Trial Outcomes & Findings for To Evaluate The Effect Of SAR153191 (REGN88) Added To Other RA Drugs In Patients With RA Who Are Not Responding To Or Intolerant Of Anti-TNF Therapy (SARIL-RA-TARGET) (NCT NCT01709578)

NCT ID: NCT01709578

Last Updated: 2017-08-08

Results Overview

ACR responses are assessed with a composite rating scale of the American College of Rheumatology that includes 7 variables: tender joint count (TJC); swollen joint count (SJC); levels of an acute phase reactant (C-reactive Protein levels \[CRP\]); participant's assessment of pain; participant's global assessment of disease activity; physician's global assessment of disease activity; participant's assessment of physical function by (health assessment questionnaire disability index \[HAQ-DI\]). ACR20 is defined as achieving at least 20% improvement in both TJC and SJC, and at least 20% improvement in at least 3 of the 5 other assessments of the ACR.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 546 participants
• Primary outcome timeframe: Week 24
• Results posted on: 2017-08-08

Participant Flow

The study was conducted at 240 centers in 27 countries. A total of 1224 participants were screened between 29 October 2012 and 7 August 2014, of whom 546 participants were randomized and 678 were screen failures. Screen failures were mainly due to failure to meet inclusion criteria.

Participants were randomized 1:1:1 (placebo q2w : sarilumab 150 mg q2w : sarilumab 200 mg q2w) via a centralized randomization system using an interactive voice response system stratified by region and number of previous anti- tumor necrosis factor (TNF) therapy (1 versus >1).

Participant milestones

Measure	Placebo q2w Placebo matched to sarilumab subcutaneous (SC) injection once every 2 weeks (q2w) was added to one or a combination of the nonbiologic disease modifying antirheumatic drug (DMARD) for 24 weeks.	Sarilumab 150 mg q2w Sarilumab 150 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.	Sarilumab 200 mg q2w Sarilumab 200 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.
Overall Study STARTED	181	181	184
Overall Study COMPLETED	101	125	133
Overall Study NOT COMPLETED	80	56	51

Reasons for withdrawal

Measure	Placebo q2w Placebo matched to sarilumab subcutaneous (SC) injection once every 2 weeks (q2w) was added to one or a combination of the nonbiologic disease modifying antirheumatic drug (DMARD) for 24 weeks.	Sarilumab 150 mg q2w Sarilumab 150 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.	Sarilumab 200 mg q2w Sarilumab 200 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.
Overall Study Rescued and entered in long term safety	63	25	26
Overall Study Adverse Event	9	18	17
Overall Study Lack of Efficacy	5	4	2
Overall Study Poor compliance to protocol	1	2	1
Overall Study Other, not related to safety or efficacy	2	7	5

Baseline Characteristics

To Evaluate The Effect Of SAR153191 (REGN88) Added To Other RA Drugs In Patients With RA Who Are Not Responding To Or Intolerant Of Anti-TNF Therapy (SARIL-RA-TARGET)

Baseline characteristics by cohort

Measure	Placebo q2w n=181 Participants Placebo matched to sarilumab SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.	Sarilumab 150 mg q2w n=181 Participants Sarilumab 150 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.	Sarilumab 200 mg q2w n=184 Participants Sarilumab 200 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.	Total n=546 Participants Total of all reporting groups
Age, Continuous	51.9 years STANDARD_DEVIATION 12.4 • n=5 Participants	54.0 years STANDARD_DEVIATION 11.7 • n=7 Participants	52.9 years STANDARD_DEVIATION 12.9 • n=5 Participants	52.9 years STANDARD_DEVIATION 12.4 • n=4 Participants
Sex: Female, Male Female	154 Participants n=5 Participants	142 Participants n=7 Participants	151 Participants n=5 Participants	447 Participants n=4 Participants
Sex: Female, Male Male	27 Participants n=5 Participants	39 Participants n=7 Participants	33 Participants n=5 Participants	99 Participants n=4 Participants

PRIMARY outcome

Timeframe: Week 24

Population: Intent-to-treat (ITT) population included all randomized participants.

ACR responses are assessed with a composite rating scale of the American College of Rheumatology that includes 7 variables: tender joint count (TJC); swollen joint count (SJC); levels of an acute phase reactant (C-reactive Protein levels [CRP]); participant's assessment of pain; participant's global assessment of disease activity; physician's global assessment of disease activity; participant's assessment of physical function by (health assessment questionnaire disability index [HAQ-DI]). ACR20 is defined as achieving at least 20% improvement in both TJC and SJC, and at least 20% improvement in at least 3 of the 5 other assessments of the ACR.

Outcome measures

Measure	Placebo q2w n=181 Participants Placebo matched to sarilumab SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.	Sarilumab 150 mg q2w n=181 Participants Sarilumab 150 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.	Sarilumab 200 mg q2w n=184 Participants Sarilumab 200 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.
Percentage of Participants Who Achieved at Least 20% Improvement in the American College of Rheumatology (ACR20) Criteria at Week 24	33.7 percentage of participants	55.8 percentage of participants	60.9 percentage of participants

PRIMARY outcome

Timeframe: Baseline, Week 12

Population: ITT population. Number of participants analyzed = number of participants with HAQ-DI assessment at both baseline and Week 12.

Physical function was assessed by HAQ-DI. It consisted of at least 2 questions per category, participant reported assessment of ability to perform tasks in 8 categories of daily living activities: dress/groom; arise; eat; walk; reach; grip; hygiene; and common activities over past week rated on a 4-point scale where 0 = no difficulty; 1 = some difficulty; 2 = much difficulty; 3 = unable to do. Overall score was computed as the sum of category scores and divided by the number of categories answered, ranging from 0 to 3, where 0 = no disability and 3 = unable to do, high-dependency disability. Least-squares (LS) means and standard errors (SE) at Week 12 were obtained from a mixed-effect model with repeated measures (MMRM) with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline HAQ-DI as a covariate.

Outcome measures

Measure	Placebo q2w n=170 Participants Placebo matched to sarilumab SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.	Sarilumab 150 mg q2w n=165 Participants Sarilumab 150 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.	Sarilumab 200 mg q2w n=171 Participants Sarilumab 200 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.
Change From Baseline in the Health Assessment Questionnaire-Disability Index (HAQ-DI) at Week 12	-0.26 units on a scale Standard Error 0.043	-0.46 units on a scale Standard Error 0.044	-0.47 units on a scale Standard Error 0.043

SECONDARY outcome

Timeframe: Baseline, Week 24

Population: ITT population. Number of participants analyzed = number of participants with DAS28--CRP Score assessment at both baseline and Week 24.

DAS28 is a composite score that includes 4 variables: TJC (based on 28 joints); SJC (based on 28 joints); General health (GH) assessment by the participant assessed from the ACR rheumatoid arthritis (RA) core set questionnaire (participant global assessment) in 100 mm visual analog scale (VAS). Marker of inflammation assessed by the high sensitivity C-reactive protein (hs-CRP) in mg/L. The DAS28 score provides a number indicating the current disease activity of the RA. DAS28 total score ranges from 2-10. A DAS28 score above 5.1 means high disease activity, whereas a DAS28 score below 3.2 indicates low disease activity and a DAS28 score below 2.6 means disease remission. LS means and SE at Week 24 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline DAS28-CRP score as a covariate.

Outcome measures

Measure	Placebo q2w n=99 Participants Placebo matched to sarilumab SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.	Sarilumab 150 mg q2w n=126 Participants Sarilumab 150 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.	Sarilumab 200 mg q2w n=136 Participants Sarilumab 200 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.
Change From Baseline in Disease Activity Score for 28 Joints -C-Reactive Protein (DAS28--CRP) Score at Week 24	-1.38 units on a scale Standard Error 0.119	-2.35 units on a scale Standard Error 0.111	-2.82 units on a scale Standard Error 0.108

SECONDARY outcome

Timeframe: Week 24

Population: ITT population.

ACR responses are assessed with a composite rating scale that includes 7 variables: TJC; SJC; levels of an acute phase reactant (CRP level); participant's assessment of pain; participant's global assessment of disease activity; physician's global assessment of disease activity; participant's assessment of physical function by HAQ--DI. ACR50 is defined as achieving at least 50% improvement in both TJC and SJC, and at least 50% improvement in at least 3 of the 5 other assessments of the ACR.

Outcome measures

Measure	Placebo q2w n=181 Participants Placebo matched to sarilumab SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.	Sarilumab 150 mg q2w n=181 Participants Sarilumab 150 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.	Sarilumab 200 mg q2w n=184 Participants Sarilumab 200 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.
Percentage of Participants Achieving ACR50 Criteria at Week 24	18.2 Percentage of participants	37.0 Percentage of participants	40.8 Percentage of participants

SECONDARY outcome

Timeframe: Week 24

Population: ITT population.

ACR responses are assessed with a composite rating scale of the American College of Rheumatology that includes 7 variables: TJC; SJC; levels of an acute phase reactant (CRP level); participant's assessment of pain; participant's global assessment of disease activity; physician's global assessment of disease activity; participant's assessment of physical function by HAQ--DI. ACR70 is defined as achieving at least 70% improvement in both TJC and SJC, and at least 70% improvement in at least 3 of the 5 other assessments of the ACR.

