Phase 4
N=149
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
Rheumatoid Arthritis · Musculoskeletal and Connective Tissue Diseases
Bottom Line
View on ClinicalTrials.gov: NCT02198651 ↗Enrolled (actual)
149
Serious AEs
2.6%
Results posted
Jun 2019
Primary outcome: Primary: 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 — 0.993 odds ratio — p=0.943
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 4
- Interventions
- Adalimumab (Biological); Placebo (Other)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- AbbVie
- Primary completion
- May 2018
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY 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 |
0.993 | 0.943 |
| PRIMARY Association Between Baseline Bone Marrow Edema RAMRIS Score and Flare up to Week 40 in the Tapering Arm |
0.959 | 0.592 |
| PRIMARY 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 |
0.979 | 0.688 |
| SECONDARY Median Time to Flare |
NA; NA | — |
| SECONDARY Physicians' Assessment of Flare Severity |
1; 1; 2; 0; 3; 0 | — |
| SECONDARY Participants' Assessment of Flare Severity |
1; 0; 2; 1; 2; 2 | — |
| SECONDARY Percentage of Participants With a Flare |
36.3; 45.0 | — |
| SECONDARY Number of Participants Who Regained Clinical Remission in the Open-Label Rescue Arm Over Time |
3; 1; 14; 1; 17; 3 | — |
| SECONDARY Median Time to Clinical Remission From the Occurrence of Flare |
6.1; 18.0 | — |
| SECONDARY Mean Change From Double-blind Baseline in Disease Activity Score 28 (DAS28) |
0.7; 0.1; 0.1; 0.1; 1.2; 0.1 | — |
| SECONDARY Mean Change From Double-blind Baseline in Clinical Disease Activity Index (CDAI) Score |
4.4; 0.6; 1.0; 1.4; 7.0; 0.4 | — |
| SECONDARY Mean Change From Double-blind Baseline in Simplified Disease Activity Index (SDAI) Score |
3.7; 0.8; 0.9; 1.3; 6.3; 0.4 | — |
| SECONDARY 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 |
102; 89; 85; 20; 19; 19 | — |
| SECONDARY Mean Change From Double-blind Baseline to Week 40 or Final Visit in Magnetic Resonance Imaging (MRI) Synovitis Score |
-0.1; 0.1; 0.0; -0.1; 0.8; 0.1 | — |
| SECONDARY Mean Change From Double-blind Baseline to Week 40 or Final Visit in Bone Marrow Edema (BME) Score |
-0.5; 0.0; 0.0; 1.2; -0.1; 0.3 | — |
| SECONDARY Mean Change From Double-blind Baseline to Week 40 or Final Visit in Bone Erosions Rheumatoid Arthritis Magnetic Resonance Imaging Scoring System (RAMRIS) Score |
-0.5; 0.1; -2.0; 0.0; 0.3; 0.1 | — |
| SECONDARY Mean Change From Double-blind Baseline in Health Assessment Questionnaire- Disability Index (HAQ-DI) Score Over Time |
0.1; 0.0; 0.3; 0.0; 0.2; -0.0 | — |
| SECONDARY Number of Participants With Health Assessment Questionnaire- Disability Index (HAQ-DI) Score ≤ 0.5 at Double-blind Baseline and at Week 40 |
21; 50; 7; 10; 2; 48 | — |
| SECONDARY Mean Change From Double-blind Baseline in Routine Assessment of Patient Index Data (RAPID3) Questionnaire Scores Assessed During In-office Visits |
1.9; 0.7; 1.4; 1.5; 4.7; 0.8 | — |
| SECONDARY Mean Change From Flare Week 0 in Routine Assessment of Patient Index Data (RAPID3) Questionnaire Scores Assessed at Home |
-1.6; 3.7; -3.1; 0.8; -3.8; -0.4 | — |
| SECONDARY Mean Change From Double-blind Baseline in Swollen Joint Count 28 |
0.9; 0.1; 0.1; -0.1; 1.2; -0.0 | — |
| SECONDARY Mean Change From Double-blind Baseline in Swollen Joint Count 66 |
1.1; 0.1; 0.1; -0.2; 1.4; -0.0 | — |
| SECONDARY Mean Change From Double-blind Baseline in Tender Joint Count 28 |
1.3; 0.1; -0.1; 0.5; 2.5; 0.1 | — |
| SECONDARY Mean Change From Double-blind Baseline in Tender Joint Count 68 |
1.9; 0.3; 0.1; 0.9; 3.5; 0.2 | — |
| SECONDARY Mean Change From Double-blind Baseline in Participant's Global Assessment of Disease Activity |
