Review
Biologics for atopic diseases: Indication, side effect management, and new developments
Uta Jappe, Hendrik Beckert, Karl-Christian Bergmann, Askin Gülsen, Ludger Klimek, Sandra Philipp, Julia Pickert, Michèle M. Rauber-Ellinghaus, Harald Renz, Christian Taube, Regina Treudler, Martin Wagenmann, Thomas Werfel, Margita Worm, and Torsten Zuberbier
Volume 5 (2021) p. 1 - 25
Abstract
Allergologie select, Vol. 5/2021 (1-25)
Biologics for atopic diseases: Indication, side effect management, and new developments
Uta Jappe1,2, Hendrik Beckert3, Karl-Christian Bergmann4, Askin Gülsen2, Ludger Klimek5, Sandra Philipp6, Julia Pickert7, Michèle M. Rauber-Ellinghaus8, Harald Renz9, Christian Taube3, Regina Treudler10, Martin Wagenmann11, Thomas Werfel12, Margita Worm13, and Torsten Zuberbier14
1Research Group Clinical and Molecular Allergology of the Research Center Borstel, Airway Research Center North (ARCN), Member of the German Center for Lung Research (DZL), 2Interdisciplinary Allergy Outpatient Clinic, Medical Clinic III, University of Lübeck, 3Department of Pulmonary Medicine, University Hospital Essen – Ruhrlandklinik, Essen, 4Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, 5Center for Rhinology and Allergology, Wiesbaden, 6Dermatology practice Dr. Markus Friedrich/Dr. Sandra Philipp, Oranienburg, 7Department of Dermatology and Allergology, University Hospital Gießen and Marburg, Marburg site, 8Experimental Dermatology and Allergology, Justus Liebig University Giessen, 9Department of Medicine, Institute of Laboratory Medicine and Pathobiochemistry – Molecular Diagnostics, Member of the German Centre for Lung Research (DZL), Philipps-University, Marburg, 10Leipzig Comprehensive Allergy Center LICA-CAC, Department of Dermatology, Venereology and Allergology, University of Leipzig, 11Department of Otorhinolaryngology, HNO-Klinik, Universitätsklinikum Düsseldorf, Düsseldorf, 12Division of Immunodermatology and Allergy Research, Department of Dermatology and Allergy, Hannover Medical School, Hannover, 13Dermatology, Venerology and Allergology, Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, 14Department of Dermatology and Allergy, Charité Universitätsmedizin, Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Comprehensive Allergy Center, Berlin, Germany
With the advent of biologicals, more and more therapeutics are available that specifically address specific switch points in the pathomechanism of immunologically dominated diseases. Thus, the focus of diagnostics and therapy (precision medicine) is more on the individual disease characteristics of the individual patient. Regarding the different phenotypes of atopic diseases, severe asthma was the first entity for which biologicals were approved, followed by urticaria, and finally atopic dermatitis and chronic rhinosinusitis with nasal polyps. Experience in the treatment of severe bronchial asthma has shown that the intensity of the response to biological therapy depends on the quality of clinical and immunological phenotyping of the patients. This also applies to different diseases of the atopic form, as patients can suffer from several atopic diseases at the same time, each with different characteristics. Biologics are already emerging that may represent a suitable therapy for allergic bronchial asthma, which often occurs together with severe neurodermatitis, and chronic rhinosinusitis with nasal polyps. In practice, however, the question of possible combinations of biologicals for the therapy of complex clinical pictures of individual patients is increasingly arising. In doing so, the side effect profile must be taken into account, including hypersensitivity reactions, whose diagnostic and logistical management must aim at a safe and efficient therapy of the underlying disease. Increased attention must also be paid to biological therapy in pregnancy and planned (predictable) vaccinations as well as existing infections, such as SARS-CoV-2 infection. Before starting a biological therapy, the immune status should be checked with regard to chronic viral and bacterial infections and, if necessary, the vaccination status should be refreshed or missing vaccinations should be made up for before starting therapy. Currently, reliable data on the effect of biologicals on the immunological situation of SARS-CoV-2 infection and COVID-19 are not available. Therefore, research and development of suitable diagnostic methods for detection of immunologically caused side effects as well as detection of potential therapy responders and non-responders is of great importance.Correspondence to:
Prof. Dr. med. Uta Jappe, Research Center Borstel, Leibniz Lung Center, Parkallee 35, 23845 Borstel
Email: [email protected]
Case Report
Omalizumab ensures compatibility to bee venom immunotherapy (VIT) after VIT-induced anaphylaxis in a patient with systemic mastocytosis
Askin Gülsen, Franziska Ruëff, and Uta Jappe
Volume 5 (2021) p. 128 - 132
Abstract
Allergologie select, Vol. 5/2021 (128-132)
Omalizumab ensures compatibility to bee venom immunotherapy (VIT) after VIT-induced anaphylaxis in a patient with systemic mastocytosis
Askin Gülsen1, Franziska Ruëff2, and Uta Jappe1,3
1Interdisciplinary Allergy Outpatient Clinic, Department of Pneumology, University of Luebeck, 2Department of Dermatology and Allergology, Klinikum der Ludwig-Maximilians-Universität, Munich, and 3Division of Clinical and Molecular Allergology, Research Center Borstel, Leibniz Lung Center, Airway Research Center North (ARCN), German Center for Lung Research (DZL), Borstel, Germany
Background: Systemic reactions and anaphylaxis due to Hymenoptera venoms occur in up to 7.5% of the European population. Fatal sting reactions are very rare. Serum tryptase levels should be measured in all patients with a history of severe reactions in order to detect mastocytosis and to determine the risk of severe reactions to venom immunotherapy (VIT). The risk to experience severe or even fatal anaphylaxis due to insect stings is quite high in patients with mastocytosis. Therefore, lifelong VIT is recommended in these highly threatened patients. Multicenter studies involving a large population report that up to 20% of patients undergoing VIT have intolerance and systemic reactions to immunotherapy. Some of these side effects occur repeatedly and cannot be managed by standard treatment. A pre-treatment with the anti-IgE antibody omalizumab was useful in many cases. However, omalizumab is not approved for the indication anaphylaxis. Therefore, there is still no defined protocol for omalizumab pre-treatment, and the optimal duration, dosage as well as long-time benefits are still unclear. Case report: We present a 60-year-old female patient with mastocytosis who developed a severe anaphylactic reaction during initiation of bee VIT. Serum tryptase was elevated, and a KIT mutation D816V was subsequently confirmed. Component-resolved diagnostic tests revealed specific IgE antibodies to recombinant Api m 1 only. The patient was treated with 150 mg omalizumab, administered subcutaneously 5 weeks, 3 weeks, and 1 week prior to re-start of immunotherapy and for 2 months in parallel to VIT. Updosing was done by a 7-day rush schedule. During this period, no anaphylactic reaction developed, and the bee VIT was well tolerated with up to 200 µg bee venom. The patient is currently in the 3rd year of treatment and tolerates the treatment very well. Conclusion: Omalizumab may be used as a premedication in patients with mastocytosis who do not tolerate VIT. Although there is no consensus on the treatment protocol, treatment for 2 – 6 months is considered adequate. The long-term benefits of such treatment require further research.Correspondence to:
Prof. Dr. Uta Jappe, FG Klinische und Molekulare Allergologie, Forschungszentrum Borstel, Leibniz, Lungenzentrum, Parkallee 1 – 40, 23845 Borstel
Email: [email protected]
Review
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]
