Rheumatoid Arthritis
Conditions
Brief summary
Primary Objective: To demonstrate that sarilumab added to disease modifying anti-rheumatic drugs (DMARDs) were effective for: * reduction of signs and symptoms at Week 24 and * improvement of physical function at Week 12 in participants with active rheumatoid arthritis (RA) who were inadequate responders or intolerant to tumor necrosis factor alpha (TNF-α) antagonists. Secondary Objectives: The secondary objectives were to investigate the effects of SAR153191 (REGN88) when added to DMARD therapy, in participants with active RA who were inadequate responders or intolerant to TNF-α antagonists, for: * Reduction of signs and symptoms at Week 12; * Improvement in physical function at Week 24; * Improvement in disease activity score as measured by other American College of Rheumatology (ACR) derived components at Weeks 12 and 24; * Improvement in quality of life as measured by participant reported outcomes (PROs) at intermediate visits and Week 24. To assess the exposure of sarilumab added to DMARD therapy in this population. To assess the safety of sarilumab in this population.
Detailed description
Total study duration was up to 34 weeks: screening up to 28 days, treatment phase of 24 weeks, and post-treatment follow-up of 6 weeks. After completion of the treatment phase of this study, participant were eligible to enter a long term safety study (LTS11210) for active treatment with SAR153191 (REGN88).
Interventions
DRUGSarilumab
Pharmaceutical form:solution Route of administration: subcutaneous
DRUGplacebo
Pharmaceutical form:solution Route of administration: subcutaneous
DRUGhydroxychloroquine
Dispensed according to the local practice.
DRUGmethotrexate
Dispensed according to the local practice.
DRUGsulfasalazine
Dispensed according to the local practice.
DRUGleflunomide
Dispensed according to the local practice.
Sponsors
Regeneron Pharmaceuticals
Sanofi
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Diagnosis of RA ≥6 months duration, according to the ACR /European League against Rheumatism (EULAR) 2010 RA Classification Criteria ACR Class I-III functional status, based on 1991 revised criteria Anti-TNF therapy failures, defined by the investigator as participants with an inadequate clinical response, after being treated for at least 3 consecutive months, and/or intolerance to at least 1 anti-TNF blocker(s), resulting in or requiring their discontinuation: * TNF-blockers included, but were not limited to, etanercept, infliximab, adalimumab, golimumab and/or certolizumab Moderate-to-severely active RA Continuous treatment with one or a combination of DMARDs (except for simultaneous combination use of leflunomide and methotrexate) for at least 12 weeks prior to baseline and on a stable dose(s) for at least 6 weeks prior to screening: * Methotrexate - 6 to 25 mg/week orally or parenterally * Leflunomide - 10 to 20 mg orally daily * Sulfasalazine - 1000 to 3000 mg orally daily * Hydroxychloroquine - 200 to 400 mg orally daily
Exclusion criteria
Participants \<18 years of age or legal adult age Past history of, or current, autoimmune or inflammatory systemic or localized joint disease(s) other than RA History of juvenile idiopathic arthritis or arthritis onset prior to age 16 Severe active systemic RA, including but not limited to vasculitis, pulmonary fibrosis, and/or Felty's syndrome. Treatment with anti-TNF agents, as follows: * Within 28 days prior to the baseline visit - etanercept * Within 42 days prior to the baseline visit - infliximab, adalimumab, golimumab, certolizumab pegol Treatment with previous RA-directed biologic agents with other than TNF antagonist mechanisms: Within 28 days prior to the randomization (baseline) visit - anakinra Within 42 days prior to the randomization (baseline) visit - abatacept Within 6 months prior to the randomization (baseline) visit - any cell depleting agents including but not limited to rituximab without a normal lymphocyte and cluster of differentiation (CD) 19+ lymphocyte count Treatment with any DMARD other than those allowed per protocol and limited to the maximum specified dosage within 12 weeks prior to baseline Treatment with prednisone \>10 mg or equivalent per day, or change in dosage within 4 weeks prior to baseline visit Any parenteral or intra-articular glucocorticoid injection within 4 weeks prior to baseline Prior treatment with anti-interleukin (IL) -6 or IL-6 receptor antagonist therapies, including tocilizumab or sarilumab, participation in a prior study of sarilumab, irrespective of treatment arm Prior treatment with a Janus kinase inhibitor (such as tofacitinib) New treatment or dose-adjustment to ongoing medication for dyslipidemia within 6 weeks prior to randomization, ie, stable dose for at least 6 weeks prior to randomization Participation in any clinical research study evaluating another investigational drug or therapy within 5 half-lives or 60 days of first investigational medicinal product (IMP) administration, whichever was longer History of alcohol or drug abuse within 5 years prior to the screening visit Participants with a history of malignancy other than adequately-treated carcinoma in-situ of the cervix, nonmetastatic squamous cell or basal cell carcinoma of the skin, within 5 years prior to the randomization (baseline) visit. Nonmalignant lymphoproliferative disorders were also excluded Participants with active tuberculosis or latent tuberculosis infection The above information was not intended to contain all considerations relevant to a participant's potential participation in a clinical trial
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Who Achieved at Least 20% Improvement in the American College of Rheumatology (ACR20) Criteria at Week 24 | Week 24 | 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. |
| Change From Baseline in the Health Assessment Questionnaire-Disability Index (HAQ-DI) at Week 12 | Baseline, 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Achieving ACR70 Criteria at Week 24 | Week 24 | 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. |
| Percentage of Participants Achieving Clinical Remission Score (DAS28-CRP) <2.6 at Week 24 | Week 24 | 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. |
| Change From Baseline in Clinical Disease Activity Index (CDAI) at Week 24 | Baseline, 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. |
| Change From Baseline in HAQ-DI at Week 24 | Baseline, 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. |
| Change From Baseline in 36-Item Short-Form Health Survey (SF-36) Physical Component Summary Scores (PCS) at Week 24 | Baseline, 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. |
| Change From Baseline in SF-36 MCS at Week 24 | Baseline, 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. |
| Change From Baseline in the Functional Assessment of Chronic Illness Therapy Fatigue (FACIT-fatigue) Score at Week 24 | Baseline, 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. |
