title: Opportunistic infections and biologic therapies in immune-mediated inflammatory diseases: consensus recommendations for infection reporting during clinical trials and postmarketing surveillance.
abstract: 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.
authors.affiliation: Division of Infectious Diseases, Oregon Health and Science University, Portland, Oregon, USA.
authors.forename: K L
authors.initials: KL
authors.lastname: Winthrop
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Oregon Health and Science University, Portland, Oregon, USA.
authors.forename: S A
authors.initials: SA
authors.lastname: Novosad
authors.affiliation: Division of Infectious Diseases, University of Alabama at Birmingham, Birmingham, Alabama, USA.
authors.forename: J W
authors.initials: JW
authors.lastname: Baddley
authors.affiliation: Department of Rheumatology, Cleveland Clinic, Cleveland, Ohio, USA.
authors.forename: L
authors.initials: L
authors.lastname: Calabrese
authors.affiliation: US Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
authors.forename: T
authors.initials: T
authors.lastname: Chiller
authors.affiliation: Division of Infectious Diseases, University of Iowa, Iowa City, Iowa, USA.
authors.forename: P
authors.initials: P
authors.lastname: Polgreen
authors.affiliation: Infectious and Tropical Diseases Unit, Careggi University Hospital, Florence, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Bartalesi
authors.affiliation: Division of Medicine, Royal Free London NHS Foundation Trust & University College London, London, UK.
authors.forename: M
authors.initials: M
authors.lastname: Lipman
authors.affiliation: Department of Rheumatology, Université Paris-Sud, Hôpitaux Universitaires Paris-Sud, INSERM U1184, Le Kremlin - Bicêtre, France.
authors.forename: X
authors.initials: X
authors.lastname: Mariette
authors.affiliation: Université Paris Descartes, Centre d'Infectiologie Necker Pasteur, IHU Imagine, Hôpital Necker Enfants maladies, and Institut Pasteur, Centre National de Référence Mycoses Invasives et Antifongiques, CNRS URA3012, Paris, France.
authors.forename: O
authors.initials: O
authors.lastname: Lortholary
authors.affiliation: Department of Rheumatology, Brigham and Women's Hospital, Boston, Massachusetts, USA.
authors.forename: M E
authors.initials: ME
authors.lastname: Weinblatt
authors.affiliation: Division of Infectious Diseases, University of Alabama at Birmingham, Birmingham, Alabama, USA.
authors.forename: M
authors.initials: M
authors.lastname: Saag
authors.affiliation: Division of Rheumatology, Department of Medicine 3, Medical University of Vienna, Vienna, Austria.
authors.forename: J
authors.identifier: http://orcid.org/0000-0002-8899-9087
authors.initials: J
authors.lastname: Smolen
mesh_terms: D001691:Biological Therapy / Q000379:methods*; D002986:Clinical Trials as Topic; D014943:Global Health; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D009017:Morbidity / Q000639:trends; D009894:Opportunistic Infections / Q000453:epidemiology / Q000276:immunology / Q000628:therapy; D011358:Product Surveillance, Postmarketing / Q000379:methods*; D012307:Risk Factors
chemical_list: D007166:Immunosuppressive Agents
keywords: Anti-TNF; Infections; Rheumatoid Arthritis