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PREDICTRA: A Phase 4 Trial Assessing the ImPact of Residual Inflammation Detected Via Imaging TEchniques, Drug Levels and Patient Characteristics on the Outcome of Dose TaperIng of Adalimumab in Clinical Remission Rheumatoid ArThritis (RA) Subjects

Sponsor
AbbVie (Industry)
Overall Status
Completed
CT.gov ID
NCT02198651
Collaborator
(none)
149
Enrollment
70
Locations
4
Arms
43.1
Actual Duration (Months)
2.1
Patients Per Site
0
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The primary objective of the study was to investigate the association between residual disease activity at Baseline as detected by Magnetic Resonance Imaging (MRI) and the occurrence of flares in participants with rheumatoid arthritis (RA) randomized to an adalimumab dose tapering regimen controlled by adalimumab withdrawal.

Condition or Disease Intervention/Treatment Phase
  • Biological: Adalimumab
  • Other: Placebo
 Phase 4

Detailed Description

This was a Phase 4, multicenter, randomized, double-blind, parallel-group study. The study included a Screening period of up to 28 days (unless extended with justification approved by study-designated physician), a 4-week Lead-In Period with open label (OL) 40 mg adalimumab administered subcutaneously (sc) every other week (eow), and a randomized 36-week double-blind period with 40 mg adalimumab sc every 3 weeks (q3wks; tapering arm) or placebo sc q3wks (withdrawal arm). Participants were randomized in a 5:1 ratio (tapering arm: withdrawal arm) after confirmation of meeting the disease activity score (DAS) criteria. Participants who experienced a protocol-defined flare at any time were to enter a rescue arm with OL 40 mg adalimumab administered sc eow for 16 weeks.

Study Design

Study Type:
Interventional
Actual Enrollment :
149 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
A Phase 4 Trial Assessing the ImPact of Residual Inflammation Detected Via Imaging TEchniques, Drug Levels and Patient Characteristics on the Outcome of Dose TaperIng of Adalimumab in Clinical Remission Rheumatoid ArThritis (RA) Subjects (PREDICTRA)
Actual Study Start Date :
Jan 5, 2015
Actual Primary Completion Date :
May 3, 2018
Actual Study Completion Date :
Aug 8, 2018

Arms and Interventions

Arm Intervention/Treatment
Experimental: Adalimumab 40 mg eow

40 mg adalimumab administered subcutaneously every other week (eow) from Week 0 to Week 4 (Lead-in Period)

Biological: Adalimumab
Pre-filled syringe, administered by subcutaneous injection
Other Names:
  • ABT-D2E7
  • Humira

    		•
    Active Comparator: Adalimumab Tapering

    40 mg adalimumab administered subcutaneously every three weeks from Week 4 to Week 40 (Double-blind Period)

    Biological: Adalimumab
    Pre-filled syringe, administered by subcutaneous injection
    Other Names:
  • ABT-D2E7
  • Humira

    		•
    Placebo Comparator: Adalimumab Withdrawal Arm

    Placebo administered subcutaneously every three weeks from Week 4 to Week 40 (Double-blind Period)

    Other: Placebo
    Pre-filled syringe, administered by subcutaneous injection in the Double-blind period
    Experimental: Adalimumab 40 mg eow Rescue Arm

    40 mg adalimumab administered subcutaneously every other week from Flare Week 0 to Flare Week 16 (Open-label Rescue Period)

    Biological: Adalimumab
    Pre-filled syringe, administered by subcutaneous injection
    Other Names:
  • ABT-D2E7
  • Humira

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Association Between Baseline Hand and Wrist Synovitis Rheumatoid Arthritis Magnetic Resonance Imaging Scoring System (RAMRIS) Score and Flare up to Week 40 in the Tapering Arm [From Week 4 to Week 40]

      Synovitis was assessed in three wrist regions (the distal radioulnar joint; the radiocarpal joint; the intercarpal and carpometacarpal joints) and in each Metacarpophalangeal joint (MCP) joint. The first carpometacarpal joint and the first MCP joint are not scored. The scale is 0-3. Score 0 is normal, and 1-3 (mild, moderate, severe) are by thirds of the presumed maximum volume of enhancing tissue in the synovial compartment. Flare is defined as an increase from Double-blind Baseline in DAS (Disease Activity Score) 28 erythrocyte sedimentation rate (ESR) of > 0.6 AND DAS28 [ESR] > 2.6, OR an increase in DAS28 (ESR) of ≥ 1.2 irrespective of the resulting DAS28 [ESR]. The association between baseline hand and wrist synovitis RAMRIS score and occurrence of rheumatoid arthritis flare up to Week 40 in the Tapering arm was examined using logistic regression, and the 95% confidence interval of the odds ratio was calculated.

    2. Association Between Baseline Bone Marrow Edema RAMRIS Score and Flare up to Week 40 in the Tapering Arm [From Week 4 to Week 40]

      Bone marrow edema in each bone was scored separately. The scale is 0-3 based on the proportion of bone with edema, as follows-0: no edema; 1: 1-33% of bone edematous; 2: 34-66% of bone edematous; 3: 67-100%. Flare is defined as an increase from Double-blind Baseline in DAS (Disease Activity Score) 28 erythrocyte sedimentation rate (ESR) of > 0.6 AND DAS28 [ESR] > 2.6, OR an increase in DAS28 (ESR) of ≥ 1.2 irrespective of the resulting DAS28 [ESR]. The association between baseline bone marrow edema rheumatoid arthritis MRI scoring system (RAMRIS) score and occurrence of rheumatoid arthritis flare up to Week 40 in the Tapering arm was examined using logistic regression, and the 95% confidence interval of the odds ratio was calculated.

    3. Association Between a Composite of Baseline Hand and Wrist Synovitis and Bone Marrow Edema RAMRIS Scores and Flare up to Week 40 in the Tapering Arm [From Week 4 to Week 40]

      The composite score is the sum of the baseline hand and wrist synovitis and bone marrow edema RAMRIS scores. Flare is defined as an increase from Double-blind Baseline in DAS (Disease Activity Score) 28 erythrocyte sedimentation rate (ESR) of > 0.6 AND DAS28 [ESR] > 2.6, OR an increase in DAS28 (ESR) of ≥ 1.2 irrespective of the resulting DAS28 [ESR]. The association between the composite baseline hand and wrist synovitis score and baseline bone marrow edema rheumatoid arthritis MRI scoring system (RAMRIS) score and occurrence of rheumatoid arthritis flare up to Week 40 in the Tapering arm was examined using logistic regression, and the 95% confidence interval of the odds ratio was calculated.

    Secondary Outcome Measures

    1. Median Time to Flare [From Week 4 to Week 40]

      Time to flare was defined as the number of weeks from the date of the first dose of study drug in the Double-blind period to the date of flare.

    2. Physicians' Assessment of Flare Severity [At the Flare Week 0 Visit]

      Physicians rated the severity of flare at the Flare Week 0 visit from 0 (not severe) to 10 (very severe). The number of participants within each level of flare severity is presented.

    3. Participants' Assessment of Flare Severity [At the Flare Week 0 Visit]

      Participants rated the severity of flare at the Flare Week 0 visit from 0 (not severe) to 10 (very severe). The number of participants within each level of flare severity is presented.

    4. Percentage of Participants With a Flare [From Week 4 to Week 40]

      Flare was defined as an increase from Double-blind Baseline in DAS (Disease Activity Score) 28 erythrocyte sedimentation rate (ESR) of > 0.6 AND DAS28 [ESR] > 2.6, OR an increase in DAS28 (ESR) of ≥ 1.2 irrespective of the resulting DAS28 [ESR].

    5. Number of Participants Who Regained Clinical Remission in the Open-Label Rescue Arm Over Time [From Flare Week 0 to Flare Week 16]

      The Disease Activity Score 28 (DAS28) is a validated index of rheumatoid arthritis disease activity. Twenty-eight tender joint counts, 28 swollen joint counts, the erythrocyte sedimentation rate (ESR; mm/hour), and the participant's assessment of global disease activity (on a visual analog scale [VAS] from 0 to 10 cm) are included in the DAS28 (ESR) score. Scores on the DAS28 range from 0 to 10; higher scores indicate more disease activity. Clinical remission was defined as DAS28 (ESR) < 2.6.

    6. Median Time to Clinical Remission From the Occurrence of Flare [From Flare Week 0 to Flare Week 16]

      The Disease Activity Score 28 (DAS28) is a validated index of rheumatoid arthritis disease activity. Twenty-eight tender joint counts, 28 swollen joint counts, the erythrocyte sedimentation rate (ESR; mm/hour), and the participant's assessment of global disease activity (on a visual analog scale [VAS] from 0 to 10 cm) are included in the DAS28 (ESR) score. Scores on the DAS28 range from 0 to 10; higher scores indicate more disease activity. Clinical remission was defined as DAS28 (ESR) < 2.6. Time to clinical remission was defined as the number of weeks from the occurrence of flare to the first date of clinical remission.

    7. Mean Change From Double-blind Baseline in Disease Activity Score 28 (DAS28) [From Week 4 to Week 40 and from Flare Week 0 to Flare Week 16]

      The Disease Activity Score 28 (DAS28) is a validated index of rheumatoid arthritis disease activity. Twenty-eight tender joint counts, 28 swollen joint counts, the erythrocyte sedimentation rate (ESR; mm/hour), and the participant's assessment of global disease activity (on a visual analog scale [VAS] from 0 to 10 cm) are included in the DAS28 (ESR) score. Scores on the DAS28 range from 0 to 10; higher scores indicate more disease activity. Negative values indicate improvement from baseline.

    8. Mean Change From Double-blind Baseline in Clinical Disease Activity Index (CDAI) Score [From Week 4 to Week 40 and from Flare Week 0 to Flare Week 16]

      The CDAI is a validated measure of rheumatoid arthritis disease activity. Twenty-eight tender joint counts, 28 swollen joint counts, global health assessed by the participant on a visual analogue scale from 0 to 10 (cm), and global health assessed by an investigator on a visual analogue scale from 0 to 10 (cm) were included in the CDAI score. Scores on the CDAI range from 0 to 76; higher scores indicate more disease activity. Negative values indicate improvement from the Double-blind baseline score.

    9. Mean Change From Double-blind Baseline in Simplified Disease Activity Index (SDAI) Score [From Week 4 to Week 40 and from Flare Week 0 to Flare Week 16]

      The SDAI is a validated measure of rheumatoid arthritis disease activity. Twenty-eight tender joint counts, 28 swollen joint counts, global health assessed by the participant on a visual analogue scale from 0 to 10 (cm), global health assessed by an investigator on a visual analogue scale from 0 to 10 (cm), and serum levels of C-reactive protein levels (mg/dL) were included in the SDAI score. Scores on the SDAI range from 0 to 86; higher scores indicate more disease activity. Negative values indicate improvement from the Double-blind baseline score.

    10. Number of Participants Maintaining Clinical Remission Defined By DAS28 (ESR) < 2.6, SDAI ≤ 3.3, and CDAI ≤ 2.8 at Each Visit By Treatment Arm [From Week 4 to Week 40 and from Flare Week 0 to Flare Week 16]

      The maintenance of clinical remission after regaining remission during the Open-label rescue period was defined as either Disease Activity Score 28 (DAS28 ESR) < 2.6, Simplified Disease Activity Index (SDAI) score ≤ 3.3, or Clinical Disease Activity Index (CDAI) score ≤ 2.8).

    11. Mean Change From Double-blind Baseline to Week 40 or Final Visit in Magnetic Resonance Imaging (MRI) Synovitis Score [From Week 4 to Week 40 or Final visit]

      Synovitis was assessed in three wrist regions (the distal radioulnar joint; the radiocarpal joint; the intercarpal and carpometacarpal joints) and in each Metacarpophalangeal joint (MCP) joint. The first carpometacarpal joint and the first MCP joint are not scored. The scale is 0-3. Score 0 is normal, and 1-3 (mild, moderate, severe) are by thirds of the presumed maximum volume of enhancing tissue in the synovial compartment.

    12. Mean Change From Double-blind Baseline to Week 40 or Final Visit in Bone Marrow Edema (BME) Score [From Week 4 to Week 40 or Final visit]

      Bone edema in each bone was scored separately. The scale is 0-3 based on the proportion of bone with edema, as follows-0: no edema; 1: 1-33% of bone edematous; 2: 34-66% of bone edematous; 3: 67-100%.

    13. Mean Change From Double-blind Baseline to Week 40 or Final Visit in Bone Erosions Rheumatoid Arthritis Magnetic Resonance Imaging Scoring System (RAMRIS) Score [From Week 4 to Week 40 or Final Visit]

      Bone erosions in each bone (wrists: carpal bones, distal radius, distal ulna, metacarpal bases; MCP joints: metacarpal heads, phalangeal bases) were scored separately. The scale is 0-10, based on the proportion of eroded bone compared to the ''assessed bone volume'', judged on all available images-0: no erosion; 1: 1-10% of bone eroded; 2; 11-20%, etc.

    14. Mean Change From Double-blind Baseline in Health Assessment Questionnaire- Disability Index (HAQ-DI) Score Over Time [From Week 4 to Week 40 and from Flare Week 0 to Flare Week 16]

      The Health Assessment Questionnaire - Disability Index (HAQ-DI) is a participant-reported questionnaire specific for rheumatoid arthritis. It consists of 20 questions referring to eight domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and daily activities. Participants assessed their ability to do each task over the past week using the following response categories: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Scores on each task were summed and averaged to provide an overall score ranging from 0 to 3, where zero represents no disability and three very severe, high-dependency disability. The minimal clinically important difference (MCID) defined for the HAQ-DI is ≥ 0.22.

    15. Number of Participants With Health Assessment Questionnaire- Disability Index (HAQ-DI) Score ≤ 0.5 at Double-blind Baseline and at Week 40 [Week 4 and Week 40]

      The Health Assessment Questionnaire - Disability Index (HAQ-DI) is a participant-reported questionnaire specific for rheumatoid arthritis. It consists of 20 questions referring to eight domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and daily activities. Participants assessed their ability to do each task over the past week using the following response categories: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Scores on each task were summed and averaged to provide an overall score ranging from 0 to 3, where zero represents no disability and three very severe, high-dependency disability. The number of participants with HAQ-DI score ≤ 0.5 (considered to be normal) was recorded.

    16. Mean Change From Double-blind Baseline in Routine Assessment of Patient Index Data (RAPID3) Questionnaire Scores Assessed During In-office Visits [From Week 4 to Week 40 and from Flare Week 0 to Flare Week 16]

      The RAPID3 is an activity index derived from the Multi-dimensional Health Assessment Questionnaire (MD-HAQ). It includes an assessment of physical function, a pain Visual Analog Scale (VAS), and a participant global assessment of disease activity VAS. The total RAPID3 score ranges from 0 to 30 where higher scores represent severe disease. Negative values indicate improvement from the Double-blind baseline score.

    17. Mean Change From Flare Week 0 in Routine Assessment of Patient Index Data (RAPID3) Questionnaire Scores Assessed at Home [Flare Week 0 and Flare Weeks 1, 2, 3, 5, 6, 7, 8, 9, 11, 12, 13, 14, 15]

      The RAPID3 is an activity index derived from the Multi-dimensional Health Assessment Questionnaire (MD-HAQ). It includes an assessment of physical function, a pain Visual Analog Scale (VAS), and a participant global assessment of disease activity VAS. The total RAPID3 score ranges from 0 to 30 where higher scores represent severe disease. Negative values indicate improvement from the Double-blind baseline score.

    18. Mean Change From Double-blind Baseline in Swollen Joint Count 28 [From Week 4 to Week 40 and from Flare Week 0 to Flare Week 16]

      Twenty-eight joints, excluding hip joints, were assessed for swelling by physical examination. Swelling of each joint was classified as present (1) or absent (0), for a total possible score of 0 (0 joints with swelling) to 28 (worst possible score/28 joints with swelling). Negative values indicate improvement from baseline.

    19. Mean Change From Double-blind Baseline in Swollen Joint Count 66 [From Week 4 to Week 40 and from Flare Week 0 to Flare Week 16]

      Sixty-six joints were assessed for swelling by physical examination. Swelling of each joint was classified as present (1) or absent (0), for a total possible score of 0 (0 joints with swelling) to 66 (worst possible score/66 joints with swelling). Negative values indicate improvement from baseline.

    20. Mean Change From Double-blind Baseline in Tender Joint Count 28 [From Week 4 to Week 40 and from Flare Week 0 to Flare Week 16]

      Twenty-eight joints were assessed for tenderness by physical examination. Pain or tenderness of each joint was classified as present (1) or absent (0), for a total possible score of 0 (0 joints with tenderness) to 28 (worst possible score/28 joints with tenderness). Negative values indicate improvement from baseline.

    21. Mean Change From Double-blind Baseline in Tender Joint Count 68 [From Week 4 to Week 40 and from Flare Week 0 to Flare Week 16]

      Sixty-eight joints were assessed for tenderness by physical examination. Pain or tenderness of each joint was classified as present (1) or absent (0), for a total possible score of 0 (0 joints with tenderness) to 68 (worst possible score/68 joints with tenderness). Negative values indicate improvement from baseline.

    22. Mean Change From Double-blind Baseline in Participant's Global Assessment of Disease Activity [From Week 4 to Week 40 and from Flare Week 0 to Flare Week 16]

      Participants rated the severity of their rheumatoid arthritis symptoms and how well they were doing during the last 24 hours by placing a vertical mark on a line with a range of 0 (very well) to 100 mm (very poorly). Negative values indicate improvement from baseline.