| Change From Baseline in Morning Stiffness VAS at Week 24 | Baseline, 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. |
| Change From Baseline in Work Productivity Survey - Rheumatoid Arthritis (WPS-RA) at Week 24: Work Days Missed Due to RA | Baseline, 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. |
| Change From Baseline in WPS-RA at Week 24: Days With Work Productivity Reduced by ≥ 50% Due to RA | Baseline, 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. |
| Change From Baseline in WPS-RA at Week 24: RA Interference With Work Productivity | Baseline, 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. |
| Change From Baseline in WPS-RA at Week 24: House Work Days Missed Due to RA | Baseline, 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. |
| Change From Baseline in WPS-RA at Week 24: Days With Household Work Productivity Reduced by ≥ 50% Due to RA | Baseline, 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. |
| Change From Baseline in WPS-RA at Week 24: Days With Family/Social/Leisure Activities Missed Due to RA | Baseline, 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. |
| Change From Baseline in WPS-RA at Week 24: Days With Outside Help Hired Due to RA | Baseline, 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. |
| Change From Baseline in WPS-RA at Week 24: RA Interference With Household Work Productivity | Baseline, 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. |
| Change From Baseline in Rheumatoid Arthritis Impact of Disease (RAID) Scores at Week 24 | Baseline, 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. |
| Change From Baseline in European Quality of Life-5 Dimension 3 Level (EQ-5D-3L) VAS Scores at Week 24 | Baseline, 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. |
| Percentage of Participants Achieving ACR20, ACR50 and ACR70 Criteria at Week 12 | Week 12 | 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. |
| Change From Baseline in DAS28-CRP at Week 12 | Baseline, 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. |
| Percentage of Participants Achieving Clinical Remission Score (DAS28--CRP <2.6) at Week 12 | 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 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. |
| Change From Baseline in SF-36 at Week 12 | Baseline, 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. |
| Change From Baseline in WPS-RA at Week 12: Work Days Missed Due to RA | Baseline, 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. |
| Change From Baseline in WPS-RA at Week 12: Days With Work Productivity Reduced by ≥ 50% Due to RA | Baseline, 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. |
| Change From Baseline in WPS-RA at Week 12: RA Interference With Work Productivity | Baseline, 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. |
| Change From Baseline in WPS-RA at Week 12: House Work Days Missed Due to RA | Baseline, 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. |
| Change From Baseline in WPS-RA at Week 12: Days With Household Work Productivity Reduced by ≥ 50% Due to RA | Baseline, 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. |
| Change From Baseline in WPS-RA at Week 12: Days With Family/Social/Leisure Activities Missed Due to RA | Baseline, 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. |
| Change From Baseline in WPS-RA at Week 12: Days With Outside Help Hired Due to RA | Baseline, 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. |
| Change From Baseline in WPS-RA at Week 12: RA Interference With Household Work Productivity | Baseline, 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. |
| Change From Baseline in the FACIT-fatigue at Week 12 | Baseline, 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. |
| Change From Baseline in EQ-5D-3L VAS Scores at Week 12 | Baseline, 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. |
| Change From Baseline in RAID Scores at Week 12 | Baseline, 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. |
| Change From Baseline in Disease Activity Score for 28 Joints -C-Reactive Protein (DAS28--CRP) Score at Week 24 | Baseline, 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. |
| Change From Baseline in Individual ACR Component - Physician Global VAS, Participant Global VAS and Pain VAS at Week 12 and Week 24 | Baseline, Week 12 and Week 24 | 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. |
| Change From Baseline in Individual ACR Component - CRP Level at Week 12 and Week 24 | Baseline, Week 12 and Week 24 | 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. |
| Change From Baseline in Individual ACR Component - HAQ-DI at Week 12 and Week 24 | Baseline, Week 12 and Week 24 | 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. |
| Change From Baseline in Individual ACR Components - TJC and SJC at Week 12 and Week 24 | Baseline, Week 12 and Week 24 | 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. |
| Percentage of Participants Achieving ACR50 Criteria at Week 24 | Week 24 | 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. |
Countries
Argentina, Australia, Austria, Brazil, Canada, Chile, Colombia, Czechia, Ecuador, Germany, Greece, Guatemala, Hungary, Israel, Italy, Lithuania, Mexico, New Zealand, Peru, Poland, Portugal, Romania, Russia, Slovakia, South Korea, Spain, Taiwan, Turkey (Türkiye), Ukraine, United States
Participant flow
Recruitment details
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.
Pre-assignment details
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).
Participants by arm
| Arm | Count |
|---|---|
| Placebo q2w Placebo matched to sarilumab SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks. | 181 |
| Sarilumab 150 mg q2w Sarilumab 150 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks. | 181 |
| Sarilumab 200 mg q2w Sarilumab 200 mg SC injection q2w was added to one or a combination of the nonbiologic DMARD for 24 weeks. | 184 |
| Total | 546 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 9 | 18 | 17 |
| Overall Study | Lack of Efficacy | 5 | 4 | 2 |
| Overall Study | Other, not related to safety or efficacy | 2 | 7 | 5 |
| Overall Study | Poor compliance to protocol | 1 | 2 | 1 |
| Overall Study | Rescued and entered in long term safety | 63 | 25 | 26 |
Baseline characteristics
| Characteristic | Placebo q2w | Sarilumab 150 mg q2w | Sarilumab 200 mg q2w | Total |
|---|---|---|---|---|
| Age, Continuous | 51.9 years STANDARD_DEVIATION 12.4 | 54.0 years STANDARD_DEVIATION 11.7 | 52.9 years STANDARD_DEVIATION 12.9 | 52.9 years STANDARD_DEVIATION 12.4 |
| Sex: Female, Male Female | 154 Participants | 142 Participants | 151 Participants | 447 Participants |
| Sex: Female, Male Male | 27 Participants | 39 Participants | 33 Participants | 99 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 26 / 181 | 60 / 181 | 57 / 184 |
| serious Total, serious adverse events | 6 / 181 | 6 / 181 | 10 / 184 |
Outcome results
Primary
Change From Baseline in the Health Assessment Questionnaire-Disability Index (HAQ-DI) at 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.
