0.00% 0/345	0.00% 0/345	0.00% 0/348	0.00% 0/58	0.00% 0/62	0.00% 0/90	0.00% 0/57	0.00% 0/73	0.00% 0/27	0.00% 0/31	0.00% 0/13	0.00% 0/22	0.00% 0/241	0.00% 0/303	0.00% 0/27	0.00% 0/27	0.00% 0/52	1.2% 1/85 • Number of events 1	0.00% 0/168
Nervous system disorders Encephalopathy	0.00% 0/345	0.00% 0/345	0.00% 0/348	0.00% 0/58	0.00% 0/62	0.00% 0/90	0.00% 0/57	0.00% 0/73	0.00% 0/27	0.00% 0/31	0.00% 0/13	0.00% 0/22	0.00% 0/241	0.00% 0/303	0.00% 0/27	0.00% 0/27	0.00% 0/52	1.2% 1/85 • Number of events 1	0.00% 0/168
Nervous system disorders Headache	0.00% 0/345	0.29% 1/345 • Number of events 1	0.00% 0/348	0.00% 0/58	0.00% 0/62	0.00% 0/90	0.00% 0/57	0.00% 0/73	0.00% 0/27	0.00% 0/31	0.00% 0/13	0.00% 0/22	0.00% 0/241	0.00% 0/303	0.00% 0/27	0.00% 0/27	0.00% 0/52	0.00% 0/85	0.00% 0/168
Nervous system disorders Hemiparesis	0.00% 0/345	0.00% 0/345	0.00% 0/348	0.00% 0/58	0.00% 0/62	0.00% 0/90	0.00% 0/57	0.00% 0/73	0.00% 0/27	0.00% 0/31	0.00% 0/13	0.00% 0/22	0.00% 0/241	0.00% 0/303	0.00% 0/27	0.00% 0/27	0.00% 0/52	1.2% 1/85 • Number of events 1	0.00% 0/168
Nervous system disorders Lumbar radiculopathy	0.29% 1/345 • Number of events 1	0.00% 0/345	0.00% 0/348	0.00% 0/58	0.00% 0/62	0.00% 0/90	0.00% 0/57	0.00% 0/73	0.00% 0/27	0.00% 0/31	0.00% 0/13	0.00% 0/22	0.00% 0/241	0.00% 0/303	0.00% 0/27	0.00% 0/27	0.00% 0/52	0.00% 0/85	0.00% 0/168
Nervous system disorders Presyncope	0.00% 0/345	0.00% 0/345	0.00% 0/348	0.00% 0/58	0.00% 0/62	0.00% 0/90	0.00% 0/57	0.00% 0/73	0.00% 0/27	0.00% 0/31	0.00% 0/13	0.00% 0/22	0.00% 0/241	0.33% 1/303 • Number of events 1	0.00% 0/27	0.00% 0/27	0.00% 0/52	0.00% 0/85	0.00% 0/168
Nervous system disorders Radiculitis lumbosacral	0.00% 0/345	0.29% 1/345 • Number of events 1	0.00% 0/348	0.00% 0/58	0.00% 0/62	0.00% 0/90	0.00% 0/57	0.00% 0/73	0.00% 0/27	0.00% 0/31	0.00% 0/13	0.00% 0/22	0.00% 0/241	0.00% 0/303	0.00% 0/27	0.00% 0/27	0.00% 0/52	0.00% 0/85	0.00% 0/168
Nervous system disorders Syncope	0.00% 0/345	0.29% 1/345 • Number of events 1	0.00% 0/348	0.00% 0/58	0.00% 0/62	0.00% 0/90	0.00% 0/57	0.00% 0/73	0.00% 0/27	0.00% 0/31	0.00% 0/13	0.00% 0/22	0.00% 0/241	0.00% 0/303	0.00% 0/27	0.00% 0/27	0.00% 0/52	0.00% 0/85	0.00% 0/168
Nervous system disorders Transient ischaemic attack	0.29% 1/345 • Number of events 1	0.00% 0/345	0.00% 0/348	0.00% 0/58	0.00% 0/62	0.00% 0/90	0.00% 0/57	0.00% 0/73	0.00% 0/27	0.00% 0/31	0.00% 0/13	0.00% 0/22	0.00% 0/241	0.00% 0/303	0.00% 0/27	0.00% 0/27	0.00% 0/52	0.00% 0/85	0.00% 0/168
Psychiatric disorders Depression	0.00% 0/345	0.00% 0/345	0.29% 1/348 • Number of events 1	0.00% 0/58	0.00% 0/62	0.00% 0/90	0.00% 0/57	0.00% 0/73	0.00% 0/27	0.00% 0/31	0.00% 0/13	0.00% 0/22	0.00% 0/241	0.00% 0/303	0.00% 0/27	0.00% 0/27	0.00% 0/52	0.00% 0/85	0.00% 0/168
Psychiatric disorders Mental status changes	0.00% 0/345	0.00% 0/345	0.00% 0/348	0.00% 0/58	0.00% 0/62	0.00% 0/90	0.00% 0/57	0.00% 0/73	0.00% 0/27	0.00% 0/31	0.00% 0/13	0.00% 0/22	0.00% 0/241	0.00% 0/303	0.00% 0/27	0.00% 0/27	0.00% 0/52	1.2% 1/85 • Number of events 1	0.00% 0/168
Psychiatric disorders Stress	0.00% 0/345	0.00% 0/345	0.00% 0/348	1.7% 1/58 • Number of events 1	0.00% 0/62	0.00% 0/90	0.00% 0/57	0.00% 0/73	0.00% 0/27	0.00% 0/31	0.00% 0/13	0.00% 0/22	0.00% 0/241	0.00% 0/303	0.00% 0/27	0.00% 0/27	0.00% 0/52	0.00% 0/85	0.00% 0/168
Psychiatric disorders Suicide attempt	0.00% 0/345	0.00% 0/345	0.00% 0/348	1.7% 1/58 • Number of events 2	0.00% 0/62	0.00% 0/90	0.00% 0/57	0.00% 0/73	0.00% 0/27	0.00% 0/31	0.00% 0/13	0.00% 0/22	0.00% 0/241	0.00% 0/303	0.00% 0/27	0.00% 0/27	1.9% 1/52 • Number of events 2	0.00% 0/85	0.00% 0/168
Renal and urinary disorders Calculus ureteric	0.00% 0/345	0.00% 0/345	0.00% 0/348	1.7% 1/58 • Number of events 1	0.00% 0/62	0.00% 0/90	0.00% 0/57	0.00% 0/73	0.00% 0/27	0.00% 0/31	0.00% 0/13	0.00% 0/22	0.00% 0/241	0.00% 0/303	0.00% 0/27	0.00% 0/27	0.00% 0/52	0.00% 0/85	0.00% 0/168
Renal and urinary disorders Nephrolithiasis	0.00% 0/345	0.29% 1/345 • Number of events 1	0.00% 0/348	0.00% 0/58	0.00% 0/62	0.00% 0/90	0.00% 0/57	0.00% 0/73	0.00% 0/27	0.00% 0/31	0.00% 0/13	0.00% 0/22	0.00% 0/241	0.00% 0/303	0.00% 0/27	0.00% 0/27	0.00% 0/52	0.00% 0/85	0.00% 0/168
Renal and urinary disorders Renal failure acute	0.29% 1/345 • Number of events 1	0.00% 0/345	0.00% 0/348	0.00% 0/58	0.00% 0/62	0.00% 0/90	0.00% 0/57	0.00% 0/73	0.00% 0/27	0.00% 0/31	0.00% 0/13	0.00% 0/22	0.00% 0/241	0.00% 0/303	0.00% 0/27	0.00% 0/27	0.00% 0/52	1.2% 1/85 • Number of events 1	0.00% 0/168
Reproductive system and breast disorders Cervical dysplasia	0.00% 0/294	0.00% 0/289	0.00% 0/291	0.00% 0/44	0.00% 0/57	0.00% 0/69	0.00% 0/51	0.00% 0/62	0.00% 0/22	0.00% 0/27	0.00% 0/9	0.00% 0/19	0.00% 0/211	0.39% 1/255 • Number of events 1	0.00% 0/22	0.00% 0/24	0.00% 0/40	0.00% 0/66	0.00% 0/146
Reproductive system and breast disorders Menorrhagia	0.00% 0/294	0.00% 0/289	0.00% 0/291	0.00% 0/44	0.00% 0/57	0.00% 0/69	0.00% 0/51	0.00% 0/62	0.00% 0/22	0.00% 0/27	0.00% 0/9	0.00% 0/19	0.00% 0/211	0.39% 1/255 • Number of events 1	0.00% 0/22	0.00% 0/24	0.00% 0/40	0.00% 0/66	0.00% 0/146
Reproductive system and breast disorders Vaginal haemorrhage	0.34% 1/294 • Number of events 1	0.00% 0/289	0.00% 0/291	0.00% 0/44	0.00% 0/57	0.00% 0/69	0.00% 0/51	0.00% 0/62	0.00% 0/22	0.00% 0/27	0.00% 0/9	0.00% 0/19	0.00% 0/211	0.00% 0/255	0.00% 0/22	0.00% 0/24	0.00% 0/40	0.00% 0/66	0.00% 0/146
Respiratory, thoracic and mediastinal disorders Acute pulmonary oedema	0.00% 0/345	0.00% 0/345	0.00% 0/348	0.00% 0/58	0.00% 0/62	0.00% 0/90	0.00% 0/57	0.00% 0/73	0.00% 0/27	0.00% 0/31	0.00% 0/13	0.00% 0/22	0.00% 0/241	0.00% 0/303	0.00% 0/27	0.00% 0/27	0.00% 0/52	0.00% 0/85	0.60% 1/168 • Number of events 1
Respiratory, thoracic and mediastinal disorders Chronic respiratory failure	0.00% 0/345	0.00% 0/345	0.29% 1/348 • Number of events 1	0.00% 0/58	0.00% 0/62	0.00% 0/90	0.00% 0/57	0.00% 0/73	0.00% 0/27	0.00% 0/31	0.00% 0/13	0.00% 0/22	0.00% 0/241	0.00% 0/303	0.00% 0/27	0.00% 0/27	0.00% 0/52	0.00% 0/85	0.00% 0/168
Respiratory, thoracic and mediastinal disorders Hypoxia	0.00% 0/345	0.00% 0/345	0.00% 0/348	0.00% 0/58	0.00% 0/62	0.00% 0/90	0.00% 0/57	0.00% 0/73	0.00% 0/27	0.00% 0/31	0.00% 0/13	0.00% 0/22	0.00% 0/241	0.00% 0/303	0.00% 0/27	0.00% 0/27	0.00% 0/52	1.2% 1/85 • Number of events 1	0.00% 0/168
Respiratory, thoracic and mediastinal disorders Interstitial lung disease	0.00% 0/345	0.29% 1/345 • Number of events 1	0.00% 0/348	0.00% 0/58	0.00% 0/62	0.00% 0/90	0.00% 0/57	0.00% 0/73	0.00% 0/27	0.00% 0/31	0.00% 0/13	0.00% 0/22	0.00% 0/241	0.66% 2/303 • Number of events 2	0.00% 0/27	0.00% 0/27	0.00% 0/52	0.00% 0/85	0.00% 0/168
Respiratory, thoracic and mediastinal disorders Lung disorder	0.00% 0/345	0.00% 0/345	0.00% 0/348	0.00% 0/58	0.00% 0/62	0.00% 0/90	0.00% 0/57	0.00% 0/73	0.00% 0/27	0.00% 0/31	0.00% 0/13	0.00% 0/22	0.00% 0/241	0.00% 0/303	0.00% 0/27	0.00% 0/27	0.00% 0/52	0.00% 0/85	0.60% 1/168 • Number of events 1
Respiratory, thoracic and mediastinal disorders Nasal septum deviation	0.00% 0/345	0.29% 1/345 • Number of events 1	0.00% 0/348	0.00% 0/58	0.00% 0/62	0.00% 0/90	0.00% 0/57	0.00% 0/73	0.00% 0/27	0.00% 0/31	0.00% 0/13	0.00% 0/22	0.00% 0/241	0.00% 0/303	0.00% 0/27	0.00% 0/27	0.00% 0/52	0.00% 0/85	0.00% 0/168
