Biologic therapy in rare eosinophil-associated disorders: remaining questions and translational research opportunities.

Fei Li Kuang, Nives Zimmermann, Bruce S Bochner, Steven J Ackerman, Michael E Wechsler, Amy D Klion, Mats W Johansson, Paneez Khoury, Praveen Akuthota, Lisa A Spencer, Florence Roufosse, Sameer K Mathur, Princess U Ogbogu

Journal: Journal of leukocyte biology 2024;116(2):307-320

PMID: 38457125

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Abstract

Rare eosinophil-associated disorders (EADs), including hypereosinophilic syndrome, eosinophilic granulomatosis with polyangiitis, and eosinophilic gastrointestinal disorders, are a heterogeneous group of conditions characterized by blood and/or tissue hypereosinophilia and eosinophil-related clinical manifestations. Although the recent availability of biologic therapies that directly and indirectly target eosinophils has the potential to dramatically improve treatment options for all EADs, clinical trials addressing their safety and efficacy in rare EADs have been relatively few. Consequently, patient access to therapy is limited for many biologics, and the establishment of evidence-based treatment guidelines has been extremely difficult. In this regard, multicenter retrospective collaborative studies focusing on disease manifestations and treatment responses in rare EADs have provided invaluable data for physicians managing patients with these conditions and helped identify important questions for future translational research. During the Clinical Pre-Meeting Workshop held in association with the July 2023 biennial meeting of the International Eosinophil Society in Hamilton, Ontario, Canada, the successes and limitations of pivotal multicenter retrospective studies in EADs were summarized and unmet needs regarding the establishment of guidelines for use of biologics in rare EADs were discussed. Key topics of interest included (1) clinical outcome measures, (2) minimally invasive biomarkers of disease activity, (3) predictors of response to biologic agents, and (4) long-term safety of eosinophil depletion. Herein, we report a summary of these discussions, presenting a state-of-the-art overview of data currently available for each of these topics, the limitations of the data, and avenues for future data generation through implementation of multidisciplinary and multicenter studies.

Published by Oxford University Press on behalf of Society for Leukocyte Biology 2024.

Address: Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 4 Memorial Drive, Bethesda, MD 20892, United States.; Department of Internal Medicine, Hôpital Erasme, Université Libre de Bruxelles, 808 Route de Lennik, Brussels 1070, Belgium.; Division of Allergy and Immunology, Department of Medicine, Northwestern University Feinberg School of Medicine, 240 East Huron Street, Chicago, IL 60611, United States.; Department of Biochemistry and Molecular Genetics, College of Medicine, University of Illinois at Chicago, 900 S. Ashland Avenue, Chicago, IL 60607, United States.; Division of Pulmonary, Critical Care, Sleep Medicine and Physiology, Department of Medicine, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093, United States.; Division of Allergy, Pulmonary and Critical Care Medicine, Department of Medicine, University of Wisconsin School of Medicine and Public Health, 600 Highland Avenue, Madison, WI 53792, United States.; Division of Pediatric Allergy, Immunology, and Rheumatology, University Hospitals Rainbow Babies and Children's Hospital, 11100 Euclid Avenue, Cleveland, OH 44106, United States.; Case Western Reserve University School of Medicine, 11100 Euclid Avenue, Cleveland, OH 44106, United States.; Section of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, University of Colorado School of Medicine, 13001 East 17th Place, Aurora, CO 80045, United States.; Digestive Health Institute, Children's Hospital Colorado, 13123 East 16th Street, Aurora, CO 80045, United States.; Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, National Jewish Health, 1400 Jackson Street, Denver, CO 80206, United States.; Department of Pathology and Laboratory Medicine, University of Cincinnati College of Medicine, 231 Albert Sabin Way, Cincinnati, OH 45267, United States.; Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, 231 Albert Sabin Way, Cincinnati, OH 45267, United States.

DOI: 10.1093/jleuko/qiae051

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MeSH Terms: Humans, Translational Research, Biomedical, Eosinophils, Biological Therapy, Rare Diseases, Eosinophilia, Hypereosinophilic Syndrome