Tumor necrosis factor antagonist therapy and lymphoma development: twenty-six cases reported to the Food and Drug Administration.
OBJECTIVE
Etanercept and infliximab are tumor necrosis factor (TNF) antagonists that have been recently approved for the treatment of rheumatoid arthritis (RA) and Crohn's disease (CD). This study was undertaken to investigate the occurrence of lymphoproliferative disorders in patients treated with these agents.


METHODS
Relevant data in the MedWatch postmarket adverse event surveillance system run by the US Food and Drug Administration were reviewed.


RESULTS
We identified 26 cases of lymphoproliferative disorders following treatment with etanercept (18 cases) or infliximab (8 cases). The majority of cases (81%) were non-Hodgkin's lymphomas. The interval between initiation of therapy with etanercept or infliximab and the development of lymphoma was very short (median 8 weeks). In 2 instances (1 infliximab, 1 etanercept), lymphoma regression was observed following discontinuation of anti-TNF treatment, in the absence of specific cytotoxic therapy directed toward the lymphoma.


CONCLUSIONS
Although data from a case series such as this cannot establish a clear causal relationship between exposure to these medications and the risk of lymphoproliferative disease, the known predisposition of patients with RA and CD to lymphoma, the known excess of lymphoma in other immunosuppressed populations, and the known immunosuppressive effects of the anti-TNF drugs provide a biologic basis for concern and justification for the initiation of additional epidemiologic studies to formally evaluate this possible association.
Brown
S Lori
SL
Center for Biologics Evaluation and Research, FDA, Rockville, Maryland 20852, USA.
Greene
Mark H
MH
Gershon
Sharon K
SK
Edwards
Evelyne T
ET
Braun
M Miles
MM
D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects*; D018501:Antirheumatic Agents / Q000008:administration & dosage / Q000009:adverse effects*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy; D003424:Crohn Disease / Q000188:drug therapy; D004334:Drug Administration Schedule; D000068800:Etanercept; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000008:administration & dosage / Q000009:adverse effects*; D000069285:Infliximab; D008228:Lymphoma, Non-Hodgkin / Q000139:chemically induced; D008232:Lymphoproliferative Disorders / Q000139:chemically induced*; D008297:Male; D008875:Middle Aged; D011358:Product Surveillance, Postmarketing; D018124:Receptors, Tumor Necrosis Factor / Q000008:administration & dosage; D014481:United States; D014486:United States Food and Drug Administration
D000911:Antibodies, Monoclonal; D018501:Antirheumatic Agents; D007074:Immunoglobulin G; D018124:Receptors, Tumor Necrosis Factor; D000069285:Infliximab; D000068800:Etanercept