Weekly split dose methotrexate more effective than single dose in RA patients

A recent study discovered that a split-dose regimen of the widely used rheumatoid arthritis (RA) drug, methotrexate (MTX), significantly outperforms the traditional single-dose approach. Methotrexate faces bioavailability challenges beyond a 15 mg oral dose, prompting research to explore innovative dosing strategies. This study was presented in American College of Rheumatology Convergence 2023.

The multicenter, open-label randomized controlled trial (RCT) involved 253 RA patients, aged 18-60, with active disease but not on disease-modifying antirheumatic drugs (DMARDs). Patients were divided into a group receiving a single weekly dose of 25 mg and the other a split dose of 10 mg in the morning and 15 mg in the evening on the same day.

After 16 weeks, the split-dose group exhibited a remarkable reduction in disease activity compared to the single-dose group, as measured by the Disease Activity Score 28 (DAS28). Also, the split-dose cohort showed a higher rate of achieving a favorable response according to the European League Against Rheumatism (EULAR) criteria, along with significantly increased rates of achieving various American College of Rheumatology (ACR) response levels.

The study revealed that the split-dose regimen reduced the need for additional DMARDs and found its potential as a standalone therapeutic option. However, caution is advised as the split-dose group showed a slightly higher frequency of persistent transaminitis, an elevation of liver enzyme levels, indicating the need for careful monitoring.

This research challenges the conventional wisdom surrounding MTX administration for RA, offering a novel perspective that could reshape treatment protocols. With its potential to enhance efficacy and decrease reliance on supplementary medications, the split-dose MTX approach opens new avenues in the pursuit of more effective and personalized rheumatoid arthritis management. As we await further validation through large-scale clinical trials, this study introduces a paradigm shift in RA treatment, paving the way for more tailored and potent therapeutic strategies.

Source:

Prasad C, Dhir V, Gupta R, Thomas K, phani kumar D, PAI V, Jain A, Naidu S, Saini P, Bidyalaxmi L, KHULLAR A, Manthri R, Sharma S, Sharma A, Aggarwal A, Jain S. Comparison of Two Dosing Schedules for Oral Methotrexate (Split-Dose versus Single-Dose) Once Weekly in Patients with Active Rheumatoid Arthritis: A Multicenter, Open Label, Parallel Group, Randomized Controlled Trial (SMART Study) [abstract]. American College of Rheumatology. 2023; 75 (suppl 9).