    23. Mean Change From Double-blind Baseline in Participant's Global Assessment of Rheumatoid Arthritis Pain [From Week 4 to Week 40 and from Flare Week 0 to Flare Week 16]

      Participants rated the severity of their rheumatoid arthritis pain in the past week by placing a vertical mark on a line with a range of 0 (no pain) to 100 mm (severe pain). Negative values indicate improvement from baseline.

    24. Mean Change From Double-blind Baseline in Physician's Global Assessment of Disease Activity [From Week 4 to Week 40 and from Flare Week 0 to Flare Week 16]

      Physicians assessed participants' current rheumatoid arthritis disease activity at the time of the visit (independent of the participant's self-assessment) by placing a vertical mark on a line with a range of 0 (very low) to 100 mm (very high). Negative values indicate improvement from baseline.

    25. Mean Change From Double-blind Baseline in Morning Stiffness Duration [From Week 4 to Week 40 and from Flare Week 0 to Flare Week 16]

      The duration of morning stiffness was reported by participants as the average daily length during the past week in minutes (from time of awaking to time of maximal improvement). Negative values indicate improvement from baseline.

    26. Mean Change From Double-blind Baseline in Morning Stiffness Severity [From Week 4 to Week 40 and from Flare Week 0 to Flare Week 16]

      Morning stiffness severity was assessed by a numeric rating-scale (NRS). Participants rated the severity of morning stiffness during the past week from 0 to 10 with 0 representing "not severe" and 10 "very severe". Negative values indicate improvement from baseline.

    27. Mean Change From Double-blind Baseline in Participant's Assessment of Sleep Disturbance [From Week 4 to Week 40 and from Flare Week 0 to Flare Week 16]

      Participants rated the severity of their sleep disturbance in the past week by placing a vertical mark on a line with a range of 0 (sleep is no problem) to 100 mm (sleep is a major problem). Negative values indicate improvement from baseline.

    28. Mean Change From Double-blind Baseline in Treatment Satisfaction Questionnaire for Medication (TSQM) Effectiveness Score [At Weeks 4, 16, 28, and 40 and from Flare Week 0 to Flare Week 16]

      Participants completed the 14-item Treatment Satisfaction Questionnaire for Medication (TSQM; Version 1.4) to assess satisfaction with their current rheumatoid arthritis treatment over the previous 2-3 weeks or since the last time that they took the medication. The TSQM consists of fourteen items over four domains (effectiveness, side effects, convenience, and global satisfaction). The 14 questions are answered either with yes/no or by means of a five or seven stage scale (ranging from very unsatisfied to satisfied). TSQM Scale scores for each domain range from 0 to 100 and higher scores represent higher satisfaction. Negative values indicate worsening from baseline.

    29. Mean Change From Double-blind Baseline in Treatment Satisfaction Questionnaire for Medication (TSQM) Side Effects Score [At Weeks 4, 16, 28, and 40 and from Flare Week 0 to Flare Week 16]

      Participants completed the 14-item Treatment Satisfaction Questionnaire for Medication (TSQM; Version 1.4) to assess satisfaction with their current rheumatoid arthritis treatment over the previous 2-3 weeks or since the last time that they took the medication. The TSQM consists of fourteen items over four domains (effectiveness, side effects, convenience, and global satisfaction). The 14 questions are answered either with yes/no or by means of a five or seven stage scale (ranging from very unsatisfied to satisfied). TSQM Scale scores for each domain range from 0 to 100 and higher scores represent higher satisfaction. Negative values indicate worsening from baseline.

    30. Mean Change From Double-blind Baseline in Treatment Satisfaction Questionnaire for Medication (TSQM) Convenience Score [At Weeks 4, 16, 28, and 40 and from Flare Week 0 to Flare Week 16]

      Participants completed the 14-item Treatment Satisfaction Questionnaire for Medication (TSQM; Version 1.4) to assess satisfaction with their current rheumatoid arthritis treatment over the previous 2-3 weeks or since the last time that they took the medication. The TSQM consists of fourteen items over four domains (effectiveness, side effects, convenience, and global satisfaction). The 14 questions are answered either with yes/no or by means of a five or seven stage scale (ranging from very unsatisfied to satisfied). TSQM Scale scores for each domain range from 0 to 100 and higher scores represent higher satisfaction. Negative values indicate worsening from baseline.

    31. Mean Change From Double-blind Baseline in Treatment Satisfaction Questionnaire for Medication (TSQM) Global Satisfaction Score [At Weeks 4, 16, 28, and 40 and from Flare Week 0 to Flare Week 16]

      Participants completed the 14-item Treatment Satisfaction Questionnaire for Medication (TSQM; Version 1.4) to assess satisfaction with their current rheumatoid arthritis treatment over the previous 2-3 weeks or since the last time that they took the medication. The TSQM consists of fourteen items over four domains (effectiveness, side effects, convenience, and global satisfaction). The 14 questions are answered either with yes/no or by means of a five or seven stage scale (ranging from very unsatisfied to satisfied). TSQM Scale scores for each domain range from 0 to 100 and higher scores represent higher satisfaction. Negative values indicate worsening from baseline.

    32. Mean Change From Double-blind Baseline in Work Productivity and Activity Impairment (WPAI) Overall Work Impairment and Activity Impairment Scores [At Weeks 4, 28, and 40 and Flare Weeks 0, 10, and 16]

      The Work Productivity and Activity Impairment (WPAI) questionnaire for general health is a validated tool in rheumatoid arthritis consisting of 6 questions, based on participant recall of the previous 7 days. WPAI assesses work time missed due to illness (absenteeism), impairment at work due to health (presenteeism), overall work impairment due to health (an aggregate measure of both absenteeism and presenteeism), and total non-occupational activity impairment due to health. WPAI scores are expressed as impairment percentages, with higher scores indicating worse outcomes. A negative change from baseline indicates improvement.

    33. Mean Change From Double-blind Baseline in Short-Form 36 Version 2 Health Survey (SF-36v2) Physical Component Summary (PCS) Score [At Weeks 4, 28, and 40 and from Flare Week 0 to Flare Week 16]

      The SF-36v2 is a non-disease specific Health Related Quality of Life (HRQoL) instrument. The SF-36v2 comprises 36 total items (questions) targeting a subject's functional health and well-being in 8 domains (physical functioning, role physical, bodily pain, general health, vitality, social functioning, role emotional and mental health) with a recall period of four weeks. Domain scores are aggregated into a Physical Component Summary (PCS) score and a Mental Component Summary (MCS) score. SF-36v2 scores for each domain and PCS/MCS range from 0-100: higher scores indicate a better state of health and a decrease from baseline represents worsening.

    34. Mean Change From Double-blind Baseline in Short-Form 36 Version 2 Health Survey (SF-36v2) Mental Component Summary (MCS) Score [At Weeks 4, 28, and 40 and from Flare Week 0 to Flare Week 16]

      The SF-36v2 is a non-disease specific Health Related Quality of Life (HRQoL) instrument. The SF-36v2 comprises 36 total items (questions) targeting a subject's functional health and well-being in 8 domains (physical functioning, role physical, bodily pain, general health, vitality, social functioning, role emotional and mental health) with a recall period of four weeks. Domain scores are aggregated into a Physical Component Summary (PCS) score and a Mental Component Summary (MCS) score. SF-36v2 scores for each domain and PCS/MCS range from 0-100: higher scores indicate a better state of health and a decrease from baseline represents worsening.

    35. Mean Change From Double-blind Baseline in Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue Scale [At Weeks 4, 16, 28, and 40 and from Flare Week 0 to Flare Week 16]

      The FACIT-Fatigue questionnaire is a participant questionnaire that consists of 13 questions designed to measure the degree of fatigue experienced by participants in the previous 7 days. Participants respond to the questions on a scale from 'not at all' (0) to 'very much' (4). The scale score is computed by summing the item scores, after reversing those items that are worded in the negative direction. The FACIT-Fatigue subscale score ranges from 0 to 52, where higher scores represent less fatigue. A negative change from baseline indicates worsening.

    36. Mean Change From Double-blind Baseline in Serum Levels of C-reactive Protein (CRP) [From Week 4 to Week 40 and from Flare Week 0 to Flare Week 16]

      C-Reactive Protein (CRP; mg/L) was measured from blood samples as a marker for inflammation. Higher levels are indicative of more inflammation. Negative values indicate improvement from baseline.

    37. Mean Change From Double-blind Baseline in Serum Levels of Erythrocyte Sedimentation Rate (ESR) [From Week 4 to Week 40 and from Flare Week 0 to Flare Week 16]

      Erythrocyte sedimentation rate (ESR; mm/hour) indirectly measures how much inflammation is in the body. A higher ESR is indicative of increased inflammation. Negative values indicate improvement from baseline.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    1. Participant had a diagnosis of rheumatoid arthritis (RA) as defined by the 1987 revised American College of Rheumatology (ACR) classification criteria and/or the ACR /European League Against Rheumatism (EULAR) 2010 classification criteria (any duration since diagnosis).

    2. Participant must have met the following criteria:

    • Must have been treated with adalimumab 40 mg subcutaneously every other week (sc eow) for at least 12 months prior to Week 0 Visit

    • Must have been treated with concomitant methotrexate (MTX) at a stable dose (oral, sc or intramuscular (im) at any dose) for at least 12 weeks prior to Week 0 Visit or if not on MTX, must have been treated with other allowed conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) at a stable dose for at least 12 weeks prior to Week 0 Visit or if not treated with csDMARDs must maintain this regimen for at least 12 weeks prior to Week 0 Visit.

    1. Participant must be in sustained clinical remission based on the following:

    • At least one documented 4 or 3 (if Patient's Global Assessment ; PGA is not available) variables Disease Activity Score 28 Erythrocyte sedimentation rate (DAS28 ESR) or DAS28 C-reactive protein (CRP) < 2.6 (or calculated based on documented components of the DAS28) in the participant's chart 6 months or longer prior to the Screening Visit;

    • 4 variables DAS28 (ESR) assessed at Screening < 2.6, with all components including ESR assessed at Screening.

    1. If participant was receiving concomitant allowed csDMARDs (in addition or not to MTX) the dose must have been stable for at least 12 weeks prior to the Week 0 Visit (e.g., chloroquine, hydroxychloroquine, sulfasalazine, gold formulations [including auranofin, gold sodium thiomalate, and aurothioglucose] and/or leflunomide).

    2. If participant was receiving concomitant oral corticosteroids, prednisone or equivalent must have been < 10 mg/day and the dose must have been stable for at least 4 weeks prior to the Week 0 Visit.

    3. If participant was receiving concomitant non-steroidal anti-inflammatory drugs (NSAIDs), tramadol or other equivalent opioids and/or non-opioid analgesics, the dose and/or therapeutic scheme must have been stable for at least 4 weeks prior to the Week 0 Visit.

    4. Participant must have been able and willing to provide written informed consent and comply with the requirements of this study protocol.

    Exclusion Criteria:

    1. Any 4 or 3 (if PGA is not available) variables DAS28 (ESR) or DAS28 (CRP) (or calculated based on documented components of the DAS28) assessed within 6 months prior to the Screening Visit ≥ 2.6.

    2. Participant was on an additional concomitant biological disease-modifying anti-rheumatic drug (bDMARD) (including but not limited to abatacept, anakinra, certolizumab, etanercept, golimumab, infliximab, rituximab or tocilizumab).

    3. Participant had been treated with intra-articular or parenteral corticosteroids within the last four weeks before Screening.

    4. Participant had undergone joint surgery within 12 weeks of Screening (at joints to be assessed by magnetic resonance imaging (MRI) and/or ultrasound).

    5. Participant had a medical condition precluding an MRI (e.g. magnetic activated implanted devices - cardiac pace-maker, insulin pump, neuro stimulators, etc. and metallic devices or fragments or clips in the eye, brain or spinal canal and in the hand/wrist undergoing MRI)

    6. Participant had a medical condition precluding a contrast MRI with gadolinium [e.g. nephrogenic systemic fibrosis, previous anaphylactic/anaphylactoid reaction to gadolinium containing contrast agent, pregnancy or breast feeding, severe renal insufficiency with an estimated Glomerular Filtration Rate (eGFR) below 30 mL/min/1.73m^2 at Screening, hepato-renal syndrome, severe chronic liver function impairment]

    7. Participant had been treated with any investigational drug of chemical or biologic nature within a minimum of 30 days or five half-lives (whichever is longer) of the drug prior to the Screening Visit.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 J Michael Grelier Research /ID# 149772 Tuscaloosa Alabama United States 35406
    2 Westlake Medical Research (WMR) Clinical Trials /ID# 155386 Thousand Oaks California United States 91360-3994
    3 University of Florida /ID# 144851 Jacksonville Florida United States 32209
    4 North Georgia Rheumatology Grp /ID# 155225 Lawrenceville Georgia United States 30045
    5 The Arthritis & Diabetes Clinic, Inc. /ID# 149017 Monroe Louisiana United States 71203
    6 Aa Mrc Llc /Id# 151933 Grand Blanc Michigan United States 48439
    7 North Mississippi Med Clinics /ID# 149443 Tupelo Mississippi United States 38801
    8 Montefiore Medical Center /ID# 155013 Bronx New York United States 10461
    9 Shanahan Rheuma & Immuno /ID# 148689 Raleigh North Carolina United States 27617
    10 Altoona Ctr Clinical Res /ID# 148448 Duncansville Pennsylvania United States 16635
    11 Low Country Rheumatology, PA /ID# 154198 Summerville South Carolina United States 29486
    12 West Tennessee Research Inst /ID# 148391 Jackson Tennessee United States 38305
    13 Arthritis Centers of Texas /ID# 152843 Dallas Texas United States 75246
    14 Royal Prince Alfred Hospital /ID# 154649 Camperdown New South Wales Australia 2050
    15 Optimus Clinical Research Pty. /ID# 133881 Kogarah New South Wales Australia 2217
    16 John Hunter Hospital /ID# 133884 Newcastle New South Wales Australia 2305
    17 Rheumatology Research Unit /ID# 133883 Maroochydore Queensland Australia 4558
    18 AKH Wien /ID# 133885 Vienna Wien Austria 1090
    19 St. Joseph's Healthcare /ID# 149233 Hamilton Ontario Canada L8N 4A6
    20 The Arthritis Program Res Grp /ID# 129056 Newmarket Ontario Canada L3Y 3R7
    21 Institut de Rhum. de Montreal /ID# 129055 Montreal Quebec Canada H2L 1S6
    22 Groupe de Recherche en Maladies Osseuses /ID# 129057 Sainte-foy Quebec Canada G1V 3M7
    23 CIUSSS de l'Estrie - CHUS /ID# 144839 Sherbrooke Quebec Canada J1G 2E8
    24 CHU de la miletrie /ID# 133928 Poitiers Poitou-Charentes France 86021
    25 CHU Amiens Picardie /ID# 144846 Amiens CEDEX 1 Somme France 80054
    26 Hospital Louis Pasteur /ID# 134708 Chartres France 28630
    27 CHU de Grenoble - Albet Michal /ID# 135953 Grenoble France 38043
    28 Asklepios Klinik /ID# 129146 Bad Abbach Germany 93077
    29 Immanuel-Krankenhaus /ID# 129143 Berlin-buch Germany 13125
    30 Charité Universitätsmedizin Campus Mitte /ID# 129142 Berlin Germany 10117
    31 Krankenhaus Porz am Rhein /ID# 129147 Cologne Germany 51149
    32 Rheumaforschungszentrum II /ID# 148554 Hamburg Germany 20095
    33 Klinikum der Univ Munich /ID# 129144 Munich Germany 80337
    34 Rheumazentrum Ratingen /ID# 129148 Ratingen Germany 40882
    35 Rheumatologische Praxis /ID# 151979 Rendsburg Germany 24768
    36 University General Hospital "Attikon" /ID# 134709 Athens Attiki Greece 12462
    37 General Hospital of Athens /ID# 129202 Athens Greece 11527
    38 General UH of Heraklion /ID# 134712 Heraklion Greece 71110
    39 Budai Irgalmasrendi Korhaz /ID# 134714 Budapest Hungary 1023
    40 Orszagos Reumatologiai es Fizi /ID# 134710 Budapest Hungary 1023
    41 Debreceni Egyetem Klinikai Koz /ID# 134715 Debrecen Hungary 4032
    42 St Vincent's University Hosp /ID# 129210 Dublin Ireland D04 T6F4
    43 AP Romano Umberto I /ID# 132895 Rome Lazio Italy 00161
    44 A.O. Univ Consorziale Policlin /ID# 133932 Bari Italy 70124
    45 Azienda Istituto Gaetano Pini /ID# 132964 Milan Italy 20122
    46 Fondazione IRCCS Policlinico /ID# 133886 Pavia Italy 27100
    47 A.O.U.I. di Verona Policlinico /ID# 132973 Verona Italy 37134
    48 Jan van Breemen Instituut /ID# 133887 Amsterdam Netherlands 1056 AB
    49 Rijnstate Hospital /ID# 129206 Arnhem Netherlands 6815 AD
    50 Medisch Centrum Leeuwarden /ID# 133888 Leeuwarden Netherlands 8934 AD
    51 UMC Utrecht /ID# 132896 Utrecht Netherlands 3584 CX
    52 Hospital Parc de Salut del Mar /ID# 148670 Barcelona Spain 08003
    53 Hosp Sant J. Despi-Moises Brog /ID# 135368 Barcelona Spain 08906
    54 Hospital Universitario Basurto /ID# 135529 Bilbao Spain 48013
    55 Hosp Clinico Virgen Arrixaca /ID# 137020 El Palmar Spain 30120
    56 Hospital General Universitario Gregorio Maranon /ID# 133889 Madrid Spain 28007
    57 Hospital Universitario La Paz /ID# 135369 Madrid Spain 28046
    58 Hospital Univ De Mostoles /ID# 134489 Mostoles Spain 28935
    59 Complejo Hosp Santiago /ID# 133890 Santiago de Compostela Spain 15706
    60 Hosp General Univ de Valencia /ID# 134488 Valencia Spain 46014
    61 Akademiska Sjukhuset /ID# 148669 Uppsala Uppsala Lan Sweden 751 85
    62 Uppsala University Hospital /ID# 133891 Uppsala Sweden 75185
    63 Vastmanlands Sjukhus /ID# 133892 Vasteras Sweden 72189
    64 Whipps Cross Univ Hospital /ID# 133893 London London, City Of United Kingdom E11 1NR
    65 Guy's and St Thomas' NHS Found /ID# 132965 London London, City Of United Kingdom SE1 9RT
    66 Mid Essex Hospitals NHS Trust /ID# 151636 Chelmsford United Kingdom CM1 7ET
    67 Western General Hospital /ID# 132966 Edinburgh United Kingdom EH4 2XU
    68 Chapel Allerton Hospital /ID# 129208 Leeds United Kingdom LS7 4SA
    69 University Hospital Aintree /ID# 132980 Liverpool United Kingdom L9 7AL
    70 Queen Alexandra Hospital /ID# 132982 Portsmouth United Kingdom PO6 3LY

