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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
286
* 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
Hôpitaux Universitaires de Strasbourg
Strasbourg, France
RECRUITINGNumbers of participant with low disease activity (DAS28-CRP<3.2) and a daily dose ≤ 7.5 mg/day of equivalent prednisone
Time frame: At 12 months
Serious adverse events rate
Time frame: At 3, 6, 9 and at 12 months
Blood concentrations of hydroxychloroquine, leflunomide, sulfasalazine and methotrexate in the triple therapy group and methotrexate, leflunomide, biologic / JAK/STAT inhibitor and anti-drug antibody in the other group.
Time frame: at 6, and 12 months
Clinical disease activity index (CDAI).
Time frame: At inclusion, 3, 6, 9 and 12 months
DAS 28 CRP score.
Time frame: at inclusion, 3, 6, 9 and 12 months.
2010 ACR (American College of Rheumatology)/EULAR classification Criteria for RA, ACR 20, 50, 70 and boolean remission.
Time frame: at 3, 6, 9 and 12 months.
Modified Sharp Van der Heijde score.
Time frame: at inclusion and at 12 months
Change in comedications (dose)
Time frame: at 3, 6, 9 and 12 months
Change in comedications (route of administration)
Time frame: at 3, 6, 9 and 12 months
Change in comedications (drug)
Time frame: at 3, 6, 9 and 12 months
QUALISEX score at inclusion, 6 months and at 12 months.
Time frame: at inclusion, 6 months and at 12 months.
Medico-economic costs.
Time frame: at inclusion, 3, 6, 9 and at 12 months.
Treatment compliance
A questionnaire will be filled by patient
Time frame: at 3, 6, 9 and 12 months
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