Outcome measures

Measure	Placebo q2w n=181 Participants Placebo matched to sarilumab SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.	Sarilumab 150 mg q2w n=181 Participants Sarilumab 150 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.	Sarilumab 200 mg q2w n=184 Participants Sarilumab 200 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.
Percentage of Participants Achieving ACR70 Criteria at Week 24	7.2 Percentage of participants	19.9 Percentage of participants	16.3 Percentage of participants

SECONDARY outcome

Timeframe: Week 24

Population: ITT population.

DAS28 is a composite score that includes 4 variables: TJC (based on 28 joints); SJC (based on 28 joints); GH by the participant assessed from the ACR rheumatoid arthritis core set questionnaire (participant global assessment) in 100 mm VAS; marker of inflammation assessed by hs-CRP in mg/L. The DAS28 provides a number indicating the current activity of the RA. DAS28 total score ranges from 2-10. A DAS28 score above 5.1 means high disease activity, whereas a DAS28 score below 3.2 indicates low disease activity and a DAS28 score below 2.6 means disease remission.

Outcome measures

Measure	Placebo q2w n=181 Participants Placebo matched to sarilumab SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.	Sarilumab 150 mg q2w n=181 Participants Sarilumab 150 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.	Sarilumab 200 mg q2w n=184 Participants Sarilumab 200 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.
Percentage of Participants Achieving Clinical Remission Score (DAS28-CRP) <2.6 at Week 24	7.2 Percentage of participants	24.9 Percentage of participants	28.8 Percentage of participants

SECONDARY outcome

Timeframe: Baseline, Week 24

Population: ITT population. Number of participants analyzed=number of participants with CDAI assessment at both baseline and Week 24.

CDAI is a composite index constructed to measure clinical remission in RA that does not include a laboratory test, and is a numerical summation of 4 components: TJC (28 joints), SJC (28 joints), Participant's Global Assessment of Disease Activity VAS (in cm), and Physician's Global Assessment of Disease VAS (in cm). Total scores ranges from 0 to 76 with a negative change in CDAI score indicating an improvement in disease activity and a positive change in score indicating a worsening of disease activity. LS means and SE at Week 24 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline CDAI as a covariate.

Outcome measures

Measure	Placebo q2w n=100 Participants Placebo matched to sarilumab SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.	Sarilumab 150 mg q2w n=127 Participants Sarilumab 150 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.	Sarilumab 200 mg q2w n=136 Participants Sarilumab 200 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.
Change From Baseline in Clinical Disease Activity Index (CDAI) at Week 24	-16.35 units on a scale Standard Error 1.195	-23.65 units on a scale Standard Error 1.136	-26.08 units on a scale Standard Error 1.109

SECONDARY outcome

Timeframe: Baseline, Week 24

Population: ITT population. Number of participants analyzed = number of participants with HAQ-DI assessment at both baseline and Week 24.

Physical function was assessed by HAQ-DI. It consisted of at least 2 questions per category, participant reported assessment of ability to perform tasks in 8 categories of daily living activities: dress/groom; arise; eat; walk; reach; grip; hygiene; and common activities over past week rated on a 4-point scale where 0 = no difficulty; 1 = some difficulty; 2 = much difficulty; 3 = unable to do. Overall score was computed as the sum of category scores and divided by the number of categories answered, ranging from 0 to 3, where 0 = no disability and 3 = unable to do, high-dependency disability. LS means and SE at Week 24 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline HAQ-DI as a covariate.

Outcome measures

Measure	Placebo q2w n=101 Participants Placebo matched to sarilumab SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.	Sarilumab 150 mg q2w n=127 Participants Sarilumab 150 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.	Sarilumab 200 mg q2w n=136 Participants Sarilumab 200 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.
Change From Baseline in HAQ-DI at Week 24	-0.34 units on a scale Standard Error 0.051	-0.52 units on a scale Standard Error 0.049	-0.58 units on a scale Standard Error 0.048

SECONDARY outcome

Timeframe: Baseline, Week 24

Population: ITT population. Number of participants analyzed = participants with SF-36 PCS assessment at both baseline and Week 24.

SF-36 is a generic 36-item questionnaire measuring health-related quality of life (HRQL) covering 2 summary measures: PCS and mental component summary (MCS). The SF-36 consists of 8 subscales. The PCS had 4 subscales: physical function, role limitations due to physical problems, pain, and general health perception. The MCS had 4 subscales: vitality, social function, role limitations due to emotional problems, and mental health. Participants self-report on items in a subscale that have between 2-6 choices per item using Likert-type responses (e.g. none of the time, some of the time, etc.). Summations of item scores of the same subscale give the subscale scores, which are transformed into a range from 0 to 100; 0= worst HRQL, 100=best HRQL. Higher scores indicate better health and well-being. LS mean and SE at Week 24 by MMRM with treatment,region,number of previous anti TNFs,visit,and treatment-by-visit interaction as fixed effects and baseline SF-36 (PCS) as a covariate.

Outcome measures

Measure	Placebo q2w n=99 Participants Placebo matched to sarilumab SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.	Sarilumab 150 mg q2w n=123 Participants Sarilumab 150 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.	Sarilumab 200 mg q2w n=134 Participants Sarilumab 200 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.
Change From Baseline in 36-Item Short-Form Health Survey (SF-36) Physical Component Summary Scores (PCS) at Week 24	4.40 units on a scale Standard Error 0.692	7.65 units on a scale Standard Error 0.653	8.48 units on a scale Standard Error 0.630

SECONDARY outcome

Timeframe: Baseline, Week 24

Population: ITT population. Number of participants analyzed=participants with SF-36 MCS assessment at both baseline and Week 24.

SF-36 is a generic 36-item questionnaire measuring HRQL covering 2 summary measures: PCS and MCS. The SF-36 consists of 8 subscales. The PCS is represented by 4 subscales: physical function, role limitations due to physical problems, pain, and general health perception. The MCS is represented by 4 subscales: vitality, social function, role limitations due to emotional problems, and mental health. Participants self-report on items in a subscale that have between 2-6 choices per item using Likert-type responses (e.g. none of the time, some of the time, etc.). Summations of item scores of the same subscale give the subscale scores, which are transformed into a range from 0 to 100; 0= worst HRQL, 100=best HRQL. Higher scores indicate better health and well-being. LS mean and SE at Week 24 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline SF-36 MCS as a covariate.

Outcome measures

Measure	Placebo q2w n=99 Participants Placebo matched to sarilumab SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.	Sarilumab 150 mg q2w n=123 Participants Sarilumab 150 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.	Sarilumab 200 mg q2w n=134 Participants Sarilumab 200 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.
Change From Baseline in SF-36 MCS at Week 24	4.74 units on a scale Standard Error 0.902	6.26 units on a scale Standard Error 0.848	6.76 units on a scale Standard Error 0.817

SECONDARY outcome

Timeframe: Baseline, Week 24

Population: ITT population. Number of Participants analyzed = number of participants with FACIT-fatigue score assessment at both baseline and Week 24.

The FACIT-Fatigue is a 13-item questionnaire assessing fatigue where participants scored each item on a 5-point scale (0-4): 0=not at all, 1=a little bit, 2=somewhat, 3=quite a bit, 4=very much. A total score ranging from 0 to 52. A higher score corresponded to a lower level of fatigue. A positive change from baseline score indicates an improvement. LS mean and SE at Week 24 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline FACIT-fatigue as a covariate.

Outcome measures

Measure	Placebo q2w n=98 Participants Placebo matched to sarilumab SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.	Sarilumab 150 mg q2w n=126 Participants Sarilumab 150 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.	Sarilumab 200 mg q2w n=136 Participants Sarilumab 200 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.
Change From Baseline in the Functional Assessment of Chronic Illness Therapy Fatigue (FACIT-fatigue) Score at Week 24	6.82 units on a scale Standard Error 0.863	9.86 units on a scale Standard Error 0.802	10.06 units on a scale Standard Error 0.778

SECONDARY outcome

Timeframe: Baseline, Week 24

Population: ITT population. Number of participants analyzed = number of participants with morning stiffness VAS assessment at both baseline and Week 24.

RA is associated with stiffness of joints, especially in the morning after prolonged stationery state. The degree of stiffness can be an indicator of disease severity. The severity of morning stiffness was assessed on a VAS scale from 0 mm (no problem) to 100 mm (major problem). LS mean and SE at Week 24 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline Morning Stiffness as a covariate.

Outcome measures

Measure	Placebo q2w n=101 Participants Placebo matched to sarilumab SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.	Sarilumab 150 mg q2w n=127 Participants Sarilumab 150 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.	Sarilumab 200 mg q2w n=136 Participants Sarilumab 200 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.
Change From Baseline in Morning Stiffness VAS at Week 24	-21.66 mm Standard Error 2.390	-32.30 mm Standard Error 2.213	-33.79 mm Standard Error 2.148

SECONDARY outcome

Timeframe: Baseline, Week 24

Population: ITT population. Number of participants analyzed=participants with WPS-RA individual items assessment at both baseline and Week 24.

The WPS-RA is a validated questionnaire that evaluates productivity limitations within work and within home associated with RA over the previous month. The questionnaire was interviewer-administered and was based on participant self-report. It contains 9 questions addressing employment status (1 item), productivity at work (3 items), and within and outside the home (5 items). Number of work days missed in the last month by the participant was reported. LS mean and SE at Week 24 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline WPS-RA as a covariate.

