[Cytopenia associated with low dose pulse methotrexate in the treatment of rheumatoid arthritis]

To assess the associated risk factors of methotrexate (MTX)-induced cytopenia in rheumatoid arthritis (RA).

We followed 420 patients started on MTX for RA. We evaluated the frequency and clinical significance of patients with cytopenia related to MTX therapy.

The prevalence of patients remaining in the follow-up in the MTX treatment was 21% at 60 months. eighty-seven patients (21%) continued treatment. The treatment termination in MTX was 28% for toxicity, 78 (19%) for no effect, 70 (17%) for relapse and 116 (28%) for toxicity and 69 (16%) for other reasons. A total of 10 patients with cytopenia related to MTX therapy were identified among them. The prevalence of cytopenia, including leukopenia (n = 6), thrombocytopenia (n = 3) and pancytopenia (n = 1), estimated to be 2.4% in MTX treated RA patients. Patients with cytopenia received 2.5-8 mg/w over a mean duration of 60.0 months (10-119 months). nine of 10 patients received NSAIDs with MTX therapy. The presence of renal abnormality (Cr > 1.2 mg/d) was in 3 cases, age over 70 years old in 4 patients, body weight under 50 kg in 8 patients, mean corpuscular volume (MCV) over 100 fl in 2 patients. High MCV value (over 94 fl) was in 7 patients, 6 of whom had some symptoms including fever (n = 3) and oral mucosa/lip abnormalities (n = 3). Low MCV value (under 84 fl) was in 3 patients, who had no symptom but arthralgia and no renal abnormality. And they were younger and received MTX in shorter period than high MCV group.

In patients with high MCV (over 94 fl), most hematological toxicities seen during the course of MTX therapy can be predictable. But, some patients may develop unpredictable hematological reaction. We need to monitor hematological examination frequently and observe patients closely for the appearance of hematological toxicity throughout the presctiption period of MTX irrespective of the duration of treatment.