Pulmonary Infectious Complications of Tumor Necrosis Factor Blockade

The understanding of the infection risks posed by tumor necrosis factor (TNF) antagonists has continued to evolve in the 10 years since these drugs first were introduced. Recent prospective studies have confirmed the risk of tuberculosis (TB) reactivation posed by TNF antibodies to be several fold greater than soluble TNF receptor. Certolizumab pegol, a monovalent anti-TNF Fab' fragment, appears to share this risk, despite its lack of Fc and its inability to cross-link transmembrane TNF or activate complement. Two-step (boosted) tuberculin skin test screening and initiation of treatment for latent TB infection can greatly reduce the TB risk of anti-TNF treatment in western countries. Current recommendations for withdrawal of anti-TNF therapy when TB is diagnosed place patients at risk for paradoxical worsening due to recovery of TNF-dependent inflammation. Further research is needed to determine how best to prevent and manage their infectious complications and to determine their potential adjunctive therapeutic role in chronic infectious diseases.