Outcome measures

Measure	Placebo q2w n=32 Participants Placebo matched to sarilumab SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.	Sarilumab 150 mg q2w n=43 Participants Sarilumab 150 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.	Sarilumab 200 mg q2w n=45 Participants Sarilumab 200 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.
Change From Baseline in Work Productivity Survey - Rheumatoid Arthritis (WPS-RA) at Week 24: Work Days Missed Due to RA	-2.01 Days Standard Error 0.458	-2.87 Days Standard Error 0.438	-3.19 Days Standard Error 0.447

SECONDARY outcome

Timeframe: Baseline, Week 24

Population: ITT population. Number of participants analyzed = participants with WPS-RA individual items assessment at both baseline and Week 24.

The WPS-RA is a validated questionnaire that evaluates productivity limitations within work and within home associated with RA over the previous month. The questionnaire was interviewer-administered and was based on participant self-report. It contains 9 questions addressing employment status (1 item), productivity at work (3 items), and within and outside the home (5 items). Number of work days with reduced productivity by ≥ 50% in the last month by the participant was reported. LS mean and SE at Week 24 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline WPS-RA as a covariate.

Outcome measures

Measure	Placebo q2w n=32 Participants Placebo matched to sarilumab SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.	Sarilumab 150 mg q2w n=43 Participants Sarilumab 150 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.	Sarilumab 200 mg q2w n=45 Participants Sarilumab 200 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.
Change From Baseline in WPS-RA at Week 24: Days With Work Productivity Reduced by ≥ 50% Due to RA	-3.64 Days Standard Error 0.589	-4.26 Days Standard Error 0.521	-4.34 Days Standard Error 0.535

SECONDARY outcome

Timeframe: Baseline, Week 24

Population: ITT population. Number of participants analyzed = participants with WPS-RA individual items assessment at both baseline and Week 24.

The WPS-RA is a validated questionnaire that evaluates productivity limitations within work and within home associated with RA over the previous month. The questionnaire was interviewer-administered and was based on participant self-report. It contains 9 questions addressing employment status (1 item), productivity at work (3 items), and within and outside the home (5 items). Interference in the last month with work productivity is measured on a scale that ranges from 0 (no interference) to 10 (complete interference). LS mean and SE at Week 24 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline WPS-RA as a covariate.

Outcome measures

Measure	Placebo q2w n=32 Participants Placebo matched to sarilumab SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.	Sarilumab 150 mg q2w n=42 Participants Sarilumab 150 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.	Sarilumab 200 mg q2w n=45 Participants Sarilumab 200 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.
Change From Baseline in WPS-RA at Week 24: RA Interference With Work Productivity	-1.632 units on a scale Standard Error 0.4186	-2.422 units on a scale Standard Error 0.3719	-2.727 units on a scale Standard Error 0.3700

SECONDARY outcome

Timeframe: Baseline, Week 24

Population: ITT population. Number of participants analyzed = participants with WPS-RA individual items assessment at both baseline and Week 24.

The WPS-RA is a validated questionnaire that evaluates productivity limitations within work and within home associated with RA over the previous month. The questionnaire was interviewer-administered and was based on participant self-report. It contains 9 questions addressing employment status (1 item), productivity at work (3 items), and within and outside the home (5 items). Number of days with no household work in the last month by the participant was reported. LS mean and SE at Week 24 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline WPS-RA as a covariate.

Outcome measures

Measure	Placebo q2w n=101 Participants Placebo matched to sarilumab SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.	Sarilumab 150 mg q2w n=126 Participants Sarilumab 150 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.	Sarilumab 200 mg q2w n=133 Participants Sarilumab 200 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.
Change From Baseline in WPS-RA at Week 24: House Work Days Missed Due to RA	-3.50 Days Standard Error 0.590	-6.13 Days Standard Error 0.551	-6.18 Days Standard Error 0.537

SECONDARY outcome

Timeframe: Baseline, Week 24

Population: ITT population. Number of participants analyzed = participants with WPS-RA individual items assessment at both baseline and Week 24.

The WPS-RA is a validated questionnaire that evaluates productivity limitations within work and within home associated with RA over the previous month. The questionnaire was interviewer-administered and was based on participant self-report. It contains 9 questions addressing employment status (1 item), productivity at work (3 items), and within and outside the home (5 items). Number of days with reduced household work productivity by ≥ 50% in the last month by the participant was reported. LS mean and SE at Week 24 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline WPS-RA as a covariate.

Outcome measures

Measure	Placebo q2w n=101 Participants Placebo matched to sarilumab SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.	Sarilumab 150 mg q2w n=125 Participants Sarilumab 150 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.	Sarilumab 200 mg q2w n=133 Participants Sarilumab 200 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.
Change From Baseline in WPS-RA at Week 24: Days With Household Work Productivity Reduced by ≥ 50% Due to RA	-3.36 Days Standard Error 0.632	-4.60 Days Standard Error 0.591	-4.88 Days Standard Error 0.574

SECONDARY outcome

Timeframe: Baseline, Week 24

Population: ITT population. Number of participants analyzed = participants with WPS-RA individual items assessment at both baseline and Week 24.

The WPS-RA is a validated questionnaire that evaluates productivity limitations within work and within home associated with RA over the previous month. The questionnaire was interviewer-administered and was based on participant self-report. It contains 9 questions addressing employment status (1 item), productivity at work (3 items), and within and outside the home (5 items). Number of days missed of family/social/leisure activities in the last month by the participant was reported. LS mean and SE at Week 24 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline WPS-RA as a covariate.

Outcome measures

Measure	Placebo q2w n=101 Participants Placebo matched to sarilumab SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.	Sarilumab 150 mg q2w n=127 Participants Sarilumab 150 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.	Sarilumab 200 mg q2w n=133 Participants Sarilumab 200 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.
Change From Baseline in WPS-RA at Week 24: Days With Family/Social/Leisure Activities Missed Due to RA	-1.97 Days Standard Error 0.479	-3.51 Days Standard Error 0.446	-4.12 Days Standard Error 0.435

SECONDARY outcome

Timeframe: Baseline, Week 24

Population: ITT population. Number of participants analyzed = participants with WPS-RA individual items assessment at both baseline and Week 24.

The WPS-RA is a validated questionnaire that evaluates productivity limitations within work and within home associated with RA over the previous month. The questionnaire was interviewer-administered and was based on participant self-report. It contains 9 questions addressing employment status (1 item), productivity at work (3 items), and within and outside the home (5 items). Number of days with outside help hired in the last month by the participant was reported. LS mean and SE at Week 24 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline WPS-RA as a covariate.

Outcome measures

Measure	Placebo q2w n=101 Participants Placebo matched to sarilumab SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.	Sarilumab 150 mg q2w n=126 Participants Sarilumab 150 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.	Sarilumab 200 mg q2w n=133 Participants Sarilumab 200 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.
Change From Baseline in WPS-RA at Week 24: Days With Outside Help Hired Due to RA	-1.60 Days Standard Error 0.567	-3.87 Days Standard Error 0.536	-3.86 Days Standard Error 0.523

SECONDARY outcome

Timeframe: Baseline, Week 24

Population: ITT population. Number of participants analyzed = participants with WPS-RA individual items assessment at both baseline and Week 24.

The WPS-RA is a validated questionnaire that evaluates productivity limitations within work and within home associated with RA over the previous month. The questionnaire was interviewer-administered and was based on participant self-report. It contains 9 questions addressing employment status (1 item), productivity at work (3 items), and within and outside the home (5 items). The RA interference in the last month with household work productivity was measured on a scale that ranges from 0 (no interference) to 10 (complete interference). LS mean and SE at Week 24 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline WPS-RA as a covariate.

Outcome measures

Measure	Placebo q2w n=100 Participants Placebo matched to sarilumab SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.	Sarilumab 150 mg q2w n=126 Participants Sarilumab 150 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.	Sarilumab 200 mg q2w n=132 Participants Sarilumab 200 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.
Change From Baseline in WPS-RA at Week 24: RA Interference With Household Work Productivity	-1.970 units on a scale Standard Error 0.2438	-3.096 units on a scale Standard Error 0.2238	-3.269 units on a scale Standard Error 0.2186

SECONDARY outcome

Timeframe: Baseline, Week 24

Population: ITT population. Number of participants analyzed = number of participants with RAID score assessment at both baseline and Week 24.

RAID is a composite measure of the impact of RA on participants that takes into account 7 domains: pain, functional disability, fatigue, physical and emotional well being, quality of sleep, and coping. The RAID is calculated based on 7 numerical rating scales (NRS) questions. Range of the final RAID value is 0-10 where 0= not affected, very good and 10 = most affected weighted and calculated with a total score range of 0 (not affected, very good) to 10 (most affected). A higher RAID value indicate worse status and lower indicate not affected. LS mean and SE at Week 24 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline RAID as a covariate.

Outcome measures

Measure	Placebo q2w n=99 Participants Placebo matched to sarilumab SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.	Sarilumab 150 mg q2w n=126 Participants Sarilumab 150 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.	Sarilumab 200 mg q2w n=136 Participants Sarilumab 200 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.
Change From Baseline in Rheumatoid Arthritis Impact of Disease (RAID) Scores at Week 24	-1.80 units on a scale Standard Error 0.203	-2.55 units on a scale Standard Error 0.189	-2.80 units on a scale Standard Error 0.183

SECONDARY outcome

Timeframe: Baseline, Week 24

Population: ITT population. Number of participants analyzed = number of participants with EQ-5D-3L score assessment at both baseline and Week 24.