    Sponsors and Collaborators

    • AbbVie

    Investigators

    • Study Director: AbbVie Inc., AbbVie

    Study Documents (Full-Text)

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    AbbVie
    ClinicalTrials.gov Identifier:
    NCT02198651
    Other Study ID Numbers:
    • M14-500
    • 2014-001114-26
    First Posted:
    Jul 24, 2014
    Last Update Posted:
    Jun 25, 2019
    Last Verified:
    Jun 1, 2019
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by AbbVie
    Rheumatoid Arthritis
    Adalimumab
    Taper
    Flare
    Arthritis
    Anti-rheumatic drugs
    Remission
    Magnetic Resonance Imaging
    Ultrasound
    Biomarker
    Drug Level
    Reduced dose
    Additional relevant MeSH terms:
    Arthritis
    Arthritis, Rheumatoid
    Connective Tissue Diseases
    Inflammation
    Adalimumab

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail All Lead-in-Treated Subject population: participants who were enrolled in the study and received at least 1 dose of study drug during the Lead-in period. Three participants enrolled in the study but were not treated during the Lead-in period.
    Arm/Group Title Adalimumab 40 mg Eow Adalimumab Tapering Adalimumab Withdrawal Arm Adalimumab Tapering to Rescue Arm Adalimumab Withdrawal to Rescue Arm
    Arm/Group Description 40 mg adalimumab administered subcutaneously every other week (eow) from Week 0 to Week 4 (Lead-in Period) 40 mg adalimumab administered subcutaneously every three weeks from Week 4 to Week 40 (Double-blind Period) Placebo administered subcutaneously every three weeks from Week 4 to Week 40 (Double-blind Period) 40 mg adalimumab administered subcutaneously every other week (eow) from Flare Week 0 to Flare Week 16 (Open-Label Rescue Period) 40 mg adalimumab administered subcutaneously every other week (eow) from Flare Week 0 to Flare Week 16 (Open-Label Rescue Period)
    Period Title: Lead-in Period
    STARTED 149 0 0 0 0
    Participants Treated in Lead-In Period 146 0 0 0 0
    COMPLETED 112 0 0 0 0
    NOT COMPLETED 37 0 0 0 0
    Period Title: Lead-in Period
    STARTED 0 102 20 0 0
    COMPLETED 0 93 19 0 0
    NOT COMPLETED 0 9 1 0 0
    Period Title: Lead-in Period
    STARTED 0 0 0 31 8
    Correctly Entered Open-label Rescue 0 0 0 30 8
    COMPLETED 0 0 0 28 8
    NOT COMPLETED 0 0 0 3 0

    Baseline Characteristics

    Arm/Group Title Adalimumab 40 mg Eow
    Arm/Group Description 40 mg adalimumab administered subcutaneously every other week (eow) from Week 0 to Week 4 (Lead-in Period)
    Overall Participants 146
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    59.6
    (10.30)
    Sex: Female, Male (Count of Participants)
    Female
    109
    74.7%
    Male
    37
    25.3%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    Asian
    2
    1.4%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    Black or African American
    2
    1.4%
    White
    139
    95.2%
    More than one race
    0
    0%
    Unknown or Not Reported
    3
    2.1%
    Tobacco Use (Count of Participants)
    Current
    22
    15.1%
    Former
    46
    31.5%
    Never
    76
    52.1%
    Unknown
    2
    1.4%
    Disease duration (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    12.9
    (9.99)
    Duration of adalimumab therapy (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    5.4
    (3.27)
    Duration of remission (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    2.2
    (1.99)
    Previous treatment with conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) (Count of Participants)
    Yes
    145
    99.3%
    No
    1
    0.7%
    Previous Tx with biological disease-modifying anti-rheumatic drugs (bDMARDs; excluding adalimumab) (Count of Participants)
    Yes
    38
    26%
    No
    108
    74%
    Previous Tx with csDMARDS or bDMARDs (excluding adalimumab) (Count of Participants)
    Yes
    146
    100%
    No
    0
    0%
    Participants' Global Assessment of Disease Activity (units on a scale) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [units on a scale]
    8.7
    (11.84)
    Mean C-Reactive Protein (CRP) (mg/L) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [mg/L]
    2.4
    (2.58)
    HAQ-DI Score (units on a scale) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [units on a scale]
    0.4
    (0.51)

    Outcome Measures

    1. Primary Outcome
    Title Association Between Baseline Hand and Wrist Synovitis Rheumatoid Arthritis Magnetic Resonance Imaging Scoring System (RAMRIS) Score and Flare up to Week 40 in the Tapering Arm
    Description Synovitis was assessed in three wrist regions (the distal radioulnar joint; the radiocarpal joint; the intercarpal and carpometacarpal joints) and in each Metacarpophalangeal joint (MCP) joint. The first carpometacarpal joint and the first MCP joint are not scored. The scale is 0-3. Score 0 is normal, and 1-3 (mild, moderate, severe) are by thirds of the presumed maximum volume of enhancing tissue in the synovial compartment. Flare is defined as an increase from Double-blind Baseline in DAS (Disease Activity Score) 28 erythrocyte sedimentation rate (ESR) of > 0.6 AND DAS28 [ESR] > 2.6, OR an increase in DAS28 (ESR) of ≥ 1.2 irrespective of the resulting DAS28 [ESR]. The association between baseline hand and wrist synovitis RAMRIS score and occurrence of rheumatoid arthritis flare up to Week 40 in the Tapering arm was examined using logistic regression, and the 95% confidence interval of the odds ratio was calculated.
    Time Frame From Week 4 to Week 40

    Outcome Measure Data

    Analysis Population Description
    Participants in the Tapering arm who received at least 1 dose of study drug during the Double-blind period
    Arm/Group Title Adalimumab Tapering
    Arm/Group Description 40 mg adalimumab administered subcutaneously every three weeks from Week 4 to Week 40 (Double-blind Period)
    Measure Participants 102
    Number (95% Confidence Interval) [odds ratio]
    0.993
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Adalimumab Tapering
    Comments
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value 0.943
    Comments
    Method Wald Chi
    Comments
    2. Primary Outcome
    Title Association Between Baseline Bone Marrow Edema RAMRIS Score and Flare up to Week 40 in the Tapering Arm
    Description Bone marrow edema in each bone was scored separately. The scale is 0-3 based on the proportion of bone with edema, as follows-0: no edema; 1: 1-33% of bone edematous; 2: 34-66% of bone edematous; 3: 67-100%. Flare is defined as an increase from Double-blind Baseline in DAS (Disease Activity Score) 28 erythrocyte sedimentation rate (ESR) of > 0.6 AND DAS28 [ESR] > 2.6, OR an increase in DAS28 (ESR) of ≥ 1.2 irrespective of the resulting DAS28 [ESR]. The association between baseline bone marrow edema rheumatoid arthritis MRI scoring system (RAMRIS) score and occurrence of rheumatoid arthritis flare up to Week 40 in the Tapering arm was examined using logistic regression, and the 95% confidence interval of the odds ratio was calculated.
    Time Frame From Week 4 to Week 40

    Outcome Measure Data

    Analysis Population Description
    Participants in the Tapering arm who received at least 1 dose of study drug during the Double-blind period
    Arm/Group Title Adalimumab Tapering
    Arm/Group Description 40 mg adalimumab administered subcutaneously every three weeks from Week 4 to Week 40 (Double-blind Period)
    Measure Participants 102
    Number (95% Confidence Interval) [odds ratio]
    0.959
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Adalimumab Tapering
    Comments
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value 0.592
    Comments
    Method Wald Chi
    Comments
    3. Primary Outcome
    Title Association Between a Composite of Baseline Hand and Wrist Synovitis and Bone Marrow Edema RAMRIS Scores and Flare up to Week 40 in the Tapering Arm
    Description The composite score is the sum of the baseline hand and wrist synovitis and bone marrow edema RAMRIS scores. Flare is defined as an increase from Double-blind Baseline in DAS (Disease Activity Score) 28 erythrocyte sedimentation rate (ESR) of > 0.6 AND DAS28 [ESR] > 2.6, OR an increase in DAS28 (ESR) of ≥ 1.2 irrespective of the resulting DAS28 [ESR]. The association between the composite baseline hand and wrist synovitis score and baseline bone marrow edema rheumatoid arthritis MRI scoring system (RAMRIS) score and occurrence of rheumatoid arthritis flare up to Week 40 in the Tapering arm was examined using logistic regression, and the 95% confidence interval of the odds ratio was calculated.
    Time Frame From Week 4 to Week 40

    Outcome Measure Data

    Analysis Population Description
    Participants in the Tapering arm who received at least 1 dose of study drug during the Double-blind period
    Arm/Group Title Adalimumab Tapering
    Arm/Group Description 40 mg adalimumab administered subcutaneously every three weeks from Week 4 to Week 40 (Double-blind Period)
    Measure Participants 102
    Number (95% Confidence Interval) [odds ratio]
    0.979
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Adalimumab Tapering
    Comments
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value 0.688
    Comments
    Method Wald Chi
    Comments
    4. Secondary Outcome
    Title Median Time to Flare
    Description Time to flare was defined as the number of weeks from the date of the first dose of study drug in the Double-blind period to the date of flare.
    Time Frame From Week 4 to Week 40

    Outcome Measure Data

    Analysis Population Description
    Double-blind Treated Subject population: participants who received at least 1 dose of study drug during the Double-blind period
    Arm/Group Title Adalimumab Tapering Adalimumab Withdrawal Arm
    Arm/Group Description 40 mg adalimumab administered subcutaneously every three weeks from Week 4 to Week 40 (Double-blind Period) Placebo administered subcutaneously every three weeks from Week 4 to Week 40 (Double-blind Period)
    Measure Participants 102 20
    Median (95% Confidence Interval) [weeks]
    NA
    NA
    5. Secondary Outcome
    Title Physicians' Assessment of Flare Severity
    Description Physicians rated the severity of flare at the Flare Week 0 visit from 0 (not severe) to 10 (very severe). The number of participants within each level of flare severity is presented.
    Time Frame At the Flare Week 0 Visit

    Outcome Measure Data

    Analysis Population Description
    All Open-label-rescue-treated participants excluding those who falsely entered the Open-label rescue period
    Arm/Group Title Adalimumab Tapering Adalimumab Withdrawal Arm
    Arm/Group Description 40 mg adalimumab administered subcutaneously every three weeks from Week 4 to Week 40 (Double-blind Period) Placebo administered subcutaneously every three weeks from Week 4 to Week 40 (Double-blind Period)
    Measure Participants 30 8
    0
    1
    0.7%
    1
    NaN
    1
    2
    1.4%
    0
    NaN
    2
    3
    2.1%
    0
    NaN
    3
    3
    2.1%
    1
    NaN
    4
    6
    4.1%
    2
    NaN
    5
    1
    0.7%
    1
    NaN
    6
    4
    2.7%
    0
    NaN
    7
    1
    0.7%
    0
    NaN
    8
    0
    0%
    0
    NaN
    9
    0
    0%
    0
    NaN
    10
    0
    0%
    0
    NaN
    Missing
    9
    6.2%
    3
    NaN
    6. Secondary Outcome
    Title Participants' Assessment of Flare Severity
    Description Participants rated the severity of flare at the Flare Week 0 visit from 0 (not severe) to 10 (very severe). The number of participants within each level of flare severity is presented.
    Time Frame At the Flare Week 0 Visit

    Outcome Measure Data

    Analysis Population Description
    All Open-label-rescue-treated participants excluding those who falsely entered the Open-label rescue period
    Arm/Group Title Adalimumab Tapering Adalimumab Withdrawal Arm
    Arm/Group Description 40 mg adalimumab administered subcutaneously every three weeks from Week 4 to Week 40 (Double-blind Period) Placebo administered subcutaneously every three weeks from Week 4 to Week 40 (Double-blind Period)
    Measure Participants 30 8
    0
    1
    0.7%
    0
    NaN
    1
    2
    1.4%
    1
    NaN
    2
    2
    1.4%
    2
    NaN
    3
    3
    2.1%
    0
    NaN
    4
    4
    2.7%
    0
    NaN
    5
    1
    0.7%
    1
    NaN
    6
    4
    2.7%
    1
    NaN
    7
    1
    0.7%
    0
    NaN
    8
    2
    1.4%
    0
    NaN
    9
    0
    0%
    0
    NaN
    10
    2
    1.4%
    0
    NaN
    Missing
    8
    5.5%
    3
    NaN
    7. Secondary Outcome
    Title Percentage of Participants With a Flare
    Description Flare was defined as an increase from Double-blind Baseline in DAS (Disease Activity Score) 28 erythrocyte sedimentation rate (ESR) of > 0.6 AND DAS28 [ESR] > 2.6, OR an increase in DAS28 (ESR) of ≥ 1.2 irrespective of the resulting DAS28 [ESR].
    Time Frame From Week 4 to Week 40

    Outcome Measure Data

    Analysis Population Description
    Double-blind Treated Subject population: participants who received at least 1 dose of study drug during the Double-blind period
    Arm/Group Title Adalimumab Tapering Adalimumab Withdrawal Arm
    Arm/Group Description 40 mg adalimumab administered subcutaneously every three weeks from Week 4 to Week 40 (Double-blind Period) Placebo administered subcutaneously every three weeks from Week 4 to Week 40 (Double-blind Period)
    Measure Participants 102 20
    Number (95% Confidence Interval) [percentage of participants]
    36.3
    24.9%
    45.0
    NaN
    8. Secondary Outcome
    Title Number of Participants Who Regained Clinical Remission in the Open-Label Rescue Arm Over Time
    Description The Disease Activity Score 28 (DAS28) is a validated index of rheumatoid arthritis disease activity. Twenty-eight tender joint counts, 28 swollen joint counts, the erythrocyte sedimentation rate (ESR; mm/hour), and the participant's assessment of global disease activity (on a visual analog scale [VAS] from 0 to 10 cm) are included in the DAS28 (ESR) score. Scores on the DAS28 range from 0 to 10; higher scores indicate more disease activity. Clinical remission was defined as DAS28 (ESR) < 2.6.
    Time Frame From Flare Week 0 to Flare Week 16

    Outcome Measure Data

    Analysis Population Description
    All Open-label rescue-treated participants excluding those who incorrectly entered the Open-label Rescue Period; last observation carried forward
    Arm/Group Title Adalimumab Tapering Adalimumab Withdrawal Arm
    Arm/Group Description 40 mg adalimumab administered subcutaneously every three weeks from Week 4 to Week 40 (Double-blind Period) Placebo administered subcutaneously every three weeks from Week 4 to Week 40 (Double-blind Period)
    Measure Participants 30 8
    Flare Week 0
    3
    2.1%
    1
    NaN
    Flare Week 4
    14
    9.6%
    1
    NaN
    Flare Week 10
    17
    11.6%
    3
    NaN
    Flare Week 16
    13
    8.9%
    4
    NaN
    9. Secondary Outcome
    Title Median Time to Clinical Remission From the Occurrence of Flare
    Description The Disease Activity Score 28 (DAS28) is a validated index of rheumatoid arthritis disease activity. Twenty-eight tender joint counts, 28 swollen joint counts, the erythrocyte sedimentation rate (ESR; mm/hour), and the participant's assessment of global disease activity (on a visual analog scale [VAS] from 0 to 10 cm) are included in the DAS28 (ESR) score. Scores on the DAS28 range from 0 to 10; higher scores indicate more disease activity. Clinical remission was defined as DAS28 (ESR) < 2.6. Time to clinical remission was defined as the number of weeks from the occurrence of flare to the first date of clinical remission.
    Time Frame From Flare Week 0 to Flare Week 16

