Real-world epidemiology and management of patients with rheumatoid arthritis treated with methotrexate in France: a decade after methotrexate first recommendations

<h2>ABSTRACT</h2><h3>Objectives</h3> Methotrexate (MTX) is the primary systemic first-line treatment of rheumatoid arthritis (RA). Following the treat-to-target principle, MTX dose and administration route should be optimised before considering advanced therapies (biologic/targeted synthetic disease-modifying antirheumatic drugs [b/tsDMARDs]), notably in case of insufficient response or intolerance. This study examined patients with RA initiating MTX, assessed MTX optimisation before b/tsDMARD escalation, and evaluated b/tsDMARD economic impact. <h3>Methods</h3> This observational cohort study used claims data from the French national insurance database, identifying patients with RA (International Classification of Diseases–10th revision M05/M06) who began MTX treatment between January 1, 2016 and December 31, 2021. Among them, patients initiating MTX in 2016-2017 were followed through the end of the study or death. MTX persistence and b/tsDMARD escalation were analysed using the Kaplan-Meier estimator. Costs were described for a 1-year period before and after b/tsDMARD escalation. <h3>Results</h3> Between 2016 and 2021, 52,462 patients with RA initiated MTX (≈8700/y), mostly orally (79.1%). Mean (SD) age was 60.8 (14.3) years, with 71.0% of women. Two-year MTX persistence was 73.7% (73.0%-74.4%), increasing by ≈20 points in the case of form switch (from 66.8% to 83.8%). Also, 17.5% (16.9%-18.1%) of patients escalated to b/tsDMARD. Among the 3582 patients who escalated to b/tsDMARD, 1121 (31.3%) were treated with oral MTX and were not optimised with subcutaneous MTX before b/tsDMARD. Mean (SD) costs increased from €6218 (€12,259) in the year before to €13,131 (€10,408) the year after b/tsDMARDs initiation. <h3>Conclusions</h3> Despite a high persistence, many patients escalated to b/tsDMARDs without complete optimisation. Full optimisation of MTX in terms of dose and administration route could be one therapeutic means of delaying escalation to b/tsDMARD, thus preserving future treatment options.