Time frame: Baseline, Week 12
Population: ITT population. Number of participants analyzed = number of participants with HAQ-DI assessment at both baseline and Week 12.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo q2w | 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 |
| Sarilumab 150 mg q2w | Change From Baseline in the Health Assessment Questionnaire-Disability Index (HAQ-DI) at Week 12 | -0.46 units on a scale | Standard Error 0.044 |
| Sarilumab 200 mg q2w | Change From Baseline in the Health Assessment Questionnaire-Disability Index (HAQ-DI) at Week 12 | -0.47 units on a scale | Standard Error 0.043 |
Comparison: Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).p-value: 0.000795% CI: [-0.318, -0.086]Mixed Models Analysis
Comparison: Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).p-value: 0.000495% CI: [-0.325, -0.095]Mixed Models Analysis
Primary
Percentage of Participants Who Achieved at Least 20% Improvement in the American College of Rheumatology (ACR20) Criteria at Week 24
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.
Time frame: Week 24
Population: Intent-to-treat (ITT) population included all randomized participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo q2w | 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 |
| Sarilumab 150 mg q2w | Percentage of Participants Who Achieved at Least 20% Improvement in the American College of Rheumatology (ACR20) Criteria at Week 24 | 55.8 percentage of participants |
| Sarilumab 200 mg q2w | Percentage of Participants Who Achieved at Least 20% Improvement in the American College of Rheumatology (ACR20) Criteria at Week 24 | 60.9 percentage of participants |
Comparison: A hierarchical testing procedure was used to control type I error rate at 0.05 and handle multiple endpoint analyses. Testing was then performed sequentially in the order the endpoints are reported. The hierarchical testing sequence continued only when previous endpoint was statistically significant at 0.025 level.p-value: <0.000195% CI: [1.73, 4.247]Mantel Haenszel
Comparison: Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).p-value: <0.000195% CI: [2.108, 5.115]Mantel Haenszel
Secondary
Change From Baseline in 36-Item Short-Form Health Survey (SF-36) Physical Component Summary Scores (PCS) at 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.
Time frame: Baseline, Week 24
Population: ITT population. Number of participants analyzed = participants with SF-36 PCS assessment at both baseline and Week 24.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo q2w | 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 |
| Sarilumab 150 mg q2w | Change From Baseline in 36-Item Short-Form Health Survey (SF-36) Physical Component Summary Scores (PCS) at Week 24 | 7.65 units on a scale | Standard Error 0.653 |
| Sarilumab 200 mg q2w | Change From Baseline in 36-Item Short-Form Health Survey (SF-36) Physical Component Summary Scores (PCS) at Week 24 | 8.48 units on a scale | Standard Error 0.63 |
Comparison: Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).p-value: 0.000495% CI: [1.45, 5.049]Mixed Models Analysis
Comparison: Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).p-value: <0.000195% CI: [2.305, 5.846]Mixed Models Analysis
Secondary
Change From Baseline in Clinical Disease Activity Index (CDAI) at 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.
Time frame: Baseline, Week 24
Population: ITT population. Number of participants analyzed=number of participants with CDAI assessment at both baseline and Week 24.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo q2w | Change From Baseline in Clinical Disease Activity Index (CDAI) at Week 24 | -16.35 units on a scale | Standard Error 1.195 |
| Sarilumab 150 mg q2w | Change From Baseline in Clinical Disease Activity Index (CDAI) at Week 24 | -23.65 units on a scale | Standard Error 1.136 |
| Sarilumab 200 mg q2w | Change From Baseline in Clinical Disease Activity Index (CDAI) at Week 24 | -26.08 units on a scale | Standard Error 1.109 |
Comparison: Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).p-value: <0.000195% CI: [-10.444, -4.167]Mixed Models Analysis
Comparison: Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).p-value: <0.000195% CI: [-12.833, -6.622]Mixed Models Analysis
Secondary
Change From Baseline in DAS28-CRP at 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.
Time frame: Baseline, Week 12
Population: ITT population. Number of participants analyzed = number of participants with DAS28-CRP- Score assessment at both baseline and Week 12.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo q2w | Change From Baseline in DAS28-CRP at Week 12 | -0.97 units on a scale | Standard Error 0.104 |
| Sarilumab 150 mg q2w | Change From Baseline in DAS28-CRP at Week 12 | -2.13 units on a scale | Standard Error 0.105 |
| Sarilumab 200 mg q2w | Change From Baseline in DAS28-CRP at Week 12 | -2.45 units on a scale | Standard Error 0.103 |
Secondary
Change From Baseline in Disease Activity Score for 28 Joints -C-Reactive Protein (DAS28--CRP) Score at 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.
Time frame: Baseline, Week 24
Population: ITT population. Number of participants analyzed = number of participants with DAS28--CRP Score assessment at both baseline and Week 24.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo q2w | 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 |
| Sarilumab 150 mg q2w | Change From Baseline in Disease Activity Score for 28 Joints -C-Reactive Protein (DAS28--CRP) Score at Week 24 | -2.35 units on a scale | Standard Error 0.111 |
| Sarilumab 200 mg q2w | Change From Baseline in Disease Activity Score for 28 Joints -C-Reactive Protein (DAS28--CRP) Score at Week 24 | -2.82 units on a scale | Standard Error 0.108 |
Comparison: Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).p-value: <0.000195% CI: [-1.283, -0.658]Mixed Models Analysis
Comparison: Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).p-value: <0.000195% CI: [-1.752, -1.135]Mixed Models Analysis
Secondary
Change From Baseline in EQ-5D-3L VAS Scores at 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.