    Outcome Measure Data

    Analysis Population Description
    All Open-label rescue treated participants excluding those who incorrectly entered the Open-label Rescue Period
    Arm/Group Title Adalimumab Tapering Adalimumab Withdrawal Arm
    Arm/Group Description 40 mg adalimumab administered subcutaneously every three weeks from Week 4 to Week 40 (Double-blind Period) Placebo administered subcutaneously every three weeks from Week 4 to Week 40 (Double-blind Period)
    Measure Participants 30 8
    Median (95% Confidence Interval) [weeks]
    6.1
    18.0
    10. Secondary Outcome
    Title Mean Change From Double-blind Baseline in Disease Activity Score 28 (DAS28)
    Description The Disease Activity Score 28 (DAS28) is a validated index of rheumatoid arthritis disease activity. Twenty-eight tender joint counts, 28 swollen joint counts, the erythrocyte sedimentation rate (ESR; mm/hour), and the participant's assessment of global disease activity (on a visual analog scale [VAS] from 0 to 10 cm) are included in the DAS28 (ESR) score. Scores on the DAS28 range from 0 to 10; higher scores indicate more disease activity. Negative values indicate improvement from baseline.
    Time Frame From Week 4 to Week 40 and from Flare Week 0 to Flare Week 16

    Outcome Measure Data

    Analysis Population Description
    Double-blind Treated Subject population: participants who received at least 1 dose of study drug during the Double-blind period and had at least Double-blind Baseline data for this endpoint
    Arm/Group Title Flared Participants Non-Flared Participants
    Arm/Group Description Participants who experienced flare during the Double-blind Period Participants who did not experience flare during the Double-blind Period
    Measure Participants 46 76
    Double Blind Week 10- Tapering Arm
    0.7
    (1.27)
    0.1
    (0.46)
    Double Blind Week 10- Withdrawal Arm
    0.1
    (0.47)
    0.1
    (0.55)
    Double Blind Week 16- Tapering Arm
    1.2
    (1.34)
    0.1
    (0.39)
    Double Blind Week 16- Withdrawal Arm
    0.9
    (0.58)
    0.0
    (0.43)
    Double Blind Week 22- Tapering Arm
    0.7
    (1.18)
    -0.0
    (0.53)
    Double Blind Week 22- Withdrawal Arm
    0.5
    (0.31)
    0.1
    (0.24)
    Double Blind Week 28- Tapering arm
    0.8
    (1.16)
    0.1
    (0.50)
    Double Blind Week 28- Withdrawal arm
    1.0
    (1.54)
    0.2
    (0.25)
    Double Blind Week 34- Tapering Arm
    0.7
    (0.59)
    -0.0
    (0.54)
    Double Blind Week 34- Withdrawal Arm
    -0.7
    (0.11)
    -0.0
    (0.46)
    Double Blind Week 40- Tapering Arm
    1.5
    (1.20)
    0.0
    (0.52)
    Double Blind Week 40- Withdrawal Arm
    0.8
    (2.18)
    0.2
    (0.38)
    Flare Week 0- Tapering Arm
    2.3
    (1.15)
    Flare Week 0- Withdrawal Arm
    1.9
    (0.96)
    Flare Week 4- Tapering Arm
    1.3
    (1.05)
    Flare Week 4- Withdrawal Arm
    1.2
    (1.14)
    Flare Week 10- Tapering Arm
    0.9
    (0.81)
    Flare Week 10- Withdrawal Arm
    0.7
    (0.50)
    Flare Week 16- Tapering Arm
    1.2
    (1.04)
    Flare Week 16- Withdrawal Arm
    0.6
    (0.80)
    11. Secondary Outcome
    Title Mean Change From Double-blind Baseline in Clinical Disease Activity Index (CDAI) Score
    Description The CDAI is a validated measure of rheumatoid arthritis disease activity. Twenty-eight tender joint counts, 28 swollen joint counts, global health assessed by the participant on a visual analogue scale from 0 to 10 (cm), and global health assessed by an investigator on a visual analogue scale from 0 to 10 (cm) were included in the CDAI score. Scores on the CDAI range from 0 to 76; higher scores indicate more disease activity. Negative values indicate improvement from the Double-blind baseline score.
    Time Frame From Week 4 to Week 40 and from Flare Week 0 to Flare Week 16

    Outcome Measure Data

    Analysis Population Description
    Double-blind Treated Subject population: participants who received at least 1 dose of study drug during the Double-blind period and had at least Double-blind Baseline data for this endpoint
    Arm/Group Title Flared Participants Non-Flared Participants
    Arm/Group Description Participants who experienced flare during the Double-blind Period Participants who did not experience flare during the Double-blind Period
    Measure Participants 46 76
    Double Blind Week 10- Tapering Arm
    4.4
    (7.68)
    0.6
    (1.34)
    Double Blind Week 10- Withdrawal Arm
    1.0
    (2.45)
    1.4
    (2.85)
    Double Blind Week 16- Tapering Arm
    7.0
    (9.35)
    0.4
    (1.30)
    Double Blind Week 16- Withdrawal Arm
    2.9
    (2.42)
    -0.1
    (0.88)
    Double Blind Week 22- Tapering Arm
    3.2
    (4.98)
    0.3
    (1.38)
    Double Blind Week 22- Withdrawal Arm
    2.2
    (1.93)
    0.1
    (0.73)
    Double Blind Week 28- Tapering arm
    3.7
    (6.19)
    0.5
    (1.37)
    Double Blind Week 28- Withdrawal arm
    6.3
    (8.40)
    -0.1
    (0.80)
    Double Blind Week 34- Tapering Arm
    2.7
    (3.04)
    0.2
    (1.08)
    Double Blind Week 34- Withdrawal Arm
    -0.1
    (0.14)
    0.0
    (0.92)
    Double Blind Week 40- Tapering Arm
    7.4
    (10.04)
    0.1
    (1.33)
    Double Blind Week 40- Withdrawal Arm
    7.7
    (11.38)
    -0.3
    (0.48)
    Flare Week 0- Tapering Arm
    12.3
    (9.56)
    Flare Week 0- Withdrawal Arm
    9.4
    (9.13)
    Flare Week 4- Tapering Arm
    5.0
    (6.55)
    Flare Week 4- Withdrawal Arm
    5.4
    (9.59)
    Flare Week 10- Tapering Arm
    3.5
    (4.55)
    Flare Week 10- Withdrawal Arm
    3.6
    (2.52)
    Flare Week 16- Tapering Arm
    4.5
    (6.14)
    Flare Week 16- Withdrawal Arm
    2.8
    (4.19)
    12. Secondary Outcome
    Title Mean Change From Double-blind Baseline in Simplified Disease Activity Index (SDAI) Score
    Description The SDAI is a validated measure of rheumatoid arthritis disease activity. Twenty-eight tender joint counts, 28 swollen joint counts, global health assessed by the participant on a visual analogue scale from 0 to 10 (cm), global health assessed by an investigator on a visual analogue scale from 0 to 10 (cm), and serum levels of C-reactive protein levels (mg/dL) were included in the SDAI score. Scores on the SDAI range from 0 to 86; higher scores indicate more disease activity. Negative values indicate improvement from the Double-blind baseline score.
    Time Frame From Week 4 to Week 40 and from Flare Week 0 to Flare Week 16

    Outcome Measure Data

    Analysis Population Description
    Double-blind Treated Subject population: participants who received at least 1 dose of study drug during the Double-blind period and had at least Double-blind Baseline data for this endpoint
    Arm/Group Title Flared Participants Non-Flared Participants
    Arm/Group Description Participants who experienced flare during the Double-blind Period Participants who did not experience flare during the Double-blind Period
    Measure Participants 46 76
    Double Blind Week 10- Tapering Arm
    3.7
    (8.57)
    0.8
    (1.85)
    Double Blind Week 10- Withdrawal Arm
    0.9
    (2.59)
    1.3
    (2.67)
    Double Blind Week 16- Tapering Arm
    6.3
    (10.25)
    0.4
    (1.35)
    Double Blind Week 16- Withdrawal Arm
    3.6
    (2.80)
    -0.1
    (0.90)
    Double Blind Week 22- Tapering Arm
    3.6
    (5.18)
    0.3
    (1.47)
    Double Blind Week 22- Withdrawal Arm
    2.3
    (1.95)
    -0.0
    (0.88)
    Double Blind Week 28- Tapering arm
    3.8
    (6.34)
    0.4
    (1.37)
    Double Blind Week 28- Withdrawal arm
    6.4
    (8.40)
    0.1
    (1.61)
    Double Blind Week 34- Tapering Arm
    3.0
    (3.29)
    0.2
    (1.17)
    Double Blind Week 34- Withdrawal Arm
    0.1
    (0.33)
    0.1
    (1.07)
    Double Blind Week 40- Tapering Arm
    7.5
    (10.27)
    0.1
    (1.37)
    Double Blind Week 40- Withdrawal Arm
    8.5
    (10.23)
    -0.3
    (0.62)
    Flare Week 0- Tapering Arm
    11.6
    (11.17)
    Flare Week 0- Withdrawal Arm
    9.9
    (8.31)
    Flare Week 4- Tapering Arm
    4.1
    (8.73)
    Flare Week 4- Withdrawal Arm
    5.2
    (9.64)
    Flare Week 10- Tapering Arm
    2.5
    (7.53)
    Flare Week 10- Withdrawal Arm
    3.5
    (2.51)
    Flare Week 16- Tapering Arm
    3.6
    (6.63)
    Flare Week 16- Withdrawal Arm
    2.7
    (4.20)
    13. Secondary Outcome
    Title Number of Participants Maintaining Clinical Remission Defined By DAS28 (ESR) < 2.6, SDAI ≤ 3.3, and CDAI ≤ 2.8 at Each Visit By Treatment Arm
    Description The maintenance of clinical remission after regaining remission during the Open-label rescue period was defined as either Disease Activity Score 28 (DAS28 ESR) < 2.6, Simplified Disease Activity Index (SDAI) score ≤ 3.3, or Clinical Disease Activity Index (CDAI) score ≤ 2.8).
    Time Frame From Week 4 to Week 40 and from Flare Week 0 to Flare Week 16

    Outcome Measure Data

    Analysis Population Description
    Double-blind Treated Subject population: participants who received at least 1 dose of study drug during the Double-blind period; last observation carried forward
    Arm/Group Title DAS28 (ESR) < 2.6 SDAI ≤ 3.3 CDAI ≤ 2.8
    Arm/Group Description Disease Activity Score 28 (DAS28 ESR) < 2.6 Simplified Disease Activity Index (SDAI) score ≤ 3.3 Clinical Disease Activity Index (CDAI) score ≤ 2.8
    Measure Participants 122 122 122
    Double Blind Baseline- Tapering Arm
    102
    69.9%
    89
    NaN
    85
    NaN
    Double Blind Baseline- Withdrawal Arm
    20
    13.7%
    19
    NaN
    19
    NaN
    Double Blind Week 10- Tapering Arm
    85
    58.2%
    63
    NaN
    62
    NaN
    Double Blind Week 10- Withdrawal Arm
    18
    12.3%
    16
    NaN
    14
    NaN
    Double Blind Week 16- Tapering Arm
    78
    53.4%
    64
    NaN
    62
    NaN
    Double Blind Week 16- Withdrawal arm
    15
    10.3%
    13
    NaN
    15
    NaN
    Double Blind Week 22- Tapering Arm
    75
    51.4%
    59
    NaN
    58
    NaN
    Double Blind Week 22- Withdrawal Arm
    14
    9.6%
    13
    NaN
    13
    NaN
    Double Blind Week 28- Tapering Arm
    69
    47.3%
    58
    NaN
    57
    NaN
    Double Blind Week 28- Withdrawal Arm
    13
    8.9%
    12
    NaN
    13
    NaN
    Double Blind Week 34- Tapering Arm
    70
    47.9%
    58
    NaN
    58
    NaN
    Double Blind Week 34- Withdrawal Arm
    13
    8.9%
    13
    NaN
    13
    NaN
    Double Blind Week 40- Tapering Arm
    64
    43.8%
    57
    NaN
    56
    NaN
    Double Blind Week 40- Withdrawal Arm
    11
    7.5%
    12
    NaN
    12
    NaN
    Flare Week 0- Tapering Arm
    4
    2.7%
    4
    NaN
    4
    NaN
    Flare Week 0- Withdrawal Arm
    1
    0.7%
    0
    NaN
    2
    NaN
    Flare Week 4- Tapering Arm
    14
    9.6%
    13
    NaN
    13
    NaN
    Flare Week 4- Withdrawal Arm
    1
    0.7%
    2
    NaN
    2
    NaN
    Flare Week 10- Tapering Arm
    17
    11.6%
    14
    NaN
    14
    NaN
    Flare Week 10- Withdrawal Arm
    3
    2.1%
    2
    NaN
    2
    NaN
    Flare Week 16- Tapering Arm
    13
    8.9%
    13
    NaN
    13
    NaN
    Flare Week 16- Withdrawal Arm
    4
    2.7%
    4
    NaN
    4
    NaN
    14. Secondary Outcome
    Title Mean Change From Double-blind Baseline to Week 40 or Final Visit in Magnetic Resonance Imaging (MRI) Synovitis Score
    Description Synovitis was assessed in three wrist regions (the distal radioulnar joint; the radiocarpal joint; the intercarpal and carpometacarpal joints) and in each Metacarpophalangeal joint (MCP) joint. The first carpometacarpal joint and the first MCP joint are not scored. The scale is 0-3. Score 0 is normal, and 1-3 (mild, moderate, severe) are by thirds of the presumed maximum volume of enhancing tissue in the synovial compartment.
    Time Frame From Week 4 to Week 40 or Final visit

    Outcome Measure Data

    Analysis Population Description
    Double-blind Treated Subject population: participants who received at least 1 dose of study drug during the Double-blind period and had at least Double-blind Baseline data for this endpoint
    Arm/Group Title Flared Participants Non-Flared Participants
    Arm/Group Description Participants who experienced flare during the Double-blind Period Participants who did not experience flare during the Double-blind Period
    Measure Participants 45 76
    Double Blind Week 40- Tapering Arm
    -0.1
    (1.20)
    0.1
    (1.33)
    Double Blind Week 40- Withdrawal Arm
    0.0
    -0.1
    (0.90)
    Flare Week 16- Tapering Arm
    0.8
    (1.84)
    Flare Week 16- Withdrawal Arm
    0.1
    (1.81)
    15. Secondary Outcome
    Title Mean Change From Double-blind Baseline to Week 40 or Final Visit in Bone Marrow Edema (BME) Score
    Description Bone edema in each bone was scored separately. The scale is 0-3 based on the proportion of bone with edema, as follows-0: no edema; 1: 1-33% of bone edematous; 2: 34-66% of bone edematous; 3: 67-100%.
    Time Frame From Week 4 to Week 40 or Final visit

    Outcome Measure Data

    Analysis Population Description
    Double-blind Treated Subject population: participants who received at least 1 dose of study drug during the Double-blind period and had at least Double-blind Baseline data for this endpoint
    Arm/Group Title Flared Participants Non-Flared Participants
    Arm/Group Description Participants who experienced flare during the Double-blind Period Participants who did not experience flare during the Double-blind Period
    Measure Participants 46 76
    Double Blind Week 40- Tapering Arm
    -0.5
    (0.84)
    0.0
    (1.07)
    Double Blind Week 40- Withdrawal Arm
    0.0
    1.2
    (3.52)
    Flare Week 16- Tapering Arm
    -0.1
    (0.47)
    Flare Week 16- Withdrawal Arm
    0.3
    (0.38)
    16. Secondary Outcome
    Title Mean Change From Double-blind Baseline to Week 40 or Final Visit in Bone Erosions Rheumatoid Arthritis Magnetic Resonance Imaging Scoring System (RAMRIS) Score
    Description Bone erosions in each bone (wrists: carpal bones, distal radius, distal ulna, metacarpal bases; MCP joints: metacarpal heads, phalangeal bases) were scored separately. The scale is 0-10, based on the proportion of eroded bone compared to the ''assessed bone volume'', judged on all available images-0: no erosion; 1: 1-10% of bone eroded; 2; 11-20%, etc.
    Time Frame From Week 4 to Week 40 or Final Visit

    Outcome Measure Data

    Analysis Population Description
    Double-blind Treated Subject population: participants who received at least 1 dose of study drug during the Double-blind period and had at least Double-blind Baseline data for this endpoint
    Arm/Group Title Flared Participants Non-Flared Participants
    Arm/Group Description Participants who experienced flare during the Double-blind Period Participants who did not experience flare during the Double-blind Period
    Measure Participants 46 76
    Double Blind Week 40- Tapering Arm
    -0.5
    (1.73)
    0.1
    (0.52)
    Double Blind Week 40- Withdrawal Arm
    -2.0
    0.0
    (1.08)
    Flare Week 16- Tapering Arm
    0.3
    (1.02)
    Flare Week 16- Withdrawal Arm
    0.1
    (0.88)
    17. Secondary Outcome
    Title Mean Change From Double-blind Baseline in Health Assessment Questionnaire- Disability Index (HAQ-DI) Score Over Time
    Description The Health Assessment Questionnaire - Disability Index (HAQ-DI) is a participant-reported questionnaire specific for rheumatoid arthritis. It consists of 20 questions referring to eight domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and daily activities. Participants assessed their ability to do each task over the past week using the following response categories: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Scores on each task were summed and averaged to provide an overall score ranging from 0 to 3, where zero represents no disability and three very severe, high-dependency disability. The minimal clinically important difference (MCID) defined for the HAQ-DI is ≥ 0.22.
    Time Frame From Week 4 to Week 40 and from Flare Week 0 to Flare Week 16

