Methotrexate and hepatic toxicity in rheumatoid arthritis and psoriatic arthritis

Clin Drug Investig. 2006;26(2):55-62. doi: 10.2165/00044011-200626020-00001.


Background: We set out in this study to demonstrate the adverse effect profile of methotrexate when used in the treatment of rheumatoid arthritis (RA) and psoriatic arthritis (PsA) in a district general hospital population, and to investigate the effect of alcohol consumption in these patients.

Methods: A prospective evaluation of 550 RA patients and 69 PsA patients was undertaken, controlling for confounding factors. Systematically randomised patients were further analysed regarding alcohol consumption. A transaminase level of three times the upper limit of normal on two or more occasions was taken to indicate hepatic injury.

Results: Gastrointestinal disturbance was the predominant adverse effect in RA patients (9.8%); hepatic disturbance was the most frequent in PsA patients (14.5%). Both groups had hepatic enzyme elevation; PsA patients were at significantly greater risk of elevated transaminases than RA patients (14.5% vs 7.5%, respectively, chi2 = 4.017). Alcohol consumption did not correlate with hepatic injury (mean 5.15 vs 6.6 alcohol units/week consumed by RA and PsA patients, respectively).

Conclusion: Our data show methotrexate-treated PsA patients have a higher incidence of hepatotoxicity compared with methotrexate-treated patients with RA. It is proposed that psoriatic patients may be inherently more susceptible to methotrexate hepatotoxicity than are rheumatoid patients.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Alcohol Drinking
  • Arthritis, Psoriatic / drug therapy*
  • Arthritis, Rheumatoid / drug therapy*
  • Child
  • Female
  • Humans
  • Immunosuppressive Agents / adverse effects*
  • Liver / drug effects*
  • Male
  • Methotrexate / adverse effects*
  • Middle Aged
  • Prospective Studies


  • Immunosuppressive Agents
  • Methotrexate