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

Status: Recruiting
Location: See all (17) locations...
Intervention Type: Drug
Study Type: Interventional
Study Phase: Phase 3
SUMMARY

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.

Eligibility
Participation Requirements
Sex: All
Minimum Age: 18
Healthy Volunteers: f
View:

• 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

Locations
Other Locations
France
CHU Bordeaux groupe Pellegrin
RECRUITING
Bordeaux
CHU de Brest La Cavale Blanche
RECRUITING
Brest
Centre Hospitalier de Cahors
NOT_YET_RECRUITING
Cahors
CHD Vendée
RECRUITING
La Roche-sur-yon
CH du Mans
RECRUITING
Le Mans
Centre Hospitalier Universitaire de Montpellier
RECRUITING
Montpellier
CHU de Nantes
RECRUITING
Nantes
CHU de Nice
RECRUITING
Nice
CHU de Nîmes Carémeau
NOT_YET_RECRUITING
Nîmes
CHR Orléans Nouvel hôpital d'Orléans
RECRUITING
Orléans
APHP Bicêtre
NOT_YET_RECRUITING
Paris
APHP Cochin
RECRUITING
Paris
APHP La Pitié Salpetrière
RECRUITING
Paris
CHU de Strasbourg Hautepierre
NOT_YET_RECRUITING
Strasbourg
Chu Purpan
NOT_YET_RECRUITING
Toulouse
CHU de Tours - Hopital Trousseau
RECRUITING
Tours
Monaco
Centre hospitalier Princesse Grace
RECRUITING
Monaco
Contact Information
Primary
Jacques MOREL, MD-PhD
j-morel@chu-montpellier.fr
467338710
Time Frame
Start Date: 2022-11-28
Estimated Completion Date: 2027-11
Participants
Target number of participants: 220
Treatments
Experimental: Experimental
All included patients will receive TNF inhibitors subcutaneous for 12 weeks. In the experimental arm, a therapeutic sequential strategy will be proposed from W12 visit.~At 12 weeks (W12), patients who have at least a moderate EULAR response (delta DAS28-CRP between 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.~In the sequential strategy (experimental) arm, the 88 randomized RA patients will be switched to abatacept subcutaneous for 36 weeks.
Active_comparator: Control
All included patients will receive TNF inhibitors subcutaneous for 12 weeks. In the control group, the 88 randomized RA patients will be treated with TNF inhibitor subcutaneous for another 36 weeks (from W12 visit).~In case of insufficient response to a first TNF inhibitor at 24 or 36 weeks, a second TNF inhibitor will be proposed.
Related Therapeutic Areas
Sponsors
Leads: University Hospital, Montpellier

This content was sourced from clinicaltrials.gov