Weekly split‐dose regimen for oral methotrexate reduced polyglutamation in red blood cells in patients with rheumatoid arthritis compared with single‐dose regimen: Results from a multicentered randomized control trial. (8th September 2020) - Nagaoka, Shouhei
Abstract: Aims: We compared the incidence of adverse events between single and divided‐dose regimens of methotrexate (MTX) by using a multicenter randomized controlled trial. Methods: Eighty‐nine patients with insufficient control on MTX 8 mg/wk were randomly assigned into single‐dose (39 patients) or triple dose (39 patients) groups. The MTX dose for all patients was gradually increased to 16 mg/wk. The primary endpoint was the occurrence of liver dysfunction during the observation period (20 weeks). Results: There were no differences in baseline data and MTX dose at Week 20 between groups. There was no significant difference in the incidence of liver dysfunction between groups (single dose, 3 [7.7%] patients vs. triple dose, 5 [13.2%] patients; P = .455). The incidence of adverse event increased in triple dose (single dose, 12 [30.8%] patients vs. triple dose, 20 [51.3%]), but the difference was not significant ( P = .066). There was no significant difference in disease activity between groups, although MTX‐triglutamate (PG3), MTX‐PG4, and MTX‐PG5 were significantly higher in the single dose group. Conclusions: Weekly split dosing reduced the polyglutamation of MTX. There was no significant difference in efficacy and safety between the 2 groups.