Opportunistic infections and biologic therapies in immune-mediated inflammatory diseases: consensus recommendations for infection reporting during clinical trials and postmarketing surveillance.

No consensus has previously been formed regarding the types and presentations of infectious pathogens to be considered as 'opportunistic infections' (OIs) within the setting of biologic therapy. We systematically reviewed published literature reporting OIs in the setting of biologic therapy for inflammatory diseases. The review sought to describe the OI definitions used within these studies and the types of OIs reported. These findings informed a consensus committee (infectious diseases and rheumatology specialists) in deliberations regarding the development of a candidate list of infections that should be considered as OIs in the setting of biologic therapy. We reviewed 368 clinical trials (randomised controlled/long-term extension), 195 observational studies and numerous case reports/series. Only 11 observational studies defined OIs within their methods; no consistent OI definition was identified across studies. Across all study formats, the most numerous OIs reported were granulomatous infections. The consensus group developed a working definition for OIs as 'indicator' infections, defined as specific pathogens or presentations of pathogens that 'indicate' the likelihood of an alteration in host immunity in the setting of biologic therapy. Using this framework, consensus was reached upon a list of OIs and case-definitions for their reporting during clinical trials and other studies. Prior studies of OIs in the setting of biologic therapy have used inconsistent definitions. The consensus committee reached agreement upon an OI definition, developed case definitions for reporting of each pathogen, and recommended these be used in future studies to facilitate comparison of infection risk between biologic therapies.

Beyond tumor necrosis factor inhibition: the expanding pipeline of biologic therapies for inflammatory diseases and their associated infectious sequelae.

Patients with rheumatoid arthritis and other immune-mediated inflammatory diseases are at higher risk for infectious morbidity and mortality, partially due to the therapies used to treat these conditions. Both prednisone and targeted biologic therapies such as tumor necrosis factor antagonists have been implicated to various degrees, although in some cases firm data are lacking with regard to certain types of infections. To date, there is a paucity of information regarding the infectious risks associated with the newer biologic agents. As new biologic agents become available for use, their potential infectious risks will challenge infectious disease clinicians who must work to prevent, diagnose, and treat infections in this setting. This article reviews our current understanding of infectious risk in the setting of targeted therapies and provides an update of the immune system targets and potential infectious sequelae of both current and emerging biologic therapies.