In rheumatoid arthritis (RA), the consensual 1st line conventional synthetic disease modifying antirheumatic drugs (csDMARD) of RA is methotrexate (MTX) (1). 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 (b) DMARD (TNF inhibitors, anti-IL6, abatacept, or rituximab) or a targeted synthetic (ts) DMARD (JAK inhibitors) is considered.~Current practice is to start a bDMARD 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.~This is the first study to propose a therapeutic sequential strategy with an induction therapy using a TNF inhibitor for 3 months to control inflammation followed by a cell-targeted biological DMARD targeting T cells (abatacept) in order to decrease auto-antibodies (rheumatoid factor and/or ACPA).~Presence of auto-antibodies (ACPA/RF) are predictive of better response to cell- targeted DMARDs.~In early AMPLE trial, RA patients ACPA+ with insufficient response to MTX were treated with abatacept or adalimumab. DAS28-CRP remission rates were 55% in abatacept group and 30% in adalimumab group.~Patients carrying the shared epitope (HLA-DR (Human Leucocyte Antigen-DR) alleles associated with RA), were also more likely to reach remission (DAS28-CRP<2.6) with abatacept (50%) than adalimumab (23%) at 24 weeks.~The clinical trial offered by investigateors here could change the paradigm in the strategy used in RA supporting the importance to first control inflammation environment in order to allow the cell-targeted bDMARDs to control immunological process which has been recently associated with a higher percentage of clinical remission.~To compare the percentage of remission (DAS28-CRP<2.6) obtained during the 9 months following randomization, with a sequential therapeutic strategy using abatacept versus a routine strategy continuing TNF inhibitors (TNFi), in ACPA positive RA patients responding to a first TNFi, initiated 3 months before randomization.~The primary endpoint will be analyzed with a generalized estimating equations (GEE) model for repeated data.~It is a multicentric, open label, randomized controlled trial comparing two different strategies of treatment with an independent efficacy assessor. For this clinical trial, to limit response bias, bDMARDs with a similar mode of administration (subcutaneous) are proposed.~In the experimental arm, a therapeutic sequential strategy will be proposed and in the control arm TNF inhibitors will be proposed for 12 months. All included patients will receive TNF inhibitors subcutaneous for 3 months. At 3 months (M3), patients who have at least a moderate EULAR response (delta DAS28-CRP between M0 and M3>0.6 and DAS28-CRP≤5.1 at M3) will be randomized with a 1:1 ratio in the sequential strategy arm or the control arm. In the sequential strategy arm, the 88 randomized RA patients will be switched to abatacept subcutaneous for 9 months. Patients who will withdraw abatacept during the follow-up will be considered as a failure.~In the control group, the 88 randomized RA patients will be treated with TNF inhibitor subcutaneous for another 9 months. In case of insufficient response to a first TNF inhibitor at 6 or 9 months, a second TNF inhibitor will be proposed. Anti-TNF drugs withdrawal will be considered as a failure. Steroids 0.1mg/kg/ day will be allowed but at stable dose 2 weeks before and with guided step-down strategy targeting withdrawal before 6 months following randomization. Clinical evaluation of disease activity using different scores (DAS28-ESR, CDAI, SDAI, Boolean criteria) and tolerance will be performed at all visits.
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 three months with a TNF inhibitor followed by a cell-targeted bDMARD (abatacept) and the other arm, receiving TNF inhibitors.