Respiratory, thoracic and mediastinal disorders Obliterative bronchiolitis	0.00% 0/345	0.00% 0/345	0.00% 0/348	0.00% 0/58	0.00% 0/62	0.00% 0/90	0.00% 0/57	0.00% 0/73	0.00% 0/27	0.00% 0/31	0.00% 0/13	0.00% 0/22	0.00% 0/241	0.00% 0/303	3.7% 1/27 • Number of events 1	0.00% 0/27	0.00% 0/52	0.00% 0/85	0.00% 0/168
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.29% 1/345 • Number of events 2	0.00% 0/345	0.00% 0/348	0.00% 0/58	0.00% 0/62	0.00% 0/90	0.00% 0/57	0.00% 0/73	0.00% 0/27	0.00% 0/31	0.00% 0/13	0.00% 0/22	0.00% 0/241	0.00% 0/303	0.00% 0/27	0.00% 0/27	0.00% 0/52	0.00% 0/85	0.00% 0/168
Vascular disorders Deep vein thrombosis	0.29% 1/345 • Number of events 1	0.00% 0/345	0.00% 0/348	0.00% 0/58	0.00% 0/62	0.00% 0/90	0.00% 0/57	0.00% 0/73	0.00% 0/27	0.00% 0/31	0.00% 0/13	0.00% 0/22	0.00% 0/241	0.00% 0/303	0.00% 0/27	0.00% 0/27	0.00% 0/52	0.00% 0/85	0.00% 0/168
Vascular disorders Hypotension	0.00% 0/345	0.00% 0/345	0.00% 0/348	0.00% 0/58	0.00% 0/62	0.00% 0/90	0.00% 0/57	0.00% 0/73	0.00% 0/27	0.00% 0/31	0.00% 0/13	0.00% 0/22	0.00% 0/241	0.00% 0/303	0.00% 0/27	0.00% 0/27	0.00% 0/52	1.2% 1/85 • Number of events 1	0.00% 0/168
Vascular disorders Peripheral ischaemia	0.29% 1/345 • Number of events 1	0.00% 0/345	0.00% 0/348	0.00% 0/58	0.00% 0/62	0.00% 0/90	0.00% 0/57	0.00% 0/73	0.00% 0/27	0.00% 0/31	0.00% 0/13	0.00% 0/22	0.00% 0/241	0.00% 0/303	0.00% 0/27	0.00% 0/27	0.00% 0/52	0.00% 0/85	0.00% 0/168

Other adverse events

Measure	LY 120 mg Q4W, Randomized Treatment Period 1 n=345 participants at risk A loading dose of 240 mg of LY2127399 (2 injections of 120 mg) followed by maintenance dosing of 120 mg of LY2127399 administered SC Q4W for 52 weeks during Treatment Period 1. At Week 16, responders received 1 injection of 120 mg of LY2127399 and 1 injection of placebo, followed by 120 mg of LY2127399 Q4W for the rest of the 52-week Treatment Period 1. For blinding purposes, participants alternated injections of LY2127399 and injections of placebo Q2W. The Randomized Treatment Period 1 was defined as the time all data was collected during the Treatment Period 1, excluding the data collected after the date of the Week 16 injection for the Week 16 NR.	LY 90 mg Q2W, Randomized Treatment Period 1 n=345 participants at risk A loading dose of 180 mg of LY2127399 (2 injections of 90 mg) followed by maintenance dosing of 90 mg of LY2127399 administered SC Q2W for 52 weeks during Treatment Period 1. At Week 16, responders received 1 injection of 90 mg of LY2127399 and 1 injection of placebo, followed by 90 mg of LY2127399 Q2W for the rest of the Treatment Period 1. The Randomized Treatment Period 1 was defined as the time all data was collected during the Treatment Period 1, excluding the data collected after the date of the Week 16 injection for the Week 16 NR.	Placebo, Randomized Treatment Period 1 n=348 participants at risk A loading dose of 2 injections of placebo followed by maintenance dosing of placebo administered SC Q2W for 52 weeks during Treatment Period 1. At Week 16, responders received 2 injections of placebo, followed by 1 injection of placebo Q2W for the rest of the Treatment Period 1. The Randomized Treatment Period 1 was defined as the time all data was collected during the Treatment Period 1, excluding the data collected after the date of the Week 16 injection for the Week 16 NR.	LY 120 mg Q4W to LY 90 mg Q2W (Week 16), Rescue Period n=58 participants at risk A loading dose of 240 mg of LY2127399 (2 injections of 120 mg) followed by maintenance dosing of 120 mg of LY2127399 administered SC Q4W for 16 weeks during Treatment Period 1. For blinding purposes, participants alternated injections of LY2127399 and injections of placebo Q2W. At Week 16, NR received 1 injection of 90 mg of LY2127399 and 1 injection of placebo, followed by 90 mg of LY2127399 Q2W for the rest of the 52-week Treatment Period 1. The Rescue Treatment Period was defined as all data collected after the date of the Week 16 injection during the Treatment Period 1 for Week 16 NR.	LY 90 mg Q2W, Rescue Period n=62 participants at risk A loading dose of 180 mg of LY2127399 (2 injections of 90 mg) followed by maintenance dosing of 90 mg of LY2127399 administered SC Q2W for 16 weeks during Treatment Period 1. At Week 16, NR received 1 injection of 90 mg of LY2127399 and 1 injection of placebo, followed by 90 mg of LY2127399 Q2W for the rest of the 52-week Treatment Period 1. The Rescue Treatment Period was defined as all data collected after the date of the Week 16 injection during the Treatment Period 1 for Week 16 NR.	Placebo to LY 90 mg Q2W (Week 16), Rescue Period n=90 participants at risk A loading dose of 2 injections of placebo followed by maintenance dosing of placebo administered SC Q2W for 16 weeks during Treatment Period 1. At Week 16, NR received a loading dose of 180 mg of LY2127399 (2 injections of 90 mg), followed by 90 mg of LY2127399 Q2W for the rest of the 52-week Treatment Period 1. The Rescue Treatment Period was defined as all data collected after the date of the Week 16 injection during the Treatment Period 1 for Week 16 NR.	LY 120 mg Q4W, Treatment Period 2 n=57 participants at risk A loading dose of 240 mg of LY2127399 (2 injections of 120 mg) followed by maintenance dosing of 120 mg of LY2127399 administered SC Q4W for 52 weeks during Treatment Period 1. At Week 16, Week 16 responders received 1 injection of 120 mg of LY2127399 and 1 injection of placebo, followed by 120 mg of LY2127399 Q4W for the rest of the 52-week Treatment Period 1. For blinding purposes, participants alternated injections of LY2127399 and injections of placebo Q2W. At Week 52, Week 16 responders received 1 injection of 120 mg of LY2127399 and 1 injection of placebo, followed by 120 mg of LY2127399 Q4W for the rest of the Treatment Period 2. Treatment Period 2 was defined as all data collected from Week 52 to Week 100 during non-blinded Treatment Period 2.	LY 90 mg Q2W, Treatment Period 2 n=73 participants at risk A loading dose of 180 mg of LY2127399 (2 injections of 90 mg) followed by maintenance dosing of 90 mg of LY2127399 administered SC Q2W for 52 weeks during Treatment Period 1. At Week 16, both Week 16 responders and NR received 1 injection of 90 mg of LY2127399 and 1 injection of placebo, followed by 90 mg of LY2127399 Q2W for the rest of the Treatment Period 1. At Week 52, both Week 16 responders and NR received 1 injection of 90 mg of LY2127399 and 1 injection of placebo, followed by 90 mg of LY2127399 Q2W for the rest of the Treatment Period 2. Treatment Period 2 was defined as all data collected from Week 52 to Week 100 during non-blinded Treatment Period 2.	Placebo to LY 120 mg Q4W (Week 52), Treatment Period 2 n=27 participants at risk A loading dose of 2 injections of placebo followed by maintenance dosing of placebo administered SC Q2W for 52 weeks during Treatment Period 1. At Week 16, Week 16 responders received 2 injections of placebo, followed by 1 injection of placebo Q2W for the rest of the Treatment Period 1. At Week 52, Week 16 responders were randomized to receive 2 injections of 120 mg of LY2127399, followed by 120 mg of LY2127399 Q4W for the rest of the Treatment Period 2 Treatment Period 2 was defined as all data collected from Week 52 to Week 100 during non-blinded Treatment Period 2.	