Tumor necrosis factor antagonist therapy and lymphoma development: Twenty‐six cases reported to the Food and Drug Administration

TLDR

Tumor necrosis factor antagonists etanercept and infliximab, recently approved for rheumatoid arthritis and Crohn’s disease, are associated with a known lymphoma risk in these patients and in other immunosuppressed populations, raising concern and prompting further epidemiologic investigation. The study aimed to assess the incidence of lymphoproliferative disorders among patients receiving etanercept or infliximab. The authors reviewed relevant adverse event reports from the FDA’s MedWatch post‑market surveillance system. Among 26 reported cases—18 linked to etanercept and 8 to infliximab—81 % were non‑Hodgkin lymphomas, with a median latency of eight weeks, and lymphoma regression occurred in two patients after drug discontinuation without specific cytotoxic therapy.

Abstract

Abstract 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. Conclusion 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.