Background Methotrexate (MTX) is the anchor drug in the management of rheumatoid arthritis (RA) in the world. In Japan, maximal dose of weekly MTX was increased up to 16 mg/week from 8 mg/week in 2011. Although RA disease activity has been controlled much better with higher dose and longer duration of MTX therapy, there are increasing reports of MTX-related lymphoproliferative diseases (MTX-LPD) especially in Japan.

Objectives To evaluate the clinical characteristics of the RA patients who developed MTX-LPD.

Methods A retrospective study was done to review the medical records of 39 patients (14 men and 25 women) with MTX-LPD in our institute.

Results Baseline characteristics of 39 patients at the diagnosis of MTX-LPD were following (average); age 64.3, RA disease duration 11.4 years, serum CRP 7.5 mg/dL, serum MMP-3 value 314.5 ng/dL, MTX dose 7.8 mg/w, MTX treatment period 4.8 years. The pathological diagnosis; 17 diffuse large B cell,5 Hodgkin, and 3 follicular lymphoma. EBV was detected in 10 of 31 cases.

MTX was stopped soon after the diagnosis of MTX-LPD in all but one patient who was very active RA and showed no aggravation of LPD. After MTX cessation, 16 patients needed chemotherapy for LPD. LPD resolved spontaneously in the other 22 patients, but DMARDs including biologics were prescribed later for RA flare and 11 developed LPD again. There were no significant difference of the prescription with or without LPD relapse. Among 8 patients who died, most of them received chemotherapy.

Conclusions MTX-LPD in RA developed more frequently in male patients who had long MTX treatment period and high CRP and MMP-3. Some of them had grave prognosis despite chemotherapy after MTX was withdrawn. In patients taking MTX for a long time with longstanding active disease may have risk of MTX-LPD.

1. Hoshida Y, et al.: Lymphoproliferative disorders in rheumatoid arthritis: clinicopathological analysis of 76 cases in relation to methotrexate medication. J Rheumatol. 2007 Feb;34(2):322-31

   Tokuhira M, et al.: Clinicopathological analyses in patients with other iatrogenic immunodeficiency-associated lymphoproliferative diseases and rheumatoid arthritis. Leuk Lymphoma. 2012 Apr;53(4):616-23

References

Acknowledgements We are very thankful to Michihide Tokuhira, Associate Professor of hematology in our institute, for his terrific advice for histological and hematological investigation of LPD.

Disclosure of Interest None Declared