Pancytopenia secondary to methotrexate therapy in rheumatoid arthritis

Arthritis Rheum. 1996 Feb;39(2):272-6. doi: 10.1002/art.1780390214.


Objective: To assess the frequency of methotrexate (MTX)-induced pancytopenia in rheumatoid arthritis (RA).

Methods: A MEDLINE literature search was conducted to identify articles published during the last 15 years (1980-1995) that presented data on MTX-associated pancytopenia. Two case reports of our own experience are also presented. In addition, articles that examined risk factors associated with MTX-related pancytopenia were identified.

Results: A total of 70 patients with pancytopenia related to MTX therapy were identified (68 reported in the literature, 2 from our own experience). Sixty-one of the patients were described in published case reports, 7 patients were from 5 long-term prospective studies. In many of these cases, predisposing factors for the development of pancytopenia were described. The 5 long-term prospective studies reported toxicity data on patients who had been treated with MTX for at least 13 weeks. A total of 511 patients were included in the prospective trials, yielding an overall incidence of pancytopenia of 1.4% (7 of 511). Of the 70 cases reported, 12 patients died (17%). Most of them had impaired renal function, hypoalbuminemia, concurrent infection, and/or concomitant medication with more than 5 drugs. The minimal cumulative MTX dose leading to fatal pancytopenia was 10 mg, observed in one of our patients.

Conclusion: Pancytopenia is not an uncommon side effect of low-dose pulse MTX therapy in RA. It can lead to serious complications, including death.

Publication types

  • Case Reports

MeSH terms

  • Administration, Oral
  • Arthritis, Rheumatoid / drug therapy*
  • Dose-Response Relationship, Drug
  • Female
  • Humans
  • Methotrexate / adverse effects*
  • Methotrexate / therapeutic use
  • Middle Aged
  • Pancytopenia / chemically induced*
  • Pancytopenia / mortality
  • Survival Analysis


  • Methotrexate