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Biologics in allergology and clinical immunology: Update on therapies for atopic diseases, urticaria, and angioedema and on safety aspects focusing on hypersensitivity reactions

Uta Jappe, Karl-Christian Bergmann, Folke Brinkmann, Valentina Faihs, Askin Gülsen, Ludger Klimek, Harald Renz, Sebastian Seurig, Christian Taube, Stephan Traidl, Regina Treudler, Martin Wagenmann, Thomas Werfel, Margitta Worm, and Torsten Zuberbier

Volume 8 (2024) p. 365 - 406

Abstract

Allergologie select, Vol. 8/2024 (365-406)

Biologics in allergology and clinical immunology: Update on therapies for atopic diseases, urticaria, and angioedema and on safety aspects focusing on hypersensitivity reactions

Uta Jappe¹#², Karl-Christian Bergmann³, Folke Brinkmann⁴, Valentina Faihs⁵, Askin Gülsen⁶, Ludger Klimek⁷, Harald Renz⁸, Sebastian Seurig⁹, Christian Taube¹⁰, Stephan Traidl¹¹, Regina Treudler¹², Martin Wagenmann¹³, Thomas Werfel¹¹, Margitta Worm¹⁴, and Torsten Zuberbier³

¹Division Clinical and Molecular Allergology, Research Center Borstel, Leibniz Lung Center, Airway Research Center North (ARCN), Member of the German Center for Lung Research (DZL), Borstel, ²Interdisciplinary Allergy Outpatient Clinic, Department of Pneumology, University Medical Center Schleswig-Holstein, Campus Lübeck, University of Lübeck, ³Institute of Allergology, Charité Universitätsmedizin Berlin und Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Allergology and Immunology, Berlin, ⁴Division of Pediatric Pulmonology and Allergology, University Children’s Hospital, German Center for Lung Research (ARCN, DZL), Lübeck, ⁵Department of Dermatology and Allergy Biederstein, Klinikum rechts der Isar, Technical University of Munich, ⁶Division of Cardiology, Pulmonary Diseases, Vascular Medicine, University Hospital Duesseldorf, ⁷Center for Rhinology and Allergology, Wiesbaden, ⁸Institute of Laboratory Medicine, Universities of Giessen and Marburg Lung Center (UGMLC), Philipps Universität Marburg, Member of the German Center for Lung Research (DZL) Marburg, ⁹Interdisciplinary Allergy Center Nuremberg (NIZA), Department of Internal Medicine ³, Pneumology, Nuremberg Hospital, Nuremberg, ¹⁰Department of Pulmonary Medicine, University Hospital Essen-Ruhrlandklinik, Essen, ¹¹Department of Dermatology and Allergy, Hannover Medical School, Hannover, ¹²Institute of Allergology IFA, Charité Universitätsmedizin corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Campus Benjamin Franklin, Berlin, ¹³Department of Otorhinolaryngology, Düsseldorf University Hospital, Heinrich Heine University, Düsseldorf, ¹⁴Division of Allergy and Immunology, Department of Dermatology and Allergology, Charité-Universitätsmedizin Berlin, Berlin, Germany
The development of targeted therapies for atopic diseases, urticaria, and angioedema with biologics is progressing rapidly: New “targets” of clinical-therapeutic relevance have been identified, the corresponding targeted antibodies developed, tested in clinical trials, and approved for therapy. These include the anti-IgE antibody omalizumab (also effective and approved for the treatment of urticaria), the anti-IL-4/13 receptor-specific antibody dupilumab, the two anti-IL-13 antibodies lebrikizumab and tralokinumab, the anti-TSLP antibody tezepelumab, the two anti-IL-5 antibodies mepolizumab and reslizumab, and the anti-IL5 receptor-specific antibody benralizumab for the treatment of atopic diseases. For the treatment of hereditary angioedema, C1 inhibitor and the antibody lanadelumab (directed against kallikrein) have also long been approved as biologics in addition to low-molecular substances. Other therapeutic antibodies are in various stages of development. Furthermore, the range of indications for some very effective biologics has been successfully expanded to include additional diseases. In this context, the first results on biologic therapy of food allergy and eosinophilic esophagitis are interesting. Biologics that address different target structures are also increasingly being administered in combination, either simultaneously or sequentially, in order to achieve optimal efficacy. A developing area is the use of biologics in children and the observation of immunological and non-immunological side effects. In some cases, new unexpected side effects and hypersensitivity reactions have emerged, which in turn raise pathomechanistic questions, such as conjunctivitis with dupilumab therapy, which only appears to occur in the treatment of atopic dermatitis but not in the treatment of other atopic diseases. In dermatology, paradoxical reactions have been described under therapy with some biologics. And immune reactions of type alpha to epsilon to biologics (hypersensitivity reactions) continue to be a clinically relevant problem, whereby the selection of an alternative therapeutic agent is a challenge and the diagnostics that support this have not yet been sufficiently incorporated into routine work.Correspondence to:
Prof. Dr. med. Uta Jappe, Division Clinical and Molecular Allergology, Research Center Borstel, Leibniz Lung Center, Parkallee 35, 23845 Borstel, Germany
Email: [email protected]

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