    Outcome Measure Data

    Analysis Population Description
    Double-blind Treated Subject population: participants who received at least 1 dose of study drug during the Double-blind period and had at least Double-blind Baseline data for this endpoint
    Arm/Group Title Flared Participants Non-Flared Participants
    Arm/Group Description Participants who experienced flare during the Double-blind Period Participants who did not experience flare during the Double-blind Period
    Measure Participants 46 76
    Double Blind Week 10- Tapering Arm
    0.1
    (0.3)
    0.0
    (0.18)
    Double Blind Week 10- Withdrawal Arm
    0.3
    (0.61)
    0.0
    (0.17)
    Double Blind Week 16- Tapering Arm
    0.2
    (0.40)
    -0.0
    (0.28)
    Double Blind Week 16- Withdrawal Arm
    0.3
    (0.54)
    -0.0
    (0.12)
    Double Blind Week 22- Tapering Arm
    0.1
    (0.37)
    -0.0
    (0.26)
    Double Blind Week 22- Withdrawal Arm
    0.4
    (0.79)
    0.1
    (0.39)
    Double Blind Week 28- Tapering Arm
    0.2
    (0.43)
    -0.0
    (0.27)
    Double Blind Week 28- Withdrawal Arm
    0.7
    (0.69)
    -0.1
    (0.15)
    Double Blind Week 34- Tapering Arm
    0.3
    (0.49)
    -0.0
    (0.30)
    Double Blind Week 34- Withdrawal Arm
    0.2
    (0.27)
    0.1
    (0.17)
    Double Blind Week 40- Tapering Arm
    0.4
    (0.40)
    -0.1
    (0.33)
    Double Blind Week 40- Withdrawal Arm
    1.9
    0.0
    (0.16)
    Flare Week 0- Tapering Arm
    0.4
    (0.57)
    Flare Week 0- Withdrawal Arm
    0.3
    (0.29)
    Flare Week 4- Tapering Arm
    0.2
    (0.49)
    Flare Week 4- Withdrawal Arm
    0.2
    (0.35)
    Flare Week 10- Tapering Arm
    0.1
    (0.24)
    Flare Week 10- Withdrawal Arm
    0.1
    (0.20)
    Flare Week 16- Tapering Arm
    0.2
    (0.39)
    Flare Week 16- Withdrawal Arm
    0.1
    (0.24)
    18. Secondary Outcome
    Title Number of Participants With Health Assessment Questionnaire- Disability Index (HAQ-DI) Score ≤ 0.5 at Double-blind Baseline and at Week 40
    Description The Health Assessment Questionnaire - Disability Index (HAQ-DI) is a participant-reported questionnaire specific for rheumatoid arthritis. It consists of 20 questions referring to eight domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and daily activities. Participants assessed their ability to do each task over the past week using the following response categories: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Scores on each task were summed and averaged to provide an overall score ranging from 0 to 3, where zero represents no disability and three very severe, high-dependency disability. The number of participants with HAQ-DI score ≤ 0.5 (considered to be normal) was recorded.
    Time Frame Week 4 and Week 40

    Outcome Measure Data

    Analysis Population Description
    Double-blind Treated Subject population: participants who received at least 1 dose of study drug during the Double-blind period and had at least Double-blind Baseline data for this endpoint
    Arm/Group Title Flared Participants Non-Flared Participants
    Arm/Group Description Participants who experienced flare during the Double-blind Period Participants who did not experience flare during the Double-blind Period
    Measure Participants 46 76
    Double Blind Week 4- Tapering Arm
    21
    14.4%
    50
    NaN
    Double Blind Week 4- Withdrawal Arm
    7
    4.8%
    10
    NaN
    Double Blind Week 40- Tapering Arm
    2
    1.4%
    48
    NaN
    Double Blind Week 40- Withdrawal Arm
    0
    0%
    9
    NaN
    19. Secondary Outcome
    Title Mean Change From Double-blind Baseline in Routine Assessment of Patient Index Data (RAPID3) Questionnaire Scores Assessed During In-office Visits
    Description The RAPID3 is an activity index derived from the Multi-dimensional Health Assessment Questionnaire (MD-HAQ). It includes an assessment of physical function, a pain Visual Analog Scale (VAS), and a participant global assessment of disease activity VAS. The total RAPID3 score ranges from 0 to 30 where higher scores represent severe disease. Negative values indicate improvement from the Double-blind baseline score.
    Time Frame From Week 4 to Week 40 and from Flare Week 0 to Flare Week 16

    Outcome Measure Data

    Analysis Population Description
    Double-blind Treated Subject population: participants who received at least 1 dose of study drug during the Double-blind period and had at least Double-blind Baseline data for this endpoint
    Arm/Group Title Flared Participants Non-Flared Participants
    Arm/Group Description Participants who experienced flare during the Double-blind Period Participants who did not experience flare during the Double-blind Period
    Measure Participants 46 76
    Double Blind Week 10- Tapering Arm
    1.9
    (3.92)
    0.7
    (3.20)
    Double Blind Week 10- Withdrawal Arm
    1.4
    (3.73)
    1.5
    (4.67)
    Double Blind Week 16- Tapering Arm
    4.7
    (5.66)
    0.8
    (2.80)
    Double Blind Week 16- Withdrawal Arm
    2.5
    (4.59)
    0.1
    (1.37)
    Double Blind Week 22- Tapering Arm
    2.6
    (4.83)
    0.3
    (2.83)
    Double Blind Week 22- Withdrawal arm
    3.6
    (4.18)
    0.6
    (3.31)
    Double Blind Week 28- Tapering arm
    2.2
    (4.20)
    0.6
    (2.47)
    Double Blind Week 28- Withdrawal Arm
    3.7
    (4.45)
    -0.3
    (1.61)
    Double Blind Week 34- Tapering Arm
    2.2
    (3.77)
    -0.0
    (1.93)
    Double Blind Week 34- Withdrawal Arm
    1.9
    (2.62)
    1.6
    (2.33)
    Double Blind Week 40- Tapering Arm
    4.7
    (6.22)
    0.0
    (2.39)
    Double Blind Week 40- Withdrawal Arm
    0.4
    (0.92)
    0.8
    (1.62)
    Flare Week 0- Tapering Arm
    6.1
    (6.64)
    Flare Week 0- Withdrawal Arm
    3.9
    (5.60)
    Flare Week 4- Tapering Arm
    3.1
    (5.38)
    Flare Week 4- Withdrawal Arm
    3.2
    (4.15)
    Flare Week 10- Tapering Arm
    2.8
    (3.93)
    Flare Week 10- Withdrawal Arm
    2.3
    (2.61)
    Flare Week 16- Tapering Arm
    2.9
    (4.22)
    Flare Week 16- Withdrawal Arm
    2.1
    (3.01)
    20. Secondary Outcome
    Title Mean Change From Flare Week 0 in Routine Assessment of Patient Index Data (RAPID3) Questionnaire Scores Assessed at Home
    Description The RAPID3 is an activity index derived from the Multi-dimensional Health Assessment Questionnaire (MD-HAQ). It includes an assessment of physical function, a pain Visual Analog Scale (VAS), and a participant global assessment of disease activity VAS. The total RAPID3 score ranges from 0 to 30 where higher scores represent severe disease. Negative values indicate improvement from the Double-blind baseline score.
    Time Frame Flare Week 0 and Flare Weeks 1, 2, 3, 5, 6, 7, 8, 9, 11, 12, 13, 14, 15

    Outcome Measure Data

    Analysis Population Description
    All Open-label rescue treated participants with available data; last observation carried forward
    Arm/Group Title Flared Participants
    Arm/Group Description Participants who experienced flare during the Double-blind Period
    Measure Participants 33
    Flare Week 1- Tapering Arm
    -1.6
    (4.92)
    Flare Week 1- Withdrawal Arm
    3.7
    (7.20)
    Flare Week 2- Tapering Arm
    -3.1
    (5.41)
    Flare Week 2- Withdrawal Arm
    0.8
    (6.89)
    Flare Week 3- Tapering Arm
    -3.8
    (6.78)
    Flare Week 3- Withdrawal Arm
    -0.4
    (7.94)
    Flare Week 5- Tapering Arm
    -3.8
    (6.61)
    Flare Week 5- Withdrawal Arm
    -0.8
    (6.56)
    Flare Week 6- Tapering Arm
    -4.1
    (6.81)
    Flare Week 6- Withdrawal Arm
    -0.9
    (6.97)
    Flare Week 7- Tapering Arm
    -3.7
    (6.86)
    Flare Week 7- Withdrawal Arm
    -0.6
    (6.26)
    Flare Week 8- Tapering Arm
    -4.4
    (7.17)
    Flare Week 8- Withdrawal Arm
    -0.6
    (5.56)
    Flare Week 9- Tapering Arm
    -3.3
    (5.81)
    Flare Week 9- Withdrawal Arm
    -1.0
    (5.89)
    Flare Week 11- Tapering Arm
    -3.7
    (5.69)
    Flare Week 11- Withdrawal Arm
    -1.0
    (5.85)
    Flare Week 12- Tapering Arm
    -3.4
    (5.84)
    Flare Week 12- Withdrawal Arm
    -2.3
    (4.46)
    Flare Week 13- Tapering Arm
    -3.5
    (5.72)
    Flare Week 13- Withdrawal Arm
    -2.5
    (4.78)
    Flare Week 14- Tapering Arm
    -3.1
    (5.54)
    Flare Week 14- Withdrawal Arm
    -2.4
    (4.79)
    Flare Week 15- Tapering Arm
    -3.5
    (6.69)
    Flare Week 15- Withdrawal Arm
    -2.2
    (4.70)
    21. Secondary Outcome
    Title Mean Change From Double-blind Baseline in Swollen Joint Count 28
    Description Twenty-eight joints, excluding hip joints, were assessed for swelling by physical examination. Swelling of each joint was classified as present (1) or absent (0), for a total possible score of 0 (0 joints with swelling) to 28 (worst possible score/28 joints with swelling). Negative values indicate improvement from baseline.
    Time Frame From Week 4 to Week 40 and from Flare Week 0 to Flare Week 16

    Outcome Measure Data

    Analysis Population Description
    Double-blind Treated Subject population: participants who received at least 1 dose of study drug during the Double-blind period and had at least Double-blind Baseline data for this endpoint
    Arm/Group Title Flared Participants Non-Flared Participants
    Arm/Group Description Participants who experienced flare during the Double-blind Period Participants who did not experience flare during the Double-blind Period
    Measure Participants 46 76
    Double Blind Week 10- Tapering Arm
    0.9
    (2.09)
    0.1
    (0.58)
    Double Blind Week 10- Withdrawal Arm
    0.1
    (0.33)
    -0.1
    (0.30)
    Double Blind Week 16- Tapering Arm
    1.2
    (2.15)
    -0.0
    (0.34)
    Double Blind Week 16- Withdrawal Arm
    0.3
    (0.50)
    0.0
    (0.45)
    Double Blind Week 22- Tapering Arm
    0.6
    (1.64)
    0.1
    (0.64)
    Double Blind Week 22- Withdrawal arm
    0.5
    (0.58)
    -0.1
    (0.30)
    Double Blind Week 28- Tapering arm
    0.5
    (0.89)
    0.0
    (0.33)
    Double Blind Week 28- Withdrawal Arm
    2.0
    (2.45)
    -0.1
    (0.30)
    Double Blind Week 34- Tapering Arm
    0.0
    (0.43)
    0.0
    (0.46)
    Double Blind Week 34- Withdrawal Arm
    0.0
    (0.00)
    -0.1
    (0.30)
    Double Blind Week 40- Tapering Arm
    1.5
    (3.01)
    0.0
    (0.42)
    Double Blind Week 40- Withdrawal Arm
    2.0
    (2.83)
    -0.1
    (0.30)
    Flare Week 0- Tapering Arm
    2.3
    (2.60)
    Flare Week 0- Withdrawal Arm
    1.9
    (2.10)
    Flare Week 4- Tapering Arm
    1.2
    (1.98)
    Flare Week 4- Withdrawal Arm
    0.6
    (1.06)
    Flare Week 10- Tapering Arm
    0.4
    (0.89)
    Flare Week 10- Withdrawal Arm
    0.1
    (0.35)
    Flare Week 16- Tapering Arm
    0.9
    (1.81)
    Flare Week 16- Withdrawal Arm
    0.3
    (0.46)
    22. Secondary Outcome
    Title Mean Change From Double-blind Baseline in Swollen Joint Count 66
    Description Sixty-six joints were assessed for swelling by physical examination. Swelling of each joint was classified as present (1) or absent (0), for a total possible score of 0 (0 joints with swelling) to 66 (worst possible score/66 joints with swelling). Negative values indicate improvement from baseline.
    Time Frame From Week 4 to Week 40 and from Flare Week 0 to Flare Week 16

    Outcome Measure Data

    Analysis Population Description
    Double-blind Treated Subject population: participants who received at least 1 dose of study drug during the Double-blind period and had at least Double-blind Baseline data for this endpoint
    Arm/Group Title Flared Participants Non-Flared Participants
    Arm/Group Description Participants who experienced flare during the Double-blind Period Participants who did not experience flare during the Double-blind Period
    Measure Participants 46 76
    Double Blind Week 10- Tapering Arm
    1.1
    (2.36)
    0.1
    (0.67)
    Double Blind Week 10- Withdrawal Arm
    0.1
    (0.33)
    -0.2
    (0.40)
    Double Blind Week 16- Tapering Arm
    1.4
    (2.56)
    -0.0
    (0.34)
    Double Blind Week 16- Withdrawal Arm
    0.4
    (0.53)
    0.0
    (0.45)
    Double Blind Week 22- Tapering Arm
    0.6
    (1.64)
    0.1
    (0.73)
    Double Blind Week 22- Withdrawal arm
    1.0
    (1.41)
    -0.1
    (0.30)
    Double Blind Week 28- Tapering arm
    0.5
    (0.89)
    0.1
    (0.66)
    Double Blind Week 28- Withdrawal Arm
    3.3
    (4.72)
    -0.2
    (0.40)
    Double Blind Week 34- Tapering Arm
    0.0
    (0.43)
    0.0
    (0.54)
    Double Blind Week 34- Withdrawal Arm
    0.0
    (0.00)
    -0.2
    (0.40)
    Double Blind Week 40- Tapering Arm
    1.5
    (3.01)
    0.0
    (0.46)
    Double Blind Week 40- Withdrawal Arm
    2.0
    (2.83)
    -0.2
    (0.40)
    Flare Week 0- Tapering Arm
    2.6
    (2.90)
    Flare Week 0- Withdrawal Arm
    2.6
    (3.38)
    Flare Week 4- Tapering Arm
    1.3
    (1.99)
    Flare Week 4- Withdrawal Arm
    0.6
    (1.06)
    Flare Week 10- Tapering Arm
    0.6
    (1.10)
    Flare Week 10- Withdrawal Arm
    0.4
    (0.52)
    Flare Week 16- Tapering Arm
    1.1
    (2.21)
    Flare Week 16- Withdrawal Arm
    0.4
    (0.74)
    23. Secondary Outcome
    Title Mean Change From Double-blind Baseline in Tender Joint Count 28
    Description Twenty-eight joints were assessed for tenderness by physical examination. Pain or tenderness of each joint was classified as present (1) or absent (0), for a total possible score of 0 (0 joints with tenderness) to 28 (worst possible score/28 joints with tenderness). Negative values indicate improvement from baseline.
    Time Frame From Week 4 to Week 40 and from Flare Week 0 to Flare Week 16

    Outcome Measure Data

    Analysis Population Description
    Double-blind Treated Subject population: participants who received at least 1 dose of study drug during the Double-blind period and had at least Double-blind Baseline data for this endpoint
    Arm/Group Title Flared Participants Non-Flared Participants
    Arm/Group Description Participants who experienced flare during the Double-blind Period Participants who did not experience flare during the Double-blind Period
    Measure Participants 46 76
    Double Blind Week 10- Tapering Arm
    1.3
    (2.74)
    0.1
    (0.54)
    Double Blind Week 10- Withdrawal Arm
    -0.1
    (0.60)
    0.5
    (1.21)
    Double Blind Week 16- Tapering Arm
    2.5
    (4.49)
    0.1
    (0.41)
    Double Blind Week 16- Withdrawal Arm
    1.0
    (0.87)
    0.0
    (0.00)
    Double Blind Week 22- Tapering Arm
    0.9
    (1.66)
    -0.0
    (0.42)
    Double Blind Week 22- Withdrawal arm
    0.8
    (1.50)
    0.1
    (0.30)
    Double Blind Week 28- Tapering arm
    1.6
    (3.39)
    0.0
    (0.51)
    Double Blind Week 28- Withdrawal Arm
    1.8
    (2.36)
    0.2
    (0.40)
    Double Blind Week 34- Tapering Arm
    1.0
    (1.65)
    -0.0
    (0.42)
    Double Blind Week 34- Withdrawal Arm
    0.0
    (0.00)
    0.0
    (0.00)
    Double Blind Week 40- Tapering Arm
    2.0
    (2.65)
    0.0
    (0.51)
    Double Blind Week 40- Withdrawal Arm
    3.5
    (4.95)
    0.0
    (0.00)
    Flare Week 0- Tapering Arm
    4.4
    (4.63)
    Flare Week 0- Withdrawal Arm
    3.6
    (3.81)
    Flare Week 4- Tapering Arm
    1.5
    (2.27)
    Flare Week 4- Withdrawal Arm
    2.5
    (5.13)
    Flare Week 10- Tapering Arm
    0.9
    (1.84)
    Flare Week 10- Withdrawal Arm
    1.1
    (1.46)
    Flare Week 16- Tapering Arm
    1.8
    (2.64)
    Flare Week 16- Withdrawal Arm
    1.1
    (1.89)
    24. Secondary Outcome
    Title Mean Change From Double-blind Baseline in Tender Joint Count 68
    Description Sixty-eight joints were assessed for tenderness by physical examination. Pain or tenderness of each joint was classified as present (1) or absent (0), for a total possible score of 0 (0 joints with tenderness) to 68 (worst possible score/68 joints with tenderness). Negative values indicate improvement from baseline.
    Time Frame From Week 4 to Week 40 and from Flare Week 0 to Flare Week 16

