To Evaluate The Effect Of SAR153191 (REGN88) Added To Other RA Drugs In Patients With RA Who Are Not Responding To Or Intolerant Of Anti-TNF Therapy (SARIL-RA-TARGET)
- Conditions
- Rheumatoid Arthritis
- Interventions
- Registration Number
- NCT01709578
- Lead Sponsor
- Sanofi
- 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).
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 546
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo q2w placebo Placebo matched to sarilumab once every 2 weeks (q2w) was added to one or a combination of the nonbiologic DMARD (hydroxychloroquine, methotrexate, sulfasalazine and/or Leflunomide), except for simultaneous combination use of leflunomide and methotrexate for 24 weeks. Placebo q2w hydroxychloroquine Placebo matched to sarilumab once every 2 weeks (q2w) was added to one or a combination of the nonbiologic DMARD (hydroxychloroquine, methotrexate, sulfasalazine and/or Leflunomide), except for simultaneous combination use of leflunomide and methotrexate for 24 weeks. Placebo q2w methotrexate Placebo matched to sarilumab once every 2 weeks (q2w) was added to one or a combination of the nonbiologic DMARD (hydroxychloroquine, methotrexate, sulfasalazine and/or Leflunomide), except for simultaneous combination use of leflunomide and methotrexate for 24 weeks. Sarilumab 150 mg q2w Sarilumab Sarilumab 150 mg q2w was added to one or a combination of the nonbiologic DMARD (hydroxychloroquine, methotrexate, sulfasalazine and/or Leflunomide), except for simultaneous combination use of leflunomide and methotrexate for 24 weeks. Sarilumab 150 mg q2w sulfasalazine Sarilumab 150 mg q2w was added to one or a combination of the nonbiologic DMARD (hydroxychloroquine, methotrexate, sulfasalazine and/or Leflunomide), except for simultaneous combination use of leflunomide and methotrexate for 24 weeks. Sarilumab 200 mg q2w Sarilumab Sarilumab 200 mg q2w was added to one or a combination of the nonbiologic DMARD (hydroxychloroquine, methotrexate, sulfasalazine and/or Leflunomide), except for simultaneous combination use of leflunomide and methotrexate for 24 weeks. Sarilumab 200 mg q2w hydroxychloroquine Sarilumab 200 mg q2w was added to one or a combination of the nonbiologic DMARD (hydroxychloroquine, methotrexate, sulfasalazine and/or Leflunomide), except for simultaneous combination use of leflunomide and methotrexate for 24 weeks. Sarilumab 200 mg q2w methotrexate Sarilumab 200 mg q2w was added to one or a combination of the nonbiologic DMARD (hydroxychloroquine, methotrexate, sulfasalazine and/or Leflunomide), except for simultaneous combination use of leflunomide and methotrexate for 24 weeks. Sarilumab 200 mg q2w leflunomide Sarilumab 200 mg q2w was added to one or a combination of the nonbiologic DMARD (hydroxychloroquine, methotrexate, sulfasalazine and/or Leflunomide), except for simultaneous combination use of leflunomide and methotrexate for 24 weeks. Placebo q2w leflunomide Placebo matched to sarilumab once every 2 weeks (q2w) was added to one or a combination of the nonbiologic DMARD (hydroxychloroquine, methotrexate, sulfasalazine and/or Leflunomide), except for simultaneous combination use of leflunomide and methotrexate for 24 weeks. Placebo q2w sulfasalazine Placebo matched to sarilumab once every 2 weeks (q2w) was added to one or a combination of the nonbiologic DMARD (hydroxychloroquine, methotrexate, sulfasalazine and/or Leflunomide), except for simultaneous combination use of leflunomide and methotrexate for 24 weeks. Sarilumab 150 mg q2w hydroxychloroquine Sarilumab 150 mg q2w was added to one or a combination of the nonbiologic DMARD (hydroxychloroquine, methotrexate, sulfasalazine and/or Leflunomide), except for simultaneous combination use of leflunomide and methotrexate for 24 weeks. Sarilumab 200 mg q2w sulfasalazine Sarilumab 200 mg q2w was added to one or a combination of the nonbiologic DMARD (hydroxychloroquine, methotrexate, sulfasalazine and/or Leflunomide), except for simultaneous combination use of leflunomide and methotrexate for 24 weeks. Sarilumab 150 mg q2w methotrexate Sarilumab 150 mg q2w was added to one or a combination of the nonbiologic DMARD (hydroxychloroquine, methotrexate, sulfasalazine and/or Leflunomide), except for simultaneous combination use of leflunomide and methotrexate for 24 weeks. Sarilumab 150 mg q2w leflunomide Sarilumab 150 mg q2w was added to one or a combination of the nonbiologic DMARD (hydroxychloroquine, methotrexate, sulfasalazine and/or Leflunomide), except for simultaneous combination use of leflunomide and methotrexate for 24 weeks.
