Sequential treatment strategies following methotrexate inadequate response in rheumatoid arthritis: a real-world...

This study aimed to compare different treatment strategies for rheumatoid arthritis (RA) patients following inadequate response to initial methotrexate (MTX) therapy, evaluating clinical outcomes, tolerability profiles, and factors influencing treatment decisions in real-world clinical practice.

We retrospectively analysed 239 MTX non-responders from health records. Patients were grouped based on subsequent treatment: direct switch to biologic/targeted synthetic DMARDs (b/tsDMARDs) (n=45) or MTX dose escalation (n=194). Those failing dose escalation were further stratified into leflunomide (LEF) (n=37) or b/tsDMARD (n=57) groups. Treatment efficacy was assessed using modified EULAR Boolean criteria (3V-remission) at 6-month intervals.

While direct b/tsDMARD initiation achieved higher 3V-remission rates than MTX dose escalation (62.2% vs. 35.0%, p<0.001), MTX dose optimisation still enabled remission in over one-third of patients. Similarly, among MTX dose escalation non-responders, LEF therapy achieved 3V-remission in 43.2% of patients, comparable to b/tsDMARDs (50.9%, p=0.469), despite higher discontinuation rates (21.6% vs. 1.8%). Importantly, sequential csDMARD optimisation did not compromise subsequent b/tsDMARD responsiveness, with similar remission rates regardless of prior treatment exposure (62.2% after initial MTX, 50.9% post-dose escalation, 46.1% post-LEF, p=0.417).

While b/tsDMARDs demonstrated superior efficacy and tolerability, approximately one-third of patients achieved remission through MTX dose optimisation, possibly reflecting suboptimal initial dosing. Importantly, prior csDMARD optimisation did not compromise subsequent b/tsDMARD responsiveness. These findings underscore the importance of appropriate initial MTX dosing, while indicating that csDMARD optimisation before b/tsDMARD initiation should be considered, given the predominantly mild nature of observed adverse events.