Placebo to LY 90 mg Q2W (Week 52), Treatment Period 2 n=31 participants at risk A loading dose of 2 injections of placebo followed by maintenance dosing of placebo administered SC Q2W for 52 weeks during Treatment Period 1. At Week 16, Week 16 responders received 2 injections of placebo, followed by 1 injection of placebo Q2W for the rest of the Treatment Period 1. At Week 52, Week 16 responders were randomized to receive 2 injections of 90 mg of LY2127399, followed by 90 mg of LY2127399 Q4W for the rest of the Treatment Period 2 Treatment Period 2 was defined as all data collected from Week 52 to Week 100 during non-blinded Treatment Period 2.	LY 120 mg Q4W to LY 90 mg Q2W (Week 16), Treatment Period 2 n=13 participants at risk A loading dose of 240 mg of LY2127399 (2 injections of 120 mg) followed by maintenance dosing of 120 mg of LY2127399 administered SC Q4W for 16 weeks during Treatment Period 1. For blinding purposes, participants alternated injections of LY2127399 and injections of placebo Q2W. At Week 16, Week 16 NR received 1 injection of 90 mg of LY2127399 and 1 injection of placebo, followed by 90 mg of LY2127399 Q2W for the rest of the 52-week Treatment Period 1. During non-blinded Treatment Period 2, Week 16 NR received 1 injection of 90 mg of LY2127399. Treatment Period 2 was defined as all data collected from Week 52 to Week 100 during non-blinded Treatment Period 2.	Placebo to LY 90 mg Q2W (Week 16), Treatment Period 2 n=22 participants at risk A loading dose of 2 injections of placebo followed by maintenance dosing of placebo administered SC Q2W for 16 weeks during Treatment Period 1. At Week 16, Week 16 NR received a loading dose of 180 mg of LY2127399 (2 injections of 90 mg), followed by 90 mg of LY2127399 Q2W for the rest of the 52-week Treatment Period 1. During non-blinded Treatment Period 2, Week 16 NR received 1 injection of 90 mg of LY2127399. Treatment Period 2 was defined as all data collected from Week 52 to Week 100 during non-blinded Treatment Period 2.	LY 120 mg Q4W, Follow-up Period n=241 participants at risk A loading dose of 240 mg of LY2127399 (2 injections of 120 mg) followed by maintenance dosing of 120 mg of LY2127399 administered SC Q4W for 52 weeks during Treatment Period 1. At Week 16, Week 16 responders received 1 injection of 120 mg of LY2127399 and 1 injection of placebo, followed by 120 mg of LY2127399 Q4W for the rest of the 52-week Treatment Period 1. For blinding purposes, participants alternated injections of LY2127399 and injections of placebo Q2W. At Week 52, Week 16 responders received 1 injection of 120 mg of LY2127399 and 1 injection of placebo, followed by 120 mg of LY2127399 Q4W for the rest of the Treatment Period 2. The Post-Treatment Follow-Up Period started after Week 100 or the early discontinuation visit and lasted up to 48 weeks following the last injection of study treatment.	LY 90 mg Q2W, Follow-up Period n=303 participants at risk A loading dose of 180 mg of LY2127399 (2 injections of 90 mg) followed by maintenance dosing of 90 mg of LY2127399 administered SC Q2W for 52 weeks during Treatment Period 1. At Week 16, both Week 16 responders and NR received 1 injection of 90 mg of LY2127399 and 1 injection of placebo, followed by 90 mg of LY2127399 Q2W for the rest of the Treatment Period 1. At Week 52, both Week 16 responders and NR received 1 injection of 90 mg of LY2127399 and 1 injection of placebo, followed by 90 mg of LY2127399 Q2W for the rest of the Treatment Period 2. The Post-Treatment Follow-Up Period started after Week 100 or the early discontinuation visit and lasted up to 48 weeks following the last injection of study treatment.	Placebo to LY 120 mg Q4W (Week 52), Follow-up Period n=27 participants at risk A loading dose of 2 injections of placebo followed by maintenance dosing of placebo administered SC Q2W for 52 weeks during Treatment Period 1. At Week 16, Week 16 responders received 2 injections of placebo, followed by 1 injection of placebo Q2W for the rest of the Treatment Period 1. At Week 52, Week 16 responders were randomized to receive 2 injections of 120 mg of LY2127399, followed by 120 mg of LY2127399 Q4W for the rest of the Treatment Period 2 The Post-Treatment Follow-Up Period started after Week 100 or the early discontinuation visit and lasted up to 48 weeks following the last injection of study treatment.	Placebo to LY 90 mg Q2W (Week 52), Follow-up Period n=27 participants at risk A loading dose of 2 injections of placebo followed by maintenance dosing of placebo administered SC Q2W for 52 weeks during Treatment Period 1. At Week 16, Week 16 responders received 2 injections of placebo, followed by 1 injection of placebo Q2W for the rest of the Treatment Period 1. At Week 52, Week 16 responders were randomized to receive 2 injections of 90 mg of LY2127399, followed by 90 mg of LY2127399 Q4W for the rest of the Treatment Period 2 The Post-Treatment Follow-Up Period started after Week 100 or the early discontinuation visit and lasted up to 48 weeks following the last injection of study treatment.	LY 120 mg Q4W to LY 90 mg Q2W (Week 16), Follow-up Period n=52 participants at risk A loading dose of 240 mg of LY2127399 (2 injections of 120 mg) followed by maintenance dosing of 120 mg of LY2127399 administered SC Q4W for 16 weeks during Treatment Period 1. For blinding purposes, participants alternated injections of LY2127399 and injections of placebo Q2W. At Week 16, Week 16 NR received 1 injection of 90 mg of LY2127399 and 1 injection of placebo, followed by 90 mg of LY2127399 Q2W for the rest of the 52-week Treatment Period 1. During non-blinded Treatment Period 2, Week 16 NR received 1 injection of 90 mg of LY2127399. The Post-Treatment Follow-Up Period started after Week 100 or the early discontinuation visit and lasted up to 48 weeks following the last injection of study treatment.	Placebo to LY 90 mg Q2W (Week 16), Follow-up Period n=85 participants at risk A loading dose of 2 injections of placebo followed by maintenance dosing of placebo administered SC Q2W for 16 weeks during Treatment Period 1. At Week 16, Week 16 NR received a loading dose of 180 mg of LY2127399 (2 injections of 90 mg), followed by 90 mg of LY2127399 Q2W for the rest of the 52-week Treatment Period 1. During non-blinded Treatment Period 2, Week 16 NR received 1 injection of 90 mg of LY2127399. The Post-Treatment Follow-Up Period started after Week 100 or the early discontinuation visit and lasted up to 48 weeks following the last injection of study treatment.	Placebo, Follow-up Period n=168 participants at risk A loading dose of 2 injections of placebo followed by maintenance dosing of placebo administered SC Q2W for 52 weeks during Treatment Period 1. At Week 16, responders received 2 injections of placebo, followed by 1 injection of placebo Q2W for the rest of the Treatment Period 1. The Post-Treatment Follow-Up Period started after Week 52 or the early discontinuation visit and lasted up to 48 weeks following the last injection of study treatment.
