Clinical Trial Evaluating Methotrexate or Leflunomide + Targeted Therapy Versus Methotrexate or Leflunomide + Sulfasalazine + Hydroxychloroquine in Patients With Rheumatoid Arthritis and Insufficient Response to Methotrexate or Leflunomide

NCT ID: NCT02714634

Last Updated: 2025-03-12

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE4
• Total Enrollment: 286 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-03-30
• Study Completion Date: 2029-03-31

Brief Summary

Approximately, 40 to 50% of patients with rheumatoid arthritis (RA), the most frequent inflammatory arthritide, are non responders to the consensual 1st line of treatment : methotrexate. In these patients, it is well demonstrated that the addition of other immunomodulatory drug(s) often results in a significant improvement. However, the best option regarding the drug(s) to add remains unclear. Rheumatologists are currently used to adding a targeted therapy, such as anti-TNFα, and more recently abatacept or tocilizumab. Triple therapy using 3 conventional disease-modifying drugs (DMARDs), methotrexate or leflunomide+salazopyrine+hydroxychloroquine could be an alternative option to targeted therapies, all the more as they have a more favorable safety profile and a much lower cost. Uncertainty remains regarding the superiority of targeted therapies on triple therapy in methotrexate or leflunomide insufficient responders (IR). Investigators decided to address this issue by performing a randomized controlled pragmatic trial.

Conditions

Rheumatoid Arthritis; Insufficient Response to Methotrexate or Leflunomide

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

methotrexate + targeted therapy group

Methotrexate or leflunomide +

targeted therapy chosen by investigator

Group Type: EXPERIMENTAL

Methotrexate + targeted therapy administration

Intervention Type: DRUG

• Methotrexate or leflunomide + adalimumab or
• Methotrexate or leflunomide + certolizumab or
• Methotrexate or leflunomide + etanercept or
• Methotrexate or leflunomide + golimumab or
• Methotrexate or leflunomide + infliximab or
• Methotrexate or leflunomide + abatacept or
• Methotrexate or leflunomide + rituximab or
• Methotrexate or leflunomide + tocilizumab or
• Methotrexate or leflunomide + sarilumab or
• Methotrexate or leflunomide + filgotinib or
• Methotrexate or leflunomide + upadacitinib or
• Methotrexate or leflunomide + Tofacitinib or
• Methotrexate or leflunomide + baricitinib

Triple therapy

Triple therapy using 3 conventional disease modifying drugs (DMARDs)

Group Type: ACTIVE_COMPARATOR

methotrexate or leflunomide + sulfasalazine + hydroxychloroquine administration

Intervention Type: DRUG

Interventions

Methotrexate + targeted therapy administration

• Methotrexate or leflunomide + adalimumab or
• Methotrexate or leflunomide + certolizumab or
• Methotrexate or leflunomide + etanercept or
• Methotrexate or leflunomide + golimumab or
• Methotrexate or leflunomide + infliximab or
• Methotrexate or leflunomide + abatacept or
• Methotrexate or leflunomide + rituximab or
• Methotrexate or leflunomide + tocilizumab or
• Methotrexate or leflunomide + sarilumab or
• Methotrexate or leflunomide + filgotinib or
• Methotrexate or leflunomide + upadacitinib or
• Methotrexate or leflunomide + Tofacitinib or
• Methotrexate or leflunomide + baricitinib

Intervention Type: DRUG

methotrexate or leflunomide + sulfasalazine + hydroxychloroquine administration

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Patient with rheumatoid arthritis according to EULAR/ACR 2010 criteria
• DAS28-CRP>3.2
• Insufficient response to methotrexate at a weekly dose≥15mg after at least 3 months or to leflunomide at a dose of 10 (in case 20 mg are not well tolerated) to 20 mg per day after 3 months of treatment
• RA radiographic erosions and/or serum rheumatoid factor associated to anti-Cyclic Citrullinated Peptide (Anti-CCP)
• Age greater or equal to 18 years
• Written informed consent, dated and signed before initiating any trial-related procedure
• Affiliation to a social insurance system
• Women of child bearing potential, negative β-HCG assay (Human chorionic gonadotropin)
• Effective method of birth control during the study and continuing after the discontinuation of the investigational drug or study. The duration will depend on the drug used (referred to the summary product characteristic).

Exclusion Criteria

• Previous treatment with or contraindication to targeted therapies (biologic or JAK/STAT inhibitor)
• Previous treatment with triple therapy
• Other inflammatory arthritis except RA associated with Sjögren's syndrome
• Contraindication to all biologics/ JAK/STAT inhibitors or to methotrexate, leflunomide, sulfasalazine and hydroxychloroquine
• Corticosteroids at a dose >15 mg/d of equivalent prednisone for at least 4 weeks before the inclusion
• Absence of tuberculosis screening
• Patient who cannot be followed during 12 months
• Pregnancy, breastfeeding, desire of pregnancy in the 12 months
• Drug addiction, addiction to alcohol
• Participation in a clinical study with an investigational product within 4 weeks prior to the start of the study treatment
• Women of child bearing potential, unless they are using an effective method of birth control
• Patient under law protection
• Prisoners

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University Hospital, Strasbourg, France

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Hôpitaux Universitaires de Strasbourg

Strasbourg, , France

Site Status: RECRUITING

Countries

France

Central Contacts

Jacques-Eric GOTTENBERG, Professor

Role: CONTACT

jacques-eric.gottenberg@chru-strasbourg.fr

3 88 12 79 53 ext. +33

Facility Contacts

Jacques-Eric Gottenberg

Role: primary

jacques-eric.gottenberg@chru-strasbourg.fr

3 88 12 81 89 ext. 0033

Other Identifiers

6020

Identifier Type: -

Identifier Source: org_study_id