Long term safety of methotrexate in routine clinical care: discontinuation is unusual and rarely the result of laboratory abnormalities

Ann Rheum Dis. 2005 Feb;64(2):207-11. doi: 10.1136/ard.2004.023408. Epub 2004 Jun 18.

Abstract

Objective: To analyse patients with rheumatoid arthritis, treated with methotrexate in a weekly academic rheumatology clinic over 13 years, for continuation of courses and reasons for discontinuation.

Methods: All 248 patients with an analysable longitudinal course who took methotrexate in standard care between 1990 and 2003 were studied. Continuation of courses was analysed using life tables. All abnormal and severely abnormal values for aspartate aminotransferase (AST) >40 U/l, >80 U/l, albumin <35 g/l, <30 g/l, white blood cell (WBC) count <4.0 x 10(9)/l, <3.0 x 10(9)/l, and platelet count <150 x 10(9)/l, <100 x 10(9)/l, were identified. Responses of the clinician and subsequent laboratory values were reviewed.

Results: Over 1007 person-years, the probability of continuing methotrexate over five years was 79% (95% confidence interval, 72% to 84%). Severe laboratory abnormalities occurred in 2.9 per 100 person-years, specifically 0.9 for AST >80 U/l, 1.1 for albumin <30 g/l, 0.7 for WBC <3.0 x 10(9)/l, and 0.3 for platelets <100 x 10(9)/l. No severe laboratory abnormality progressed to further severity or clinical disease. Permanent discontinuations of methotrexate occurred in 46 patients (19%), 26 (10% of all patients) for adverse effects, 15 (32.6%) for inefficacy; only two discontinuations resulted from laboratory abnormalities, both of WBC, possibly from other sources.

Conclusions: Methotrexate was associated with a high rate of continuation, and few clinically significant laboratory abnormalities. Discontinuation primarily reflected clinical rather than laboratory findings. Vigilance for methotrexate toxicity is required but methotrexate appears among the safest treatments for rheumatoid arthritis.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Antirheumatic Agents / adverse effects*
  • Antirheumatic Agents / therapeutic use
  • Arthritis, Rheumatoid / drug therapy*
  • Chemical and Drug Induced Liver Injury
  • Drug Administration Schedule
  • Drug Monitoring / methods
  • Female
  • Follow-Up Studies
  • Hematologic Diseases / chemically induced
  • Humans
  • Male
  • Methotrexate / adverse effects*
  • Methotrexate / therapeutic use
  • Middle Aged
  • Risk Assessment / methods
  • Treatment Failure

Substances

  • Antirheumatic Agents
  • Methotrexate