Blood and lymphatic system disorders Leukocytosis	0.29% 1/345 • Number of events 1	0.00% 0/345	0.00% 0/348	1.7% 1/58 • Number of events 1	1.6% 1/62 • Number of events 1	0.00% 0/90	0.00% 0/57	0.00% 0/73	3.7% 1/27 • Number of events 1	0.00% 0/31	0.00% 0/13	0.00% 0/22	0.00% 0/241	0.00% 0/303	0.00% 0/27	0.00% 0/27	0.00% 0/52	0.00% 0/85	0.00% 0/168
Blood and lymphatic system disorders Lymphopenia	1.4% 5/345 • Number of events 6	0.29% 1/345 • Number of events 2	0.57% 2/348 • Number of events 2	1.7% 1/58 • Number of events 1	0.00% 0/62	0.00% 0/90	0.00% 0/57	0.00% 0/73	0.00% 0/27	0.00% 0/31	0.00% 0/13	0.00% 0/22	0.83% 2/241 • Number of events 2	0.33% 1/303 • Number of events 1	3.7% 1/27 • Number of events 1	0.00% 0/27	0.00% 0/52	0.00% 0/85	0.00% 0/168
Metabolism and nutrition disorders Hyponatraemia	0.00% 0/345	0.00% 0/345	0.00% 0/348	0.00% 0/58	0.00% 0/62	0.00% 0/90	0.00% 0/57	0.00% 0/73	3.7% 1/27 • Number of events 1	0.00% 0/31	0.00% 0/13	0.00% 0/22	0.00% 0/241	0.00% 0/303	0.00% 0/27	0.00% 0/27	0.00% 0/52	0.00% 0/85	0.00% 0/168
Metabolism and nutrition disorders Type 2 diabetes mellitus	1.2% 4/345 • Number of events 4	0.00% 0/345	0.00% 0/348	0.00% 0/58	1.6% 1/62 • Number of events 2	1.1% 1/90 • Number of events 1	0.00% 0/57	1.4% 1/73 • Number of events 2	0.00% 0/27	0.00% 0/31	0.00% 0/13	9.1% 2/22 • Number of events 2	0.00% 0/241	0.00% 0/303	0.00% 0/27	0.00% 0/27	0.00% 0/52	0.00% 0/85	0.00% 0/168
Blood and lymphatic system disorders Anaemia	2.3% 8/345 • Number of events 8	1.7% 6/345 • Number of events 6	3.2% 11/348 • Number of events 11	1.7% 1/58 • Number of events 1	0.00% 0/62	5.6% 5/90 • Number of events 5	0.00% 0/57	0.00% 0/73	3.7% 1/27 • Number of events 1	0.00% 0/31	0.00% 0/13	0.00% 0/22	0.41% 1/241 • Number of events 1	0.33% 1/303 • Number of events 1	0.00% 0/27	0.00% 0/27	0.00% 0/52	0.00% 0/85	0.00% 0/168
Musculoskeletal and connective tissue disorders Arthralgia	1.7% 6/345 • Number of events 9	2.6% 9/345 • Number of events 10	2.0% 7/348 • Number of events 7	3.4% 2/58 • Number of events 8	0.00% 0/62	1.1% 1/90 • Number of events 1	1.8% 1/57 • Number of events 1	2.7% 2/73 • Number of events 2	0.00% 0/27	0.00% 0/31	0.00% 0/13	4.5% 1/22 • Number of events 1	0.83% 2/241 • Number of events 2	0.00% 0/303	0.00% 0/27	0.00% 0/27	0.00% 0/52	1.2% 1/85 • Number of events 1	0.00% 0/168
Cardiac disorders Tachycardia	0.58% 2/345 • Number of events 2	0.00% 0/345	0.00% 0/348	0.00% 0/58	0.00% 0/62	1.1% 1/90 • Number of events 1	0.00% 0/57	0.00% 0/73	0.00% 0/27	0.00% 0/31	0.00% 0/13	0.00% 0/22	0.00% 0/241	0.00% 0/303	0.00% 0/27	3.7% 1/27 • Number of events 1	0.00% 0/52	0.00% 0/85	0.00% 0/168
Eye disorders Cataract	0.58% 2/345 • Number of events 2	0.58% 2/345 • Number of events 2	0.29% 1/348 • Number of events 1	0.00% 0/58	3.2% 2/62 • Number of events 3	0.00% 0/90	1.8% 1/57 • Number of events 1	4.1% 3/73 • Number of events 3	0.00% 0/27	0.00% 0/31	0.00% 0/13	0.00% 0/22	0.41% 1/241 • Number of events 1	0.33% 1/303 • Number of events 1	0.00% 0/27	0.00% 0/27	0.00% 0/52	0.00% 0/85	0.60% 1/168 • Number of events 1
Gastrointestinal disorders Abdominal pain upper	0.58% 2/345 • Number of events 2	0.58% 2/345 • Number of events 2	0.29% 1/348 • Number of events 1	1.7% 1/58 • Number of events 1	0.00% 0/62	1.1% 1/90 • Number of events 1	0.00% 0/57	0.00% 0/73	0.00% 0/27	0.00% 0/31	0.00% 0/13	0.00% 0/22	0.00% 0/241	0.33% 1/303 • Number of events 1	0.00% 0/27	0.00% 0/27	3.8% 2/52 • Number of events 2	0.00% 0/85	0.60% 1/168 • Number of events 1
Gastrointestinal disorders Constipation	1.2% 4/345 • Number of events 4	0.87% 3/345 • Number of events 3	1.7% 6/348 • Number of events 6	0.00% 0/58	1.6% 1/62 • Number of events 1	0.00% 0/90	5.3% 3/57 • Number of events 3	0.00% 0/73	0.00% 0/27	3.2% 1/31 • Number of events 1	0.00% 0/13	0.00% 0/22	1.2% 3/241 • Number of events 3	0.66% 2/303 • Number of events 2	0.00% 0/27	0.00% 0/27	0.00% 0/52	0.00% 0/85	0.00% 0/168
Gastrointestinal disorders Diarrhoea	2.0% 7/345 • Number of events 7	2.6% 9/345 • Number of events 9	1.4% 5/348 • Number of events 6	1.7% 1/58 • Number of events 1	1.6% 1/62 • Number of events 1	0.00% 0/90	0.00% 0/57	0.00% 0/73	0.00% 0/27	0.00% 0/31	0.00% 0/13	0.00% 0/22	1.2% 3/241 • Number of events 3	0.33% 1/303 • Number of events 1	0.00% 0/27	0.00% 0/27	0.00% 0/52	0.00% 0/85	0.60% 1/168 • Number of events 1
Gastrointestinal disorders Dyspepsia	0.87% 3/345 • Number of events 3	0.29% 1/345 • Number of events 1	0.57% 2/348 • Number of events 2	3.4% 2/58 • Number of events 2	0.00% 0/62	0.00% 0/90	0.00% 0/57	0.00% 0/73	0.00% 0/27	0.00% 0/31	0.00% 0/13	0.00% 0/22	0.00% 0/241	0.00% 0/303	0.00% 0/27	0.00% 0/27	0.00% 0/52	1.2% 1/85 • Number of events 1	0.00% 0/168
Gastrointestinal disorders Gastrooesophageal reflux disease	0.58% 2/345 • Number of events 2	0.29% 1/345 • Number of events 1	1.4% 5/348 • Number of events 5	0.00% 0/58	0.00% 0/62	0.00% 0/90	1.8% 1/57 • Number of events 1	0.00% 0/73	3.7% 1/27 • Number of events 1	0.00% 0/31	0.00% 0/13	0.00% 0/22	0.83% 2/241 • Number of events 2	0.33% 1/303 • Number of events 1	0.00% 0/27	0.00% 0/27	0.00% 0/52	0.00% 0/85	0.60% 1/168 • Number of events 1
Gastrointestinal disorders Nausea	2.0% 7/345 • Number of events 7	2.0% 7/345 • Number of events 11	0.86% 3/348 • Number of events 3	3.4% 2/58 • Number of events 2	1.6% 1/62 • Number of events 1	1.1% 1/90 • Number of events 1	1.8% 1/57 • Number of events 1	0.00% 0/73	0.00% 0/27	0.00% 0/31	0.00% 0/13	4.5% 1/22 • Number of events 1	0.41% 1/241 • Number of events 1	0.33% 1/303 • Number of events 1	0.00% 0/27	0.00% 0/27	1.9% 1/52 • Number of events 1	0.00% 0/85	1.8% 3/168 • Number of events 3
Gastrointestinal disorders Stomatitis	0.87% 3/345 • Number of events 4	0.00% 0/345	0.29% 1/348 • Number of events 1	0.00% 0/58	0.00% 0/62	0.00% 0/90	0.00% 0/57	0.00% 0/73	3.7% 1/27 • Number of events 1	3.2% 1/31 • Number of events 1	0.00% 0/13	0.00% 0/22	0.41% 1/241 • Number of events 1	0.00% 0/303	0.00% 0/27	0.00% 0/27	0.00% 0/52	0.00% 0/85	0.60% 1/168 • Number of events 1
Musculoskeletal and connective tissue disorders Back pain	2.9% 10/345 • Number of events 10	1.7% 6/345 • Number of events 6	1.4% 5/348 • Number of events 5	1.7% 1/58 • Number of events 1	0.00% 0/62	0.00% 0/90	3.5% 2/57 • Number of events 2	0.00% 0/73	0.00% 0/27	0.00% 0/31	0.00% 0/13	0.00% 0/22	0.41% 1/241 • Number of events 1	0.00% 0/303	0.00% 0/27	0.00% 0/27	3.8% 2/52 • Number of events 2	1.2% 1/85 • Number of events 1	0.00% 0/168
