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ESCMID Study Group for Infections in Compromised Hosts (ESGICH) Consensus Document on the safety of targeted and biological therapies: an infectious diseases perspective (Soluble immune effector molecules [II]: agents targeting interleukins, immunoglobulins and complement factors)

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Winthrop KL1, Mariette X2, Silva JT3, Benamu E4, Calabrese LH5, Dumusc A6, Smolen JS7, Aguado JM8, Fernández-Ruiz M8. Clin Microbiol Infect. 2018 Feb 12. pii: S1198-743X(18)30150-2. doi: 10.1016/j.cmi.2018.02.002. [Epub ahead of print]


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1 Division of Infectious Diseases, Oregon Health and Science University, Portland, OR, USA. Electronic address: winthrop@ohsu.edu.

2 Department of Rheumatology, Hôpitaux Universitaire Paris-Sud, Université Paris-Sud, INSERM U1184, Paris, France.

3 Department of Infectious Diseases, University Hospital of Badajoz, Fundación para La Formación e Investigación de Los Profesionales de La Salud (FundeSalud), Badajoz, Spain.

4 Division of Infectious Diseases and Geographic Medicine, Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA.

5 Department of Rheumatic and Immunological Diseases, Cleveland Clinic Foundation, Cleveland Clinic, Cleveland Clinic Lerner College of Medicine, Case Western University, Cleveland, OH, USA.

6 Department of Rheumatology, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland.

7 Division of Rheumatology, Department of Medicine 3, Medical University of Vienna, Vienna, Austria.

8 Unit of Infectious Diseases, Hospital Universitario "12 de Octubre", Instituto de Investigación Hospital "12 de Octubre" (i+12), School of Medicine, Universidad Complutense, Madrid, Spain; Spanish Network for Research in Infectious Diseases (REIPI RD16/0016), Instituto de Salud Carlos III, Madrid, Spain.


BACKGROUND: The present review is part of the ESCMID Study Group for Infections in Compromised Hosts (ESGICH) Consensus Document on the safety of targeted and biological therapies.

AIMS: To review, from an Infectious Diseases perspective, the safety profile of agents targeting interleukins, immunoglobulins and complement factors and to suggest preventive recommendations.

SOURCES: Computer-based MEDLINE searches with MeSH terms pertaining to each agent or therapeutic family.

CONTENT: Patients receiving interleukin-1 (IL-1) -targeted (anakinra, canakinumab or rilonacept) or IL-5-targeted (mepolizumab) agents have a moderate risk of infection and no specific prevention strategies are recommended. The use of IL-6/IL-6 receptor-targeted agents (tocilizumab and siltuximab) is associated with a risk increase similar to that observed with anti-tumour necrosis factor-α agents. IL-12/23-targeted agents (ustekinumab) do not seem to pose a meaningful risk of infection, although screening for latent tuberculosis infection may be considered and antiviral prophylaxis should be given to hepatitis B surface antigen-positive patients. Therapy with IL-17-targeted agents (secukinumab, brodalumab and ixekizumab) may result in the development of mild-to-moderate mucocutaneous candidiasis. Pre-treatment screening for Strongyloides stercoralis and other geohelminths should be considered in patients who come from areas where these are endemic who are receiving IgE-targeted agents (omalizumab). C5-targeted agents (eculizumab) are associated with a markedly increased risk of infection due to encapsulated bacteria, particularly Neisseria spp. Meningococcal vaccination and chemoprophylaxis must be administered 2-4 weeks before initiating eculizumab. Patients with high-risk behaviours and their partners should also be screened for gonococcal infection.

IMPLICATIONS: Preventive strategies are particularly encouraged to minimize the occurrence of neisserial infection associated with eculizumab.