Efficacy of Switching from oral to Subcutaneous Methotrexate in Alleviating Methotrexate-related Intolerance Symptoms in Japanese Patients with Rheumatoid Arthritis: The METOJECTIVE Study

Objectives To investigate the efficacy of switching from oral to subcutaneous methotrexate (MTX) in alleviating MTX-related intolerance symptoms in Japanese patients with rheumatoid arthritis (RA). Methods This non-randomized, prospective, observational study included Japanese patients with RA who experienced intolerance symptoms despite combination therapy with folic acid. Patients were assigned to switch to subcutaneous MTX (switching group) or continue oral MTX (continuation group). The primary endpoint was the change in patient nausea visual analog scale (VAS) from baseline to week 13. The secondary endpoints were the change in patient fatigue VAS and the change in RA activity from baseline to week 13 before and after adjusting for patient characteristics. Results Of the 60 patients enrolled, 28 were assigned to the switching group and 32 to the continuation group. In the adjusted analysis, the switching group showed a significantly greater reduction in patient nausea VAS and a numerically greater reduction in patient fatigue VAS than that in the continuation group. Changes in the RA activity were similar between the groups. Multivariate logistic regression analyses demonstrated that switching to subcutaneous MTX significantly improved the patient-reported nausea. Conclusions Switching from oral to subcutaneous MTX reduced intolerance symptoms compared with oral MTX in Japanese patients with RA.