    Outcome Measure Data

    Analysis Population Description
    Double-blind Treated Subject population: participants who received at least 1 dose of study drug during the Double-blind period and had at least Double-blind Baseline data for this endpoint
    Arm/Group Title Flared Participants Non-Flared Participants
    Arm/Group Description Participants who experienced flare during the Double-blind Period Participants who did not experience flare during the Double-blind Period
    Measure Participants 46 76
    Double Blind Week 10- Tapering Arm
    1.9
    (3.45)
    0.3
    (1.47)
    Double Blind Week 10- Withdrawal Arm
    0.1
    (0.60)
    0.9
    (1.64)
    Double Blind Week 16- Tapering Arm
    3.5
    (6.33)
    0.2
    (1.36)
    Double Blind Week 16- Withdrawal Arm
    1.4
    (1.13)
    0.2
    (0.60)
    Double Blind Week 22- Tapering Arm
    1.2
    (2.27)
    0.2
    (1.35)
    Double Blind Week 22- Withdrawal arm
    2.0
    (2.83)
    0.4
    (1.03)
    Double Blind Week 28- Tapering arm
    2.5
    (5.34)
    0.1
    (0.96)
    Double Blind Week 28- Withdrawal Arm
    3.8
    (4.50)
    0.3
    (0.47)
    Double Blind Week 34- Tapering Arm
    1.9
    (2.87)
    0.0
    (0.73)
    Double Blind Week 34- Withdrawal Arm
    0.0
    (0.00)
    0.1
    (0.30)
    Double Blind Week 40- Tapering Arm
    3.0
    (4.24)
    0.0
    (0.68)
    Double Blind Week 40- Withdrawal Arm
    9.0
    (12.73)
    -0.1
    (0.30)
    Flare Week 0- Tapering Arm
    6.2
    (6.93)
    Flare Week 0- Withdrawal Arm
    6.1
    (6.27)
    Flare Week 4- Tapering Arm
    1.9
    (2.50)
    Flare Week 4- Withdrawal Arm
    4.1
    (8.48)
    Flare Week 10- Tapering Arm
    1.5
    (2.69)
    Flare Week 10- Withdrawal Arm
    2.3
    (2.31)
    Flare Week 16- Tapering Arm
    2.1
    (3.37)
    Flare Week 16- Withdrawal Arm
    1.6
    (1.85)
    25. Secondary Outcome
    Title Mean Change From Double-blind Baseline in Participant's Global Assessment of Disease Activity
    Description Participants rated the severity of their rheumatoid arthritis symptoms and how well they were doing during the last 24 hours by placing a vertical mark on a line with a range of 0 (very well) to 100 mm (very poorly). Negative values indicate improvement from baseline.
    Time Frame From Week 4 to Week 40 and from Flare Week 0 to Flare Week 16

    Outcome Measure Data

    Analysis Population Description
    Double-blind Treated Subject population: participants who received at least 1 dose of study drug during the Double-blind period and had at least Double-blind Baseline data for this endpoint
    Arm/Group Title Flared Participants Non-Flared Participants
    Arm/Group Description Participants who experienced flare during the Double-blind Period Participants who did not experience flare during the Double-blind Period
    Measure Participants 46 76
    Double Blind Week 10- Tapering Arm
    11.6
    (19.00)
    2.6
    (8.49)
    Double Blind Week 10- Withdrawal Arm
    8.0
    (21.66)
    9.6
    (20.27)
    Double Blind Week 16- Tapering Arm
    20.5
    (26.97)
    2.4
    (9.27)
    Double Blind Week 16- Withdrawal Arm
    10.7
    (19.97)
    -0.3
    (5.76)
    Double Blind Week 22- Tapering Arm
    10.7
    (17.74)
    1.7
    (9.14)
    Double Blind Week 22- Withdrawal arm
    5.8
    (8.73)
    0.2
    (8.87)
    Double Blind Week 28- Tapering arm
    9.4
    (21.03)
    2.7
    (10.03)
    Double Blind Week 28- Withdrawal Arm
    15.0
    (25.76)
    -1.0
    (7.82)
    Double Blind Week 34- Tapering Arm
    11.5
    (13.70)
    1.2
    (7.23)
    Double Blind Week 34- Withdrawal Arm
    -1.0
    (1.41)
    0.7
    (7.25)
    Double Blind Week 40- Tapering Arm
    22.9
    (35.32)
    0.0
    (7.60)
    Double Blind Week 40- Withdrawal Arm
    2.0
    (9.90)
    -1.7
    (4.45)
    Flare Week 0- Tapering Arm
    29.5
    (29.43)
    Flare Week 0- Withdrawal Arm
    21.6
    (27.07)
    Flare Week 4- Tapering Arm
    13.7
    (22.93)
    Flare Week 4- Withdrawal Arm
    11.7
    (21.96)
    Flare Week 10- Tapering Arm
    11.7
    (16.89)
    Flare Week 10- Withdrawal Arm
    14.1
    (10.35)
    Flare Week 16- Tapering Arm
    9.4
    (13.47)
    Flare Week 16- Withdrawal Arm
    6.9
    (9.31)
    26. Secondary Outcome
    Title Mean Change From Double-blind Baseline in Participant's Global Assessment of Rheumatoid Arthritis Pain
    Description Participants rated the severity of their rheumatoid arthritis pain in the past week by placing a vertical mark on a line with a range of 0 (no pain) to 100 mm (severe pain). Negative values indicate improvement from baseline.
    Time Frame From Week 4 to Week 40 and from Flare Week 0 to Flare Week 16

    Outcome Measure Data

    Analysis Population Description
    Double-blind Treated Subject population: participants who received at least 1 dose of study drug during the Double-blind period and had at least Double-blind Baseline data for this endpoint
    Arm/Group Title Flared Participants Non-Flared Participants
    Arm/Group Description Participants who experienced flare during the Double-blind Period Participants who did not experience flare during the Double-blind Period
    Measure Participants 46 76
    Double Blind Week 10- Tapering Arm
    8.0
    (17.96)
    3.5
    (14.33)
    Double Blind Week 10- Withdrawal Arm
    6.4
    (19.05)
    9.3
    (21.04)
    Double Blind Week 16- Tapering Arm
    17.8
    (27.16)
    3.0
    (12.48)
    Double Blind Week 16- Withdrawal Arm
    10.7
    (18.93)
    -0.6
    (9.65)
    Double Blind Week 22- Tapering Arm
    10.4
    (19.55)
    0.3
    (7.82)
    Double Blind Week 22- Withdrawal arm
    4.0
    (4.90)
    -1.1
    (11.20)
    Double Blind Week 28- Tapering arm
    8.3
    (17.57)
    1.6
    (9.83)
    Double Blind Week 28- Withdrawal Arm
    14.0
    (24.59)
    -1.4
    (10.93)
    Double Blind Week 34- Tapering Arm
    11.6
    (14.61)
    -0.3
    (7.61)
    Double Blind Week 34- Withdrawal Arm
    -3.5
    (2.12)
    2.1
    (8.40)
    Double Blind Week 40- Tapering Arm
    24.0
    (32.67)
    -0.5
    (10.00)
    Double Blind Week 40- Withdrawal Arm
    -0.5
    (20.51)
    -0.9
    (5.07)
    Flare Week 0- Tapering Arm
    24.4
    (31.66)
    Flare Week 0- Withdrawal Arm
    17.0
    (19.38)
    Flare Week 4- Tapering Arm
    9.0
    (21.68)
    Flare Week 4- Withdrawal Arm
    11.1
    (17.46)
    Flare Week 10- Tapering Arm
    7.5
    (14.93)
    Flare Week 10- Withdrawal Arm
    8.3
    (9.60)
    Flare Week 16- Tapering Arm
    8.0
    (14.41)
    Flare Week 16- Withdrawal Arm
    4.3
    (6.32)
    27. Secondary Outcome
    Title Mean Change From Double-blind Baseline in Physician's Global Assessment of Disease Activity
    Description Physicians assessed participants' current rheumatoid arthritis disease activity at the time of the visit (independent of the participant's self-assessment) by placing a vertical mark on a line with a range of 0 (very low) to 100 mm (very high). Negative values indicate improvement from baseline.
    Time Frame From Week 4 to Week 40 and from Flare Week 0 to Flare Week 16

    Outcome Measure Data

    Analysis Population Description
    Double-blind Treated Subject population: participants who received at least 1 dose of study drug during the Double-blind period and had at least Double-blind Baseline data for this endpoint
    Arm/Group Title Flared Participants Non-Flared Participants
    Arm/Group Description Participants who experienced flare during the Double-blind Period Participants who did not experience flare during the Double-blind Period
    Measure Participants 46 76
    Double Blind Week 10- Tapering Arm
    10.2
    (19.54)
    1.3
    (4.27)
    Double Blind Week 10- Withdrawal Arm
    1.6
    (4.67)
    0.5
    (4.74)
    Double Blind Week 16- Tapering Arm
    13.2
    (21.48)
    0.9
    (5.07)
    Double Blind Week 16- Withdrawal Arm
    5.0
    (3.35)
    -0.5
    (2.98)
    Double Blind Week 22- Tapering Arm
    6.9
    (14.83)
    0.9
    (5.05)
    Double Blind Week 22- Withdrawal arm
    3.8
    (2.87)
    0.4
    (3.26)
    Double Blind Week 28- Tapering arm
    7.3
    (16.51)
    1.7
    (5.51)
    Double Blind Week 28- Withdrawal Arm
    10.0
    (10.89)
    -0.9
    (2.74)
    Double Blind Week 34- Tapering Arm
    5.5
    (12.27)
    0.8
    (3.60)
    Double Blind Week 34- Withdrawal Arm
    0.0
    (0.00)
    0.6
    (4.13)
    Double Blind Week 40- Tapering Arm
    16.2
    (26.91)
    1.0
    (5.32)
    Double Blind Week 40- Withdrawal Arm
    19.5
    (26.16)
    -0.6
    (2.42)
    Flare Week 0- Tapering Arm
    26.5
    (23.28)
    Flare Week 0- Withdrawal Arm
    17.4
    (15.37)
    Flare Week 4- Tapering Arm
    12.2
    (17.06)
    Flare Week 4- Withdrawal Arm
    9.3
    (20.27)
    Flare Week 10- Tapering Arm
    10.2
    (13.82)
    Flare Week 10- Withdrawal Arm
    12.9
    (11.51)
    Flare Week 16- Tapering Arm
    8.6
    (12.48)
    Flare Week 16- Withdrawal Arm
    7.6
    (20.00)
    28. Secondary Outcome
    Title Mean Change From Double-blind Baseline in Morning Stiffness Duration
    Description The duration of morning stiffness was reported by participants as the average daily length during the past week in minutes (from time of awaking to time of maximal improvement). Negative values indicate improvement from baseline.
    Time Frame From Week 4 to Week 40 and from Flare Week 0 to Flare Week 16

    Outcome Measure Data

    Analysis Population Description
    Double-blind Treated Subject population: participants who received at least 1 dose of study drug during the Double-blind period and had at least Double-blind Baseline data for this endpoint
    Arm/Group Title Flared Participants Non-Flared Participants
    Arm/Group Description Participants who experienced flare during the Double-blind Period Participants who did not experience flare during the Double-blind Period
    Measure Participants 45 74
    Double Blind Week 10- Tapering Arm
    3.5
    (17.33)
    1.8
    (7.19)
    Double Blind Week 10- Withdrawal Arm
    1.1
    (3.60)
    1.5
    (5.97)
    Double Blind Week 16- Tapering Arm
    6.6
    (24.41)
    2.3
    (12.54)
    Double Blind Week 16- Withdrawal Arm
    9.2
    (19.78)
    -0.6
    (5.05)
    Double Blind Week 22- Tapering Arm
    -1.6
    (8.07)
    1.5
    (9.67)
    Double Blind Week 22- Withdrawal arm
    1.0
    (2.00)
    0.5
    (3.70)
    Double Blind Week 28- Tapering arm
    2.6
    (13.09)
    2.4
    (10.53)
    Double Blind Week 28- Withdrawal Arm
    17.3
    (28.81)
    0.0
    (3.71)
    Double Blind Week 34- Tapering Arm
    0.6
    (10.97)
    1.4
    (8.86)
    Double Blind Week 34- Withdrawal Arm
    0.0
    (0.00)
    -1.1
    (6.64)
    Double Blind Week 40- Tapering Arm
    2.0
    (12.49)
    0.4
    (9.33)
    Double Blind Week 40- Withdrawal Arm
    0.0
    (0.00)
    -0.2
    (5.78)
    Flare Week 0- Tapering Arm
    13.5
    (25.21)
    Flare Week 0- Withdrawal Arm
    18.5
    (26.25)
    Flare Week 4- Tapering Arm
    25.0
    (110.77)
    Flare Week 4- Withdrawal Arm
    19.9
    (26.51)
    Flare Week 10- Tapering Arm
    8.1
    (30.20)
    Flare Week 10- Withdrawal Arm
    7.9
    (9.72)
    Flare Week 16- Tapering Arm
    17.3
    (36.46)
    Flare Week 16- Withdrawal Arm
    9.6
    (20.65)
    29. Secondary Outcome
    Title Mean Change From Double-blind Baseline in Morning Stiffness Severity
    Description Morning stiffness severity was assessed by a numeric rating-scale (NRS). Participants rated the severity of morning stiffness during the past week from 0 to 10 with 0 representing "not severe" and 10 "very severe". Negative values indicate improvement from baseline.
    Time Frame From Week 4 to Week 40 and from Flare Week 0 to Flare Week 16

    Outcome Measure Data

    Analysis Population Description
    Double-blind Treated Subject population: participants who received at least 1 dose of study drug during the Double-blind period and had at least Double-blind Baseline data for this endpoint
    Arm/Group Title Flared Participants Non-Flared Participants
    Arm/Group Description Participants who experienced flare during the Double-blind Period Participants who did not experience flare during the Double-blind Period
    Measure Participants 46 76
    Double Blind Week 10- Tapering Arm
    0.6
    (1.51)
    0.4
    (1.01)
    Double Blind Week 10- Withdrawal Arm
    0.4
    (1.81)
    0.6
    (1.29)
    Double Blind Week 16- Tapering Arm
    0.8
    (1.73)
    0.3
    (1.11)
    Double Blind Week 16- Withdrawal Arm
    0.7
    (2.24)
    -0.1
    (1.04)
    Double Blind Week 22- Tapering Arm
    0.9
    (1.27)
    0.2
    (0.85)
    Double Blind Week 22- Withdrawal arm
    0.8
    (0.96)
    0.4
    (1.75)
    Double Blind Week 28- Tapering arm
    0.9
    (1.69)
    0.2
    (1.10)
    Double Blind Week 28- Withdrawal Arm
    1.3
    (2.75)
    -0.2
    (0.87)
    Double Blind Week 34- Tapering Arm
    1.3
    (1.71)
    0.1
    (0.85)
    Double Blind Week 34- Withdrawal Arm
    0.0
    (1.41)
    -0.2
    (1.08)
    Double Blind Week 40- Tapering Arm
    1.8
    (2.52)
    0.1
    (0.94)
    Double Blind Week 40- Withdrawal Arm
    -1.0
    (1.41)
    -0.4
    (1.03)
    Flare Week 0- Tapering Arm
    1.6
    (2.11)
    Flare Week 0- Withdrawal Arm
    0.9
    (1.96)
    Flare Week 4- Tapering Arm
    0.8
    (2.21)
    Flare Week 4- Withdrawal Arm
    0.6
    (1.72)
    Flare Week 10- Tapering Arm
    0.6
    (1.40)
    Flare Week 10- Withdrawal Arm
    0.6
    (1.27)
    Flare Week 16- Tapering Arm
    0.6
    (1.45)
    Flare Week 16- Withdrawal Arm
    -0.1
    (1.13)
    30. Secondary Outcome
    Title Mean Change From Double-blind Baseline in Participant's Assessment of Sleep Disturbance
    Description Participants rated the severity of their sleep disturbance in the past week by placing a vertical mark on a line with a range of 0 (sleep is no problem) to 100 mm (sleep is a major problem). Negative values indicate improvement from baseline.
    Time Frame From Week 4 to Week 40 and from Flare Week 0 to Flare Week 16

