Sequential treatment strategy for rheumatoid arthritis

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

This study is testing a new treatment plan for people with rheumatoid arthritis that starts with a specific medication to reduce inflammation and then switches to another medication to see if it helps them feel better when other treatments haven't worked.

Quick facts

• Phase: Phase 3
• Study type: Interventional
• Enrollment: 220 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: University Hospital, Montpellier (Academic / other)
• Drugs / interventions: methotrexate, rituximab, adalimumab
• Locations: 17 sites (Montpellier, France and 16 other locations)
• Trial ID: NCT05428488 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates a sequential treatment approach for rheumatoid arthritis (RA) that begins with a TNF inhibitor for 12 weeks to control inflammation, followed by the use of abatacept, a targeted biological DMARD. The study aims to determine the efficacy of this strategy in patients who have not achieved treatment targets with conventional synthetic DMARDs. Participants must be ACPA positive and have been on methotrexate or leflunomide for at least three months. The trial will assess the reduction of auto-antibodies and overall disease management.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with rheumatoid arthritis who are ACPA positive and have not responded adequately to methotrexate or leflunomide.

Not a fit: Patients with conditions such as dementia or fibromyalgia, or those who are not eligible for TNF inhibitors, may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could lead to improved management of rheumatoid arthritis and better long-term outcomes for patients.

How similar studies have performed: Previous studies have shown success with similar sequential treatment strategies, indicating potential for this novel approach.

Eligibility criteria

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)

Where this trial is running

Montpellier, France and 16 other locations

• Centre Hospitalier Universitaire de Montpellier — Montpellier, France, France (Recruiting)
• CHU Bordeaux groupe Pellegrin — Bordeaux, France (Recruiting)
• CHU de Brest La Cavale Blanche — Brest, France (Recruiting)
• Centre Hospitalier de Cahors — Cahors, France (Not_yet_recruiting)
• CHD Vendée — La Roche-sur-Yon, France (Recruiting)
• CH du Mans — Le Mans, France (Recruiting)
• CHU de Nantes — Nantes, France (Recruiting)
• CHU de Nice — Nice, France (Recruiting)
• CHU de Nîmes Carémeau — Nîmes, France (Not_yet_recruiting)
• CHR Orléans Nouvel hôpital d'Orléans — Orléans, France (Recruiting)
• APHP Bicêtre — Paris, France (Not_yet_recruiting)
• APHP Cochin — Paris, France (Recruiting)
• APHP La Pitié Salpetrière — Paris, France (Recruiting)
• CHU de Strasbourg Hautepierre — Strasbourg, France (Not_yet_recruiting)
• Chu Purpan — Toulouse, France (Not_yet_recruiting)
• CHU de Tours - Hopital Trousseau — Tours, France (Recruiting)
• Centre hospitalier Princesse Grace — Monaco, Monaco (Recruiting)

Study contacts

• Study coordinator: Jacques MOREL, MD-PhD

Conditions Rheumatoid Arthritis; Rheumatoid arthritis; sequential therapeutic strategy; immunological remission; anti-TNF; abatacept