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).


CONCLUSIONS
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.
Mariette
X
X
Hôpital de Bicêtre, Le Kremlin Bicêtre, France. xavier.mariette@bct.ap-hop-paris.fr
Tubach
F
F
Bagheri
H
H
Bardet
M
M
Berthelot
J M
JM
Gaudin
P
P
Heresbach
D
D
Martin
A
A
Schaeverbeke
T
T
Salmon
D
D
Lemann
M
M
Hermine
O
O
Raphael
M
M
Ravaud
P
P
D000368:Aged; D018501:Antirheumatic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D001168:Arthritis / Q000188:drug therapy; D004812:Epidemiologic Methods; D005260:Female; D005602:France / Q000453:epidemiology; D006801:Humans; D016867:Immunocompromised Host; D007166:Immunosuppressive Agents / Q000009:adverse effects* / Q000627:therapeutic use; D008223:Lymphoma / Q000139:chemically induced* / Q000453:epidemiology / Q000276:immunology; D008297:Male; D008875:Middle Aged; D012042:Registries; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
D018501:Antirheumatic Agents; D007166:Immunosuppressive Agents; D014409:Tumor Necrosis Factor-alpha