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
Condition: Rheumatoid Arthritis; Musculoskeletal and Connective Tissue Diseases
MeSH terms: Arthritis; Arthritis, Rheumatoid; Connective Tissue Diseases; Inflammation
Intervention: Adalimumab; Placebo
Intervention description: Pre-filled syringe, administered by subcutaneous injection; Pre-filled syringe, administered by subcutaneous injection in the Double-blind period
Intervention MeSH terms: Adalimumab
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 149.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Rheumatoid Arthritis; Adalimumab; Taper; Flare; Arthritis; Anti-rheumatic drugs; Remission; Magnetic Resonance Imaging; Ultrasound; Biomarker; Drug Level; Reduced dose

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:

          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.

          3. 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.

          4. 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).

          5. 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.

          6. 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.

          7. 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.