Safety of tumour necrosis factor-alpha antagonists.
Tumour necrosis factor-alpha (TNFalpha) is a proinflammatory cytokine that is synthesised by a variety of cell types in response to infectious or inflammatory stimuli. Although TNFalpha plays an adaptive role in immune protection and wound healing at 'physiological' levels, excess TNFalpha production can lead to adverse consequences. TNFalpha is a pivotal cytokine involved in the pathogenesis and progression of rheumatoid arthritis (RA). TNFalpha antagonists have been shown to be effective in the treatment of signs and symptoms of RA and the US FDA has approved three TNFalpha antagonists, etanercept, infliximab, and most recently, adalimumab, for the treatment of RA. However, differences have emerged, with respect to their demonstrated efficacy in other diseases (e.g. Crohn's disease). Worldwide, over half a million patients have been treated with TNFalpha antagonists and concerns regarding their safety have been raised. There is a risk of reactivation of granulomatous diseases, especially tuberculosis, with all three agents and appropriate measures should be taken for detection and treatment of latent infections. An association between non-Hodgkin's lymphoma and treatment with TNFalpha antagonists has been reported, although patients with active, long-standing RA are already known to have an increased incidence of non-Hodgkin's lymphoma. No associations with solid tumours have been found to date. The biological plausibility of lymphomas associated with immunomodulatory agents raises concern and vigilance is appropriate until the relationship is fully characterised. Large phase II and III trials have shown a detrimental effect of TNFalpha antagonists in advanced heart failure and these agents should be avoided in this population. Rare case reports of drug-induced lupus, seizure disorder, pancytopenia and demyelinating diseases have been noted after TNFalpha antagonists and continued vigilance is warranted in patients on TNFalpha antagonists for the development of these diseases. At present there is no evidence implicating TNFalpha antagonists with embryotoxicity, teratogenicity or increased pregnancy loss.
Khanna
Dinesh
D
Division of Rheumatology, David Geffen School of Medicine at UCLA, Los Angeles, California, USA.
McMahon
Maureen
M
Furst
Daniel E
DE
D000818:Animals; D000890:Anti-Infective Agents / Q000009:adverse effects / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D003711:Demyelinating Diseases / Q000188:drug therapy; D006402:Hematologic Diseases / Q000188:drug therapy; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000139:chemically induced / Q000188:drug therapy; D011358:Product Surveillance, Postmarketing; D012640:Seizures / Q000188:drug therapy; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000276:immunology
D000890:Anti-Infective Agents; D000970:Antineoplastic Agents; D014409:Tumor Necrosis Factor-alpha