Time frame: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo q2w | Change From Baseline in EQ-5D-3L VAS Scores at Week 12 | 8.39 units on a scale | Standard Error 1.699 |
| Sarilumab 150 mg q2w | Change From Baseline in EQ-5D-3L VAS Scores at Week 12 | 17.16 units on a scale | Standard Error 1.72 |
| Sarilumab 200 mg q2w | Change From Baseline in EQ-5D-3L VAS Scores at Week 12 | 15.23 units on a scale | Standard Error 1.68 |
Secondary
Change From Baseline in European Quality of Life-5 Dimension 3 Level (EQ-5D-3L) VAS Scores at 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.
Time frame: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo q2w | 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 |
| Sarilumab 150 mg q2w | Change From Baseline in European Quality of Life-5 Dimension 3 Level (EQ-5D-3L) VAS Scores at Week 24 | 20.06 units on a scale | Standard Error 1.891 |
| Sarilumab 200 mg q2w | Change From Baseline in European Quality of Life-5 Dimension 3 Level (EQ-5D-3L) VAS Scores at Week 24 | 18.40 units on a scale | Standard Error 1.842 |
Secondary
Change From Baseline in HAQ-DI at 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.
Time frame: Baseline, Week 24
Population: ITT population. Number of participants analyzed = number of participants with HAQ-DI assessment at both baseline and Week 24.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo q2w | Change From Baseline in HAQ-DI at Week 24 | -0.34 units on a scale | Standard Error 0.051 |
| Sarilumab 150 mg q2w | Change From Baseline in HAQ-DI at Week 24 | -0.52 units on a scale | Standard Error 0.049 |
| Sarilumab 200 mg q2w | Change From Baseline in HAQ-DI at Week 24 | -0.58 units on a scale | Standard Error 0.048 |
Comparison: Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).p-value: 0.007895% CI: [-0.318, -0.048]Mixed Models Analysis
Comparison: Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).p-value: 0.000495% CI: [-0.376, -0.109]Mixed Models Analysis
Secondary
Change From Baseline in Individual ACR Component - CRP Level at Week 12 and Week 24
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.
Time frame: Baseline, Week 12 and Week 24
Population: ITT population. Number analyzed = number of participants with CRP assessment at both baseline and specified time points.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo q2w | 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 |
| Placebo q2w | 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 |
| Sarilumab 150 mg q2w | Change From Baseline in Individual ACR Component - CRP Level at Week 12 and Week 24 | CRP at week 12 | -15.08 mg/L | Standard Error 1.452 |
| Sarilumab 150 mg q2w | Change From Baseline in Individual ACR Component - CRP Level at Week 12 and Week 24 | CRP at week 24 | -15.24 mg/L | Standard Error 1.457 |
| Sarilumab 200 mg q2w | Change From Baseline in Individual ACR Component - CRP Level at Week 12 and Week 24 | CRP at week 12 | -22.98 mg/L | Standard Error 1.432 |
| Sarilumab 200 mg q2w | Change From Baseline in Individual ACR Component - CRP Level at Week 12 and Week 24 | CRP at week 24 | -23.27 mg/L | Standard Error 1.421 |
Secondary
Change From Baseline in Individual ACR Component - HAQ-DI at Week 12 and Week 24
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.
Time frame: 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.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo q2w | 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 |
| Placebo q2w | 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 |
| Sarilumab 150 mg q2w | Change From Baseline in Individual ACR Component - HAQ-DI at Week 12 and Week 24 | HAQ-DI at week 12 | -0.46 units on a scale | Standard Error 0.044 |
| Sarilumab 150 mg q2w | Change From Baseline in Individual ACR Component - HAQ-DI at Week 12 and Week 24 | HAQ-DI at week 24 | -0.52 units on a scale | Standard Error 0.049 |
| Sarilumab 200 mg q2w | Change From Baseline in Individual ACR Component - HAQ-DI at Week 12 and Week 24 | HAQ-DI at week 12 | -0.47 units on a scale | Standard Error 0.043 |
| Sarilumab 200 mg q2w | Change From Baseline in Individual ACR Component - HAQ-DI at Week 12 and Week 24 | HAQ-DI at week 24 | -0.58 units on a scale | Standard Error 0.048 |
Secondary
Change From Baseline in Individual ACR Component - Physician Global VAS, Participant Global VAS and Pain VAS at Week 12 and Week 24
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.
Time frame: 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.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo q2w | 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 2.25 |
| Placebo q2w | 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 |
| Placebo q2w | 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 |
| Placebo q2w | 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 |
| Placebo q2w | 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 |
| Placebo q2w | 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 |
| Sarilumab 150 mg q2w | 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 | -40.65 mm | Standard Error 1.695 |
| Sarilumab 150 mg q2w | 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 | -29.59 mm | Standard Error 2.046 |
| Sarilumab 150 mg q2w | 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 | -25.28 mm | Standard Error 1.836 |
| Sarilumab 150 mg q2w | 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 | -31.90 mm | Standard Error 2.086 |
| Sarilumab 150 mg q2w | 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 | -33.64 mm | Standard Error 1.775 |
| Sarilumab 150 mg q2w | 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 | -26.93 mm | Standard Error 1.933 |
| Sarilumab 200 mg q2w | 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 | -30.56 mm | Standard Error 1.901 |
| Sarilumab 200 mg q2w | 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 | -35.44 mm | Standard Error 1.74 |
| Sarilumab 200 mg q2w | 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 | -27.38 mm | Standard Error 1.803 |
| Sarilumab 200 mg q2w | 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 | -33.65 mm | Standard Error 2.037 |
| Sarilumab 200 mg q2w | 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 | -43.22 mm | Standard Error 1.646 |
| Sarilumab 200 mg q2w | 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 | -31.28 mm | Standard Error 1.997 |
Secondary
Change From Baseline in Individual ACR Components - TJC and SJC at Week 12 and Week 24
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.