- Primary Outcome Measures
Name Time Method 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 Outcome Measures
Name Time Method 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.
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.
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 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.
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.
Trial Locations
- Locations (196)
Investigational Site Number 840018
🇺🇸Idaho Falls, Idaho, United States
Investigational Site Number 840058
🇺🇸Columbia, South Carolina, United States
Investigational Site Number 840124
🇺🇸Clarksburg, West Virginia, United States
Investigational Site Number 616015
🇵🇱Elblag, Poland
Investigational Site Number 804027
🇺🇦Kyiv, Ukraine
Investigational Site Number 804011
🇺🇦Vinnytsia, Ukraine
Investigational Site Number 152015
🇨🇱Temuco, Chile
Investigational Site Number 170006
🇨🇴Bogotá, Colombia
Investigational Site Number 440006
🇱🇹Klaipeda, Lithuania
Investigational Site Number 484023
🇲🇽Chihuahua, Mexico
Investigational Site Number 484010
🇲🇽Mexicali, Mexico
Investigational Site Number 170001
🇨🇴Bogota, Colombia
Investigational Site Number 170009
🇨🇴Bucaramanga, Colombia
Investigational Site Number 170014
🇨🇴Chia, Colombia
Investigational Site Number 218001
🇪🇨Guayaquil, Ecuador
Investigational Site Number 320003
🇬🇹Guatemala City, Guatemala
Investigational Site Number 170012
🇨🇴Bogota, Colombia
Investigational Site Number 440007
🇱🇹Vilnius, Lithuania
Investigational Site Number 604010
🇵🇪Lima, Peru
Investigational Site Number 604006
🇵🇪Lima, Peru
Investigational Site Number 440005
🇱🇹Kaunas, Lithuania
Investigational Site Number 484002
🇲🇽Guadalajara, Mexico
Investigational Site Number 604005
🇵🇪Lima, Peru
Investigational Site Number 604014
🇵🇪Lima, Peru
Investigational Site Number 158006
🇨🇳Taipei, Taiwan
Investigational Site Number 040003
🇦🇹Wien, Austria
Investigational Site Number 320002
🇬🇹Guatemala City, Guatemala
Investigational Site Number 484020
🇲🇽Monterrey, Mexico
Investigational Site Number 604013
🇵🇪Lima, Peru
Investigational Site Number 604001
🇵🇪Lima, Peru
Investigational Site Number 484019
🇲🇽Monterrey, Mexico
Investigational Site Number 620002
🇵🇹Lisboa, Portugal
Investigational Site Number 620007
🇵🇹Ponte De Lima, Portugal
Investigational Site Number 076005
🇧🇷Rio De Janeiro, Brazil
Investigational Site Number 840070
🇺🇸Anniston, Alabama, United States
Investigational Site Number 840100
🇺🇸Stanford, California, United States
Investigational Site Number 840130
🇺🇸Lewes, Delaware, United States
Investigational Site Number 840134
🇺🇸Fullerton, California, United States
Investigational Site Number 840128
🇺🇸Ormond Beach, Florida, United States
Investigational Site Number 840137
🇺🇸Saint Clair Shores, Michigan, United States
Investigational Site Number 840117
🇺🇸Pittsburgh, Pennsylvania, United States
Investigational Site Number 840139
🇺🇸Syracuse, New York, United States
Investigational Site Number 032008
🇦🇷Buenos Aires, Argentina
Investigational Site Number 032006
🇦🇷Caba, Argentina
