title: TNFalpha blockade in human diseases: an overview of efficacy and safety.
abstract: Tumor necrosis factor-alpha (TNFalpha) antagonists including antibodies and soluble receptors have shown remarkable efficacy in various immune-mediated inflammatory diseases (IMID). As experience with these agents has matured, there is an emerging need to integrate and critically assess the utility of these agents across disease states and clinical sub-specialties. Their remarkable efficacy in reducing chronic damage in Crohn's disease and rheumatoid arthritis has led many investigators to propose a new, 'top down' paradigm for treating patients initially with aggressive regimens to quickly control disease. Intriguingly, in diseases such as rheumatoid arthritis and asthma, anti-TNFalpha agents appear to more profoundly benefit patients with more chronic stages of disease but have a relatively weaker or little effect in early disease. While the spectrum of therapeutic efficacy of TNFalpha antagonists widens to include diseases such as recalcitrant uveitis and vasculitis, these agents have failed or even exacerbated diseases such as heart failure and multiple sclerosis. Increasing use of these agents has also led to recognition of new toxicities as well as to understanding of their excellent long-term tolerability. Disconcertingly, new cases of active tuberculosis still occur in patients treated with all TNFalpha antagonists due to lack of compliance with recommendations to prevent reactivation of latent tuberculosis infection. These safety issues as well as guidelines to prevent treatment-associated complications are reviewed in detail in this article. New data on mechanisms of action and development of newer TNFalpha antagonists are discussed in a subsequent article in the Journal. It is hoped that these two review articles will stimulate a fresh assessment of the priorities for research and clinical innovation to improve and extend therapeutic use and safety of TNFalpha antagonism.
authors.affiliation: UCLA David Geffen School of Medicine, Los Angeles, CA 90095, USA.
authors.forename: Jan
authors.initials: J
authors.lastname: Lin
authors.forename: David
authors.initials: D
authors.lastname: Ziring
authors.forename: Sheetal
authors.initials: S
authors.lastname: Desai
authors.forename: Sungjin
authors.initials: S
authors.lastname: Kim
authors.forename: Maida
authors.initials: M
authors.lastname: Wong
authors.forename: Yael
authors.initials: Y
authors.lastname: Korin
authors.forename: Jonathan
authors.initials: J
authors.lastname: Braun
authors.forename: Elaine
authors.initials: E
authors.lastname: Reed
authors.forename: David
authors.initials: D
authors.lastname: Gjertson
authors.forename: Ram Raj
authors.initials: RR
authors.lastname: Singh
mesh_terms: D000068879:Adalimumab; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D001168:Arthritis / Q000188:drug therapy*; D000068800:Etanercept; D006801:Humans; D007074:Immunoglobulin G / Q000009:adverse effects / Q000627:therapeutic use; D007249:Inflammation / Q000188:drug therapy*; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy*; D000069285:Infliximab; D018124:Receptors, Tumor Necrosis Factor / Q000627:therapeutic use; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D007074:Immunoglobulin G; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab; D000068879:Adalimumab; D000068800:Etanercept