Post-marketing surveillance of high-dose methotrexate (>8 mg/week) in Japanese patients with rheumatoid arthritis: A post hoc sub-analysis of patients according to duration of prior methotrexate use

Mod Rheumatol. 2021 May;31(3):575-586. doi: 10.1080/14397595.2020.1823604. Epub 2021 Jan 21.

Abstract

Objectives: To explore whether the duration of prior low-dose methotrexate treatment (MTX; ≤8 mg/week) influences the safety and effectiveness of high-dose MTX (>8 mg/week) in Japanese patients with rheumatoid arthritis (RA).

Methods: This post hoc sub-analysis of a Japanese post-marketing surveillance study evaluated patients initiating high-dose MTX with ≥1 year or <1 year prior low-dose MTX use. Over 24 or 52 weeks, adverse drug reactions (ADRs) were monitored, and effectiveness was assessed using the Disease Activity Score in 28 joints, erythrocyte sedimentation rate [DAS28-4 (ESR)].

Results: One thousand two hundred and ninety-two MTX ≥1 year and 1001 MTX <1 year patients were included. The incidence of ADRs during the 24- and 52-week follow-up period was significantly more frequent in MTX <1 year than ≥1 year patients and serious ADRs were significantly higher in MTX <1 year than ≥1 year patients during the 52-week follow-up period (all p < .05). Over both follow-up periods, the mean DAS28-4 (ESR) significantly decreased from baseline for all groups. Remission and low disease activity rates (DAS28-4 (ESR) <2.6 and <3.2, respectively) increased from baseline for all groups.

Conclusion: High-dose MTX reduced disease activity regardless of prior treatment duration, but ADRs occurred more frequently among MTX <1 year patients compared to MTX ≥1 year patients.

Keywords: Effectiveness; methotrexate; post-marketing surveillance; rheumatoid arthritis; safety.

MeSH terms

  • Adult
  • Antirheumatic Agents / administration & dosage
  • Antirheumatic Agents / therapeutic use*
  • Arthritis, Rheumatoid / drug therapy*
  • Female
  • Humans
  • Japan
  • Male
  • Methotrexate / administration & dosage
  • Methotrexate / therapeutic use*
  • Middle Aged
  • Product Surveillance, Postmarketing*
  • Treatment Outcome

Substances

  • Antirheumatic Agents
  • Methotrexate