Lymphomas in rheumatoid arthritis patients treated with methotrexate: a 3-year prospective study in France

A national prospective study was designed to collect all cases of lymphoma appearing in patients with rheumatoid arthritis (RA) treated with methotrexate (MTX) throughout France over a period of 3 years. A total of 25 cases of lymphoma were recorded, 18 cases of non-Hodgkin lymphoma (NHL), 3 of which were associated with the presence of Epstein-Barr virus (EBV) in lymphoma cells, and 7 cases of Hodgkin disease (HD), 5 of them associated with EBV. Among the 8 patients who were treated by MTX withdrawal alone, 3 underwent remission, but 2 of them had a relapse, the third patient with clonal EBV-associated large granular lymphocytes T-cell NHL remaining alive in complete remission. The estimated annual incidence rate of NHL in RA patients treated with MTX was 33.3.10(-5) (0-80.5) among men and 16.7.10(-5) (0-33.3) among women. There was no significant excess with the French population as a comparison: the standardized mortality ratio (SMR) adjusted for age and sex was 1.07 (0.6-1.7). The estimated annual incidence rate of HD among men and women was, respectively, 27.8.10(-5) (0-70.1) and 2.8.10(-5) (0- 9.6). The incidence of HD was significantly increased compared with the French incidence, with an SMR adjusted for age and sex of 7.4 (3.0-15.3; P <.001). Thus, this 3-year prospective study indicated that, whereas the risk of NHL was not significantly increased in RA patients treated with MTX, the incidence of HD appeared to be higher in these patients compared to the French population.