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Weekly split-dose regimen for oral methotrexate reduced polyglutamation in red blood cells in patients with

Shouhei Nagaoka1, Kou Katayama2, Tsuyoshi Kasama3

  • 1Yokohama Minami Kyosai Hospital, Yokohama city, Kanagawa, Japan.

International Journal of Rheumatic Diseases
|September 8, 2020
PubMed
Abstract

Insights

Comparing single versus divided doses of methotrexate (MTX) showed no significant differences in liver dysfunction or overall efficacy. However, split dosing increased methotrexate polyglutamation, suggesting potential benefits for MTX treatment effectiveness.

Area of Science:

  • Rheumatology
  • Pharmacology
  • Clinical Trials

Background:

  • Methotrexate (MTX) is a cornerstone therapy for various autoimmune diseases.
  • Optimizing MTX dosing regimens is crucial for improving patient outcomes and minimizing adverse events.
  • Understanding the impact of dosing frequency on MTX metabolism and toxicity is an ongoing area of research.

Purpose of the Study:

  • To compare the incidence of adverse events, specifically liver dysfunction, between single and divided-dose regimens of methotrexate.
  • To evaluate the efficacy and safety profiles of single versus triple divided-dose methotrexate regimens in patients with autoimmune conditions.
  • To investigate the effect of different dosing schedules on methotrexate polyglutamation.

Main Methods:

  • A multicenter randomized controlled trial involving 89 patients with insufficient disease control on 8 mg/wk MTX.
  • Patients were randomized into either a single-dose or a triple divided-dose group, with MTX dosage escalated to 16 mg/wk.
  • The primary endpoint was liver dysfunction over a 20-week observation period; secondary endpoints included adverse events and disease activity.

Main Results:

  • No significant difference was observed in the incidence of liver dysfunction between the single-dose (7.7%) and triple-dose (13.2%) groups (P = .455).
  • While the triple-dose group showed a higher incidence of adverse events (51.3% vs. 30.8%), this difference was not statistically significant (P = .066).
  • Disease activity did not differ significantly between groups, though higher levels of methotrexate polyglutamates (PG3, PG4, PG5) were noted in the single-dose group.

Conclusions:

  • Weekly split dosing of methotrexate appears to increase its polyglutamation, a potential indicator of enhanced intracellular activity.
  • There were no statistically significant differences in efficacy or safety outcomes between single and divided-dose methotrexate regimens in this study.
  • Further research may be warranted to explore the clinical implications of increased polyglutamation with split-dose methotrexate therapy.
Keywords:
methotrexatepolyglutamaterheumatoid arthritis

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