Investigational Site Number 032019
🇦🇷Caba, Argentina
Investigational Site Number 032016
🇦🇷Capital Federal, Argentina
Investigational Site Number 032017
🇦🇷La Plata, Argentina
Investigational Site Number 032009
🇦🇷Zarate, Argentina
Investigational Site Number 032013
🇦🇷Rosario, Argentina
Investigational Site Number 076010
🇧🇷Juiz De Fora, Brazil
Investigational Site Number 170019
🇨🇴Medellin, Colombia
Investigational Site Number 036014
🇦🇺Victoria Park, Australia
Investigational Site Number 203004
🇨🇿Ostrava, Czechia
Investigational Site Number 203007
🇨🇿Praha 2, Czechia
Investigational Site Number 076001
🇧🇷Curitiba, Brazil
Investigational Site Number 203006
🇨🇿Zlin, Czechia
Investigational Site Number 203008
🇨🇿Hostivice, Czechia
Investigational Site Number 300002
🇬🇷Heraklion, Greece
Investigational Site Number 276010
🇩🇪Berlin, Germany
Investigational Site Number 218003
🇪🇨Cuenca, Ecuador
Investigational Site Number 218002
🇪🇨Quito, Ecuador
Investigational Site Number 276011
🇩🇪Bad Nauheim, Germany
Investigational Site Number 276001
🇩🇪Berlin, Germany
Investigational Site Number 276004
🇩🇪Erlangen, Germany
Investigational Site Number 276018
🇩🇪Deggingen, Germany
Investigational Site Number 276013
🇩🇪Hamburg, Germany
Investigational Site Number 276015
🇩🇪Halle/Saale, Germany
Investigational Site Number 320001
🇬🇹Guatemala City, Guatemala
Investigational Site Number 348022
🇭🇺Budapest, Hungary
Investigational Site Number 348003
🇭🇺Debrecen, Hungary
Investigational Site Number 348004
🇭🇺Veszprém, Hungary
Investigational Site Number 410016
🇰🇷Seoul, Korea, Republic of
Investigational Site Number 376002
🇮🇱Tel Hashomer, Israel
Investigational Site Number 380014
🇮🇹Milano, Italy
Investigational Site Number 554007
🇳🇿Otahuhu, New Zealand
Investigational Site Number 554011
🇳🇿Nelson, New Zealand
Investigational Site Number 380013
🇮🇹Udine, Italy
Investigational Site Number 484024
🇲🇽Guadalajara, Mexico
Investigational Site Number 484005
🇲🇽Monterrey, Mexico
Investigational Site Number 484017
🇲🇽México, Mexico
Investigational Site Number 484021
🇲🇽Queretaro, Mexico
Investigational Site Number 642001
🇷🇴Bucuresti, Romania
Investigational Site Number 554006
🇳🇿Wellington, New Zealand
Investigational Site Number 642014
🇷🇴Iasi, Romania
Investigational Site Number 616016
🇵🇱Szczecin, Poland
Investigational Site Number 616020
🇵🇱Wroclaw, Poland
Investigational Site Number 604012
🇵🇪Lima, Peru
Investigational Site Number 620004
🇵🇹Lisboa, Portugal
Investigational Site Number 616017
🇵🇱Warszawa, Poland
Investigational Site Number 158002
🇨🇳Taoyuan County, Taiwan
Investigational Site Number 604008
🇵🇪Lima, Peru
Investigational Site Number 616004
🇵🇱Warszawa, Poland
Investigational Site Number 642012
🇷🇴Bucuresti, Romania
Investigational Site Number 642002
🇷🇴Bucuresti, Romania
Investigational Site Number 703001
🇸🇰Kosice, Slovakia
Investigational Site Number 616014
🇵🇱Bialystok, Poland
Investigational Site Number 616018
🇵🇱Poznan, Poland
Investigational Site Number 616019
🇵🇱Bydgoszcz, Poland
Investigational Site Number 804009
🇺🇦Zaporizhzhya, Ukraine
Investigational Site Number 158005
