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The complex clinical picture of side effects to biologicals.

Type of publication Peer-reviewed
Publikationsform Review article (peer-reviewed)
Publication date 2010
Author Hausmann Oliver V, Seitz Michael, Villiger Peter M, Pichler Werner J,
Project Investigating the primary immune response against drugs in humans
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Review article (peer-reviewed)

Journal The Medical clinics of North America
Volume (Issue) 94(4)
Page(s) 791 - 804
Title of proceedings The Medical clinics of North America
DOI 10.1016/j.mcna.2010.03.001


Biologicals are proteins used as drugs. Biologicals target clearly defined molecular structures, being part of established pathogenetic pathways. Therefore, their focused mode of action seems to render them superior to classic small molecular drugs regarding "off-target" adverse drug reactions (ADR). Nevertheless, the increasing use of biologicals for the treatment of different diseases has revealed partially unexpected adverse reactions. The often direct interaction of a biological with the immune system provides a clue to most side effects, which have consequently been subclassified, based on pathogenetic principles, into 5 subtypes named alpha, beta, gamma, delta, and epsilon, reflecting overstimulation (high cytokine values, type alpha), hypersensitivity (type beta), immune deviation (including immunodeficiency, type gamma), cross-reactivity (type delta), and nonimmune mediated side effects (type epsilon). This article presents typical clinical manifestations of these subtypes of ADR to biologicals, proposes general rules for treating them, and provides a scheme for a thorough allergological workup. This approach should help in future handling of these often very efficient drugs.