11.6; 2.6; 8.0; 9.6; 20.5; 2.4 | — |
| SECONDARY Mean Change From Double-blind Baseline in Participant's Global Assessment of Rheumatoid Arthritis Pain |
8.0; 3.5; 6.4; 9.3; 17.8; 3.0 | — |
| SECONDARY Mean Change From Double-blind Baseline in Physician's Global Assessment of Disease Activity |
10.2; 1.3; 1.6; 0.5; 13.2; 0.9 | — |
| SECONDARY Mean Change From Double-blind Baseline in Morning Stiffness Duration |
3.5; 1.8; 1.1; 1.5; 6.6; 2.3 | — |
| SECONDARY Mean Change From Double-blind Baseline in Morning Stiffness Severity |
0.6; 0.4; 0.4; 0.6; 0.8; 0.3 | — |
| SECONDARY Mean Change From Double-blind Baseline in Participant's Assessment of Sleep Disturbance |
2.1; 0.0; -3.2; 0.8; 10.2; 1.7 | — |
| SECONDARY Mean Change From Double-blind Baseline in Treatment Satisfaction Questionnaire for Medication (TSQM) Effectiveness Score |
-8.3; 0.2; 2.8; -13.6; -10.1; -3.8 | — |
| SECONDARY Mean Change From Double-blind Baseline in Treatment Satisfaction Questionnaire for Medication (TSQM) Side Effects Score |
-8.0; -0.5; 9.4; 2.8; -2.7; 1.1 | — |
| SECONDARY Mean Change From Double-blind Baseline in Treatment Satisfaction Questionnaire for Medication (TSQM) Convenience Score |
-0.2; 0.8; -4.9; 4.0; 0.0; -1.0 | — |
| SECONDARY Mean Change From Double-blind Baseline in Treatment Satisfaction Questionnaire for Medication (TSQM) Global Satisfaction Score |
-11.6; -3.4; -2.7; 0.6; -2.2; -5.7 | — |
| SECONDARY Mean Change From Double-blind Baseline in Work Productivity and Activity Impairment (WPAI) Overall Work Impairment and Activity Impairment Scores |
15.0; 3.5; 0.0; 0.6; 5.0; 2.8 | — |
| SECONDARY Mean Change From Double-blind Baseline in Short-Form 36 Version 2 Health Survey (SF-36v2) Physical Component Summary (PCS) Score |
-2.9; -1.1; -1.9; -2.4; -5.5; -0.4 | — |
| SECONDARY Mean Change From Double-blind Baseline in Short-Form 36 Version 2 Health Survey (SF-36v2) Mental Component Summary (MCS) Score |
-5.5; -0.8; -5.2; -0.1; -3.5; -0.8 | — |
| SECONDARY Mean Change From Double-blind Baseline in Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue Scale |
-6.0; -1.5; -2.3; -1.9; -3.5; -1.6 | — |
| SECONDARY Mean Change From Double-blind Baseline in Serum Levels of C-reactive Protein (CRP) |
-7.9; 1.7; -0.2; -0.6; -7.4; -0.4 | — |
| SECONDARY Mean Change From Double-blind Baseline in Serum Levels of Erythrocyte Sedimentation Rate (ESR) |
4.1; 0.7; 0.9; -1.5; 4.6; 0.5 | — |
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.
Eligibility Criteria
Inclusion Criteria
- 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).
- 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.
- 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.
- 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).
- 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.
- 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.
- Participant must have been able and willing to provide written informed consent and comply with the requirements of this study protocol.
Exclusion Criteria
- 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.
- 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).
- Participant had been treated with intra-articular or parenteral corticosteroids within the last four weeks before Screening.
- Participant had undergone joint surgery within 12 weeks of Screening (at joints to be assessed by magnetic resonance imaging (MRI) and/or ultrasound).
- 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)
- 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]
- 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 long
Data sourced from ClinicalTrials.gov (NCT02198651). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.