Time frame: 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.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo q2w | 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 |
| Placebo q2w | 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 |
| Placebo q2w | 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 1.06 |
| Placebo q2w | 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 |
| Sarilumab 150 mg q2w | Change From Baseline in Individual ACR Components - TJC and SJC at Week 12 and Week 24 | SJC at week 24 | -11.56 joints | Standard Error 0.691 |
| Sarilumab 150 mg q2w | Change From Baseline in Individual ACR Components - TJC and SJC at Week 12 and Week 24 | TJC at week 12 | -13.74 joints | Standard Error 0.975 |
| Sarilumab 150 mg q2w | Change From Baseline in Individual ACR Components - TJC and SJC at Week 12 and Week 24 | TJC at week 24 | -14.44 joints | Standard Error 1.017 |
| Sarilumab 150 mg q2w | Change From Baseline in Individual ACR Components - TJC and SJC at Week 12 and Week 24 | SJC at week 12 | -10.54 joints | Standard Error 0.698 |
| Sarilumab 200 mg q2w | Change From Baseline in Individual ACR Components - TJC and SJC at Week 12 and Week 24 | SJC at week 24 | -11.94 joints | Standard Error 0.674 |
| Sarilumab 200 mg q2w | Change From Baseline in Individual ACR Components - TJC and SJC at Week 12 and Week 24 | SJC at week 12 | -10.59 joints | Standard Error 0.684 |
| Sarilumab 200 mg q2w | Change From Baseline in Individual ACR Components - TJC and SJC at Week 12 and Week 24 | TJC at week 24 | -16.95 joints | Standard Error 0.992 |
| Sarilumab 200 mg q2w | Change From Baseline in Individual ACR Components - TJC and SJC at Week 12 and Week 24 | TJC at week 12 | -14.87 joints | Standard Error 0.954 |
Secondary
Change From Baseline in Morning Stiffness VAS at 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.
Time frame: Baseline, Week 24
Population: ITT population. Number of participants analyzed = number of participants with morning stiffness VAS assessment at both baseline and Week 24.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo q2w | Change From Baseline in Morning Stiffness VAS at Week 24 | -21.66 mm | Standard Error 2.39 |
| Sarilumab 150 mg q2w | Change From Baseline in Morning Stiffness VAS at Week 24 | -32.30 mm | Standard Error 2.213 |
| Sarilumab 200 mg q2w | Change From Baseline in Morning Stiffness VAS at Week 24 | -33.79 mm | Standard Error 2.148 |
Secondary
Change From Baseline in RAID Scores at 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.
Time frame: Baseline, Week 12
Population: ITT population. Number of participants analyzed = number of participants with RAID score assessment at both baseline and Week 12.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo q2w | Change From Baseline in RAID Scores at Week 12 | -1.34 units on a scale | Standard Error 0.163 |
| Sarilumab 150 mg q2w | Change From Baseline in RAID Scores at Week 12 | -2.27 units on a scale | Standard Error 0.165 |
| Sarilumab 200 mg q2w | Change From Baseline in RAID Scores at Week 12 | -2.47 units on a scale | Standard Error 0.161 |
Secondary
Change From Baseline in Rheumatoid Arthritis Impact of Disease (RAID) Scores at 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.
Time frame: Baseline, Week 24
Population: ITT population. Number of participants analyzed = number of participants with RAID score assessment at both baseline and Week 24.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo q2w | Change From Baseline in Rheumatoid Arthritis Impact of Disease (RAID) Scores at Week 24 | -1.80 units on a scale | Standard Error 0.203 |
| Sarilumab 150 mg q2w | Change From Baseline in Rheumatoid Arthritis Impact of Disease (RAID) Scores at Week 24 | -2.55 units on a scale | Standard Error 0.189 |
| Sarilumab 200 mg q2w | Change From Baseline in Rheumatoid Arthritis Impact of Disease (RAID) Scores at Week 24 | -2.80 units on a scale | Standard Error 0.183 |
Secondary
Change From Baseline in SF-36 at 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.
Time frame: Baseline, Week 12
Population: ITT population. Number of participants analyzed=participants with SF-36 assessment at both baseline and Week 12.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo q2w | 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 |
| Placebo q2w | 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 |
| Sarilumab 150 mg q2w | Change From Baseline in SF-36 at Week 12 | Physical Component Summary Score at Week 12 | 6.93 units on a scale | Standard Error 0.596 |
| Sarilumab 150 mg q2w | Change From Baseline in SF-36 at Week 12 | Mental Component Summary Score at Week 12 | 5.14 units on a scale | Standard Error 0.758 |
| Sarilumab 200 mg q2w | Change From Baseline in SF-36 at Week 12 | Physical Component Summary Score at Week 12 | 6.84 units on a scale | Standard Error 0.584 |
| Sarilumab 200 mg q2w | Change From Baseline in SF-36 at Week 12 | Mental Component Summary Score at Week 12 | 6.47 units on a scale | Standard Error 0.741 |
Secondary
Change From Baseline in SF-36 MCS at 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.
Time frame: Baseline, Week 24
Population: ITT population. Number of participants analyzed=participants with SF-36 MCS assessment at both baseline and Week 24.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo q2w | Change From Baseline in SF-36 MCS at Week 24 | 4.74 units on a scale | Standard Error 0.902 |
| Sarilumab 150 mg q2w | Change From Baseline in SF-36 MCS at Week 24 | 6.26 units on a scale | Standard Error 0.848 |
| Sarilumab 200 mg q2w | Change From Baseline in SF-36 MCS at Week 24 | 6.76 units on a scale | Standard Error 0.817 |
Comparison: Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).p-value: 0.202695% CI: [-0.818, 3.848]Mixed Models Analysis
Comparison: Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).p-value: 0.085495% CI: [-0.282, 4.309]Mixed Models Analysis
Secondary
Change From Baseline in the FACIT-fatigue at 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.
