Infectious complications of tumor necrosis factor blockade.
OBJECTIVE
Our understanding of the infection risks posed by tumor necrosis factor (TNF) antagonists has continued to evolve in the 10 years since these drugs were first introduced. This review summarizes recent data regarding infection risk, examines potential structure-function relationships that may account for the differences, and discusses their implications with regard to tuberculosis prevention and management.


RESULTS
Recent prospective studies have confirmed the risk of tuberculosis 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. Screening and initiation of treatment for latent tuberculosis (TB) infection can greatly reduce the TB risk of anti-TNF treatment in western countries. However, alternative strategies to prevent TB because of new transmission may be required as these therapies become available worldwide. Current recommendations for withdrawal of anti-TNF therapy when TB is diagnosed place patients at risk for paradoxical worsening because of recovery of TNF-dependent inflammation. Recent case reports suggest reinstitution of TNF blockade may be safe and effective adjunctive treatment in such cases, but prospective studies are needed to confirm these observations.


CONCLUSIONS
TNF blockers have transformed treatment of several chronic inflammatory conditions. 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 infection diseases.
Wallis
Robert S
RS
Pfizer, New London, Connecticut 06320, USA. rswallis@gmail.com
D061067:Antibodies, Monoclonal, Humanized; D000068582:Certolizumab Pegol; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000009:adverse effects / Q000627:therapeutic use; D007166:Immunosuppressive Agents / Q000009:adverse effects* / Q000627:therapeutic use*; D011092:Polyethylene Glycols / Q000009:adverse effects / Q000627:therapeutic use; D014376:Tuberculosis / Q000276:immunology* / Q000517:prevention & control*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
D061067:Antibodies, Monoclonal, Humanized; D007140:Immunoglobulin Fab Fragments; D007166:Immunosuppressive Agents; C439524:TNF protein, human; D014409:Tumor Necrosis Factor-alpha; D011092:Polyethylene Glycols; D000068582:Certolizumab Pegol