The EQ-5D-3L is a standardized, generic measure of health outcome. It was designed for self-completion by participants. It was specifically included to address concerns regarding the health economic impact of RA. The EQ-5D-3L comprises 5 questions on mobility, self-care, pain, usual activities, and psychological status with 3 possible answers for each item (1=no problem, 2=moderate problems, 3=severe problems) and a vertical VAS that allows the participants to indicate their health state today that can range from 0 (worst imaginable) to 100 (best imaginable). LS mean and SE at Week 24 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline EQ-5D-3L Scores as a covariate.

Outcome measures

Measure	Placebo q2w n=96 Participants Placebo matched to sarilumab SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.	Sarilumab 150 mg q2w n=126 Participants Sarilumab 150 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.	Sarilumab 200 mg q2w n=133 Participants Sarilumab 200 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.
Change From Baseline in European Quality of Life-5 Dimension 3 Level (EQ-5D-3L) VAS Scores at Week 24	14.85 units on a scale Standard Error 2.098	20.06 units on a scale Standard Error 1.891	18.40 units on a scale Standard Error 1.842

SECONDARY outcome

Timeframe: Week 12

Population: ITT population.

ACR responses are assessed with a composite rating scale of the American College of Rheumatology that includes 7 variables: TJC; SJC; levels of an acute phase reactant (CRP level); participant's assessment of pain; participant's global assessment of disease activity; physician's global assessment of disease activity; participant's assessment of physical function by HAQ--DI. ACR20 is defined as achieving at least 20% improvement in both TJC and SJC, and at least 20% improvement in at least 3 of the 5 other assessments of the ACR. ACR50 is defined as achieving at least 50% improvement in both TJC and SJC, and at least 50% improvement in at least 3 of the 5 other assessments of the ACR. ACR70 is defined as achieving at least 70% improvement in both TJC and SJC, and at least 70% improvement in at least 3 of the 5 other assessments of the ACR.

Outcome measures

Measure	Placebo q2w n=181 Participants Placebo matched to sarilumab SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.	Sarilumab 150 mg q2w n=181 Participants Sarilumab 150 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.	Sarilumab 200 mg q2w n=184 Participants Sarilumab 200 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.
Percentage of Participants Achieving ACR20, ACR50 and ACR70 Criteria at Week 12 ACR20	37.6 Percentage of participants	54.1 Percentage of participants	62.5 Percentage of participants
Percentage of Participants Achieving ACR20, ACR50 and ACR70 Criteria at Week 12 ACR50	13.3 Percentage of participants	30.4 Percentage of participants	33.2 Percentage of participants
Percentage of Participants Achieving ACR20, ACR50 and ACR70 Criteria at Week 12 ACR70	2.2 Percentage of participants	13.8 Percentage of participants	14.7 Percentage of participants

SECONDARY outcome

Timeframe: Baseline, Week 12

Population: ITT population. Number of participants analyzed = number of participants with DAS28-CRP- Score assessment at both baseline and Week 12.

DAS28 is a composite score that includes 4 variables: TJC (based on 28 joints); SJC (based on 28 joints); GH by the participant assessed from the ACR rheumatoid arthritis core set questionnaire (participant global assessment) in 100 mm VAS; marker of inflammation assessed by hs-CRP in mg/L. The DAS28 provides a number indicating the current activity of the RA. DAS28 total score ranges from 2-10. A DAS28 score above 5.1 means high disease activity, whereas a DAS28 score below 3.2 indicates low disease activity and a DAS28 score below 2.6 means disease remission. LS mean and SE at Week 12 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline DAS score as a covariate.

Outcome measures

Measure	Placebo q2w n=168 Participants Placebo matched to sarilumab SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.	Sarilumab 150 mg q2w n=163 Participants Sarilumab 150 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.	Sarilumab 200 mg q2w n=169 Participants Sarilumab 200 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.
Change From Baseline in DAS28-CRP at Week 12	-0.97 units on a scale Standard Error 0.104	-2.13 units on a scale Standard Error 0.105	-2.45 units on a scale Standard Error 0.103

SECONDARY outcome

Timeframe: Week 12

Population: ITT population.

DAS28 is a composite score that includes 4 variables: TJC (based on 28 joints); SJC (based on 28 joints); GH by the participant assessed from the ACR RA core set questionnaire (participant global assessment) in 100 mm VAS; marker of inflammation assessed by hs-CRP in mg/L. The DAS28 provides a number indicating the current activity of the RA. DAS28 total score ranges from 2-10. A DAS28 score above 5.1 means high disease activity, whereas a DAS28 score below 3.2 indicates low disease activity and a DAS28 score below 2.6 means disease remission.

Outcome measures

Measure	Placebo q2w n=181 Participants Placebo matched to sarilumab SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.	Sarilumab 150 mg q2w n=181 Participants Sarilumab 150 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.	Sarilumab 200 mg q2w n=184 Participants Sarilumab 200 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.
Percentage of Participants Achieving Clinical Remission Score (DAS28--CRP <2.6) at Week 12	3.9 Percentage of participants	17.1 Percentage of participants	17.9 Percentage of participants

SECONDARY outcome

Timeframe: Baseline, Week 12

Population: ITT population. Number of participants analyzed=participants with SF-36 assessment at both baseline and Week 12.

SF-36 is a generic 36-item questionnaire measuring HRQL covering 2 summary measures: PCS and MCS. The SF-36 consists of 8 subscales. The PCS is represented by 4 subscales: physical function, role limitations due to physical problems, pain, and general health perception. The MCS is represented by 4 subscales: vitality, social function, role limitations due to emotional problems, and mental health. Participants self-report on items in a subscale that have between 2-6 choices per item using Likert-type responses (e.g. none of the time, some of the time, etc.). Summations of item scores of the same subscale give the subscale scores, which are transformed into a range from 0 to 100; 0= worst HRQL, 100=best HRQL. Higher scores indicate better health and well-being. LS mean and SE at Week 12 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline SF-36 as a covariate.

Outcome measures

Measure	Placebo q2w n=169 Participants Placebo matched to sarilumab SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.	Sarilumab 150 mg q2w n=160 Participants Sarilumab 150 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.	Sarilumab 200 mg q2w n=165 Participants Sarilumab 200 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.
Change From Baseline in SF-36 at Week 12 Physical Component Summary Score at Week 12	3.74 units on a scale Standard Error 0.582	6.93 units on a scale Standard Error 0.596	6.84 units on a scale Standard Error 0.584
Change From Baseline in SF-36 at Week 12 Mental Component Summary Score at Week 12	3.50 units on a scale Standard Error 0.738	5.14 units on a scale Standard Error 0.758	6.47 units on a scale Standard Error 0.741

SECONDARY outcome

Timeframe: Baseline, Week 12

Population: ITT population. Number of participants analyzed=participants with WPS-RA individual items assessment at both baseline and Week 12.

The WPS-RA is a validated questionnaire that evaluates productivity limitations within work and within home associated with RA over the previous month. The questionnaire was interviewer-administered and was based on participant self-report. It contains 9 questions addressing employment status (1 item), productivity at work (3 items), and within and outside the home (5 items). Number of work days missed in the last month by the participant was reported. LS mean and SE at Week 12 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline WPS-RA as a covariate.

Outcome measures

Measure	Placebo q2w n=54 Participants Placebo matched to sarilumab SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.	Sarilumab 150 mg q2w n=54 Participants Sarilumab 150 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.	Sarilumab 200 mg q2w n=56 Participants Sarilumab 200 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.
Change From Baseline in WPS-RA at Week 12: Work Days Missed Due to RA	-1.20 Days Standard Error 0.581	-1.97 Days Standard Error 0.571	-2.98 Days Standard Error 0.585

SECONDARY outcome

Timeframe: Baseline, Week 12

Population: ITT population. Number of participants analyzed = participants with WPS-RA individual items assessment at both baseline and Week 12.

The WPS-RA is a validated questionnaire that evaluates productivity limitations within work and within home associated with RA over the previous month. The questionnaire was interviewer-administered and was based on participant self-report. It contains 9 questions addressing employment status (1 item), productivity at work (3 items), and within and outside the home (5 items). Number of work days with reduced productivity by ≥ 50% in the last month by the participant was reported. LS mean and SE at Week 12 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline WPS-RA as a covariate.

Outcome measures

Measure	Placebo q2w n=54 Participants Placebo matched to sarilumab SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.	Sarilumab 150 mg q2w n=54 Participants Sarilumab 150 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.	Sarilumab 200 mg q2w n=56 Participants Sarilumab 200 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.
Change From Baseline in WPS-RA at Week 12: Days With Work Productivity Reduced by ≥ 50% Due to RA	-1.69 Days Standard Error 0.784	-4.24 Days Standard Error 0.773	-3.20 Days Standard Error 0.785

SECONDARY outcome

Timeframe: Baseline, Week 12

Population: ITT population. Number of participants analyzed = participants with WPS-RA individual items assessment at both baseline and Week 12.

The WPS-RA is a validated questionnaire that evaluates productivity limitations within work and within home associated with RA over the previous month. The questionnaire was interviewer-administered and was based on participant self-report. It contains 9 questions addressing employment status (1 item), productivity at work (3 items), and within and outside the home (5 items). Interference in the last month with work productivity was measured on a scale that ranges from 0 (no interference) to 10 (complete interference). LS mean and SE at Week 12 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline WPS-RA as a covariate.

