Pancytopenia secondary to methotrexate therapy in rheumatoid arthritis

Abstract 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.