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. 2014 Sep;24(5):763-5.
doi: 10.3109/14397595.2013.878016. Epub 2014 Feb 5.

Clinical characteristics and incidence of methotrexate-related lymphoproliferative disorders of patients with rheumatoid arthritis

Yuji Yoshida  1 , Yuko Takahashi, Hiroyuki Yamashita, Toshikazu Kano, Hiroshi Kaneko, Akio Mimori
Affiliations

Clinical characteristics and incidence of methotrexate-related lymphoproliferative disorders of patients with rheumatoid arthritis

Yuji Yoshida et al. Mod Rheumatol. 2014 Sep.

Abstract

Objective: To investigate the incidence and clinical features of methotrexate (MTX)-related lymphoproliferative disorders (MTX-LPDs) in patients with rheumatoid arthritis (RA).

Patients: In total, 589 RA outpatients were examined at the National Center for Global Health and Medicine in the period from January 1990 to October 2010.

Results: MTX was used in 403 cases, and the duration of follow-up was 2379 person-years. Four patients developed MTX-LPDs; the incidence of MTX-LPDs was calculated as 0.00168/person-year and the standardized incidence as 8.21 (95% CI: 0.16-24.30). The mean total dosage of MTX was 1142 ± 871 mg, and the dosage at LPD onset was 7.4 ± 1.9 mg/week. The patients who developed MTX-LPDs had significantly shorter disease duration of RA compared with the patients who had not received MTX, but who had not progressed to LPDs (3.1 years vs. 12.5 years; P = 0.01). The following LPD subtypes were observed: diffuse large B-cell lymphoma (N = 2); Hodgkin's lymphoma (N = 1); and T-cell lymphoma (N = 1). After withdrawal of MTX, two of these patients showed spontaneous regression of the tumor, one did not have a recurrence, while the other patient relapsed and required chemotherapy.

Conclusion: Our study revealed that MTX-LPDs are not rare complications of RA outpatients. The MTX-LPDs were associated with a relatively shorter RA duration, and half of them showed tumor regression after MTX withdrawal, which suggested an association with MTX. It is important to consider the possibility of MTX-LPD in RA patients who have received MTX.

Keywords: Incidence; Lymphoproliferative disorder; Methotrexate; Rheumatoid arthritis.

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