Letter to the Editor

Severe serum sickness–like syndrome after omalizumab therapy for asthma

Biologic agents are a rapidly expanding class of medications, and several options are now available for the management of allergic and immunologic disorders. The risks of biologic therapy need to be understood in order to adequately counsel patients and appropriately monitor for potential adverse events. We sought to provide a comprehensive review of the risks and adverse effects reported for the current FDA-approved biologics used in management of allergic and immunologic disorders, including omalizumab, benralizumab, dupilumab, mepolizumab, reslizumab, tezepelumab and tralokinumab. Our review focuses on the risk of hypersensitivity reactions, pregnancy-specific considerations, risk of infection and risk of malignancy. We also highlight drug-specific adverse events and unique safety issues identified in case reports.

As the number of monoclonal antibodies in clinical use increases, our understanding of hypersensitivity and other adverse reactions to these agents becomes more intricate. The use of a classification scheme of these reactions can help elucidate possible underlying mechanisms and offer insights into management of reactions, including consideration of future administrations. Book chapters and journal articles relevant to monoclonal antibody production, adverse reactions, and desensitization were reviewed without restrictions on publication date. Selected case reports and meeting abstracts were included if no other evidence was available. We examine in this chapter the manifestations and possible mechanisms of adverse reactions to monoclonal antibodies, with emphasis on hypersensitivity and infusion reactions. Rituximab, omalizumab, and cetuximab provide specific illustrations of the complexities and heterogeneity of monoclonal antibody reactions. We consider the role of skin testing and rapid desensitization in diagnosis and treatment of monoclonal antibody hypersensitivity reactions.

As the number of monoclonal antibodies in clinical use increases, our understanding of hypersensitivity and other adverse reactions to these agents becomes more intricate. The use of a classification scheme of these reactions can help elucidate possible underlying mechanisms and offer insights into management of reactions, including consideration of future administrations. Book chapters and journal articles relevant to monoclonal antibody production, adverse reactions, and desensitization were reviewed without restrictions on publication date. Selected case reports and meeting abstracts were included if no other evidence was available. We examine in this chapter the manifestations and possible mechanisms of adverse reactions to monoclonal antibodies, with emphasis on hypersensitivity and infusion reactions. Rituximab, omalizumab, and cetuximab provide specific illustrations of the complexities and heterogeneity of monoclonal antibody reactions. We consider the role of skin testing and rapid desensitization in diagnosis and treatment of monoclonal antibody hypersensitivity reactions.

There has been a great expanse in the use of biological agents during the past decade. However, there are significant differences between biologics and typical pharmaceutical drugs. This review focuses on 3 separate types of adverse reactions to biologics, namely high cytokine reactions, hypersensitivity reactions, and secondary immunodeficiency.

A PubMed literature search restricted to the previous 10 years using combinations of search terms, including omalizumab, rituximab, TGN1412, biologic agent, anaphylaxis, hypogammaglobulinemia, desensitization, and cytokine storm, was performed. The results were manually filtered to identify relevant articles with additional references identified from bibliographies.

Reports were selected for TGN1412 cytokine storm, omalizumab anaphylaxis and desensitization, rituximab-induced hypogammaglobulinemia, rituximab anaphylaxis and serum sickness, and monoclonal antibody desensitization.

A phase 1 clinical trial using a humanized anti-CD28 monoclonal antibody (TGN1412) caused severe cytokine storm reactions in all 6 subjects, resulting in multiorgan failure. Omalizumab has been reported to cause anaphylaxis in fewer than 0.1% of patients, many with delayed reactions. The mechanism for this anaphylactic reaction is unclear. Rituximab has been associated with hypogammaglobulinemia, serum sickness-like reactions, and anaphylaxis. Rapid drug desensitizations to monoclonal antibodies, including rituximab, suspected of causing immunoglobulin E-mediated reactions have been found to be generally safe and effective.

Hypersensitivity reactions and immune dysregulation from biologic agents are not rare. The allergist and immunologist should be involved in managing these patients for optimal care.