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Publications

Journal Article Review Epublish

PubMed: 42894560 DOI: 10.1016/j.waojou.2026.101474

Long-term prophylaxis for hereditary angioedema: Navigating the switch between therapies.

World Allergy Organ J 19(10):101474

Authors: Aleena Banerji, Jonathan A Bernstein, Laurence Bouillet, Paula J Busse, Mauro Cancian, Danny M Cohn, Timothy Craig, Mar Guilarte, William R Lumry, Markus Magerl, Cristine Radojicic, Avner Reshef, Marc A Riedl, Raffi Tachdjian

Affiliations

  • Division of Allergy and Clinical Immunology, Department of Medicine, Massachusetts General Brigham, Harvard Medical School, Boston, MA, USA.
  • Division of Rheumatology, Allergy, and Immunology, Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
  • Bernstein Clinical Research Center, LLC, Cincinnati, OH, USA.
  • T-RAIG Unit, CNRS, UMR, University of Grenoble Alpes, CHU Grenoble Alpes, TIMC, Grenoble, 5525, France.
  • Internal Medicine Department, French National Reference Center for Angioedema (CREAK), Grenoble University Hospital, Grenoble, France.
  • Division of Rheumatology, Allergy, and Immunology, Department of Medicine, Mount Sinai School of Medicine, New York, NY, USA.
  • Department of Systems Medicine, University Hospital of Padua, Padua, Italy.
  • Department of Vascular Medicine, Amsterdam Cardiovascular Sciences, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands.
  • Departments of Medicine, Pediatrics, Obstetrics and Gynecology, Maternal-Fetal Medicine, and Biomedical Sciences, Penn State University, Hershey, PA, USA. Vinmec International Hospital, Times City, Hanoi, Vietnam. College of Health Sciences, VinUniversity, Hanoi, Vietnam.
  • Department of Allergy, Hospital Universitari Vall d'Hebron, Vall d'Hebron Research Institute (VHIR), Barcelona, Spain.
  • Asthma and Allergy Research Associates, Dallas, TX, USA.
  • Institute of Allergology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universitätsmedizin Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
  • Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Immunology and Allergology, Berlin, Germany.
  • Duke Health, Durham, NC, USA.
  • Allergy, Immunology, and Angioedema Center, Barzilai University Hospital, Ashkelon, Israel.
  • Division of Allergy and Immunology, University of California San Diego School of Medicine, La Jolla, CA, USA.
  • Division of Allergy, Immunology, and Rheumatology, University of California Los Angeles, Los Angeles, CA, USA.

Abstract

Long-term prophylactic treatments (LTPs) are a major component of disease management for patients with hereditary angioedema (HAE). Patients with HAE experience considerable disease burden, as the frequent, unpredictable, and potentially life-threatening nature of HAE attacks negatively impacts patients' quality of life. LTPs aim to mitigate HAE symptoms by reducing HAE attack frequency and severity, leading to improved disease management and quality of life. As the treatment landscape has recently expanded with the addition of approved LTPs (namely, garadacimab and donidalorsen in 2025), the decision to switch between therapies is becoming increasingly common in clinical practice, and physicians and patients must carefully navigate these treatment transitions to minimize the risk of breakthrough HAE attacks and other safety concerns. Across clinical studies, treatment switching was reported for a variety of reasons, including suboptimal efficacy or frequent breakthrough attacks, safety and adverse events, family planning, treatment burden (including the LTP dosing frequency and route of administration), and drug costs and access. As these treatment options have unique mechanisms of action, durations of effect, and drug clearance rates, clinicians must carefully evaluate approaches for patients to safely switch between therapies while aiming to minimize the risk of breakthrough attacks due to lapses in prophylaxis. This review summarizes the current clinical data available in patients who have switched between first-line LTPs (namely, C1 inhibitor, lanadelumab, and berotralstat), recently approved LTPs garadacimab and donidalorsen, and second-line LTPs (androgens and antifibrinolytics) and it aims to inform health care providers as they navigate this complex treatment landscape. Clinical data available that directly evaluate or compare switching strategies between LTPs are limited, highlighting the need for further prospective studies to better characterize treatment outcomes and guide switching treatments for patients with HAE.

MeSH

Disease Management, Quality Of Life, Safety, Pharmaceutical Preparations, Angioedemas, Hereditary, Therapeutics, Angioedema