Efficacy of a Sequential Treatment Strategy in Rheumatoid Arthritis

• Status: Not yet recruiting
• Trial end date: 2025-09-01
• Target enrollment: 0
• Participant gender: All

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 three months with a TNF inhibitor followed by a cell-targeted bDMARD (abatacept) and the other arm, receiving TNF inhibitors.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University Hospital, Montpellier
• Treatments: Abatacept; Tumor Necrosis Factor Inhibitors

Criteria

Inclusion Criteria:

• Aged between 18 and 85 years

• 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

• CRP>5mg/l

• 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 a targeted biological DMARDS (current or recent cancer, active infection, multiple sclerosis)

• Absence of tuberculosis screening

• Patient with active tuberculosis

• Patient who cannot be followed during 12 months

• 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 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 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

• Known to be positive for hepatitis B

• Subject who received live virus vaccination within 30 days before recruitment into the study and up to 3 months after the last injection