Outcome measures

Measure	Placebo q2w n=53 Participants Placebo matched to sarilumab SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.	Sarilumab 150 mg q2w n=54 Participants Sarilumab 150 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.	Sarilumab 200 mg q2w n=56 Participants Sarilumab 200 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.
Change From Baseline in WPS-RA at Week 12: RA Interference With Work Productivity	-1.043 units on a scale Standard Error 0.3803	-1.924 units on a scale Standard Error 0.3742	-1.873 units on a scale Standard Error 0.3764

SECONDARY outcome

Timeframe: Baseline, Week 12

Population: ITT population. Number of participants analyzed = participants with WPS-RA individual items assessment at both baseline and Week 12.

The WPS-RA is a validated questionnaire that evaluates productivity limitations within work and within home associated with RA over the previous month. The questionnaire was interviewer-administered and was based on participant self-report. It contains 9 questions addressing employment status (1 item), productivity at work (3 items), and within and outside the home (5 items). Number of days with no household work in the last month by the participant was reported. LS mean and SE at Week 12 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline WPS-RA as a covariate.

Outcome measures

Measure	Placebo q2w n=170 Participants Placebo matched to sarilumab SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.	Sarilumab 150 mg q2w n=164 Participants Sarilumab 150 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.	Sarilumab 200 mg q2w n=169 Participants Sarilumab 200 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.
Change From Baseline in WPS-RA at Week 12: House Work Days Missed Due to RA	-2.10 Days Standard Error 0.551	-5.52 Days Standard Error 0.563	-5.54 Days Standard Error 0.553

SECONDARY outcome

Timeframe: Baseline, Week 12

Population: ITT population. Number of participants analyzed = participants with WPS-RA individual items assessment at both baseline and Week 12.

The WPS-RA is a validated questionnaire that evaluates productivity limitations within work and within home associated with RA over the previous month. The questionnaire was interviewer-administered and was based on participant self-report. It contains 9 questions addressing employment status (1 item), productivity at work (3 items), and within and outside the home (5 items). Number of days with reduced household work productivity by ≥ 50% in the last month by the participant was reported. LS mean and SE at Week 12 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline WPS-RA as a covariate.

Outcome measures

Measure	Placebo q2w n=169 Participants Placebo matched to sarilumab SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.	Sarilumab 150 mg q2w n=163 Participants Sarilumab 150 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.	Sarilumab 200 mg q2w n=169 Participants Sarilumab 200 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.
Change From Baseline in WPS-RA at Week 12: Days With Household Work Productivity Reduced by ≥ 50% Due to RA	-2.60 Days Standard Error 0.576	-3.97 Days Standard Error 0.587	-3.98 Days Standard Error 0.575

SECONDARY outcome

Timeframe: Baseline, Week 12

Population: ITT population. Number of participants analyzed = participants with WPS-RA individual items assessment at both baseline and Week 12.

The WPS-RA is a validated questionnaire that evaluates productivity limitations within work and within home associated with RA over the previous month. The questionnaire was interviewer-administered and was based on participant self-report. It contains 9 questions addressing employment status (1 item), productivity at work (3 items), and within and outside the home (5 items). Number of days missed of family/social/leisure activities in the last month by the participant was reported. LS mean and SE at Week 12 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline WPS-RA as a covariate.

Outcome measures

Measure	Placebo q2w n=170 Participants Placebo matched to sarilumab SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.	Sarilumab 150 mg q2w n=164 Participants Sarilumab 150 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.	Sarilumab 200 mg q2w n=169 Participants Sarilumab 200 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.
Change From Baseline in WPS-RA at Week 12: Days With Family/Social/Leisure Activities Missed Due to RA	-2.23 Days Standard Error 0.433	-2.53 Days Standard Error 0.442	-3.26 Days Standard Error 0.434

SECONDARY outcome

Timeframe: Baseline, Week 12

Population: ITT population. Number of participants analyzed = participants with WPS-RA individual items assessment at both baseline and Week 12.

The WPS-RA is a validated questionnaire that evaluates productivity limitations within work and within home associated with RA over the previous month. The questionnaire was interviewer-administered and was based on participant self-report. It contains 9 questions addressing employment status (1 item), productivity at work (3 items), and within and outside the home (5 items). Number of days with outside help hired in the last month by the participant was reported. LS mean and SE at Week 12 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline WPS-RA as a covariate.

Outcome measures

Measure	Placebo q2w n=170 Participants Placebo matched to sarilumab SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.	Sarilumab 150 mg q2w n=164 Participants Sarilumab 150 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.	Sarilumab 200 mg q2w n=169 Participants Sarilumab 200 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.
Change From Baseline in WPS-RA at Week 12: Days With Outside Help Hired Due to RA	-0.77 Days Standard Error 0.558	-3.07 Days Standard Error 0.570	-2.94 Days Standard Error 0.560

SECONDARY outcome

Timeframe: Baseline, Week 12

Population: ITT population. Number of participants analyzed = participants with WPS-RA individual items assessment at both baseline and Week 12.

The WPS-RA is a validated questionnaire that evaluates productivity limitations within work and within home associated with RA over the previous month. The questionnaire was interviewer-administered and was based on participant self-report. It contains 9 questions addressing employment status (1 item), productivity at work (3 items), and within and outside the home (5 items). The RA interference in the last month with household work productivity was measured on a scale that ranges from 0 (no interference) to 10 (complete interference). LS mean and SE at Week 12 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline WPS-RA as a covariate.

Outcome measures

Measure	Placebo q2w n=169 Participants Placebo matched to sarilumab SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.	Sarilumab 150 mg q2w n=164 Participants Sarilumab 150 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.	Sarilumab 200 mg q2w n=167 Participants Sarilumab 200 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.
Change From Baseline in WPS-RA at Week 12: RA Interference With Household Work Productivity	-1.210 units on a scale Standard Error 0.2428	-2.772 units on a scale Standard Error 0.2474	-2.404 units on a scale Standard Error 0.2443

SECONDARY outcome

Timeframe: Baseline, Week 12

Population: ITT population. Number of Participants analyzed = number of participants with FACIT-fatigue score assessment at both baseline and Week 12.

The FACIT-Fatigue is a 13-item questionnaire assessing fatigue where participants scored each item on a 5-point scale (0-4): 0=not at all, 1=a little bit, 2=somewhat, 3=quite a bit, 4=very much. A total score ranging from 0 to 52. A higher score corresponded to a lower level of fatigue. A positive change from baseline score indicates an improvement. LS mean and SE at Week 12 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline FACIT-fatigue as a covariate.

Outcome measures

Measure	Placebo q2w n=169 Participants Placebo matched to sarilumab SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.	Sarilumab 150 mg q2w n=165 Participants Sarilumab 150 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.	Sarilumab 200 mg q2w n=172 Participants Sarilumab 200 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.
Change From Baseline in the FACIT-fatigue at Week 12	5.56 units on a scale Standard Error 0.721	8.02 units on a scale Standard Error 0.729	9.45 units on a scale Standard Error 0.714

SECONDARY outcome

Timeframe: Baseline, Week 12

Population: ITT population. Number of participants analyzed = number of participants with EQ-5D-3L score assessment at both baseline and Week 12.

The EQ-5D-3L is a standardized, generic measure of health outcome. EQ-5D was designed for self-completion by participants. The EQ-5D was specifically included to address concerns regarding the health economic impact of RA. The EQ-5D-3L comprises 5 questions on mobility, self-care, pain, usual activities, and psychological status with 3 possible answers for each item (1=no problem, 2=moderate problems, 3=severe problems) and a vertical VAS that allows the participants to indicate their health state today that can range from 0 (worst imaginable) to 100 (best imaginable). LS mean and SE at Week 12 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline EQ-5D-3L scores as a covariate.

Outcome measures

Measure	Placebo q2w n=167 Participants Placebo matched to sarilumab SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.	Sarilumab 150 mg q2w n=163 Participants Sarilumab 150 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.	Sarilumab 200 mg q2w n=171 Participants Sarilumab 200 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.
Change From Baseline in EQ-5D-3L VAS Scores at Week 12	8.39 units on a scale Standard Error 1.699	17.16 units on a scale Standard Error 1.720	15.23 units on a scale Standard Error 1.680

SECONDARY outcome

Timeframe: Baseline, Week 12

Population: ITT population. Number of participants analyzed = number of participants with RAID score assessment at both baseline and Week 12.

RAID score is a composite measure of the impact of RA on participants that takes into account 7 domains: pain, functional disability, fatigue, physical and emotional well being, quality of sleep, and coping. The RAID is calculated based on 7 NRS questions. Range of the final RAID value is 0-10 where 0= not affected, very good and 10 = most affected weighted and calculated with a total score range of 0 (not affected, very good) to 10 (most affected). A higher RAID value indicates worse status and lower indicates not affected. LS mean and SE at Week 12 were obtained from a MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline RAID scores as a covariate.

