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Blood, 1 June 2002, Vol. 99, No. 11, pp. 3909-3915
CLINICAL OBSERVATIONS, INTERVENTIONS, AND THERAPEUTIC TRIALS
Lymphomas in rheumatoid arthritis patients treated with
methotrexate: a 3-year prospective study in France
Xavier Mariette,
Dominique Cazals-Hatem,
Josiane Warszawki,
Frédéric Liote,
Nathalie Balandraud,
Jean Sibilia, and
the investigators of the
Club Rhumatismes et Inflammation
From the Service de Rhumatologie, Hôpital de
Bicêtre (Assistance publique-Hôpitaux de Paris [AP-HP]),
Le Kremlin Bicêtre, France; Service d'Anatomo-pathologie,
Hôpital Beaujon (AP-HP), Paris, France; Service
d'Epidémiologie, Hôpital de Bicêtre (AP-HP), Le
Kremlin Bicêtre, France; Fédération de Rhumatologie,
Hôpital Lariboisière (AP-HP), Paris, France; Service de
Rhumatologie, Centre Hospitalier Lyon-Sud, Lyon, France; and the
Service de Rhumatologie, Hôpital de Hautepierre, Strasbourg,
France. CRI (Club Rhumatismes et Inflammation): the practitioners who
referred patients are listed in an appendix.
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
16.7.105 (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, 27.8.105 (0-70.1) and 2.8.105
(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.
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