How Fast Can Methotrexate Be Escalated In Rheumatoid Arthritis? A Multicentre, Parallel-Group Randomized Controlled Trial (Meira)

Background: Literature regarding the optimal dose escalation strategy of methotrexate (MTX) in RA is scant and ambiguous (1). Concerns regarding the safety of rapid escalation may lead to delayed attainment of the optimal dose and treatment target. Objectives: To compare the efficacy, safety and tolerability of fast versus usual dose escalation of oral MTX in RA. Methods: This multicenter, open-label (assessor blinded) RCT included patients with active RA (SJC≥2 and TJC≥4) aged 18-55 years, not on DMARDs (except HCQ and/or low-dose prednisolone) and with disease duration Trial Reg: CTRI/2018/12/016549 Results: 178 patients (mean age 39.8 (8.6) years, 84% females) with mean disease duration of 1.9 (1.4) years were randomized (89 in each group). Mean DAS28ESR-3 and DAS28CRP-3 at enrollment were 6.3 (0.9) and 5.4 (1.1). At 16 weeks, there was no significant difference in good EULAR response by DAS28ESR-3 (5.6, 7.9%, p=0.9) or DAS28CRP-3 (28.1, 22.5%, p=0.8) between the two groups (Figure 1). The change in DAS28-ESR-3 at 8, 16 and 24 weeks (or by DASCRP-3, not shown) and improvement in HAQ at 16 weeks were also not significantly different (Table 1). Notably, there was no significant difference in symptomatic GI or CNS adverse effects, incidence of cytopenia, transaminitis or rates of drug discontinuation. RBC MTX polyglutamate-3 levels at 8 and 16 weeks were also similar (Table 1). Conclusion: A faster escalation of MTX (5 mg every 2 weeks) reaching 25 mg/week by 4 weeks did not have a significantly higher rate of adverse effects (symptomatic or laboratory) compared to an escalation by 5 mg every 4 weeks. Although not more efficacious, it may shorten the time to recognize MTX failure, and optimize treat-to-target. References: [1]Visser K, Katchamart W, Loza E, et al. Multinational evidence-based recommendations for the use of methotrexate in rheumatic disorders with a focus on RA: integrating systematic literature research and expert opinion of a broad international panel of rheumatologists in the 3E Initiative. Ann Rheum Dis. 2009;68(7):1086–93 Disclosure of Interests: None declared