🇨🇳Kaohsiung, Taiwan
Investigational Site Number 724001
🇪🇸Málaga, Spain
Investigational Site Number 724009
🇪🇸La Coruña, Spain
Investigational Site Number 724016
🇪🇸Barakaldo, Spain
Investigational Site Number 724017
🇪🇸Santiago De Compostela, Spain
Investigational Site Number 792007
🇹🇷Edirne, Turkey
Investigational Site Number 792009
🇹🇷Samsun, Turkey
Investigational Site Number 840129
🇺🇸Houston, Texas, United States
Investigational Site Number 840133
🇺🇸Houston, Texas, United States
Investigational Site Number 840138
🇺🇸Birmingham, Alabama, United States
Investigational Site Number 840142
🇺🇸Phoenix, Arizona, United States
Investigational Site Number 840201
🇺🇸Denver, Colorado, United States
Investigational Site Number 840048
🇺🇸Miami, Florida, United States
Investigational Site Number 840127
🇺🇸Oklahoma City, Oklahoma, United States
Investigational Site Number 724014
🇪🇸Cadiz, Spain
Investigational Site Number 276021
🇩🇪Osnabrück, Germany
Investigational Site Number 276020
🇩🇪Tübingen, Germany
Investigational Site Number 840140
🇺🇸Tampa, Florida, United States
Investigational Site Number 840049
🇺🇸Upland, California, United States
Investigational Site Number 840141
🇺🇸Glendale, California, United States
Investigational Site Number 840111
🇺🇸La Jolla, California, United States
Investigational Site Number 840135
🇺🇸San Diego, California, United States
Investigational Site Number 840021
🇺🇸Santa Maria, California, United States
Investigational Site Number 840131
🇺🇸Whittier, California, United States
Investigational Site Number 840125
🇺🇸DeBary, Florida, United States
Investigational Site Number 840060
🇺🇸Sarasota, Florida, United States
Investigational Site Number 840024
🇺🇸Naples, Florida, United States
Investigational Site Number 840063
🇺🇸Palm Harbor, Florida, United States
Investigational Site Number 840126
🇺🇸Vero Beach, Florida, United States
Investigational Site Number 840110
🇺🇸Meridian, Idaho, United States
Investigational Site Number 840052
🇺🇸Kansas City, Kansas, United States
Investigational Site Number 840150
🇺🇸Lansing, Michigan, United States
Investigational Site Number 840055
🇺🇸Frederick, Maryland, United States
Investigational Site Number 840120
🇺🇸Baton Rouge, Louisiana, United States
Investigational Site Number 840109
🇺🇸Lake Charles, Louisiana, United States
Investigational Site Number 840037
🇺🇸Tupelo, Mississippi, United States
Investigational Site Number 840121
🇺🇸Rochester, New York, United States
Investigational Site Number 840106
🇺🇸Orchard Park, New York, United States
Investigational Site Number 840112
🇺🇸Lincoln, Nebraska, United States
Investigational Site Number 840118
🇺🇸Smithtown, New York, United States
Investigational Site Number 840115
🇺🇸Roslyn, New York, United States
Investigational Site Number 840116
🇺🇸Wilmington, North Carolina, United States
Investigational Site Number 840123
🇺🇸Charlotte, North Carolina, United States
Investigational Site Number 840011
🇺🇸Tulsa, Oklahoma, United States
Investigational Site Number 840009
🇺🇸Duncansville, Pennsylvania, United States
Investigational Site Number 840062
