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  • Review Article
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Adverse reactions to biologic agents and their medical management

Nature Reviews Rheumatology volume 10, pages 612–627 (2014)Cite this article

Subjects

Key Points

  • Biologic agents used for the treatment of rheumatic and immunological disorders can cause allergic adverse events (AEs), including standard infusion reactions and hypersensitivity reactions

  • Biologic agents are associated with an increased risk of severe infection, including reactivation of tuberculosis (high risk: infliximab, adalimumab; intermediate risk: etanercept, abatacept, tocilizumab; low risk: rituximab, anakinra)

  • Combination therapy using biologic agents and immunosuppressive drugs has a higher risk of serious infections than monotherapy, especially in the first 12 months of treatment

  • Organ-specific AEs are commonly hepatic, cutaneous or haematological AEs, whereas immunological syndromes and cardiovascular, noninfectious pulmonary, gastrointestinal and neurological AEs are rare

  • Whether patients receiving biologic therapy have an increased incidence of lymphomas and skin cancers, especially after combination therapy, is unknown

  • Biologic therapy decreases the immune response to primary (but not booster) vaccination; therefore, live vaccines (nasal flu; Bacillus Calmette–Guérin; measles, mumps and rubella; and yellow fever vaccines) during active biologic therapy are prohibited

Abstract

Biologic agents have substantially advanced the treatment of immunological disorders, including chronic inflammatory and autoimmune diseases. However, these drugs are often associated with adverse events (AEs), including allergic, immunological and other unwanted reactions. AEs can affect almost any organ or system in the body and can occur immediately, within minutes to hours, or with a delay of several days or more after initiation of biologic therapy. Although some AEs are a direct consequence of the functional inhibition of biologic-agent-targeted antigens, the pathogenesis of other AEs results from a drug-induced imbalance of the immune system, intermediary factors and cofactors, a complexity that complicates their prediction. Herein, we review the AEs associated with biologic therapy most relevant to rheumatic and immunological diseases, and discuss their underlying pathogenesis. We also include our recommendations for the medical management of such AEs. Increased understanding and improved risk management of AEs induced by biologic agents will enable better use of these versatile immune-response modifiers.

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Figure 1: Proinflammatory networks in autoimmune and chronic inflammatory diseases.
Figure 2: Biologic agents can inhibit immunity to pathogens.

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Acknowledgements

O.B. is funded by Swiss National Science Foundation grants PP00P3-128421 and PP00P3-150751, Stiftung für wissenschaftliche Forschung from the University of Zurich, National Psoriasis Foundation, and a Novartis Foundation grant. D.C. is funded by a SICPA Foundation grant.

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  1. Department of Immunology, University Hospital Zurich, Gloriastrasse 30, Zurich, CH-8091, Switzerland

    Onur Boyman

  2. Division of Immunology and Allergy, Centre Hospitalier Universitaire Vaudois, Rue du Bugnon 46, Lausanne, CH-1011, Switzerland

    Denis Comte & François Spertini

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Boyman, O., Comte, D. & Spertini, F. Adverse reactions to biologic agents and their medical management. Nat Rev Rheumatol 10, 612–627 (2014). https://doi.org/10.1038/nrrheum.2014.123

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