General disorders Injection site erythema	1.2% 4/345 • Number of events 5	1.2% 4/345 • Number of events 5	0.29% 1/348 • Number of events 1	0.00% 0/58	3.2% 2/62 • Number of events 2	0.00% 0/90	0.00% 0/57	0.00% 0/73	0.00% 0/27	0.00% 0/31	0.00% 0/13	0.00% 0/22	0.00% 0/241	0.33% 1/303 • Number of events 1	0.00% 0/27	0.00% 0/27	0.00% 0/52	0.00% 0/85	0.00% 0/168
General disorders Malaise	0.29% 1/345 • Number of events 1	0.00% 0/345	0.57% 2/348 • Number of events 2	0.00% 0/58	0.00% 0/62	0.00% 0/90	0.00% 0/57	0.00% 0/73	0.00% 0/27	0.00% 0/31	0.00% 0/13	0.00% 0/22	0.00% 0/241	0.00% 0/303	0.00% 0/27	3.7% 1/27 • Number of events 1	0.00% 0/52	0.00% 0/85	0.00% 0/168
General disorders Oedema peripheral	0.87% 3/345 • Number of events 3	0.29% 1/345 • Number of events 1	0.86% 3/348 • Number of events 3	0.00% 0/58	0.00% 0/62	0.00% 0/90	0.00% 0/57	0.00% 0/73	0.00% 0/27	0.00% 0/31	0.00% 0/13	4.5% 1/22 • Number of events 1	0.00% 0/241	0.00% 0/303	0.00% 0/27	0.00% 0/27	0.00% 0/52	1.2% 1/85 • Number of events 1	0.60% 1/168 • Number of events 1
General disorders Pyrexia	0.87% 3/345 • Number of events 3	0.87% 3/345 • Number of events 3	0.29% 1/348 • Number of events 1	1.7% 1/58 • Number of events 1	0.00% 0/62	1.1% 1/90 • Number of events 2	0.00% 0/57	0.00% 0/73	0.00% 0/27	0.00% 0/31	0.00% 0/13	0.00% 0/22	0.00% 0/241	0.66% 2/303 • Number of events 3	0.00% 0/27	3.7% 1/27 • Number of events 1	0.00% 0/52	0.00% 0/85	0.00% 0/168
Hepatobiliary disorders Hepatic function abnormal	0.87% 3/345 • Number of events 3	0.29% 1/345 • Number of events 1	0.57% 2/348 • Number of events 2	0.00% 0/58	0.00% 0/62	0.00% 0/90	0.00% 0/57	0.00% 0/73	0.00% 0/27	0.00% 0/31	0.00% 0/13	0.00% 0/22	0.00% 0/241	0.00% 0/303	0.00% 0/27	3.7% 1/27 • Number of events 1	0.00% 0/52	0.00% 0/85	0.00% 0/168
Infections and infestations Bronchitis	2.3% 8/345 • Number of events 8	2.3% 8/345 • Number of events 8	3.2% 11/348 • Number of events 11	1.7% 1/58 • Number of events 1	4.8% 3/62 • Number of events 3	1.1% 1/90 • Number of events 1	1.8% 1/57 • Number of events 1	1.4% 1/73 • Number of events 1	3.7% 1/27 • Number of events 1	0.00% 0/31	0.00% 0/13	0.00% 0/22	0.41% 1/241 • Number of events 1	0.33% 1/303 • Number of events 1	0.00% 0/27	0.00% 0/27	0.00% 0/52	0.00% 0/85	0.60% 1/168 • Number of events 1
Infections and infestations Candidiasis	0.00% 0/345	0.00% 0/345	0.00% 0/348	0.00% 0/58	0.00% 0/62	0.00% 0/90	0.00% 0/57	0.00% 0/73	3.7% 1/27 • Number of events 1	0.00% 0/31	0.00% 0/13	0.00% 0/22	0.00% 0/241	0.00% 0/303	0.00% 0/27	0.00% 0/27	0.00% 0/52	0.00% 0/85	0.00% 0/168
Infections and infestations Cellulitis	0.29% 1/345 • Number of events 2	0.29% 1/345 • Number of events 1	0.00% 0/348	0.00% 0/58	0.00% 0/62	1.1% 1/90 • Number of events 1	0.00% 0/57	0.00% 0/73	3.7% 1/27 • Number of events 1	0.00% 0/31	0.00% 0/13	4.5% 1/22 • Number of events 1	0.00% 0/241	0.33% 1/303 • Number of events 1	0.00% 0/27	0.00% 0/27	0.00% 0/52	0.00% 0/85	0.00% 0/168
Infections and infestations Cystitis bacterial	0.00% 0/345	0.00% 0/345	0.00% 0/348	0.00% 0/58	0.00% 0/62	0.00% 0/90	0.00% 0/57	0.00% 0/73	3.7% 1/27 • Number of events 1	0.00% 0/31	0.00% 0/13	0.00% 0/22	0.00% 0/241	0.00% 0/303	0.00% 0/27	0.00% 0/27	0.00% 0/52	0.00% 0/85	0.00% 0/168
Infections and infestations Herpes zoster	0.29% 1/345 • Number of events 1	0.58% 2/345 • Number of events 2	0.57% 2/348 • Number of events 2	0.00% 0/58	0.00% 0/62	1.1% 1/90 • Number of events 1	3.5% 2/57 • Number of events 2	0.00% 0/73	0.00% 0/27	0.00% 0/31	0.00% 0/13	4.5% 1/22 • Number of events 1	0.83% 2/241 • Number of events 2	0.33% 1/303 • Number of events 1	0.00% 0/27	0.00% 0/27	0.00% 0/52	0.00% 0/85	0.00% 0/168
Infections and infestations Influenza	0.29% 1/345 • Number of events 1	0.58% 2/345 • Number of events 2	2.3% 8/348 • Number of events 8	0.00% 0/58	1.6% 1/62 • Number of events 1	1.1% 1/90 • Number of events 1	0.00% 0/57	0.00% 0/73	0.00% 0/27	0.00% 0/31	0.00% 0/13	0.00% 0/22	0.41% 1/241 • Number of events 1	0.66% 2/303 • Number of events 2	3.7% 1/27 • Number of events 1	0.00% 0/27	0.00% 0/52	0.00% 0/85	1.2% 2/168 • Number of events 2
Infections and infestations Nasopharyngitis	5.8% 20/345 • Number of events 25	4.3% 15/345 • Number of events 22	7.2% 25/348 • Number of events 34	3.4% 2/58 • Number of events 2	4.8% 3/62 • Number of events 4	2.2% 2/90 • Number of events 2	1.8% 1/57 • Number of events 1	4.1% 3/73 • Number of events 3	3.7% 1/27 • Number of events 1	0.00% 0/31	0.00% 0/13	0.00% 0/22	2.9% 7/241 • Number of events 8	2.3% 7/303 • Number of events 9	0.00% 0/27	11.1% 3/27 • Number of events 3	1.9% 1/52 • Number of events 1	0.00% 0/85	3.0% 5/168 • Number of events 5
Infections and infestations Onychomycosis	0.00% 0/345	0.00% 0/345	0.00% 0/348	0.00% 0/58	0.00% 0/62	0.00% 0/90	0.00% 0/57	0.00% 0/73	0.00% 0/27	0.00% 0/31	7.7% 1/13 • Number of events 1	0.00% 0/22	0.41% 1/241 • Number of events 1	0.00% 0/303	0.00% 0/27	0.00% 0/27	0.00% 0/52	0.00% 0/85	0.00% 0/168
Infections and infestations Pharyngitis	2.0% 7/345 • Number of events 7	1.2% 4/345 • Number of events 4	1.4% 5/348 • Number of events 5	0.00% 0/58	0.00% 0/62	1.1% 1/90 • Number of events 1	0.00% 0/57	0.00% 0/73	0.00% 0/27	0.00% 0/31	0.00% 0/13	0.00% 0/22	0.00% 0/241	0.33% 1/303 • Number of events 1	0.00% 0/27	0.00% 0/27	1.9% 1/52 • Number of events 1	0.00% 0/85	0.00% 0/168
Infections and infestations Pulpitis dental	0.00% 0/345	0.00% 0/345	0.00% 0/348	0.00% 0/58	0.00% 0/62	0.00% 0/90	0.00% 0/57	0.00% 0/73	0.00% 0/27	0.00% 0/31	0.00% 0/13	0.00% 0/22	0.00% 0/241	0.00% 0/303	3.7% 1/27 • Number of events 1	0.00% 0/27	0.00% 0/52	0.00% 0/85	0.00% 0/168
Infections and infestations Upper respiratory tract infection	5.2% 18/345 • Number of events 21	5.8% 20/345 • Number of events 21	5.2% 18/348 • Number of events 20	0.00% 0/58	1.6% 1/62 • Number of events 1	2.2% 2/90 • Number of events 2	1.8% 1/57 • Number of events 1	0.00% 0/73	0.00% 0/27	0.00% 0/31	0.00% 0/13	4.5% 1/22 • Number of events 1	1.7% 4/241 • Number of events 4	1.3% 4/303 • Number of events 5	0.00% 0/27	0.00% 0/27	0.00% 0/52	2.4% 2/85 • Number of events 2	3.0% 5/168 • Number of events 5
