Extended Report

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

X Mariette^1,*, F Tubach², H Bagheri³, M Bardet⁴, J M Berthelot⁵, P Gaudin⁶, D Heresbach⁷, A Martin⁸, T Schaeverbeke⁹, D Salmon¹⁰, M Lemann¹¹, O Hermine¹², M Raphael¹, P Ravaud²

¹ Hopital Bicetre, Assistance Publique-Hopitaux de Paris, France;
² Hopital Bichat, Assistance Publique-Hopitaux de Paris, France;
³ Centre Midi-Pyrénées de Pharmacovigilance, Toulouse, France;
⁴ Hopital d'Orléans, France;
⁵ CHU de Nantes, France;
⁶ CHU de Grenoble, France;
⁷ CHU de Rennes, France;
⁸ Hopital de Saint-Brieux, France;
⁹ CHU de Bordeaux, France;
¹⁰ Hopital Cochin, Assistance Publique-Hopitaux de Paris, France;
¹¹ Hopital Saint-Louis, Assistance Publique-Hopitaux de Paris, France;
¹² Hopital Necker, Assistance Publique-Hopitaux de Paris, France

Correspondence to: Xavier Mariette, Service de Rhumatologie, Service de Rhumatologie, Hôpital de Bicêtre, 78 rue du général leclerc, Le Kremlin Bicetre, 94275, France; xavier.mariette{at}bct.ap-hop-paris.fr

Accepted 17 September 2009

Objective: To describe cases of lymphoma associated with anti-TNF therapy, identify risk factors, estimate the incidence and compare risks for different anti-TNF agents.

Methods: We designed a national prospective registry (RATIO) from 2004 to 2006, for collecting all cases of lymphoma in French patients receiving anti-TNF therapy, whatever the indication. We conducted a case-control analysis including two controls treated with anti-TNF per case and an incidence study of lymphoma with the French population used as reference.

Results: We collected 38 cases of lymphoma, 31 non-Hodgkin’s lymphoma (NHL) (26 B-cell and 5 T-cell), 5 Hodgkin’s lymphoma (HL) and 2 Hodgkin’s-like lymphoma. Epstein-Barr virus (EBV) was detected in 2 of 2 Hodgkin’s-like lymphoma, 3 of 5 HL and one NHL. Patients receiving adalimumab or infliximab had a higher risk than those treated with etanercept: 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 standardized incidence ratio (SIR) was 2.4 (95% confidence interval [CI] 1.7–3.2).

Conclusion: The two to threefold increased risk of lymphoma in patients receiving anti-TNF therapy is similar as that expected for such patients with severe inflammatory diseases. However, some lymphomas associated with immunosuppression may occur, and the risk of lymphoma is higher with monoclonal-antibody therapy than with soluble-receptor therapy.

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