Methotrexate: long-term safety and efficacy in an Australian consultant rheumatology practice

Intern Med J. 2009 Apr;39(4):228-36. doi: 10.1111/j.1445-5994.2009.01800.x.

Abstract

Background: The aim of this study was to evaluate the rate and cause of methotrexate (MTX) termination in clinical practice, describe the types of toxicities noted, assess the incidence of achieving remission in rheumatoid arthritis (RA) patients and review the appropriateness of current clinical guidelines for monitoring MTX treatment.

Methods: A retrospective, case review of patients seen in a private rheumatology practice attached to a major Sydney Teaching Hospital was undertaken over an 18-year period. The primary outcome was time to cessation of MTX.

Results: Seven hundred and ninety patients satisfied the inclusion criteria. MTX was terminated in 272 patients (34.4%). Toxicity-related discontinuation occurred in 93 patients (11.8%) and due to non-adverse reactions in 179 patients. The median duration of therapy in these two groups was 2.0 and 2.9 years, respectively. There was no difference in the average maximum weekly dose of MTX. Of patients with RA, 47.5% were in remission at last follow up. Cox proportional hazards analyses showed that those of the female sex remained on treatment significantly longer than the male sex (hazard ratio (HR) 0.73, 95% confidence interval (CI) 0.57-0.96; P = 0.014); patients with RA remained on treatment significantly longer than patients with seronegative arthritis (HR 0.56, 95%CI 0.42-0.74; P < 0.001). Being of the male sex aged more than 60 years and having a non-RA diagnosis predisposed to stopping MTX earlier.

Conclusion: MTX is a safe and effective medication. Notable remission rates are achievable in patients with RA with current conventional treatment protocols. MTX has a low toxicity profile and this study stresses the need to re-evaluate and revise the current monitoring guidelines.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Arthritis, Rheumatoid / drug therapy*
  • Biopsy
  • Chemical and Drug Induced Liver Injury / etiology
  • Chemical and Drug Induced Liver Injury / pathology
  • Female
  • Gastrointestinal Diseases / chemically induced
  • Hospitals, Teaching / statistics & numerical data
  • Humans
  • Immunosuppressive Agents / adverse effects*
  • Immunosuppressive Agents / therapeutic use
  • Kaplan-Meier Estimate
  • Liver / drug effects
  • Liver / pathology
  • Male
  • Methotrexate / adverse effects*
  • Methotrexate / therapeutic use
  • Middle Aged
  • New South Wales
  • Practice Guidelines as Topic
  • Remission Induction
  • Retrospective Studies
  • Rheumatology / statistics & numerical data*
  • Young Adult

Substances

  • Immunosuppressive Agents
  • Methotrexate