Infections and infestations Upper respiratory tract infection bacterial	0.00% 0/345	0.00% 0/345	0.29% 1/348 • Number of events 1	0.00% 0/58	0.00% 0/62	0.00% 0/90	0.00% 0/57	0.00% 0/73	0.00% 0/27	0.00% 0/31	0.00% 0/13	0.00% 0/22	0.00% 0/241	0.00% 0/303	0.00% 0/27	3.7% 1/27 • Number of events 1	0.00% 0/52	0.00% 0/85	0.00% 0/168
Infections and infestations Urinary tract infection	2.9% 10/345 • Number of events 12	1.7% 6/345 • Number of events 8	1.4% 5/348 • Number of events 6	1.7% 1/58 • Number of events 1	1.6% 1/62 • Number of events 1	1.1% 1/90 • Number of events 1	1.8% 1/57 • Number of events 1	0.00% 0/73	0.00% 0/27	3.2% 1/31 • Number of events 1	0.00% 0/13	0.00% 0/22	0.83% 2/241 • Number of events 2	0.99% 3/303 • Number of events 3	0.00% 0/27	0.00% 0/27	0.00% 0/52	1.2% 1/85 • Number of events 1	1.2% 2/168 • Number of events 2
Infections and infestations Viral infection	0.00% 0/345	0.00% 0/345	0.57% 2/348 • Number of events 2	0.00% 0/58	0.00% 0/62	0.00% 0/90	0.00% 0/57	0.00% 0/73	0.00% 0/27	0.00% 0/31	0.00% 0/13	0.00% 0/22	0.00% 0/241	0.00% 0/303	0.00% 0/27	3.7% 1/27 • Number of events 1	0.00% 0/52	0.00% 0/85	0.00% 0/168
Infections and infestations Vulvovaginitis	0.00% 0/294	0.00% 0/289	0.00% 0/291	2.3% 1/44 • Number of events 1	0.00% 0/57	0.00% 0/69	0.00% 0/51	0.00% 0/62	0.00% 0/22	0.00% 0/27	0.00% 0/9	0.00% 0/19	0.00% 0/211	0.00% 0/255	0.00% 0/22	0.00% 0/24	0.00% 0/40	0.00% 0/66	0.00% 0/146
Injury, poisoning and procedural complications Contusion	0.87% 3/345 • Number of events 3	0.29% 1/345 • Number of events 1	1.1% 4/348 • Number of events 4	0.00% 0/58	1.6% 1/62 • Number of events 1	0.00% 0/90	0.00% 0/57	2.7% 2/73 • Number of events 2	0.00% 0/27	3.2% 1/31 • Number of events 1	0.00% 0/13	0.00% 0/22	0.00% 0/241	0.00% 0/303	0.00% 0/27	0.00% 0/27	0.00% 0/52	0.00% 0/85	0.60% 1/168 • Number of events 1
Injury, poisoning and procedural complications Ligament sprain	0.58% 2/345 • Number of events 2	0.29% 1/345 • Number of events 1	0.57% 2/348 • Number of events 2	0.00% 0/58	0.00% 0/62	0.00% 0/90	3.5% 2/57 • Number of events 2	0.00% 0/73	0.00% 0/27	0.00% 0/31	0.00% 0/13	0.00% 0/22	0.41% 1/241 • Number of events 1	0.00% 0/303	0.00% 0/27	0.00% 0/27	0.00% 0/52	0.00% 0/85	0.00% 0/168
Injury, poisoning and procedural complications Muscle strain	0.00% 0/345	0.00% 0/345	0.00% 0/348	0.00% 0/58	0.00% 0/62	1.1% 1/90 • Number of events 1	0.00% 0/57	0.00% 0/73	0.00% 0/27	0.00% 0/31	0.00% 0/13	4.5% 1/22 • Number of events 1	0.00% 0/241	0.00% 0/303	3.7% 1/27 • Number of events 1	0.00% 0/27	0.00% 0/52	0.00% 0/85	0.00% 0/168
Injury, poisoning and procedural complications Radius fracture	0.00% 0/345	0.00% 0/345	0.00% 0/348	0.00% 0/58	0.00% 0/62	0.00% 0/90	0.00% 0/57	0.00% 0/73	0.00% 0/27	0.00% 0/31	0.00% 0/13	0.00% 0/22	0.00% 0/241	0.00% 0/303	3.7% 1/27 • Number of events 1	0.00% 0/27	0.00% 0/52	0.00% 0/85	0.00% 0/168
Injury, poisoning and procedural complications Tendon injury	0.00% 0/345	0.00% 0/345	0.00% 0/348	1.7% 1/58 • Number of events 1	0.00% 0/62	0.00% 0/90	0.00% 0/57	0.00% 0/73	0.00% 0/27	0.00% 0/31	7.7% 1/13 • Number of events 1	0.00% 0/22	0.00% 0/241	0.00% 0/303	0.00% 0/27	0.00% 0/27	0.00% 0/52	0.00% 0/85	0.00% 0/168
Investigations Alanine aminotransferase increased	1.2% 4/345 • Number of events 4	0.58% 2/345 • Number of events 2	1.7% 6/348 • Number of events 6	0.00% 0/58	0.00% 0/62	0.00% 0/90	0.00% 0/57	0.00% 0/73	0.00% 0/27	0.00% 0/31	0.00% 0/13	4.5% 1/22 • Number of events 2	0.41% 1/241 • Number of events 1	0.33% 1/303 • Number of events 1	0.00% 0/27	0.00% 0/27	0.00% 0/52	0.00% 0/85	0.00% 0/168
Investigations Blood alkaline phosphatase increased	0.00% 0/345	0.00% 0/345	0.29% 1/348 • Number of events 1	1.7% 1/58 • Number of events 1	0.00% 0/62	0.00% 0/90	0.00% 0/57	0.00% 0/73	0.00% 0/27	0.00% 0/31	0.00% 0/13	4.5% 1/22 • Number of events 1	0.00% 0/241	0.00% 0/303	0.00% 0/27	0.00% 0/27	1.9% 1/52 • Number of events 1	0.00% 0/85	0.00% 0/168
Investigations Blood glucose increased	0.58% 2/345 • Number of events 2	0.00% 0/345	0.00% 0/348	1.7% 1/58 • Number of events 1	0.00% 0/62	0.00% 0/90	0.00% 0/57	0.00% 0/73	0.00% 0/27	0.00% 0/31	7.7% 1/13 • Number of events 1	0.00% 0/22	0.41% 1/241 • Number of events 1	0.00% 0/303	0.00% 0/27	0.00% 0/27	0.00% 0/52	0.00% 0/85	0.00% 0/168
Investigations Blood potassium decreased	0.00% 0/345	0.00% 0/345	0.00% 0/348	0.00% 0/58	0.00% 0/62	0.00% 0/90	0.00% 0/57	1.4% 1/73 • Number of events 1	0.00% 0/27	0.00% 0/31	0.00% 0/13	0.00% 0/22	0.00% 0/241	0.33% 1/303 • Number of events 1	0.00% 0/27	3.7% 1/27 • Number of events 1	0.00% 0/52	0.00% 0/85	0.00% 0/168
Investigations Gamma-glutamyltransferase increased	0.00% 0/345	0.58% 2/345 • Number of events 2	0.29% 1/348 • Number of events 1	3.4% 2/58 • Number of events 2	1.6% 1/62 • Number of events 1	0.00% 0/90	0.00% 0/57	0.00% 0/73	0.00% 0/27	3.2% 1/31 • Number of events 1	0.00% 0/13	4.5% 1/22 • Number of events 1	0.00% 0/241	0.33% 1/303 • Number of events 1	0.00% 0/27	0.00% 0/27	0.00% 0/52	0.00% 0/85	0.00% 0/168
Investigations Haemoglobin decreased	0.58% 2/345 • Number of events 2	0.00% 0/345	0.29% 1/348 • Number of events 1	1.7% 1/58 • Number of events 1	0.00% 0/62	0.00% 0/90	0.00% 0/57	0.00% 0/73	0.00% 0/27	0.00% 0/31	7.7% 1/13 • Number of events 1	0.00% 0/22	0.41% 1/241 • Number of events 1	0.00% 0/303	0.00% 0/27	0.00% 0/27	0.00% 0/52	0.00% 0/85	0.00% 0/168
Investigations Liver function test abnormal	0.29% 1/345 • Number of events 1	0.00% 0/345	0.00% 0/348	1.7% 1/58 • Number of events 1	1.6% 1/62 • Number of events 1	0.00% 0/90	0.00% 0/57	0.00% 0/73	0.00% 0/27	0.00% 0/31	7.7% 1/13 • Number of events 1	0.00% 0/22	0.00% 0/241	0.33% 1/303 • Number of events 1	0.00% 0/27	0.00% 0/27	1.9% 1/52 • Number of events 1	0.00% 0/85	0.00% 0/168
Investigations White blood cell count decreased	0.00% 0/345	0.29% 1/345 • Number of events 1	0.29% 1/348 • Number of events 1	0.00% 0/58	0.00% 0/62	0.00% 0/90	0.00% 0/57	1.4% 1/73 • Number of events 1	3.7% 1/27 • Number of events 1	0.00% 0/31	7.7% 1/13 • Number of events 1	0.00% 0/22	0.00% 0/241	0.00% 0/303	0.00% 0/27	0.00% 0/27	0.00% 0/52	0.00% 0/85	0.00% 0/168
Metabolism and nutrition disorders Diabetes mellitus	0.29% 1/345 • Number of events 1	0.29% 1/345 • Number of events 1	0.29% 1/348 • Number of events 1	1.7% 1/58 • Number of events 1	1.6% 1/62 • Number of events 1	0.00% 0/90	0.00% 0/57	0.00% 0/73	3.7% 1/27 • Number of events 1	0.00% 0/31	0.00% 0/13	0.00% 0/22	0.00% 0/241	0.00% 0/303	0.00% 0/27	0.00% 0/27	1.9% 1/52 • Number of events 1	0.00% 0/85	0.00% 0/168