Time frame: Baseline, Week 12
Population: ITT population. Number of Participants analyzed = number of participants with FACIT-fatigue score assessment at both baseline and Week 12.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo q2w | Change From Baseline in the FACIT-fatigue at Week 12 | 5.56 units on a scale | Standard Error 0.721 |
| Sarilumab 150 mg q2w | Change From Baseline in the FACIT-fatigue at Week 12 | 8.02 units on a scale | Standard Error 0.729 |
| Sarilumab 200 mg q2w | Change From Baseline in the FACIT-fatigue at Week 12 | 9.45 units on a scale | Standard Error 0.714 |
Secondary
Change From Baseline in the Functional Assessment of Chronic Illness Therapy Fatigue (FACIT-fatigue) Score at 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.
Time frame: Baseline, Week 24
Population: ITT population. Number of Participants analyzed = number of participants with FACIT-fatigue score assessment at both baseline and Week 24.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo q2w | 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 |
| Sarilumab 150 mg q2w | Change From Baseline in the Functional Assessment of Chronic Illness Therapy Fatigue (FACIT-fatigue) Score at Week 24 | 9.86 units on a scale | Standard Error 0.802 |
| Sarilumab 200 mg q2w | Change From Baseline in the Functional Assessment of Chronic Illness Therapy Fatigue (FACIT-fatigue) Score at Week 24 | 10.06 units on a scale | Standard Error 0.778 |
Secondary
Change From Baseline in Work Productivity Survey - Rheumatoid Arthritis (WPS-RA) at Week 24: Work Days Missed Due to RA
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.
Time frame: Baseline, Week 24
Population: ITT population. Number of participants analyzed=participants with WPS-RA individual items assessment at both baseline and Week 24.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo q2w | 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 |
| Sarilumab 150 mg q2w | Change From Baseline in Work Productivity Survey - Rheumatoid Arthritis (WPS-RA) at Week 24: Work Days Missed Due to RA | -2.87 Days | Standard Error 0.438 |
| Sarilumab 200 mg q2w | Change From Baseline in Work Productivity Survey - Rheumatoid Arthritis (WPS-RA) at Week 24: Work Days Missed Due to RA | -3.19 Days | Standard Error 0.447 |
Secondary
Change From Baseline in WPS-RA at Week 12: Days With Family/Social/Leisure Activities Missed Due to RA
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.
Time frame: Baseline, Week 12
Population: ITT population. Number of participants analyzed = participants with WPS-RA individual items assessment at both baseline and Week 12.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo q2w | 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 |
| Sarilumab 150 mg q2w | Change From Baseline in WPS-RA at Week 12: Days With Family/Social/Leisure Activities Missed Due to RA | -2.53 Days | Standard Error 0.442 |
| Sarilumab 200 mg q2w | Change From Baseline in WPS-RA at Week 12: Days With Family/Social/Leisure Activities Missed Due to RA | -3.26 Days | Standard Error 0.434 |
Secondary
Change From Baseline in WPS-RA at Week 12: Days With Household Work Productivity Reduced by ≥ 50% Due to RA
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.
Time frame: Baseline, Week 12
Population: ITT population. Number of participants analyzed = participants with WPS-RA individual items assessment at both baseline and Week 12.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo q2w | 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 |
| Sarilumab 150 mg q2w | Change From Baseline in WPS-RA at Week 12: Days With Household Work Productivity Reduced by ≥ 50% Due to RA | -3.97 Days | Standard Error 0.587 |
| Sarilumab 200 mg q2w | Change From Baseline in WPS-RA at Week 12: Days With Household Work Productivity Reduced by ≥ 50% Due to RA | -3.98 Days | Standard Error 0.575 |
Secondary
Change From Baseline in WPS-RA at Week 12: Days With Outside Help Hired Due to RA
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.
Time frame: Baseline, Week 12
Population: ITT population. Number of participants analyzed = participants with WPS-RA individual items assessment at both baseline and Week 12.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo q2w | Change From Baseline in WPS-RA at Week 12: Days With Outside Help Hired Due to RA | -0.77 Days | Standard Error 0.558 |
| Sarilumab 150 mg q2w | Change From Baseline in WPS-RA at Week 12: Days With Outside Help Hired Due to RA | -3.07 Days | Standard Error 0.57 |
| Sarilumab 200 mg q2w | Change From Baseline in WPS-RA at Week 12: Days With Outside Help Hired Due to RA | -2.94 Days | Standard Error 0.56 |
Secondary
Change From Baseline in WPS-RA at Week 12: Days With Work Productivity Reduced by ≥ 50% Due to RA
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.
Time frame: Baseline, Week 12
Population: ITT population. Number of participants analyzed = participants with WPS-RA individual items assessment at both baseline and Week 12.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo q2w | 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 |
| Sarilumab 150 mg q2w | Change From Baseline in WPS-RA at Week 12: Days With Work Productivity Reduced by ≥ 50% Due to RA | -4.24 Days | Standard Error 0.773 |
| Sarilumab 200 mg q2w | Change From Baseline in WPS-RA at Week 12: Days With Work Productivity Reduced by ≥ 50% Due to RA | -3.20 Days | Standard Error 0.785 |
Secondary
Change From Baseline in WPS-RA at Week 12: House Work Days Missed Due to RA
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.
Time frame: Baseline, Week 12
Population: ITT population. Number of participants analyzed = participants with WPS-RA individual items assessment at both baseline and Week 12.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo q2w | Change From Baseline in WPS-RA at Week 12: House Work Days Missed Due to RA | -2.10 Days | Standard Error 0.551 |
| Sarilumab 150 mg q2w | Change From Baseline in WPS-RA at Week 12: House Work Days Missed Due to RA | -5.52 Days | Standard Error 0.563 |
| Sarilumab 200 mg q2w | Change From Baseline in WPS-RA at Week 12: House Work Days Missed Due to RA | -5.54 Days | Standard Error 0.553 |
Secondary
Change From Baseline in WPS-RA at Week 12: RA Interference With Household Work Productivity
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.
