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Opportunistic infections and biologic therapies in immune-mediated inflammatory diseases: consensus recommendations for infection reporting during clinical trials and postmarketing surveillance
  1. K L Winthrop1,
  2. S A Novosad2,
  3. J W Baddley3,
  4. L Calabrese4,
  5. T Chiller5,
  6. P Polgreen6,
  7. F Bartalesi7,
  8. M Lipman8,
  9. X Mariette9,
  10. O Lortholary10,
  11. M E Weinblatt11,
  12. M Saag3,
  13. J Smolen12
  1. 1Division of Infectious Diseases, Oregon Health and Science University, Portland, Oregon, USA
  2. 2Division of Pulmonary and Critical Care Medicine, Oregon Health and Science University, Portland, Oregon, USA
  3. 3Division of Infectious Diseases, University of Alabama at Birmingham, Birmingham, Alabama, USA
  4. 4Department of Rheumatology, Cleveland Clinic, Cleveland, Ohio, USA
  5. 5US Centers for Disease Control and Prevention, Atlanta, Georgia, USA
  6. 6Division of Infectious Diseases, University of Iowa, Iowa City, Iowa, USA
  7. 7Infectious and Tropical Diseases Unit, Careggi University Hospital, Florence, Italy
  8. 8Division of Medicine, Royal Free London NHS Foundation Trust & University College London, London, UK
  9. 9Department of Rheumatology, Université Paris-Sud, Hôpitaux Universitaires Paris-Sud, INSERM U1184, Le Kremlin – Bicêtre, France
  10. 10Université 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
  11. 11Department of Rheumatology, Brigham and Women's Hospital, Boston, Massachusetts, USA
  12. 12Division of Rheumatology, Department of Medicine 3, Medical University of Vienna, Vienna, Austria
  1. Correspondence to Dr Kevin L Winthrop, Division of Infectious Diseases, Oregon Health and Science University, 3375 SW Terwilliger Blvd, Portland, OR 97239, USA; Winthrop{at}


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.

  • Infections
  • Anti-TNF
  • Rheumatoid Arthritis

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