Methotrexate (MTX), the anchor drug for rheumatoid arthritis (RA), has limited bioavailability above an oral dose of 15 mg. Split-dose oral MTX (morning, evening same day) has been shown to lead to higher blood levels compared to single-dose, however, its effect on clinical efficacy is unknown. 

- The American College of Rheumatology (ACR) 2023 Annual Meeting showcased that a weekly split-dose of oral methotrexate (MTX) in RA patients had significantly higher efficacy and reduced the need for additional DMARDs, compared to a single-dose of MTX given once a week. 
- Patients were randomized 1:1 and allocated into either single dose (25 mg) or split-dose (10 mg morning, 15 mg evening, same day) once weekly MTX for 24 weeks. 
- There were no major adverse events, but a slight increase in the frequency of persistent transaminitis was observed in the split-dose group.

Source: ACR Convergence 2023 | [Read full story](https://acrabstracts.org/abstract/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/)