Metabolism and nutrition disorders Hypercholesterolaemia	0.29% 1/345 • Number of events 1	0.00% 0/345	0.29% 1/348 • Number of events 1	0.00% 0/58	1.6% 1/62 • Number of events 1	0.00% 0/90	0.00% 0/57	0.00% 0/73	3.7% 1/27 • Number of events 1	0.00% 0/31	0.00% 0/13	0.00% 0/22	0.00% 0/241	0.00% 0/303	0.00% 0/27	0.00% 0/27	0.00% 0/52	0.00% 0/85	0.60% 1/168 • Number of events 1
Metabolism and nutrition disorders Hyperglycaemia	0.29% 1/345 • Number of events 1	0.29% 1/345 • Number of events 1	0.00% 0/348	0.00% 0/58	0.00% 0/62	0.00% 0/90	0.00% 0/57	0.00% 0/73	3.7% 1/27 • Number of events 1	0.00% 0/31	0.00% 0/13	0.00% 0/22	0.00% 0/241	0.00% 0/303	0.00% 0/27	0.00% 0/27	0.00% 0/52	0.00% 0/85	0.00% 0/168
Metabolism and nutrition disorders Hyperlipidaemia	0.00% 0/345	0.00% 0/345	0.00% 0/348	1.7% 1/58 • Number of events 1	0.00% 0/62	0.00% 0/90	0.00% 0/57	0.00% 0/73	0.00% 0/27	0.00% 0/31	7.7% 1/13 • Number of events 1	0.00% 0/22	0.00% 0/241	0.33% 1/303 • Number of events 1	0.00% 0/27	0.00% 0/27	1.9% 1/52 • Number of events 1	0.00% 0/85	0.00% 0/168
Metabolism and nutrition disorders Hypoalbuminaemia	0.00% 0/345	0.00% 0/345	0.00% 0/348	3.4% 2/58 • Number of events 2	0.00% 0/62	0.00% 0/90	0.00% 0/57	0.00% 0/73	0.00% 0/27	0.00% 0/31	0.00% 0/13	0.00% 0/22	0.00% 0/241	0.00% 0/303	0.00% 0/27	0.00% 0/27	0.00% 0/52	0.00% 0/85	0.00% 0/168
Musculoskeletal and connective tissue disorders Bunion	0.00% 0/345	0.00% 0/345	0.29% 1/348 • Number of events 1	0.00% 0/58	0.00% 0/62	0.00% 0/90	0.00% 0/57	0.00% 0/73	0.00% 0/27	0.00% 0/31	0.00% 0/13	4.5% 1/22 • Number of events 1	0.00% 0/241	0.00% 0/303	0.00% 0/27	0.00% 0/27	0.00% 0/52	1.2% 1/85 • Number of events 2	0.00% 0/168
Musculoskeletal and connective tissue disorders Foot deformity	0.29% 1/345 • Number of events 1	0.29% 1/345 • Number of events 1	0.29% 1/348 • Number of events 1	0.00% 0/58	0.00% 0/62	0.00% 0/90	1.8% 1/57 • Number of events 1	0.00% 0/73	0.00% 0/27	0.00% 0/31	0.00% 0/13	4.5% 1/22 • Number of events 1	0.00% 0/241	0.00% 0/303	0.00% 0/27	0.00% 0/27	0.00% 0/52	0.00% 0/85	0.00% 0/168
Musculoskeletal and connective tissue disorders Osteoarthritis	0.87% 3/345 • Number of events 3	0.00% 0/345	0.29% 1/348 • Number of events 1	3.4% 2/58 • Number of events 2	0.00% 0/62	0.00% 0/90	0.00% 0/57	0.00% 0/73	0.00% 0/27	0.00% 0/31	0.00% 0/13	0.00% 0/22	0.00% 0/241	0.00% 0/303	0.00% 0/27	0.00% 0/27	0.00% 0/52	0.00% 0/85	0.00% 0/168
Musculoskeletal and connective tissue disorders Pain in extremity	1.2% 4/345 • Number of events 5	0.29% 1/345 • Number of events 1	0.86% 3/348 • Number of events 3	3.4% 2/58 • Number of events 3	1.6% 1/62 • Number of events 1	0.00% 0/90	0.00% 0/57	1.4% 1/73 • Number of events 1	0.00% 0/27	0.00% 0/31	0.00% 0/13	0.00% 0/22	0.00% 0/241	0.33% 1/303 • Number of events 1	0.00% 0/27	0.00% 0/27	0.00% 0/52	0.00% 0/85	0.00% 0/168
Musculoskeletal and connective tissue disorders Rheumatoid arthritis	3.5% 12/345 • Number of events 14	5.5% 19/345 • Number of events 20	4.3% 15/348 • Number of events 18	5.2% 3/58 • Number of events 3	8.1% 5/62 • Number of events 5	0.00% 0/90	8.8% 5/57 • Number of events 5	4.1% 3/73 • Number of events 3	0.00% 0/27	0.00% 0/31	15.4% 2/13 • Number of events 2	0.00% 0/22	2.1% 5/241 • Number of events 5	1.3% 4/303 • Number of events 4	0.00% 0/27	7.4% 2/27 • Number of events 2	1.9% 1/52 • Number of events 1	0.00% 0/85	1.8% 3/168 • Number of events 3
Musculoskeletal and connective tissue disorders Tenosynovitis	0.00% 0/345	0.29% 1/345 • Number of events 1	0.00% 0/348	0.00% 0/58	0.00% 0/62	0.00% 0/90	0.00% 0/57	0.00% 0/73	0.00% 0/27	0.00% 0/31	0.00% 0/13	4.5% 1/22 • Number of events 1	0.00% 0/241	0.00% 0/303	0.00% 0/27	0.00% 0/27	0.00% 0/52	0.00% 0/85	0.00% 0/168
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neuroma	0.00% 0/345	0.00% 0/345	0.00% 0/348	0.00% 0/58	0.00% 0/62	1.1% 1/90 • Number of events 1	0.00% 0/57	0.00% 0/73	0.00% 0/27	0.00% 0/31	0.00% 0/13	4.5% 1/22 • Number of events 1	0.00% 0/241	0.00% 0/303	0.00% 0/27	0.00% 0/27	0.00% 0/52	0.00% 0/85	0.00% 0/168
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Ovarian germ cell teratoma benign	0.00% 0/294	0.00% 0/289	0.00% 0/291	0.00% 0/44	0.00% 0/57	0.00% 0/69	0.00% 0/51	0.00% 0/62	0.00% 0/22	0.00% 0/27	0.00% 0/9	0.00% 0/19	0.00% 0/211	0.00% 0/255	0.00% 0/22	4.2% 1/24 • Number of events 1	0.00% 0/40	0.00% 0/66	0.00% 0/146
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Uterine leiomyoma	0.34% 1/294 • Number of events 1	0.35% 1/289 • Number of events 1	0.00% 0/291	2.3% 1/44 • Number of events 1	0.00% 0/57	0.00% 0/69	2.0% 1/51 • Number of events 1	1.6% 1/62 • Number of events 1	0.00% 0/22	0.00% 0/27	0.00% 0/9	0.00% 0/19	0.00% 0/211	0.00% 0/255	0.00% 0/22	0.00% 0/24	0.00% 0/40	0.00% 0/66	0.00% 0/146
Nervous system disorders Carpal tunnel syndrome	0.58% 2/345 • Number of events 2	0.00% 0/345	0.57% 2/348 • Number of events 3	0.00% 0/58	0.00% 0/62	1.1% 1/90 • Number of events 1	0.00% 0/57	0.00% 0/73	0.00% 0/27	0.00% 0/31	0.00% 0/13	4.5% 1/22 • Number of events 1	0.00% 0/241	0.00% 0/303	0.00% 0/27	0.00% 0/27	0.00% 0/52	0.00% 0/85	0.00% 0/168
Nervous system disorders Dizziness	1.2% 4/345 • Number of events 4	1.7% 6/345 • Number of events 6	1.4% 5/348 • Number of events 5	0.00% 0/58	0.00% 0/62	0.00% 0/90	3.5% 2/57 • Number of events 2	1.4% 1/73 • Number of events 1	0.00% 0/27	0.00% 0/31	0.00% 0/13	0.00% 0/22	0.00% 0/241	0.00% 0/303	0.00% 0/27	0.00% 0/27	0.00% 0/52	1.2% 1/85 • Number of events 1	0.00% 0/168
Nervous system disorders Headache	2.0% 7/345 • Number of events 10	1.7% 6/345 • Number of events 6	0.86% 3/348 • Number of events 3	1.7% 1/58 • Number of events 1	0.00% 0/62	0.00% 0/90	0.00% 0/57	1.4% 1/73 • Number of events 1	0.00% 0/27	0.00% 0/31	0.00% 0/13	0.00% 0/22	0.83% 2/241 • Number of events 2	0.33% 1/303 • Number of events 1	0.00% 0/27	0.00% 0/27	0.00% 0/52	2.4% 2/85 • Number of events 2	0.60% 1/168 • Number of events 1
Nervous system disorders Hypoaesthesia	0.00% 0/345	0.00% 0/345	0.57% 2/348 • Number of events 2	1.7% 1/58 • Number of events 1	0.00% 0/62	0.00% 0/90	0.00% 0/57	1.4% 1/73 • Number of events 1	0.00% 0/27	0.00% 0/31	7.7% 1/13 • Number of events 1	0.00% 0/22	0.00% 0/241	0.00% 0/303	0.00% 0/27	0.00% 0/27	0.00% 0/52	0.00% 0/85	0.00% 0/168
