Risk of infection associated with anti-TNF-α therapy

ABSTRACT

Introduction: The advent, more than two decades ago, of monoclonal antibodies and soluble receptors targeting tumor necrosis factor (TNF)-α has revolutionized the therapeutic approach to otherwise difficult-to-treat autoimmune and inflammatory diseases. However, due to the pleiotropic functions played by this pro-inflammatory cytokine (with particular relevance in granuloma maintenance), TNF-α blockade may increase the incidence of serious infections.

Areas covered: The present review summarizes the biological rationale supporting the impact of anti-TNF-α therapy on the host’s susceptibility to infection. The structure, mode of action, and indications of available agents are reviewed, as well as the clinical evidence coming from clinical trials and observational registries. We discuss the impact of patient- and disease-related factors influencing the occurrence of infection. Finally, strategies for risk minimization are also covered, with particular attention to recommendations for screening of latent tuberculosis infection and management of chronic hepatitis B infection.

Expert commentary: Methodological limitations (confounding by indication bias, patient dropout, or switching therapies) should be considered when interpreting observational data. Clinicians must individualize the infection risk assessment not only on the basis of the specific anti-TNF-α agent used or the expected duration of therapy, but also by taking into account the baseline susceptibility of a given patient.

KEYWORDS:

• tumor necrosis factor-α
• biological therapy
• infection
• risk
• infliximab

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This research was partially supported by Plan Nacional de I+D+I 2013–2016 and Instituto de Salud Carlos III, Subdirección General de Redes y Centros de Investigación Cooperativa, Spanish Ministry of Economy and Competitiveness, Spanish Network for Research in Infectious Diseases [REIPI RD16/0016/0002] – co-financed by the European Development Regional Fund (EDRF) ‘A way to achieve Europe’.