title: Anti-tumour necrosis factor agents and tuberculosis risk: mechanisms of action and clinical management.
abstract: Cases of active tuberculosis have been reported worldwide with the use of therapeutic agents that inhibit tumour necrosis factor (TNF) alpha. TNFalpha has a central role in mycobacterial infection and disease. Accordingly, progression of recently acquired tuberculosis infection or reactivation of remotely acquired infection should be expected with the use of anti-TNF agents. The available in-vitro and epidemiological evidence for the two currently approved agents, infliximab and etanercept, shows that the risk of development of active tuberculosis is greater with infliximab. Tuberculin skin testing (TST) should be undertaken before any significant immunosuppressive therapy including these agents, though the possibility of false-negative reactions in immunocompromised populations must be borne in mind. A positive TST should be followed by medical assessment and chest radiography, as well as by other tests judged appropriate by the physician to identify active disease. Active tuberculosis must be treated appropriately before initiation of treatment with an anti-TNF agent. Treatment of latent tuberculosis can be considered on an individual basis for TST-negative patients receiving anti-TNF agents when significant risk factors for infection are present.
authors.affiliation: Infection Prevention and Control and Tuberculosis Clinic, Division of Infectious Disease, University Health Network, Ontario, Toronto, Canada. michael.gardam@uhn.on.ca
authors.forename: Michael A
authors.initials: MA
authors.lastname: Gardam
authors.forename: Edward C
authors.initials: EC
authors.lastname: Keystone
authors.forename: Richard
authors.initials: R
authors.lastname: Menzies
authors.forename: Steven
authors.initials: S
authors.lastname: Manners
authors.forename: Emil
authors.initials: E
authors.lastname: Skamene
authors.forename: Richard
authors.initials: R
authors.lastname: Long
authors.forename: Donald C
authors.initials: DC
authors.lastname: Vinh
mesh_terms: D000465:Algorithms; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D018450:Disease Progression; D000068800:Etanercept; D006801:Humans; D007074:Immunoglobulin G / Q000494:pharmacology*; D000069285:Infliximab; D009169:Mycobacterium tuberculosis; D018124:Receptors, Tumor Necrosis Factor; D012306:Risk; D014376:Tuberculosis / Q000139:chemically induced* / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000378:metabolism*
chemical_list: D000911:Antibodies, Monoclonal; D007074:Immunoglobulin G; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab; D000068800:Etanercept