Outcome measures

Measure	Placebo q2w n=167 Participants Placebo matched to sarilumab SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.	Sarilumab 150 mg q2w n=162 Participants Sarilumab 150 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.	Sarilumab 200 mg q2w n=171 Participants Sarilumab 200 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.
Change From Baseline in RAID Scores at Week 12	-1.34 units on a scale Standard Error 0.163	-2.27 units on a scale Standard Error 0.165	-2.47 units on a scale Standard Error 0.161

SECONDARY outcome

Timeframe: Baseline, Week 12 and Week 24

Population: ITT population. Number analyzed = number of participants with TJC and SJC assessments at both baseline and specified time points.

ACR components were: TJC, SJC, physician global VAS, participant global VAS, pain VAS,HAQ-DI & CRP. 68 joints were assessed for tenderness (TJC scoring 0-68) and 66 joints for swelling (SJC scoring 0-66). The 66 SJC evaluated the following joints: temporomandibular, sternoclavicular, acromioclavicular, shoulder, elbow, wrist, metacarpophalangeal, interphalangeal of thumb, distal interphalangeal, proximal interphalangeal, knee, ankle mortise, ankle tarsus, metatarsophalangeal, interphalangeal of great toe, and proximal/distal interphalangeal of the toes. The TJC examined hip joints, in addition to the joints assessed for SJC. Increase in number of tender joints/swollen joints indicated severity. LS mean and SE at Week 12 & 24 by MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline ACR components as a covariate.

Outcome measures

Measure	Placebo q2w n=181 Participants Placebo matched to sarilumab SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.	Sarilumab 150 mg q2w n=181 Participants Sarilumab 150 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.	Sarilumab 200 mg q2w n=184 Participants Sarilumab 200 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.
Change From Baseline in Individual ACR Components - TJC and SJC at Week 12 and Week 24 TJC at week 24	-10.55 joints Standard Error 1.060	-14.44 joints Standard Error 1.017	-16.95 joints Standard Error 0.992
Change From Baseline in Individual ACR Components - TJC and SJC at Week 12 and Week 24 TJC at week 12	-8.55 joints Standard Error 0.959	-13.74 joints Standard Error 0.975	-14.87 joints Standard Error 0.954
Change From Baseline in Individual ACR Components - TJC and SJC at Week 12 and Week 24 SJC at week 12	-6.75 joints Standard Error 0.687	-10.54 joints Standard Error 0.698	-10.59 joints Standard Error 0.684
Change From Baseline in Individual ACR Components - TJC and SJC at Week 12 and Week 24 SJC at week 24	-8.19 joints Standard Error 0.721	-11.56 joints Standard Error 0.691	-11.94 joints Standard Error 0.674

SECONDARY outcome

Timeframe: Baseline, Week 12 and Week 24

Population: ITT population. Number analyzed = number of participants with individual ACR components assessment at both baseline and specified time points.

ACR components were: TJC, SJC, physician global VAS, participant global VAS, pain VAS, HAQ-DI & CRP. Physician global VAS & participant global VAS was done by 100 mm non-anchored VAS, from no arthritis (0) activity to maximal arthritis (100) activity. Pain VAS by 100 mm VAS ranging from 0 "no pain" to 100 "worst pain". LS mean and SE at Week 12 & 24 by MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline ACR components as a covariate.

Outcome measures

Measure	Placebo q2w n=181 Participants Placebo matched to sarilumab SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.	Sarilumab 150 mg q2w n=181 Participants Sarilumab 150 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.	Sarilumab 200 mg q2w n=184 Participants Sarilumab 200 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.
Change From Baseline in Individual ACR Component - Physician Global VAS, Participant Global VAS and Pain VAS at Week 12 and Week 24 Physician global VAS at week 12	-22.74 mm Standard Error 1.744	-33.64 mm Standard Error 1.775	-35.44 mm Standard Error 1.740
Change From Baseline in Individual ACR Component - Physician Global VAS, Participant Global VAS and Pain VAS at Week 12 and Week 24 Participant global VAS at week 12	-13.75 mm Standard Error 1.807	-25.28 mm Standard Error 1.836	-27.38 mm Standard Error 1.803
Change From Baseline in Individual ACR Component - Physician Global VAS, Participant Global VAS and Pain VAS at Week 12 and Week 24 Pain VAS at week 12	-15.13 mm Standard Error 1.908	-26.93 mm Standard Error 1.933	-30.56 mm Standard Error 1.901
Change From Baseline in Individual ACR Component - Physician Global VAS, Participant Global VAS and Pain VAS at Week 12 and Week 24 Physician global VAS at week 24	-28.55 mm Standard Error 1.806	-40.65 mm Standard Error 1.695	-43.22 mm Standard Error 1.646
Change From Baseline in Individual ACR Component - Physician Global VAS, Participant Global VAS and Pain VAS at Week 12 and Week 24 Participant global VAS at week 24	-19.76 mm Standard Error 2.171	-29.59 mm Standard Error 2.046	-31.28 mm Standard Error 1.997
Change From Baseline in Individual ACR Component - Physician Global VAS, Participant Global VAS and Pain VAS at Week 12 and Week 24 Pain VAS at week 24	-21.27 mm Standard Error 2.250	-31.90 mm Standard Error 2.086	-33.65 mm Standard Error 2.037

SECONDARY outcome

Timeframe: Baseline, Week 12 and Week 24

Population: ITT population. Number analyzed = number of participants with CRP assessment at both baseline and specified time points.

ACR components were: TJC, SJC, physician global VAS, participant global VAS, pain VAS, HAQ-DI & CRP. An elevated CRP level was considered a non-specific "marker" for RA. A reduction level indicates improvement. LS mean and SE at Week 12 & 24 by MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline ACR components as a covariate.

Outcome measures

Measure	Placebo q2w n=181 Participants Placebo matched to sarilumab SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.	Sarilumab 150 mg q2w n=181 Participants Sarilumab 150 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.	Sarilumab 200 mg q2w n=184 Participants Sarilumab 200 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.
Change From Baseline in Individual ACR Component - CRP Level at Week 12 and Week 24 CRP at week 12	-3.63 mg/L Standard Error 1.436	-15.08 mg/L Standard Error 1.452	-22.98 mg/L Standard Error 1.432
Change From Baseline in Individual ACR Component - CRP Level at Week 12 and Week 24 CRP at week 24	-3.60 mg/L Standard Error 1.556	-15.24 mg/L Standard Error 1.457	-23.27 mg/L Standard Error 1.421

SECONDARY outcome

Timeframe: Baseline, Week 12 and Week 24

Population: ITT population. Number analyzed = number of participants with HAQ-DI assessment at both baseline and specified time points.

ACR components were: TJC, SJC, physician global VAS, participant global VAS, pain VAS,HAQ-DI & CRP. HAQ-DI consisted of at least 2 questions per category, participant reported assessment of ability to perform tasks in 8 categories of daily living activities: dress/groom; arise; eat; walk; reach; grip; hygiene; and common activities over past week rated on a 4-point scale where 0 = no difficulty; 1 = some difficulty; 2 = much difficulty; 3 = unable to do. Overall score was computed as the sum of category scores and divided by the number of categories answered, ranging from 0 to 3, where 0 = no disability and 3 = unable to do, high-dependency disability. LS mean and SE at Week 12 & 24 by MMRM with treatment, region, number of previous anti-TNFs, visit, and treatment-by-visit interaction as fixed effects and baseline ACR components as a covariate.

Outcome measures

Measure	Placebo q2w n=181 Participants Placebo matched to sarilumab SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.	Sarilumab 150 mg q2w n=181 Participants Sarilumab 150 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.	Sarilumab 200 mg q2w n=184 Participants Sarilumab 200 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.
Change From Baseline in Individual ACR Component - HAQ-DI at Week 12 and Week 24 HAQ-DI at week 12	-0.26 units on a scale Standard Error 0.043	-0.46 units on a scale Standard Error 0.044	-0.47 units on a scale Standard Error 0.043
Change From Baseline in Individual ACR Component - HAQ-DI at Week 12 and Week 24 HAQ-DI at week 24	-0.34 units on a scale Standard Error 0.051	-0.52 units on a scale Standard Error 0.049	-0.58 units on a scale Standard Error 0.048

