Efficacy of a Sequential Treatment Strategy in Rheumatoid Arthritis. A Randomized Controlled Trial With an Independent Efficacy Assessor.

RECHMPL_21_0568

In rheumatoid arthritis (RA), the consensual 1st line conventional synthetic disease modifying antirheumatic drugs (csDMARD) of RA is methotrexate (MTX). In case of contra-indication or intolerance to MTX, leflunomide is an alternative. If the treatment target is not achieved with csDMARD strategy, addition of a biological DMARD (TNF inhibitors, anti-Interleukin 6 (anti-IL6)), abatacept, or rituximab) or a targeted synthetic (ts) DMARD (JAK inhibitors) is considered. Current practice is to start a bDMARD (biologic Disease Modifying Antirheumatic Drugs) and especially TNF inhibitors (etanercept or monoclonal anti-TNF antibodies) with the benefit of hindsight. However, abatacept and TNF inhibitors have demonstrated similar efficacy in patients with insufficient response to csDMARD (AMPLE trial). Although abatacept has shown a very good tolerance profile that might be superior to other bDMARDs rheumatologists might be reluctant to use it as a first line bDMARD as there is a belief of a slower efficacy compared to other bDMARDs or JAK inhibitors. Indeed, in real world study, compared to TNF inhibitors it seems that discontinuation of abatacept is more related to lack of effectiveness than safety issues. Investigators have hypothesized that first rapidly controlling the inflammation phase, using TNF inhibitors followed by abatacept to induce an immunological remission would optimize response and tolerance of ACPA positive patients with RA. To demonstrate our hypothesis, the investigaors propose a randomized controlled trial with one arm receiving an induction therapy for 12 weeks with a TNF inhibitor followed by a cell-targeted bDMARD (abatacept) and the other arm, receiving TNF inhibitors.

2022-11-28

2024-11-01

2025-11-01

Recruiting

Early phase I

220

Inclusion Criteria: * Aged between 18 or above * Rheumatoid arthritis according to ACR-EULAR 2010 (American College of Rheumatology-European League Against Rheumatism) * ACPA positive * Under methotrexate or leflunomide treatment for at least 3 months * DAS28-CRP\>3.2 under methotrexate or leflunomide calculated with CRP dated less than 7 days from baseline * Escape under synthetic background treatment defined by an elevation of C-reactive protein (CRP) (CRP\> 5mg/L ) or Erythrocyte sedimentation rate (ESR) (for men: \> age in years/2 ; for women: \> age (+10) /2)) within the last 6 months before baseline * Targeted DMARDs (biological and targeted synthetic DMARDs) naïve * Indication for a TNF inhibitor Exclusion Criteria: * Subject unable to read or/and write * Planned longer stay outside the region that prevents compliance with the visit plan * Subject unable to sign informed consent form * Subject not covered by public health insurance * Dementia * Fibromyalgia * Contra-indications to TNF inhibitor and/or Abatacept * Absence of tuberculosis screening in the previous 3 months before baseline * Patient with untreated active tuberculosis * Patient who cannot be followed during 48 weeks * Drug addiction, addiction to alcohol * Protected populations according to the French Public Health Code Articles L1121-5,6,8 (For example, pregnant, parturient or lactating women, prisoners, adults under guardianship or otherwise unable to consent). * Women of child bearing potential, unless they are using an effective method of birth control * Patient under law protection * Prisoners * Subject who are in a dependency or employment with the sponsor or the investigator * Participation in another interventional clinical trial or administration of an investigational product within the last 4 weeks before the screening date * Subject with moderate to severe heart failure (class 3 or class 4 cardiac disease as defined by the New York Heart Association Functional Classification) * Patients had a history of chronic obstructive pulmonary disease (COPD) and heavy smoking * Patients had a planned surgical procedure at least 30 days before the screening day * Known allergy or intolerance to an anti-TNF therapy * Hypersensitivity to the Abatacept or to any of its excipients * Patient with untreated active hepatitis B * Patient vaccinated with a live vaccine within 30 days prior to screening * Patients with an Inflammatory Bowel Disease (IBD) (loss of chance if switching from an anti-TNF to abatacept)

{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE3'], 'designInfo': {'allocation': 'RANDOMIZED', 'interventionModel': 'SEQUENTIAL', 'interventionModelDescription': 'This study will include a 12 weeks non-randomized phase. This phase will include RA patients ACPA+ with insufficient response to cs DMARDs and eligible for TNF inhibitors. All included patients will receive TNF inhibitors subcutaneous for 12 weeks.\n\nAt 12 weeks visit (W12), patients who have at least a moderate EULAR response (delta DAS28-CRP between and W0 and W12\\>0.6 and DAS28-CRP≤5.1 at W12) will be randomized with a 1:1 ratio in the sequential strategy arm or the control arm. Then, the randomized phase will be 36 weeks long.', 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'NONE'}}, 'enrollmentInfo': {'count': 220, 'type': 'ESTIMATED'}}

2023-09-28