Background Methotrexate (MTX) is one of the most commonly used drugs for the treatment of rheumatoid arthritis (RA). Recommendations by an international panel state that oral MTX should be started at 10–15mg/week, with escalation of 5mg every 2–4 weeks up to 20–30mg/week (1). In the UK, practice varies in terms of the starting dose prescribed for MTX, likely because of a lack of published evidence on the importance of MTX dose on its efficacy and safety.
Objectives To compare 6 month response to MTX in RA patients starting 7.5mg/wk versus those starting a 15mg/wk.
Methods Patients were recruited to the national, UK, multi-centre (n=35) longitudinal observational Rheumatoid Arthritis Medication Study (RAMS), including patients starting MTX for the first time with complete DAS28 at baseline and six months were included in this analysis. Patients were categorized into EULAR non-responders, moderate responders or good responders. Patients were categorised into those starting a low dose of MTX (≤7.5mg/wk) (LM-group) or a high dose of MTX (≥15mg/wk) (HM-group). A multinomial logistic regression model was used to test the association between MTX start dose and EULAR response at 6 months,with adjustments (see table) (relative risk ratio (RRR), 95% CI). The model was clustered by centre to account for the prescribing preferences of individual centres.
Results 810 patients were included in this study: 171/810 (21%) starting low dose MTX and 639/810 (79%) starting high dose MTX. Patients in the HM-group had significantly lower physician and patient VAS scores and less functional disability compared to those in the LM-group (table). These patients were also less likely to be prescribed concomitant (nbDMARDs) (17% vs. 10%). DAS28 score at 6 months was significantly lower for patients in the HM-group.
A fully adjusted multinomial logistic regression model, clustered by centre, showed that being in the high dose MTX group does not affect the odds of having a moderate response rather than no response, but does increase the odds of having a good response (RRR: 2.65 (95% CI 1.37, 5.14)).
Conclusions Patients with RA starting MTX on a higher dose have increased odds of having a good EULAR response compared to non-response at 6 months.
Visser, K. et al (2009). Multinational evidence-based recommendations for the use of methotrexate in rheumatic disorders with a focus on rheumatoid arthritis: integrating systematic literature research and expert opinion of a broad international panel of rheumatologists in the 3E Initiative. Ann Rheum Dis, 68: 1086–1093.
Disclosure of Interest None declared