Adverse Events

Placebo q2w

Serious events: 6 serious events

Other events: 26 other events

Deaths: 0 deaths

Sarilumab 150 mg q2w

Serious events: 6 serious events

Other events: 60 other events

Deaths: 0 deaths

Sarilumab 200 mg q2w

Serious events: 10 serious events

Other events: 57 other events

Deaths: 0 deaths

Serious adverse events

Measure	Placebo q2w n=181 participants at risk Placebo matched to sarilumab SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.	Sarilumab 150 mg q2w n=181 participants at risk Sarilumab 150 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.	Sarilumab 200 mg q2w n=184 participants at risk Sarilumab 200 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.
Infections and infestations Bacteraemia	0.55% 1/181 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 30) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (time from the first dose injection of study drug to the end of follow-up period). Safety population included all participants from the randomized population who received at least 1 dose or part of a dose of study drug.	0.00% 0/181 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 30) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (time from the first dose injection of study drug to the end of follow-up period). Safety population included all participants from the randomized population who received at least 1 dose or part of a dose of study drug.	0.00% 0/184 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 30) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (time from the first dose injection of study drug to the end of follow-up period). Safety population included all participants from the randomized population who received at least 1 dose or part of a dose of study drug.
Infections and infestations Bronchitis	0.55% 1/181 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 30) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (time from the first dose injection of study drug to the end of follow-up period). Safety population included all participants from the randomized population who received at least 1 dose or part of a dose of study drug.	0.00% 0/181 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 30) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (time from the first dose injection of study drug to the end of follow-up period). Safety population included all participants from the randomized population who received at least 1 dose or part of a dose of study drug.	0.00% 0/184 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 30) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (time from the first dose injection of study drug to the end of follow-up period). Safety population included all participants from the randomized population who received at least 1 dose or part of a dose of study drug.
Infections and infestations Cellulitis	0.55% 1/181 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 30) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (time from the first dose injection of study drug to the end of follow-up period). Safety population included all participants from the randomized population who received at least 1 dose or part of a dose of study drug.	0.55% 1/181 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 30) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (time from the first dose injection of study drug to the end of follow-up period). Safety population included all participants from the randomized population who received at least 1 dose or part of a dose of study drug.	0.54% 1/184 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 30) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (time from the first dose injection of study drug to the end of follow-up period). Safety population included all participants from the randomized population who received at least 1 dose or part of a dose of study drug.
Infections and infestations Osteomyelitis	0.00% 0/181 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 30) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (time from the first dose injection of study drug to the end of follow-up period). Safety population included all participants from the randomized population who received at least 1 dose or part of a dose of study drug.	0.55% 1/181 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 30) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (time from the first dose injection of study drug to the end of follow-up period). Safety population included all participants from the randomized population who received at least 1 dose or part of a dose of study drug.	0.00% 0/184 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 30) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (time from the first dose injection of study drug to the end of follow-up period). Safety population included all participants from the randomized population who received at least 1 dose or part of a dose of study drug.
Infections and infestations Pneumonia	0.00% 0/181 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 30) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (time from the first dose injection of study drug to the end of follow-up period). Safety population included all participants from the randomized population who received at least 1 dose or part of a dose of study drug.	0.00% 0/181 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 30) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (time from the first dose injection of study drug to the end of follow-up period). Safety population included all participants from the randomized population who received at least 1 dose or part of a dose of study drug.	0.54% 1/184 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 30) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (time from the first dose injection of study drug to the end of follow-up period). Safety population included all participants from the randomized population who received at least 1 dose or part of a dose of study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Ureteric cancer	0.55% 1/181 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 30) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (time from the first dose injection of study drug to the end of follow-up period). Safety population included all participants from the randomized population who received at least 1 dose or part of a dose of study drug.	0.00% 0/181 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 30) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (time from the first dose injection of study drug to the end of follow-up period). Safety population included all participants from the randomized population who received at least 1 dose or part of a dose of study drug.	0.00% 0/184 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 30) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (time from the first dose injection of study drug to the end of follow-up period). Safety population included all participants from the randomized population who received at least 1 dose or part of a dose of study drug.
Blood and lymphatic system disorders Anaemia	0.55% 1/181 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 30) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (time from the first dose injection of study drug to the end of follow-up period). Safety population included all participants from the randomized population who received at least 1 dose or part of a dose of study drug.	0.00% 0/181 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 30) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (time from the first dose injection of study drug to the end of follow-up period). Safety population included all participants from the randomized population who received at least 1 dose or part of a dose of study drug.	0.00% 0/184 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 30) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (time from the first dose injection of study drug to the end of follow-up period). Safety population included all participants from the randomized population who received at least 1 dose or part of a dose of study drug.
Blood and lymphatic system disorders Neutropenia	0.00% 0/181 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 30) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (time from the first dose injection of study drug to the end of follow-up period). Safety population included all participants from the randomized population who received at least 1 dose or part of a dose of study drug.	0.55% 1/181 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 30) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (time from the first dose injection of study drug to the end of follow-up period). Safety population included all participants from the randomized population who received at least 1 dose or part of a dose of study drug.	0.54% 1/184 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 30) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (time from the first dose injection of study drug to the end of follow-up period). Safety population included all participants from the randomized population who received at least 1 dose or part of a dose of study drug.
Nervous system disorders Ischaemic stroke	0.00% 0/181 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 30) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (time from the first dose injection of study drug to the end of follow-up period). Safety population included all participants from the randomized population who received at least 1 dose or part of a dose of study drug.	0.00% 0/181 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 30) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (time from the first dose injection of study drug to the end of follow-up period). Safety population included all participants from the randomized population who received at least 1 dose or part of a dose of study drug.	0.54% 1/184 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 30) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (time from the first dose injection of study drug to the end of follow-up period). Safety population included all participants from the randomized population who received at least 1 dose or part of a dose of study drug.
Nervous system disorders Syncope	0.00% 0/181 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 30) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (time from the first dose injection of study drug to the end of follow-up period). Safety population included all participants from the randomized population who received at least 1 dose or part of a dose of study drug.	0.55% 1/181 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 30) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (time from the first dose injection of study drug to the end of follow-up period). Safety population included all participants from the randomized population who received at least 1 dose or part of a dose of study drug.	0.00% 0/184 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 30) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (time from the first dose injection of study drug to the end of follow-up period). Safety population included all participants from the randomized population who received at least 1 dose or part of a dose of study drug.
Cardiac disorders Acute myocardial infarction	0.00% 0/181 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 30) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (time from the first dose injection of study drug to the end of follow-up period). Safety population included all participants from the randomized population who received at least 1 dose or part of a dose of study drug.	0.00% 0/181 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 30) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (time from the first dose injection of study drug to the end of follow-up period). Safety population included all participants from the randomized population who received at least 1 dose or part of a dose of study drug.	0.54% 1/184 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 30) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (time from the first dose injection of study drug to the end of follow-up period). Safety population included all participants from the randomized population who received at least 1 dose or part of a dose of study drug.
Cardiac disorders Atrioventricular block second degree	0.00% 0/181 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 30) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (time from the first dose injection of study drug to the end of follow-up period). Safety population included all participants from the randomized population who received at least 1 dose or part of a dose of study drug.	0.00% 0/181 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 30) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (time from the first dose injection of study drug to the end of follow-up period). Safety population included all participants from the randomized population who received at least 1 dose or part of a dose of study drug.	0.54% 1/184 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 30) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (time from the first dose injection of study drug to the end of follow-up period). Safety population included all participants from the randomized population who received at least 1 dose or part of a dose of study drug.
Cardiac disorders Endocarditis noninfective	0.00% 0/181 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 30) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (time from the first dose injection of study drug to the end of follow-up period). Safety population included all participants from the randomized population who received at least 1 dose or part of a dose of study drug.	0.00% 0/181 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 30) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (time from the first dose injection of study drug to the end of follow-up period). Safety population included all participants from the randomized population who received at least 1 dose or part of a dose of study drug.	0.54% 1/184 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 30) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (time from the first dose injection of study drug to the end of follow-up period). Safety population included all participants from the randomized population who received at least 1 dose or part of a dose of study drug.
Vascular disorders Venous thrombosis limb	0.00% 0/181 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 30) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (time from the first dose injection of study drug to the end of follow-up period). Safety population included all participants from the randomized population who received at least 1 dose or part of a dose of study drug.	0.00% 0/181 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 30) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (time from the first dose injection of study drug to the end of follow-up period). Safety population included all participants from the randomized population who received at least 1 dose or part of a dose of study drug.	0.54% 1/184 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 30) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (time from the first dose injection of study drug to the end of follow-up period). Safety population included all participants from the randomized population who received at least 1 dose or part of a dose of study drug.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.00% 0/181 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 30) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (time from the first dose injection of study drug to the end of follow-up period). Safety population included all participants from the randomized population who received at least 1 dose or part of a dose of study drug.	0.55% 1/181 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 30) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (time from the first dose injection of study drug to the end of follow-up period). Safety population included all participants from the randomized population who received at least 1 dose or part of a dose of study drug.	0.00% 0/184 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 30) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (time from the first dose injection of study drug to the end of follow-up period). Safety population included all participants from the randomized population who received at least 1 dose or part of a dose of study drug.
Gastrointestinal disorders Gastric ulcer haemorrhage	0.00% 0/181 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 30) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (time from the first dose injection of study drug to the end of follow-up period). Safety population included all participants from the randomized population who received at least 1 dose or part of a dose of study drug.	0.55% 1/181 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 30) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (time from the first dose injection of study drug to the end of follow-up period). Safety population included all participants from the randomized population who received at least 1 dose or part of a dose of study drug.	0.00% 0/184 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 30) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (time from the first dose injection of study drug to the end of follow-up period). Safety population included all participants from the randomized population who received at least 1 dose or part of a dose of study drug.
Gastrointestinal disorders Inguinal hernia	0.00% 0/181 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 30) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (time from the first dose injection of study drug to the end of follow-up period). Safety population included all participants from the randomized population who received at least 1 dose or part of a dose of study drug.	0.00% 0/181 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 30) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (time from the first dose injection of study drug to the end of follow-up period). Safety population included all participants from the randomized population who received at least 1 dose or part of a dose of study drug.	0.54% 1/184 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 30) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (time from the first dose injection of study drug to the end of follow-up period). Safety population included all participants from the randomized population who received at least 1 dose or part of a dose of study drug.
Hepatobiliary disorders Mixed liver injury	0.55% 1/181 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 30) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (time from the first dose injection of study drug to the end of follow-up period). Safety population included all participants from the randomized population who received at least 1 dose or part of a dose of study drug.	0.00% 0/181 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 30) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (time from the first dose injection of study drug to the end of follow-up period). Safety population included all participants from the randomized population who received at least 1 dose or part of a dose of study drug.	0.00% 0/184 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 30) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (time from the first dose injection of study drug to the end of follow-up period). Safety population included all participants from the randomized population who received at least 1 dose or part of a dose of study drug.
Musculoskeletal and connective tissue disorders Intervertebral disc disorder	0.00% 0/181 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 30) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (time from the first dose injection of study drug to the end of follow-up period). Safety population included all participants from the randomized population who received at least 1 dose or part of a dose of study drug.	0.00% 0/181 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 30) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (time from the first dose injection of study drug to the end of follow-up period). Safety population included all participants from the randomized population who received at least 1 dose or part of a dose of study drug.	0.54% 1/184 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 30) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (time from the first dose injection of study drug to the end of follow-up period). Safety population included all participants from the randomized population who received at least 1 dose or part of a dose of study drug.
Musculoskeletal and connective tissue disorders Intervertebral disc protrusion	0.00% 0/181 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 30) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (time from the first dose injection of study drug to the end of follow-up period). Safety population included all participants from the randomized population who received at least 1 dose or part of a dose of study drug.	0.55% 1/181 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 30) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (time from the first dose injection of study drug to the end of follow-up period). Safety population included all participants from the randomized population who received at least 1 dose or part of a dose of study drug.	0.00% 0/184 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 30) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (time from the first dose injection of study drug to the end of follow-up period). Safety population included all participants from the randomized population who received at least 1 dose or part of a dose of study drug.
Musculoskeletal and connective tissue disorders Rheumatoid arthritis	0.55% 1/181 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 30) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (time from the first dose injection of study drug to the end of follow-up period). Safety population included all participants from the randomized population who received at least 1 dose or part of a dose of study drug.	0.00% 0/181 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 30) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (time from the first dose injection of study drug to the end of follow-up period). Safety population included all participants from the randomized population who received at least 1 dose or part of a dose of study drug.	0.00% 0/184 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 30) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (time from the first dose injection of study drug to the end of follow-up period). Safety population included all participants from the randomized population who received at least 1 dose or part of a dose of study drug.
Investigations Neutrophil count decreased	0.00% 0/181 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 30) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (time from the first dose injection of study drug to the end of follow-up period). Safety population included all participants from the randomized population who received at least 1 dose or part of a dose of study drug.	0.00% 0/181 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 30) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (time from the first dose injection of study drug to the end of follow-up period). Safety population included all participants from the randomized population who received at least 1 dose or part of a dose of study drug.	0.54% 1/184 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 30) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (time from the first dose injection of study drug to the end of follow-up period). Safety population included all participants from the randomized population who received at least 1 dose or part of a dose of study drug.
Investigations Transaminases increased	0.00% 0/181 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 30) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (time from the first dose injection of study drug to the end of follow-up period). Safety population included all participants from the randomized population who received at least 1 dose or part of a dose of study drug.	0.00% 0/181 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 30) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (time from the first dose injection of study drug to the end of follow-up period). Safety population included all participants from the randomized population who received at least 1 dose or part of a dose of study drug.	0.54% 1/184 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 30) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (time from the first dose injection of study drug to the end of follow-up period). Safety population included all participants from the randomized population who received at least 1 dose or part of a dose of study drug.
Injury, poisoning and procedural complications Ankle fracture	0.55% 1/181 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 30) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (time from the first dose injection of study drug to the end of follow-up period). Safety population included all participants from the randomized population who received at least 1 dose or part of a dose of study drug.	0.00% 0/181 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 30) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (time from the first dose injection of study drug to the end of follow-up period). Safety population included all participants from the randomized population who received at least 1 dose or part of a dose of study drug.	0.00% 0/184 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 30) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (time from the first dose injection of study drug to the end of follow-up period). Safety population included all participants from the randomized population who received at least 1 dose or part of a dose of study drug.
Injury, poisoning and procedural complications Post procedural haemorrhage	0.00% 0/181 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 30) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (time from the first dose injection of study drug to the end of follow-up period). Safety population included all participants from the randomized population who received at least 1 dose or part of a dose of study drug.	0.00% 0/181 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 30) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (time from the first dose injection of study drug to the end of follow-up period). Safety population included all participants from the randomized population who received at least 1 dose or part of a dose of study drug.	0.54% 1/184 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 30) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (time from the first dose injection of study drug to the end of follow-up period). Safety population included all participants from the randomized population who received at least 1 dose or part of a dose of study drug.
Injury, poisoning and procedural complications Road traffic accident	0.55% 1/181 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 30) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (time from the first dose injection of study drug to the end of follow-up period). Safety population included all participants from the randomized population who received at least 1 dose or part of a dose of study drug.	0.00% 0/181 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 30) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (time from the first dose injection of study drug to the end of follow-up period). Safety population included all participants from the randomized population who received at least 1 dose or part of a dose of study drug.	0.00% 0/184 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 30) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (time from the first dose injection of study drug to the end of follow-up period). Safety population included all participants from the randomized population who received at least 1 dose or part of a dose of study drug.

