Immediate adverse reactions to biologicals: from pathogenic mechanisms to prophylactic management

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Abstract
The rapid expansion of the use of biologics has resulted in an increase in adverse drug reactions, some of which can be life-threatening, due to the immunogenicity of these new drugs. This review summarizes the current knowledge of the pathogenic mechanisms of biologics-induced hypersensitivity reactions and highlights the most useful diagnostic and prophylactic tools now available in the clinical management of immunogenicity associated with biologics. Over the last few years, many drug-related or patient-related factors contributing to the immunogenicity of biologics have been identified, thus allowing a better identification of patients at risk of reaction. Recent studies show that different mechanisms sustain hypersensitivity reactions toward biologics, and the application of novel methods for detecting antidrug antibodies has allowed the involvement of specific IgE isotypes. Additionally, experience with procedures of desensitization to biologics continues to grow. Considering the increased use of the biological therapies in different clinical conditions, the definition of diagnostic and prophylactic strategies represents an unavoidable necessity in the management of potentially reactive patients in order to improve the safety profile of biologics.

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