    Outcome Measure Data

    Analysis Population Description
    Double-blind Treated Subject population: participants who received at least 1 dose of study drug during the Double-blind period and had at least Double-blind Baseline data for this endpoint
    Arm/Group Title Flared Participants Non-Flared Participants
    Arm/Group Description Participants who experienced flare during the Double-blind Period Participants who did not experience flare during the Double-blind Period
    Measure Participants 46 76
    Double Blind Week 10- Tapering Arm
    2.1
    (15.37)
    0.0
    (8.99)
    Double Blind Week 10- Withdrawal Arm
    -3.2
    (29.39)
    0.8
    (1.54)
    Double Blind Week 16- Tapering Arm
    10.2
    (19.12)
    1.7
    (15.96)
    Double Blind Week 16- Withdrawal Arm
    7.1
    (22.42)
    1.1
    (3.02)
    Double Blind Week 22- Tapering Arm
    8.2
    (19.59)
    -0.3
    (10.91)
    Double Blind Week 22- Withdrawal arm
    8.3
    (31.35)
    3.5
    (8.70)
    Double Blind Week 28- Tapering arm
    1.8
    (27.81)
    2.1
    (12.67)
    Double Blind Week 28- Withdrawal Arm
    4.5
    (19.82)
    -1.0
    (7.63)
    Double Blind Week 34- Tapering Arm
    5.6
    (22.99)
    -0.4
    (11.48)
    Double Blind Week 34- Withdrawal Arm
    -0.5
    (30.41)
    -0.4
    (2.77)
    Double Blind Week 40- Tapering Arm
    17.7
    (34.04)
    -0.2
    (12.40)
    Double Blind Week 40- Withdrawal Arm
    -8.0
    (15.56)
    -1.0
    (4.43)
    Flare Week 0- Tapering Arm
    18.9
    (26.53)
    Flare Week 0- Withdrawal Arm
    4.0
    (14.61)
    Flare Week 4- Tapering Arm
    4.9
    (24.33)
    Flare Week 4- Withdrawal Arm
    1.6
    (10.05)
    Flare Week 10- Tapering Arm
    0.2
    (21.26)
    Flare Week 10- Withdrawal Arm
    3.9
    (12.98)
    Flare Week 16- Tapering Arm
    2.3
    (20.17)
    Flare Week 16- Withdrawal Arm
    -7.3
    (14.14)
    31. Secondary Outcome
    Title Mean Change From Double-blind Baseline in Treatment Satisfaction Questionnaire for Medication (TSQM) Effectiveness Score
    Description Participants completed the 14-item Treatment Satisfaction Questionnaire for Medication (TSQM; Version 1.4) to assess satisfaction with their current rheumatoid arthritis treatment over the previous 2-3 weeks or since the last time that they took the medication. The TSQM consists of fourteen items over four domains (effectiveness, side effects, convenience, and global satisfaction). The 14 questions are answered either with yes/no or by means of a five or seven stage scale (ranging from very unsatisfied to satisfied). TSQM Scale scores for each domain range from 0 to 100 and higher scores represent higher satisfaction. Negative values indicate worsening from baseline.
    Time Frame At Weeks 4, 16, 28, and 40 and from Flare Week 0 to Flare Week 16

    Outcome Measure Data

    Analysis Population Description
    Double-blind Treated Subject population: participants who received at least 1 dose of study drug during the Double-blind period and had at least Double-blind Baseline data for this endpoint
    Arm/Group Title Flared Participants Non-Flared Participants
    Arm/Group Description Participants who experienced flare during the Double-blind Period Participants who did not experience flare during the Double-blind Period
    Measure Participants 46 74
    Double Blind Week 16- Tapering Arm
    -8.3
    (35.30)
    0.2
    (23.74)
    Double Blind Week 16- Withdrawal Arm
    2.8
    (39.51)
    -13.6
    (43.84)
    Double Blind Week 28- Tapering arm
    -10.1
    (24.28)
    -3.8
    (17.82)
    Double Blind Week 28- Withdrawal Arm
    -5.6
    (45.59)
    -17.2
    (30.48)
    Double Blind Week 40- Tapering Arm
    -15.2
    (33.53)
    -4.4
    (27.82)
    Double Blind Week 40- Withdrawal Arm
    -19.4
    (27.50)
    -16.2
    (45.10)
    Flare Week 0- Tapering Arm
    -10.9
    (39.82)
    Flare Week 0- Withdrawal Arm
    -9.5
    (38.05)
    Flare Week 4- Tapering Arm
    -17.3
    (40.07)
    Flare Week 4- Withdrawal Arm
    -6.5
    (48.23)
    Flare Week 10- Tapering Arm
    -10.7
    (44.07)
    Flare Week 10- Withdrawal Arm
    7.9
    (34.23)
    Flare Week 16- Tapering Arm
    -7.5
    (25.49)
    Flare Week 16- Withdrawal Arm
    -16.7
    (39.67)
    32. Secondary Outcome
    Title Mean Change From Double-blind Baseline in Treatment Satisfaction Questionnaire for Medication (TSQM) Side Effects Score
    Description Participants completed the 14-item Treatment Satisfaction Questionnaire for Medication (TSQM; Version 1.4) to assess satisfaction with their current rheumatoid arthritis treatment over the previous 2-3 weeks or since the last time that they took the medication. The TSQM consists of fourteen items over four domains (effectiveness, side effects, convenience, and global satisfaction). The 14 questions are answered either with yes/no or by means of a five or seven stage scale (ranging from very unsatisfied to satisfied). TSQM Scale scores for each domain range from 0 to 100 and higher scores represent higher satisfaction. Negative values indicate worsening from baseline.
    Time Frame At Weeks 4, 16, 28, and 40 and from Flare Week 0 to Flare Week 16

    Outcome Measure Data

    Analysis Population Description
    Double-blind Treated Subject population: participants who received at least 1 dose of study drug during the Double-blind period and had at least Double-blind Baseline data for this endpoint
    Arm/Group Title Flared Participants Non-Flared Participants
    Arm/Group Description Participants who experienced flare during the Double-blind Period Participants who did not experience flare during the Double-blind Period
    Measure Participants 46 74
    Double Blind Week 16- Tapering Arm
    -8.0
    (17.25)
    -0.5
    (11.26)
    Double Blind Week 16- Withdrawal Arm
    9.4
    (20.04)
    2.8
    (9.42)
    Double Blind Week 28- Tapering arm
    -2.7
    (12.28)
    1.1
    (7.44)
    Double Blind Week 28- Withdrawal Arm
    14.1
    (28.13)
    2.8
    (9.42)
    Double Blind Week 40- Tapering Arm
    -2.3
    (14.86)
    1.1
    (11.61)
    Double Blind Week 40- Withdrawal Arm
    28.1
    (39.77)
    2.8
    (9.42)
    Flare Week 0- Tapering Arm
    -5.1
    (15.96)
    Flare Week 0- Withdrawal Arm
    2.7
    (7.09)
    Flare Week 4- Tapering Arm
    -5.0
    (19.52)
    Flare Week 4- Withdrawal Arm
    3.1
    (7.65)
    Flare Week 10- Tapering Arm
    -3.7
    (13.90)
    Flare Week 10- Withdrawal Arm
    2.7
    (7.09)
    Flare Week 16- Tapering Arm
    -2.0
    (6.60)
    Flare Week 16- Withdrawal Arm
    2.7
    (7.09)
    33. Secondary Outcome
    Title Mean Change From Double-blind Baseline in Treatment Satisfaction Questionnaire for Medication (TSQM) Convenience Score
    Description Participants completed the 14-item Treatment Satisfaction Questionnaire for Medication (TSQM; Version 1.4) to assess satisfaction with their current rheumatoid arthritis treatment over the previous 2-3 weeks or since the last time that they took the medication. The TSQM consists of fourteen items over four domains (effectiveness, side effects, convenience, and global satisfaction). The 14 questions are answered either with yes/no or by means of a five or seven stage scale (ranging from very unsatisfied to satisfied). TSQM Scale scores for each domain range from 0 to 100 and higher scores represent higher satisfaction. Negative values indicate worsening from baseline.
    Time Frame At Weeks 4, 16, 28, and 40 and from Flare Week 0 to Flare Week 16

    Outcome Measure Data

    Analysis Population Description
    Double-blind Treated Subject population: participants who received at least 1 dose of study drug during the Double-blind period and had at least Double-blind Baseline data for this endpoint
    Arm/Group Title Flared Participants Non-Flared Participants
    Arm/Group Description Participants who experienced flare during the Double-blind Period Participants who did not experience flare during the Double-blind Period
    Measure Participants 46 74
    Double Blind Week 16- Tapering Arm
    -0.2
    (16.96)
    0.8
    (13.45)
    Double Blind Week 16- Withdrawal Arm
    -4.9
    (19.57)
    4.0
    (10.86)
    Double Blind Week 28- Tapering arm
    0.0
    (18.70)
    -1.0
    (15.47)
    Double Blind Week 28- Withdrawal Arm
    -4.2
    (12.32)
    -3.5
    (13.21)
    Double Blind Week 40- Tapering Arm
    -4.0
    (9.65)
    -0.1
    (16.50)
    Double Blind Week 40- Withdrawal Arm
    -16.7
    (23.57)
    2.5
    (18.32)
    Flare Week 0- Tapering Arm
    4.2
    (12.53)
    Flare Week 0- Withdrawal Arm
    -7.1
    (14.60)
    Flare Week 4- Tapering Arm
    4.4
    (19.84)
    Flare Week 4- Withdrawal Arm
    5.6
    (18.92)
    Flare Week 10- Tapering Arm
    1.2
    (10.60)
    Flare Week 10- Withdrawal Arm
    0.8
    (16.49)
    Flare Week 16- Tapering Arm
    1.6
    (19.65)
    Flare Week 16- Withdrawal Arm
    0.8
    (20.89)
    34. Secondary Outcome
    Title Mean Change From Double-blind Baseline in Treatment Satisfaction Questionnaire for Medication (TSQM) Global Satisfaction Score
    Description Participants completed the 14-item Treatment Satisfaction Questionnaire for Medication (TSQM; Version 1.4) to assess satisfaction with their current rheumatoid arthritis treatment over the previous 2-3 weeks or since the last time that they took the medication. The TSQM consists of fourteen items over four domains (effectiveness, side effects, convenience, and global satisfaction). The 14 questions are answered either with yes/no or by means of a five or seven stage scale (ranging from very unsatisfied to satisfied). TSQM Scale scores for each domain range from 0 to 100 and higher scores represent higher satisfaction. Negative values indicate worsening from baseline.
    Time Frame At Weeks 4, 16, 28, and 40 and from Flare Week 0 to Flare Week 16

    Outcome Measure Data

    Analysis Population Description
    Double-blind Treated Subject population: participants who received at least 1 dose of study drug during the Double-blind period and had at least Double-blind Baseline data for this endpoint
    Arm/Group Title Flared Participants Non-Flared Participants
    Arm/Group Description Participants who experienced flare during the Double-blind Period Participants who did not experience flare during the Double-blind Period
    Measure Participants 46 74
    Double Blind Week 16- Tapering Arm
    -11.6
    (24.99)
    -3.4
    (17.91)
    Double Blind Week 16- Withdrawal Arm
    -2.7
    (15.24)
    0.6
    (22.69)
    Double Blind Week 28- Tapering arm
    -2.2
    (12.70)
    -5.7
    (14.97)
    Double Blind Week 28- Withdrawal Arm
    5.4
    (15.84)
    -4.5
    (25.81)
    Double Blind Week 40- Tapering Arm
    -3.2
    (13.31)
    -2.6
    (15.10)
    Double Blind Week 40- Withdrawal Arm
    0.0
    (10.10)
    -3.2
    (21.98)
    Flare Week 0- Tapering Arm
    -11.7
    (27.58)
    Flare Week 0- Withdrawal Arm
    -9.2
    (25.66)
    Flare Week 4- Tapering Arm
    -3.1
    (20.32)
    Flare Week 4- Withdrawal Arm
    -1.2
    (24.08)
    Flare Week 10- Tapering Arm
    -0.8
    (13.77)
    Flare Week 10- Withdrawal Arm
    -2.0
    (18.77)
    Flare Week 16- Tapering Arm
    -6.6
    (24.20)
    Flare Week 16- Withdrawal Arm
    -8.2
    (16.72)
    35. Secondary Outcome
    Title Mean Change From Double-blind Baseline in Work Productivity and Activity Impairment (WPAI) Overall Work Impairment and Activity Impairment Scores
    Description The Work Productivity and Activity Impairment (WPAI) questionnaire for general health is a validated tool in rheumatoid arthritis consisting of 6 questions, based on participant recall of the previous 7 days. WPAI assesses work time missed due to illness (absenteeism), impairment at work due to health (presenteeism), overall work impairment due to health (an aggregate measure of both absenteeism and presenteeism), and total non-occupational activity impairment due to health. WPAI scores are expressed as impairment percentages, with higher scores indicating worse outcomes. A negative change from baseline indicates improvement.
    Time Frame At Weeks 4, 28, and 40 and Flare Weeks 0, 10, and 16

    Outcome Measure Data

    Analysis Population Description
    Double-blind Treated Subject population: participants who received at least 1 dose of study drug during the Double-blind period and had at least Double-blind Baseline data for this endpoint
    Arm/Group Title Flared Participants Non-Flared Participants
    Arm/Group Description Participants who experienced flare during the Double-blind Period Participants who did not experience flare during the Double-blind Period
    Measure Participants 46 75
    Overall Work Impairment at Week 28- Tapering Arm
    15.0
    (21.21)
    3.5
    (10.68)
    Overall Work Impairment at Week 28- Withdrawal Arm
    0.0
    0.6
    (8.12)
    Activity Impairment at Week 28- Tapering arm
    5.0
    (19.51)
    2.8
    (13.43)
    Activity Impairment at Week 28- Withdrawal Arm
    10.0
    (17.32)
    -0.9
    (7.01)
    Overall Work Impairment at Week 40- Tapering Arm
    3.4
    (18.78)
    Overall Work Impairment at Week 40- Withdrawal Arm
    0.6
    (8.12)
    Activity Impairment at Week 40- Tapering arm
    15.7
    (9.76)
    0.5
    (13.59)
    Activity Impairment at Week 40- Withdrawal Arm
    20.0
    0.0
    (6.32)
    Overall Work Impairment Flare Wk 0- Tapering Arm
    14.0
    (27.02)
    Overall Work Impairment Flare Wk 0- Withdrawal Arm
    5.0
    (7.07)
    Activity Impairment Flare Week 0- Tapering Arm
    25.9
    (31.57)
    Activity Impairment Flare Week 0- Withdrawal Arm
    8.0
    (25.88)
    Overall Work Impairment Flare Wk 10- Tapering Arm
    -0.2
    (8.78)
    Overall Work Impairment Flare W 10- Withdrawal Arm
    5.0
    (7.07)
    Activity Impairment Flare Wk 10- Tapering Arm
    6.5
    (15.48)
    Activity Impairment Flare W 10- Withdrawal Arm
    12.9
    (13.80)
    Overall Work Impairment Flare Wk 16- Tapering Arm
    10.0
    (14.82)
    Overall Work Impairment Flare W 16- Withdrawal Arm
    10.0
    (10.00)
    Activity Impairment Flare Wk 16- Tapering Arm
    11.0
    (17.39)
    Activity Impairment Flare Wk 16- Withdrawal Arm
    8.8
    (11.26)
    36. Secondary Outcome
    Title Mean Change From Double-blind Baseline in Short-Form 36 Version 2 Health Survey (SF-36v2) Physical Component Summary (PCS) Score
    Description The SF-36v2 is a non-disease specific Health Related Quality of Life (HRQoL) instrument. The SF-36v2 comprises 36 total items (questions) targeting a subject's functional health and well-being in 8 domains (physical functioning, role physical, bodily pain, general health, vitality, social functioning, role emotional and mental health) with a recall period of four weeks. Domain scores are aggregated into a Physical Component Summary (PCS) score and a Mental Component Summary (MCS) score. SF-36v2 scores for each domain and PCS/MCS range from 0-100: higher scores indicate a better state of health and a decrease from baseline represents worsening.
    Time Frame At Weeks 4, 28, and 40 and from Flare Week 0 to Flare Week 16

    Outcome Measure Data

    Analysis Population Description
    Double-blind Treated Subject population: participants who received at least 1 dose of study drug during the Double-blind period and had at least Double-blind Baseline data for this endpoint
    Arm/Group Title Flared Participants Non-Flared Participants
    Arm/Group Description Participants who experienced flare during the Double-blind Period Participants who did not experience flare during the Double-blind Period
    Measure Participants 45 74
    Double Blind Week 28- Tapering arm
    -2.9
    (7.53)
    -1.1
    (4.18)
    Double Blind Week 28- Withdrawal Arm
    -1.9
    (7.39)
    -2.4
    (3.97)
    Double Blind Week 40- Tapering Arm
    -5.5
    (6.42)
    -0.4
    (5.53)
    Double Blind Week 40- Withdrawal Arm
    -1.6
    -2.1
    (5.22)
    Flare Week 0- Tapering Arm
    -10.8
    (10.85)
    Flare Week 0- Withdrawal Arm
    -2.4
    (10.81)
    Flare Week 4- Tapering Arm
    -5.2
    (8.37)
    Flare Week 4- Withdrawal Arm
    -8.0
    (7.35)
    Flare Week 10- Tapering Arm
    -4.0
    (7.22)
    Flare Week 10- Withdrawal Arm
    -4.0
    (4.57)
    Flare Week 16- Tapering Arm
    -3.8
    (7.38)
    Flare Week 16- Withdrawal Arm
    -2.5
    (2.80)
    37. Secondary Outcome
    Title Mean Change From Double-blind Baseline in Short-Form 36 Version 2 Health Survey (SF-36v2) Mental Component Summary (MCS) Score
    Description The SF-36v2 is a non-disease specific Health Related Quality of Life (HRQoL) instrument. The SF-36v2 comprises 36 total items (questions) targeting a subject's functional health and well-being in 8 domains (physical functioning, role physical, bodily pain, general health, vitality, social functioning, role emotional and mental health) with a recall period of four weeks. Domain scores are aggregated into a Physical Component Summary (PCS) score and a Mental Component Summary (MCS) score. SF-36v2 scores for each domain and PCS/MCS range from 0-100: higher scores indicate a better state of health and a decrease from baseline represents worsening.
    Time Frame At Weeks 4, 28, and 40 and from Flare Week 0 to Flare Week 16