Time frame: Baseline, Week 12
Population: ITT population. Number of participants analyzed = participants with WPS-RA individual items assessment at both baseline and Week 12.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo q2w | 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 |
| Sarilumab 150 mg q2w | Change From Baseline in WPS-RA at Week 12: RA Interference With Household Work Productivity | -2.772 units on a scale | Standard Error 0.2474 |
| Sarilumab 200 mg q2w | Change From Baseline in WPS-RA at Week 12: RA Interference With Household Work Productivity | -2.404 units on a scale | Standard Error 0.2443 |
Secondary
Change From Baseline in WPS-RA at Week 12: RA Interference With Work Productivity
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.
Time frame: Baseline, Week 12
Population: ITT population. Number of participants analyzed = participants with WPS-RA individual items assessment at both baseline and Week 12.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo q2w | Change From Baseline in WPS-RA at Week 12: RA Interference With Work Productivity | -1.043 units on a scale | Standard Error 0.3803 |
| Sarilumab 150 mg q2w | Change From Baseline in WPS-RA at Week 12: RA Interference With Work Productivity | -1.924 units on a scale | Standard Error 0.3742 |
| Sarilumab 200 mg q2w | Change From Baseline in WPS-RA at Week 12: RA Interference With Work Productivity | -1.873 units on a scale | Standard Error 0.3764 |
Secondary
Change From Baseline in WPS-RA at Week 12: Work Days Missed Due to RA
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.
Time frame: Baseline, Week 12
Population: ITT population. Number of participants analyzed=participants with WPS-RA individual items assessment at both baseline and Week 12.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo q2w | Change From Baseline in WPS-RA at Week 12: Work Days Missed Due to RA | -1.20 Days | Standard Error 0.581 |
| Sarilumab 150 mg q2w | Change From Baseline in WPS-RA at Week 12: Work Days Missed Due to RA | -1.97 Days | Standard Error 0.571 |
| Sarilumab 200 mg q2w | Change From Baseline in WPS-RA at Week 12: Work Days Missed Due to RA | -2.98 Days | Standard Error 0.585 |
Secondary
Change From Baseline in WPS-RA at Week 24: Days With Family/Social/Leisure Activities Missed Due to RA
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.
Time frame: Baseline, Week 24
Population: ITT population. Number of participants analyzed = participants with WPS-RA individual items assessment at both baseline and Week 24.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo q2w | 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 |
| Sarilumab 150 mg q2w | Change From Baseline in WPS-RA at Week 24: Days With Family/Social/Leisure Activities Missed Due to RA | -3.51 Days | Standard Error 0.446 |
| Sarilumab 200 mg q2w | Change From Baseline in WPS-RA at Week 24: Days With Family/Social/Leisure Activities Missed Due to RA | -4.12 Days | Standard Error 0.435 |
Secondary
Change From Baseline in WPS-RA at Week 24: Days With Household Work Productivity Reduced by ≥ 50% Due to RA
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.
Time frame: Baseline, Week 24
Population: ITT population. Number of participants analyzed = participants with WPS-RA individual items assessment at both baseline and Week 24.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo q2w | 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 |
| Sarilumab 150 mg q2w | Change From Baseline in WPS-RA at Week 24: Days With Household Work Productivity Reduced by ≥ 50% Due to RA | -4.60 Days | Standard Error 0.591 |
| Sarilumab 200 mg q2w | Change From Baseline in WPS-RA at Week 24: Days With Household Work Productivity Reduced by ≥ 50% Due to RA | -4.88 Days | Standard Error 0.574 |
Secondary
Change From Baseline in WPS-RA at Week 24: Days With Outside Help Hired Due to RA
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.
Time frame: Baseline, Week 24
Population: ITT population. Number of participants analyzed = participants with WPS-RA individual items assessment at both baseline and Week 24.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo q2w | Change From Baseline in WPS-RA at Week 24: Days With Outside Help Hired Due to RA | -1.60 Days | Standard Error 0.567 |
| Sarilumab 150 mg q2w | Change From Baseline in WPS-RA at Week 24: Days With Outside Help Hired Due to RA | -3.87 Days | Standard Error 0.536 |
| Sarilumab 200 mg q2w | Change From Baseline in WPS-RA at Week 24: Days With Outside Help Hired Due to RA | -3.86 Days | Standard Error 0.523 |
Secondary
Change From Baseline in WPS-RA at Week 24: Days With Work Productivity Reduced by ≥ 50% Due to RA
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.
Time frame: Baseline, Week 24
Population: ITT population. Number of participants analyzed = participants with WPS-RA individual items assessment at both baseline and Week 24.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo q2w | 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 |
| Sarilumab 150 mg q2w | Change From Baseline in WPS-RA at Week 24: Days With Work Productivity Reduced by ≥ 50% Due to RA | -4.26 Days | Standard Error 0.521 |
| Sarilumab 200 mg q2w | Change From Baseline in WPS-RA at Week 24: Days With Work Productivity Reduced by ≥ 50% Due to RA | -4.34 Days | Standard Error 0.535 |
Secondary
Change From Baseline in WPS-RA at Week 24: House Work Days Missed Due to RA
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.
Time frame: Baseline, Week 24
Population: ITT population. Number of participants analyzed = participants with WPS-RA individual items assessment at both baseline and Week 24.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo q2w | Change From Baseline in WPS-RA at Week 24: House Work Days Missed Due to RA | -3.50 Days | Standard Error 0.59 |
| Sarilumab 150 mg q2w | Change From Baseline in WPS-RA at Week 24: House Work Days Missed Due to RA | -6.13 Days | Standard Error 0.551 |
| Sarilumab 200 mg q2w | Change From Baseline in WPS-RA at Week 24: House Work Days Missed Due to RA | -6.18 Days | Standard Error 0.537 |
Secondary
Change From Baseline in WPS-RA at Week 24: RA Interference With Household Work Productivity
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.
