{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T21:50:30Z","timestamp":1779313830477,"version":"3.51.4"},"reference-count":26,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2025,10,23]],"date-time":"2025-10-23T00:00:00Z","timestamp":1761177600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medicina"],"abstract":"<jats:p>Background and Objectives: Hereditary angioedema caused by C1 inhibitor deficiency (HAE-C1-INH) is a rare genetic condition characterized by recurrent, potentially life-threatening episodes of angioedema. Long-term prophylaxis (LTP) is essential for decreasing the frequency and severity of attacks. This study aims to compare the safety profiles of two first-line LTP therapies, both of which inhibit kallikrein: berotralstat (oral) and lanadelumab (subcutaneous), using data from the WHO\u2019s VigiBase pharmacovigilance database. Materials and Methods: The study employed a retrospective quantitative design, utilizing the World Health Organization\u2019s pharmacovigilance database, VigiAccess, which contains individual case safety reports of adverse drug reactions (ADRs) to identify cases of ADRs associated with HAE-C1-INH long-term prophylaxis. Results: A total of 644 reports for berotralstat and 3432 reports for lanadelumab were analyzed. Berotralstat was mainly associated with gastrointestinal adverse events (47.9%), while lanadelumab was linked to injection site reactions (45.9%), infections (23.3%), musculoskeletal and connective tissue disorders (10%), immune system disorders (5.3%), vascular disorders (4.7%), and metabolic issues (3.9%). Female patients were more frequently affected in both groups. Statistically significant differences were observed, reflecting the differences in administration methods and pharmacological profiles between the two drugs. Limitations include the self-reported nature of the data and the absence of detailed clinical information. Conclusions: The results confirmed the literature\u2019s data on the gastrointestinal adverse effects of berotralstat, as well as site reactions and infections associated with lanadelumab. Notably, musculoskeletal and connective tissue disorders, immune system disorders, vascular disorders, and metabolic issues occurred more frequently in patients using lanadelumab.<\/jats:p>","DOI":"10.3390\/medicina61111897","type":"journal-article","created":{"date-parts":[[2025,10,23]],"date-time":"2025-10-23T09:44:30Z","timestamp":1761212670000},"page":"1897","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Hereditary Angioedema Prophylaxis Therapy: Berotralstat and Lanadelumab Safety Profile"],"prefix":"10.3390","volume":"61","author":[{"given":"Mattia","family":"Donadoni","sequence":"first","affiliation":[{"name":"Internal Medicine, L. Sacco Hospital, ASST Fbf-Sacco, 20146 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leyla","family":"La Cava","sequence":"additional","affiliation":[{"name":"Internal Medicine, L. Sacco Hospital, ASST Fbf-Sacco, 20146 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emanuele","family":"Bizzi","sequence":"additional","affiliation":[{"name":"Fatebenefratelli Hospital, ASST Fbf-Sacco, 20146 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Valentina","family":"Popescu Janu","sequence":"additional","affiliation":[{"name":"Internal Medicine, L. Sacco Hospital, ASST Fbf-Sacco, 20146 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alessia","family":"Meschia","sequence":"additional","affiliation":[{"name":"Internal Medicine, L. Sacco Hospital, ASST Fbf-Sacco, 20146 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Federica","family":"Cirigliano","sequence":"additional","affiliation":[{"name":"Internal Medicine, L. Sacco Hospital, ASST Fbf-Sacco, 20146 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chiara","family":"Cogliati","sequence":"additional","affiliation":[{"name":"Internal Medicine, L. Sacco Hospital, ASST Fbf-Sacco, 20146 Milan, Italy"},{"name":"Department of Biomedical and Clinical Sciences, Universit\u00e0 degli Studi di Milano, 20146 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5379-1091","authenticated-orcid":false,"given":"Antonio","family":"Gidaro","sequence":"additional","affiliation":[{"name":"Internal Medicine, L. Sacco Hospital, ASST Fbf-Sacco, 20146 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2108","DOI":"10.1001\/jama.2018.16773","article-title":"Effect of Lanadelumab Compared with Placebo on Prevention of Hereditary Angioedema Attacks: A Randomized Clinical Trial","volume":"320","author":"Banerji","year":"2018","journal-title":"JAMA"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1961","DOI":"10.1111\/all.15214","article-title":"The international WAO\/EAACI guideline for the management of hereditary angioedema-The 2021 revision and update","volume":"77","author":"Maurer","year":"2022","journal-title":"Allergy"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"e12035","DOI":"10.1002\/clt2.12035","article-title":"Long-term safety and effectiveness of berotralstat for hereditary angioedema: The open-label APeX-S study","volume":"11","author":"Farkas","year":"2021","journal-title":"Clin. 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