🇺🇸Reading, Pennsylvania, United States
Investigational Site Number 840059
🇺🇸Memphis, Tennessee, United States
Investigational Site Number 840025
🇺🇸Jackson, Tennessee, United States
Investigational Site Number 840114
🇺🇸El Paso, Texas, United States
Investigational Site Number 840022
🇺🇸Dallas, Texas, United States
Investigational Site Number 840074
🇺🇸Mesquite, Texas, United States
Investigational Site Number 840036
🇺🇸Spokane, Washington, United States
Investigational Site Number 032015
🇦🇷Buenos Aires, Argentina
Investigational Site Number 032010
🇦🇷Ramos Mejia, Argentina
Investigational Site Number 032020
🇦🇷Cordoba, Argentina
Investigational Site Number 032004
🇦🇷San Miguel De Tucuman, Argentina
Investigational Site Number 040004
🇦🇹Stockerau, Austria
Investigational Site Number 124104
🇨🇦Victoria, Canada
Investigational Site Number 076015
🇧🇷Rio De Janeiro, Brazil
Investigational Site Number 076016
🇧🇷Curitiba, Brazil
Investigational Site Number 124005
🇨🇦Toronto, Canada
Investigational Site Number 124009
🇨🇦Trois-Rivières, Canada
Investigational Site Number 076006
🇧🇷Goiania, Brazil
Investigational Site Number 203002
🇨🇿Uherske Hradiste, Czechia
Investigational Site Number 170007
🇨🇴Bucaramanga, Colombia
Investigational Site Number 276014
🇩🇪Berlin, Germany
Investigational Site Number 276017
🇩🇪München, Germany
Investigational Site Number 276016
🇩🇪Leipzig, Germany
Investigational Site Number 276019
🇩🇪Zerbst, Germany
Investigational Site Number 300005
🇬🇷Thessaloniki, Greece
Investigational Site Number 348017
🇭🇺Veszprém, Hungary
Investigational Site Number 376003
🇮🇱Petach Tikva, Israel
Investigational Site Number 380002
🇮🇹Firenze, Italy
Investigational Site Number 380011
🇮🇹Catania, Italy
Investigational Site Number 376001
🇮🇱Haifa, Israel
Investigational Site Number 380005
🇮🇹Genova, Italy
Investigational Site Number 410017
🇰🇷Daejeon, Korea, Republic of
Investigational Site Number 484018
🇲🇽Guadalajara, Mexico
Investigational Site Number 604009
🇵🇪Lima, Peru
Investigational Site Number 554005
🇳🇿Hamilton, New Zealand
Investigational Site Number 554001
🇳🇿Timaru, New Zealand
Investigational Site Number 604007
🇵🇪Lima, Peru
Investigational Site Number 643001
🇷🇺Moscow, Russian Federation
Investigational Site Number 643021
🇷🇺Moscow, Russian Federation
Investigational Site Number 643022
🇷🇺Novosibirsk, Russian Federation
Investigational Site Number 643010
🇷🇺Samara, Russian Federation
Investigational Site Number 643008
🇷🇺Saint-Petersburg, Russian Federation
Investigational Site Number 724015
🇪🇸Barcelona, Spain
Investigational Site Number 724011
🇪🇸Sabadell, Spain
Investigational Site Number 724013
🇪🇸Santiago De Compostela, Spain
Investigational Site Number 724007
🇪🇸Sevilla, Spain
Investigational Site Number 792008
🇹🇷Gaziantep, Turkey
Investigational Site Number 804013
🇺🇦Kharkiv, Ukraine
Investigational Site Number 804014
🇺🇦Kyiv, Ukraine
Investigational Site Number 840006
🇺🇸Orlando, Florida, United States
Investigational Site Number 840015
🇺🇸Lexington, Kentucky, United States
Investigational Site Number 840132
🇺🇸Austin, Texas, United States