Other adverse events

Measure	Placebo q2w n=181 participants at risk Placebo matched to sarilumab SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.	Sarilumab 150 mg q2w n=181 participants at risk Sarilumab 150 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.	Sarilumab 200 mg q2w n=184 participants at risk Sarilumab 200 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks.
Infections and infestations Nasopharyngitis	5.0% 9/181 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 30) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (time from the first dose injection of study drug to the end of follow-up period). Safety population included all participants from the randomized population who received at least 1 dose or part of a dose of study drug.	6.1% 11/181 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 30) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (time from the first dose injection of study drug to the end of follow-up period). Safety population included all participants from the randomized population who received at least 1 dose or part of a dose of study drug.	3.8% 7/184 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 30) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (time from the first dose injection of study drug to the end of follow-up period). Safety population included all participants from the randomized population who received at least 1 dose or part of a dose of study drug.
Infections and infestations Urinary tract infection	6.6% 12/181 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 30) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (time from the first dose injection of study drug to the end of follow-up period). Safety population included all participants from the randomized population who received at least 1 dose or part of a dose of study drug.	3.3% 6/181 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 30) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (time from the first dose injection of study drug to the end of follow-up period). Safety population included all participants from the randomized population who received at least 1 dose or part of a dose of study drug.	7.1% 13/184 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 30) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (time from the first dose injection of study drug to the end of follow-up period). Safety population included all participants from the randomized population who received at least 1 dose or part of a dose of study drug.
Blood and lymphatic system disorders Neutropenia	1.1% 2/181 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 30) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (time from the first dose injection of study drug to the end of follow-up period). Safety population included all participants from the randomized population who received at least 1 dose or part of a dose of study drug.	12.7% 23/181 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 30) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (time from the first dose injection of study drug to the end of follow-up period). Safety population included all participants from the randomized population who received at least 1 dose or part of a dose of study drug.	12.0% 22/184 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 30) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (time from the first dose injection of study drug to the end of follow-up period). Safety population included all participants from the randomized population who received at least 1 dose or part of a dose of study drug.
Metabolism and nutrition disorders Hypertriglyceridaemia	1.7% 3/181 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 30) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (time from the first dose injection of study drug to the end of follow-up period). Safety population included all participants from the randomized population who received at least 1 dose or part of a dose of study drug.	6.1% 11/181 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 30) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (time from the first dose injection of study drug to the end of follow-up period). Safety population included all participants from the randomized population who received at least 1 dose or part of a dose of study drug.	2.7% 5/184 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 30) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (time from the first dose injection of study drug to the end of follow-up period). Safety population included all participants from the randomized population who received at least 1 dose or part of a dose of study drug.
General disorders Injection site erythema	0.00% 0/181 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 30) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (time from the first dose injection of study drug to the end of follow-up period). Safety population included all participants from the randomized population who received at least 1 dose or part of a dose of study drug.	6.1% 11/181 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 30) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (time from the first dose injection of study drug to the end of follow-up period). Safety population included all participants from the randomized population who received at least 1 dose or part of a dose of study drug.	3.8% 7/184 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 30) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (time from the first dose injection of study drug to the end of follow-up period). Safety population included all participants from the randomized population who received at least 1 dose or part of a dose of study drug.
Investigations Alanine aminotransferase increased	1.1% 2/181 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 30) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (time from the first dose injection of study drug to the end of follow-up period). Safety population included all participants from the randomized population who received at least 1 dose or part of a dose of study drug.	2.8% 5/181 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 30) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (time from the first dose injection of study drug to the end of follow-up period). Safety population included all participants from the randomized population who received at least 1 dose or part of a dose of study drug.	5.4% 10/184 • All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 30) regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'on treatment period' (time from the first dose injection of study drug to the end of follow-up period). Safety population included all participants from the randomized population who received at least 1 dose or part of a dose of study drug.

Additional Information

Trial Transparency Team

Sanofi

Email: Contact-US@sanofi.com

Results disclosure agreements

• Principal investigator is a sponsor employee If no publication has occurred within 12 months of the completion of the study, the Investigator shall have the right to publish/present independently the results of the study. The Investigator shall provide the Sponsor with a copy of any such presentation/publication for comment at least 30 days before any presentation/submission for publication. If requested by the Sponsor, any presentation/submission shall be delayed up to 90 days, to allow the Sponsor to preserve its proprietary rights.
• Publication restrictions are in place

Restriction type: OTHER