Nervous system disorders Migraine	0.29% 1/345 • Number of events 1	0.58% 2/345 • Number of events 2	0.00% 0/348	0.00% 0/58	1.6% 1/62 • Number of events 1	0.00% 0/90	0.00% 0/57	2.7% 2/73 • Number of events 2	0.00% 0/27	0.00% 0/31	0.00% 0/13	0.00% 0/22	0.00% 0/241	0.00% 0/303	0.00% 0/27	0.00% 0/27	0.00% 0/52	0.00% 0/85	0.00% 0/168
Nervous system disorders Paraesthesia	0.29% 1/345 • Number of events 1	0.00% 0/345	0.29% 1/348 • Number of events 1	0.00% 0/58	0.00% 0/62	0.00% 0/90	1.8% 1/57 • Number of events 1	0.00% 0/73	0.00% 0/27	0.00% 0/31	0.00% 0/13	0.00% 0/22	0.00% 0/241	0.00% 0/303	0.00% 0/27	3.7% 1/27 • Number of events 1	0.00% 0/52	0.00% 0/85	0.00% 0/168
Psychiatric disorders Anxiety	0.87% 3/345 • Number of events 3	0.29% 1/345 • Number of events 1	0.29% 1/348 • Number of events 1	0.00% 0/58	0.00% 0/62	1.1% 1/90 • Number of events 1	0.00% 0/57	2.7% 2/73 • Number of events 2	0.00% 0/27	0.00% 0/31	0.00% 0/13	4.5% 1/22 • Number of events 1	0.41% 1/241 • Number of events 1	0.00% 0/303	0.00% 0/27	0.00% 0/27	0.00% 0/52	0.00% 0/85	0.60% 1/168 • Number of events 1
Psychiatric disorders Depression	0.58% 2/345 • Number of events 2	0.29% 1/345 • Number of events 1	0.29% 1/348 • Number of events 1	0.00% 0/58	3.2% 2/62 • Number of events 2	1.1% 1/90 • Number of events 1	0.00% 0/57	4.1% 3/73 • Number of events 3	0.00% 0/27	0.00% 0/31	0.00% 0/13	4.5% 1/22 • Number of events 1	0.00% 0/241	0.33% 1/303 • Number of events 1	0.00% 0/27	0.00% 0/27	0.00% 0/52	0.00% 0/85	0.00% 0/168
Psychiatric disorders Insomnia	2.0% 7/345 • Number of events 7	0.87% 3/345 • Number of events 3	0.86% 3/348 • Number of events 3	0.00% 0/58	0.00% 0/62	1.1% 1/90 • Number of events 1	3.5% 2/57 • Number of events 2	0.00% 0/73	0.00% 0/27	0.00% 0/31	0.00% 0/13	0.00% 0/22	0.00% 0/241	0.00% 0/303	0.00% 0/27	0.00% 0/27	0.00% 0/52	0.00% 0/85	0.00% 0/168
Renal and urinary disorders Pollakiuria	0.00% 0/345	0.00% 0/345	0.00% 0/348	1.7% 1/58 • Number of events 1	0.00% 0/62	0.00% 0/90	0.00% 0/57	0.00% 0/73	0.00% 0/27	0.00% 0/31	0.00% 0/13	0.00% 0/22	0.41% 1/241 • Number of events 1	0.33% 1/303 • Number of events 1	0.00% 0/27	3.7% 1/27 • Number of events 1	0.00% 0/52	0.00% 0/85	0.60% 1/168 • Number of events 1
Renal and urinary disorders Stress urinary incontinence	0.00% 0/345	0.00% 0/345	0.00% 0/348	0.00% 0/58	0.00% 0/62	0.00% 0/90	0.00% 0/57	0.00% 0/73	0.00% 0/27	0.00% 0/31	0.00% 0/13	0.00% 0/22	0.00% 0/241	0.00% 0/303	3.7% 1/27 • Number of events 1	0.00% 0/27	0.00% 0/52	0.00% 0/85	0.00% 0/168
Reproductive system and breast disorders Benign prostatic hyperplasia	0.00% 0/51	1.8% 1/56 • Number of events 1	0.00% 0/57	0.00% 0/14	20.0% 1/5 • Number of events 1	0.00% 0/21	0.00% 0/6	0.00% 0/11	0.00% 0/5	0.00% 0/4	0.00% 0/4	0.00% 0/3	0.00% 0/30	2.1% 1/48 • Number of events 1	0.00% 0/5	0.00% 0/3	0.00% 0/12	0.00% 0/19	0.00% 0/22
Reproductive system and breast disorders Metrorrhagia	0.00% 0/294	0.00% 0/289	0.00% 0/291	2.3% 1/44 • Number of events 1	0.00% 0/57	0.00% 0/69	0.00% 0/51	0.00% 0/62	0.00% 0/22	0.00% 0/27	0.00% 0/9	0.00% 0/19	0.00% 0/211	0.00% 0/255	0.00% 0/22	0.00% 0/24	0.00% 0/40	0.00% 0/66	0.00% 0/146
Reproductive system and breast disorders Uterine prolapse	0.34% 1/294 • Number of events 1	0.00% 0/289	0.00% 0/291	2.3% 1/44 • Number of events 1	0.00% 0/57	0.00% 0/69	0.00% 0/51	0.00% 0/62	0.00% 0/22	0.00% 0/27	0.00% 0/9	0.00% 0/19	0.00% 0/211	0.00% 0/255	0.00% 0/22	0.00% 0/24	0.00% 0/40	0.00% 0/66	0.00% 0/146
Respiratory, thoracic and mediastinal disorders Asthma	0.00% 0/345	0.00% 0/345	0.00% 0/348	0.00% 0/58	0.00% 0/62	0.00% 0/90	0.00% 0/57	0.00% 0/73	0.00% 0/27	0.00% 0/31	0.00% 0/13	0.00% 0/22	0.00% 0/241	0.00% 0/303	0.00% 0/27	3.7% 1/27 • Number of events 1	0.00% 0/52	0.00% 0/85	0.00% 0/168
Respiratory, thoracic and mediastinal disorders Cough	2.0% 7/345 • Number of events 8	0.87% 3/345 • Number of events 3	1.4% 5/348 • Number of events 5	1.7% 1/58 • Number of events 1	0.00% 0/62	2.2% 2/90 • Number of events 2	1.8% 1/57 • Number of events 1	0.00% 0/73	0.00% 0/27	0.00% 0/31	0.00% 0/13	0.00% 0/22	1.2% 3/241 • Number of events 3	0.00% 0/303	0.00% 0/27	0.00% 0/27	0.00% 0/52	1.2% 1/85 • Number of events 1	0.00% 0/168
Skin and subcutaneous tissue disorders Alopecia	0.29% 1/345 • Number of events 1	0.87% 3/345 • Number of events 3	0.29% 1/348 • Number of events 1	0.00% 0/58	1.6% 1/62 • Number of events 1	0.00% 0/90	1.8% 1/57 • Number of events 1	2.7% 2/73 • Number of events 2	0.00% 0/27	0.00% 0/31	0.00% 0/13	0.00% 0/22	0.00% 0/241	0.00% 0/303	0.00% 0/27	0.00% 0/27	0.00% 0/52	0.00% 0/85	0.00% 0/168
Skin and subcutaneous tissue disorders Rash	1.7% 6/345 • Number of events 6	0.87% 3/345 • Number of events 3	1.4% 5/348 • Number of events 6	0.00% 0/58	0.00% 0/62	0.00% 0/90	3.5% 2/57 • Number of events 2	0.00% 0/73	0.00% 0/27	0.00% 0/31	0.00% 0/13	0.00% 0/22	0.41% 1/241 • Number of events 1	0.00% 0/303	0.00% 0/27	0.00% 0/27	0.00% 0/52	0.00% 0/85	0.00% 0/168
Vascular disorders Haematoma	0.00% 0/345	0.00% 0/345	0.00% 0/348	0.00% 0/58	0.00% 0/62	0.00% 0/90	3.5% 2/57 • Number of events 2	0.00% 0/73	0.00% 0/27	0.00% 0/31	0.00% 0/13	0.00% 0/22	0.00% 0/241	0.00% 0/303	0.00% 0/27	0.00% 0/27	0.00% 0/52	0.00% 0/85	0.00% 0/168
Vascular disorders Hypertension	3.5% 12/345 • Number of events 13	0.87% 3/345 • Number of events 3	2.0% 7/348 • Number of events 7	3.4% 2/58 • Number of events 2	0.00% 0/62	0.00% 0/90	3.5% 2/57 • Number of events 2	2.7% 2/73 • Number of events 2	3.7% 1/27 • Number of events 1	0.00% 0/31	0.00% 0/13	0.00% 0/22	0.41% 1/241 • Number of events 1	0.66% 2/303 • Number of events 2	0.00% 0/27	3.7% 1/27 • Number of events 1	0.00% 0/52	0.00% 0/85	0.60% 1/168 • Number of events 1
Vascular disorders Hypotension	0.29% 1/345 • Number of events 1	0.58% 2/345 • Number of events 2	0.00% 0/348	0.00% 0/58	0.00% 0/62	0.00% 0/90	0.00% 0/57	0.00% 0/73	3.7% 1/27 • Number of events 1	0.00% 0/31	0.00% 0/13	0.00% 0/22	0.00% 0/241	0.00% 0/303	3.7% 1/27 • Number of events 1	0.00% 0/27	0.00% 0/52	0.00% 0/85	0.00% 0/168

Additional Information

Chief Medical Officer

Eli Lilly and Company

Phone: 800-545-5979

Results disclosure agreements

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

Restriction type: GT60