    Outcome Measure Data

    Analysis Population Description
    Double-blind Treated Subject population: participants who received at least 1 dose of study drug during the Double-blind period and had at least Double-blind Baseline data for this endpoint
    Arm/Group Title Flared Participants Non-Flared Participants
    Arm/Group Description Participants who experienced flare during the Double-blind Period Participants who did not experience flare during the Double-blind Period
    Measure Participants 45 74
    Double Blind Week 28- Tapering arm
    -5.5
    (11.31)
    -0.8
    (6.02)
    Double Blind Week 28- Withdrawal Arm
    -5.2
    (5.90)
    -0.1
    (7.20)
    Double Blind Week 40- Tapering Arm
    -3.5
    (11.14)
    -0.8
    (5.89)
    Double Blind Week 40- Withdrawal Arm
    -8.5
    -0.4
    (6.71)
    Flare Week 0- Tapering Arm
    -4.1
    (11.43)
    Flare Week 0- Withdrawal Arm
    0.4
    (4.59)
    Flare Week 4- Tapering Arm
    -2.0
    (5.95)
    Flare Week 4- Withdrawal Arm
    -0.5
    (2.51)
    Flare Week 10- Tapering Arm
    -1.1
    (10.14)
    Flare Week 10- Withdrawal Arm
    -0.4
    (3.06)
    Flare Week 16- Tapering Arm
    -4.0
    (11.01)
    Flare Week 16- Withdrawal Arm
    0.1
    (2.55)
    38. Secondary Outcome
    Title Mean Change From Double-blind Baseline in Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue Scale
    Description The FACIT-Fatigue questionnaire is a participant questionnaire that consists of 13 questions designed to measure the degree of fatigue experienced by participants in the previous 7 days. Participants respond to the questions on a scale from 'not at all' (0) to 'very much' (4). The scale score is computed by summing the item scores, after reversing those items that are worded in the negative direction. The FACIT-Fatigue subscale score ranges from 0 to 52, where higher scores represent less fatigue. A negative change from baseline indicates worsening.
    Time Frame At Weeks 4, 16, 28, and 40 and from Flare Week 0 to Flare Week 16

    Outcome Measure Data

    Analysis Population Description
    Double-blind Treated Subject population: participants who received at least 1 dose of study drug during the Double-blind period and had at least Double-blind Baseline data for this endpoint
    Arm/Group Title Flared Participants Non-Flared Participants
    Arm/Group Description Participants who experienced flare during the Double-blind Period Participants who did not experience flare during the Double-blind Period
    Measure Participants 46 74
    Double Blind Week 16- Tapering Arm
    -6.0
    (9.80)
    -1.5
    (5.42)
    Double Blind Week 16- Withdrawal Arm
    -2.3
    (3.39)
    -1.9
    (3.27)
    Double Blind Week 28- Tapering arm
    -3.5
    (7.58)
    -1.6
    (5.60)
    Double Blind Week 28- Withdrawal Arm
    -4.3
    (7.23)
    -2.2
    (4.67)
    Double Blind Week 40- Tapering Arm
    -6.4
    (8.44)
    -0.4
    (4.00)
    Double Blind Week 40- Withdrawal Arm
    -2.5
    (6.36)
    -1.5
    (4.78)
    Flare Week 0- Tapering Arm
    -7.4
    (11.17)
    Flare Week 0- Withdrawal Arm
    -3.6
    (4.75)
    Flare Week 4- Tapering Arm
    -3.8
    (9.19)
    Flare Week 4- Withdrawal Arm
    -4.7
    (5.43)
    Flare Week 10- Tapering Arm
    -3.9
    (8.44)
    Flare Week 10- Withdrawal Arm
    -2.4
    (4.47)
    Flare Week 16- Tapering Arm
    -4.5
    (9.01)
    Flare Week 16- Withdrawal Arm
    -1.7
    (1.89)
    39. Secondary Outcome
    Title Mean Change From Double-blind Baseline in Serum Levels of C-reactive Protein (CRP)
    Description C-Reactive Protein (CRP; mg/L) was measured from blood samples as a marker for inflammation. Higher levels are indicative of more inflammation. Negative values indicate improvement from baseline.
    Time Frame From Week 4 to Week 40 and from Flare Week 0 to Flare Week 16

    Outcome Measure Data

    Analysis Population Description
    Double-blind Treated Subject population: participants who received at least 1 dose of study drug during the Double-blind period and had at least Double-blind Baseline data for this endpoint
    Arm/Group Title Flared Participants Non-Flared Participants
    Arm/Group Description Participants who experienced flare during the Double-blind Period Participants who did not experience flare during the Double-blind Period
    Measure Participants 46 76
    Double Blind Week 10- Tapering Arm
    -7.9
    (48.87)
    1.7
    (12.92)
    Double Blind Week 10- Withdrawal Arm
    -0.2
    (3.55)
    -0.6
    (2.53)
    Double Blind Week 16- Tapering Arm
    -7.4
    (49.77)
    -0.4
    (4.26)
    Double Blind Week 16- Withdrawal Arm
    6.6
    (12.26)
    -0.1
    (3.67)
    Double Blind Week 22- Tapering Arm
    3.6
    (9.69)
    -0.0
    (5.43)
    Double Blind Week 22- Withdrawal arm
    0.6
    (0.37)
    -0.9
    (3.38)
    Double Blind Week 28- Tapering arm
    0.5
    (3.85)
    -0.4
    (4.65)
    Double Blind Week 28- Withdrawal Arm
    1.1
    (1.34)
    2.5
    (11.60)
    Double Blind Week 34- Tapering Arm
    3.2
    (10.13)
    -0.4
    (4.41)
    Double Blind Week 34- Withdrawal Arm
    1.8
    (1.89)
    0.3
    (5.98)
    Double Blind Week 40- Tapering Arm
    1.0
    (5.69)
    -0.3
    (4.18)
    Double Blind Week 40- Withdrawal Arm
    8.3
    (11.60)
    -0.1
    (3.43)
    Flare Week 0- Tapering Arm
    -7.4
    (54.12)
    Flare Week 0- Withdrawal Arm
    5.4
    (12.67)
    Flare Week 4- Tapering Arm
    -8.5
    (55.47)
    Flare Week 4- Withdrawal Arm
    -1.3
    (4.01)
    Flare Week 10- Tapering Arm
    -9.5
    (55.61)
    Flare Week 10- Withdrawal Arm
    -0.6
    (0.97)
    Flare Week 16- Tapering Arm
    -9.1
    (53.70)
    Flare Week 16- Withdrawal Arm
    -0.8
    (2.74)
    40. Secondary Outcome
    Title Mean Change From Double-blind Baseline in Serum Levels of Erythrocyte Sedimentation Rate (ESR)
    Description Erythrocyte sedimentation rate (ESR; mm/hour) indirectly measures how much inflammation is in the body. A higher ESR is indicative of increased inflammation. Negative values indicate improvement from baseline.
    Time Frame From Week 4 to Week 40 and from Flare Week 0 to Flare Week 16

    Outcome Measure Data

    Analysis Population Description
    Double-blind Treated Subject population: participants who received at least 1 dose of study drug during the Double-blind period and had at least Double-blind Baseline data for this endpoint
    Arm/Group Title Flared Participants Non-Flared Participants
    Arm/Group Description Participants who experienced flare during the Double-blind Period Participants who did not experience flare during the Double-blind Period
    Measure Participants 46 76
    Double Blind Week 10- Tapering Arm
    4.1
    (11.25)
    0.7
    (5.22)
    Double Blind Week 10- Withdrawal Arm
    0.9
    (9.24)
    -1.5
    (5.43)
    Double Blind Week 16- Tapering Arm
    4.6
    (10.73)
    0.5
    (5.82)
    Double Blind Week 16- Withdrawal Arm
    5.2
    (15.23)
    -0.3
    (5.31)
    Double Blind Week 22- Tapering Arm
    3.5
    (10.73)
    -0.5
    (7.38)
    Double Blind Week 22- Withdrawal arm
    2.8
    (9.22)
    -0.3
    (4.22)
    Double Blind Week 28- Tapering arm
    3.4
    (8.18)
    0.4
    (6.93)
    Double Blind Week 28- Withdrawal Arm
    6.0
    (10.10)
    1.0
    (5.04)
    Double Blind Week 34- Tapering Arm
    4.8
    (7.28)
    0.3
    (7.57)
    Double Blind Week 34- Withdrawal Arm
    -5.0
    (1.41)
    -0.5
    (5.94)
    Double Blind Week 40- Tapering Arm
    10.2
    (13.22)
    1.4
    (7.19)
    Double Blind Week 40- Withdrawal Arm
    -2.0
    (5.66)
    4.7
    (8.89)
    Flare Week 0- Tapering Arm
    10.4
    (12.50)
    Flare Week 0- Withdrawal Arm
    13.0
    (11.90)
    Flare Week 4- Tapering Arm
    7.2
    (9.82)
    Flare Week 4- Withdrawal Arm
    8.5
    (9.52)
    Flare Week 10- Tapering Arm
    5.8
    (10.16)
    Flare Week 10- Withdrawal Arm
    4.4
    (6.91)
    Flare Week 16- Tapering Arm
    8.0
    (10.95)
    Flare Week 16- Withdrawal Arm
    7.0
    (14.40)

    Adverse Events

    Time Frame Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) were collected from first dose of study drug until 70 days after the last dose of study drug in the Double-blind Period (up to 50 weeks); for participants who experienced flare during the double-blind period, AEs were collected until 70 days after the last dose of study drug in the 16-week Open-label Rescue Period (up to 66 weeks).
    Adverse Event Reporting Description TEAEs and TESAEs are defined as any adverse event (AE) with an onset date that is on or after the first dose of study drug until 70 days after the last dose of study drug and were collected whether elicited or spontaneously reported by the participant.
    Arm/Group Title Adalimumab 40 mg Eow Adalimumab Tapering Adalimumab Withdrawal Arm Adalimumab 40 mg Eow Rescue Arm
    Arm/Group Description 40 mg adalimumab administered subcutaneously every other week (eow) from Week 0 to Week 4 40 mg adalimumab administered subcutaneously every three weeks from Week 4 to Week 40 (Double-blind Period) Placebo administered subcutaneously every three weeks from Week 4 to Week 40 (Double-blind Period) 40 mg adalimumab administered subcutaneously every other week from Flare Week 0 to Flare Week 16 (Open-label Rescue Period)
    All Cause Mortality
    Adalimumab 40 mg Eow Adalimumab Tapering Adalimumab Withdrawal Arm Adalimumab 40 mg Eow Rescue Arm
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/146 (0%) 0/102 (0%) 0/20 (0%) 0/39 (0%)
    Serious Adverse Events
    Adalimumab 40 mg Eow Adalimumab Tapering Adalimumab Withdrawal Arm Adalimumab 40 mg Eow Rescue Arm
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 4/146 (2.7%) 1/102 (1%) 0/20 (0%) 3/39 (7.7%)
    Cardiac disorders
    ATRIAL FIBRILLATION 1/146 (0.7%) 1 0/102 (0%) 0 0/20 (0%) 0 0/39 (0%) 0
    Eye disorders
    RETINAL VEIN OCCLUSION 0/146 (0%) 0 0/102 (0%) 0 0/20 (0%) 0 1/39 (2.6%) 1
    Infections and infestations
    PNEUMONIA 1/146 (0.7%) 1 0/102 (0%) 0 0/20 (0%) 0 0/39 (0%) 0
    Injury, poisoning and procedural complications
    COMMINUTED FRACTURE 1/146 (0.7%) 1 0/102 (0%) 0 0/20 (0%) 0 0/39 (0%) 0
    Musculoskeletal and connective tissue disorders
    OSTEOARTHRITIS 0/146 (0%) 0 0/102 (0%) 0 0/20 (0%) 0 1/39 (2.6%) 1
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    BREAST CANCER 0/146 (0%) 0 1/102 (1%) 1 0/20 (0%) 0 0/39 (0%) 0
    Nervous system disorders
    TRANSIENT ISCHAEMIC ATTACK 1/146 (0.7%) 1 0/102 (0%) 0 0/20 (0%) 0 0/39 (0%) 0
    Respiratory, thoracic and mediastinal disorders
    PLEURAL EFFUSION 0/146 (0%) 0 0/102 (0%) 0 0/20 (0%) 0 1/39 (2.6%) 1
    Other (Not Including Serious) Adverse Events
    Adalimumab 40 mg Eow Adalimumab Tapering Adalimumab Withdrawal Arm Adalimumab 40 mg Eow Rescue Arm
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 11/146 (7.5%) 33/102 (32.4%) 12/20 (60%) 13/39 (33.3%)
    General disorders
    OEDEMA PERIPHERAL 0/146 (0%) 0 0/102 (0%) 0 1/20 (5%) 1 1/39 (2.6%) 1
    Infections and infestations
    INFLUENZA 0/146 (0%) 0 5/102 (4.9%) 6 2/20 (10%) 2 0/39 (0%) 0
    LOWER RESPIRATORY TRACT INFECTION 1/146 (0.7%) 1 3/102 (2.9%) 3 1/20 (5%) 1 1/39 (2.6%) 1
    NASOPHARYNGITIS 4/146 (2.7%) 4 16/102 (15.7%) 17 4/20 (20%) 5 4/39 (10.3%) 4
    PHARYNGOTONSILLITIS 0/146 (0%) 0 0/102 (0%) 0 1/20 (5%) 1 0/39 (0%) 0
    TONSILLITIS 0/146 (0%) 0 0/102 (0%) 0 1/20 (5%) 1 0/39 (0%) 0
    TOOTH INFECTION 1/146 (0.7%) 1 0/102 (0%) 0 1/20 (5%) 1 1/39 (2.6%) 1
    UPPER RESPIRATORY TRACT INFECTION 0/146 (0%) 0 1/102 (1%) 1 0/20 (0%) 0 3/39 (7.7%) 3
    URINARY TRACT INFECTION 2/146 (1.4%) 2 0/102 (0%) 0 0/20 (0%) 0 2/39 (5.1%) 2
    Injury, poisoning and procedural complications
    LIMB INJURY 0/146 (0%) 0 0/102 (0%) 0 2/20 (10%) 2 1/39 (2.6%) 1
    MUSCLE STRAIN 0/146 (0%) 0 0/102 (0%) 0 1/20 (5%) 1 0/39 (0%) 0
    Investigations
    C-REACTIVE PROTEIN INCREASED 0/146 (0%) 0 1/102 (1%) 1 1/20 (5%) 1 0/39 (0%) 0
    HEPATIC ENZYME INCREASED 0/146 (0%) 0 0/102 (0%) 0 0/20 (0%) 0 2/39 (5.1%) 2
    Musculoskeletal and connective tissue disorders
    ARTHRALGIA 0/146 (0%) 0 6/102 (5.9%) 10 0/20 (0%) 0 1/39 (2.6%) 1
    BACK PAIN 0/146 (0%) 0 1/102 (1%) 1 1/20 (5%) 1 0/39 (0%) 0
    MUSCULOSKELETAL STIFFNESS 0/146 (0%) 0 1/102 (1%) 1 1/20 (5%) 1 0/39 (0%) 0
    NECK PAIN 0/146 (0%) 0 0/102 (0%) 0 1/20 (5%) 1 0/39 (0%) 0
    OSTEOPOROSIS 0/146 (0%) 0 0/102 (0%) 0 1/20 (5%) 1 0/39 (0%) 0
    PAIN IN EXTREMITY 0/146 (0%) 0 1/102 (1%) 1 1/20 (5%) 1 0/39 (0%) 0
    RHEUMATOID ARTHRITIS 0/146 (0%) 0 5/102 (4.9%) 5 1/20 (5%) 1 0/39 (0%) 0
    Renal and urinary disorders
    URINARY RETENTION 0/146 (0%) 0 0/102 (0%) 0 1/20 (5%) 1 0/39 (0%) 0
    Respiratory, thoracic and mediastinal disorders
    COUGH 4/146 (2.7%) 4 4/102 (3.9%) 4 1/20 (5%) 1 0/39 (0%) 0

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    AbbVie requests that any investigator or institution that plans on presenting/publishing results disclosure, provide written notification of their request 60 days prior to their presentation/publication. AbbVie requests that no presentation/publication will be instituted until 12 months after a study is completed, or after the first presentation/publication whichever occurs first. A delay may be proposed of a presentation/publication if AbbVie needs to secure patent or proprietary protection.

    Results Point of Contact

    Name/Title Global Medical Services
    Organization AbbVie
    Phone 800-633-9110
    Email abbvieclinicaltrials@abbvie.com
    Responsible Party:
    AbbVie
    ClinicalTrials.gov Identifier:
    NCT02198651
    Other Study ID Numbers:
    • M14-500
    • 2014-001114-26
    First Posted:
    Jul 24, 2014
    Last Update Posted:
    Jun 25, 2019
    Last Verified:
    Jun 1, 2019