Time frame: Baseline, Week 24
Population: ITT population. Number of participants analyzed = participants with WPS-RA individual items assessment at both baseline and Week 24.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo q2w | 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 |
| Sarilumab 150 mg q2w | Change From Baseline in WPS-RA at Week 24: RA Interference With Household Work Productivity | -3.096 units on a scale | Standard Error 0.2238 |
| Sarilumab 200 mg q2w | Change From Baseline in WPS-RA at Week 24: RA Interference With Household Work Productivity | -3.269 units on a scale | Standard Error 0.2186 |
Secondary
Change From Baseline in WPS-RA at Week 24: RA Interference With Work Productivity
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.
Time frame: Baseline, Week 24
Population: ITT population. Number of participants analyzed = participants with WPS-RA individual items assessment at both baseline and Week 24.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo q2w | Change From Baseline in WPS-RA at Week 24: RA Interference With Work Productivity | -1.632 units on a scale | Standard Error 0.4186 |
| Sarilumab 150 mg q2w | Change From Baseline in WPS-RA at Week 24: RA Interference With Work Productivity | -2.422 units on a scale | Standard Error 0.3719 |
| Sarilumab 200 mg q2w | Change From Baseline in WPS-RA at Week 24: RA Interference With Work Productivity | -2.727 units on a scale | Standard Error 0.37 |
Secondary
Percentage of Participants Achieving ACR20, ACR50 and ACR70 Criteria at Week 12
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.
Time frame: Week 12
Population: ITT population.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo q2w | Percentage of Participants Achieving ACR20, ACR50 and ACR70 Criteria at Week 12 | ACR50 | 13.3 Percentage of participants |
| Placebo q2w | Percentage of Participants Achieving ACR20, ACR50 and ACR70 Criteria at Week 12 | ACR20 | 37.6 Percentage of participants |
| Placebo q2w | Percentage of Participants Achieving ACR20, ACR50 and ACR70 Criteria at Week 12 | ACR70 | 2.2 Percentage of participants |
| Sarilumab 150 mg q2w | Percentage of Participants Achieving ACR20, ACR50 and ACR70 Criteria at Week 12 | ACR50 | 30.4 Percentage of participants |
| Sarilumab 150 mg q2w | Percentage of Participants Achieving ACR20, ACR50 and ACR70 Criteria at Week 12 | ACR20 | 54.1 Percentage of participants |
| Sarilumab 150 mg q2w | Percentage of Participants Achieving ACR20, ACR50 and ACR70 Criteria at Week 12 | ACR70 | 13.8 Percentage of participants |
| Sarilumab 200 mg q2w | Percentage of Participants Achieving ACR20, ACR50 and ACR70 Criteria at Week 12 | ACR20 | 62.5 Percentage of participants |
| Sarilumab 200 mg q2w | Percentage of Participants Achieving ACR20, ACR50 and ACR70 Criteria at Week 12 | ACR70 | 14.7 Percentage of participants |
| Sarilumab 200 mg q2w | Percentage of Participants Achieving ACR20, ACR50 and ACR70 Criteria at Week 12 | ACR50 | 33.2 Percentage of participants |
Secondary
Percentage of Participants Achieving ACR50 Criteria at Week 24
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.
Time frame: Week 24
Population: ITT population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo q2w | Percentage of Participants Achieving ACR50 Criteria at Week 24 | 18.2 Percentage of participants |
| Sarilumab 150 mg q2w | Percentage of Participants Achieving ACR50 Criteria at Week 24 | 37.0 Percentage of participants |
| Sarilumab 200 mg q2w | Percentage of Participants Achieving ACR50 Criteria at Week 24 | 40.8 Percentage of participants |
Comparison: Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).p-value: <0.000195% CI: [1.764, 4.959]Mantel Haenszel
Comparison: Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).p-value: <0.000195% CI: [2.045, 5.566]Mantel Haenszel
Secondary
Percentage of Participants Achieving ACR70 Criteria at Week 24
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.
Time frame: Week 24
Population: ITT population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo q2w | Percentage of Participants Achieving ACR70 Criteria at Week 24 | 7.2 Percentage of participants |
| Sarilumab 150 mg q2w | Percentage of Participants Achieving ACR70 Criteria at Week 24 | 19.9 Percentage of participants |
| Sarilumab 200 mg q2w | Percentage of Participants Achieving ACR70 Criteria at Week 24 | 16.3 Percentage of participants |
Comparison: Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).p-value: 0.000295% CI: [1.774, 7.332]Mantel Haenszel
Comparison: Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).p-value: 0.005695% CI: [1.308, 5.383]Mantel Haenszel
Secondary
Percentage of Participants Achieving Clinical Remission Score (DAS28--CRP <2.6) at 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 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.
Time frame: Week 12
Population: ITT population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo q2w | Percentage of Participants Achieving Clinical Remission Score (DAS28--CRP <2.6) at Week 12 | 3.9 Percentage of participants |
| Sarilumab 150 mg q2w | Percentage of Participants Achieving Clinical Remission Score (DAS28--CRP <2.6) at Week 12 | 17.1 Percentage of participants |
| Sarilumab 200 mg q2w | Percentage of Participants Achieving Clinical Remission Score (DAS28--CRP <2.6) at Week 12 | 17.9 Percentage of participants |
Secondary
Percentage of Participants Achieving Clinical Remission Score (DAS28-CRP) <2.6 at Week 24
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.
Time frame: Week 24
Population: ITT population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo q2w | Percentage of Participants Achieving Clinical Remission Score (DAS28-CRP) <2.6 at Week 24 | 7.2 Percentage of participants |
| Sarilumab 150 mg q2w | Percentage of Participants Achieving Clinical Remission Score (DAS28-CRP) <2.6 at Week 24 | 24.9 Percentage of participants |
| Sarilumab 200 mg q2w | Percentage of Participants Achieving Clinical Remission Score (DAS28-CRP) <2.6 at Week 24 | 28.8 Percentage of participants |
Comparison: Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).p-value: <0.000195% CI: [2.339, 9.132]Mantel Haenszel
Comparison: Testing according to the hierarchical testing procedure (only performed if the previous endpoint was statistically significant).p-value: <0.000195% CI: [2.948, 11.413]Mantel Haenszel