Lymphoma in patients treated with anti-TNF: results of the 3-year prospective French RATIO registry

Objective: To describe cases of lymphoma associated with anti-TNF therapy, identify risk factors, estimate the incidence and compare the risks for different anti-TNF agents. Methods: A national prospective registry was designed (Research Axed on Tolerance of bIOtherapies; RATIO) to collect all cases of lymphoma in French patients receiving anti-TNF therapy from 2004 to 2006, whatever the indication. A case-control analysis was conducted including two controls treated with anti-TNF per case and an incidence study of lymphoma with the French population was used as the reference. Results: 38 cases of lymphoma, 31 non-Hodgkin's lymphoma (NHL) (26 B cell and five T cell), five Hodgkin's lymphoma (HL) and two Hodgkin's-like lymphoma were collected. Epstein-Barr virus was detected in both of two Hodgkin's-like lymphoma, three of five HL and one NHL. Patients receiving adalimumab or infliximab had a higher risk than those treated with etanercept: standardised incidence ratio (SIR) 4.1 (2.3-7.1) and 3.6 (2.3-5.6) versus 0.9 (0.4-1.8). The exposure to adalimumab or infliximab versus etanercept was an independent risk factor for lymphoma in the case-control study: odds ratio 4.7 (1.3-17.7) and 4.1 (1.4-12.5), respectively. The sex and age-adjusted incidence rate of lymphoma was 42.1 per 100 000 patient-years. The SIR was 2.4 (95% CI 1.7 to 3.2). Conclusion: The two to threefold increased risk of lymphoma in patients receiving anti-TNF therapy is similar to that expected for such patients with severe inflammatory diseases. Some lymphomas associated with immunosuppression may occur, and the risk of lymphoma is higher with monoclonal-antibody therapy than with soluble-receptor therapy.