{
  "abstract": "Hereditary angioedema (HAE) attacks are recurrent, debilitating, and potentially life-threatening. Across the clinical program, garadacimab long-term prophylaxis demonstrated early onset and durable, sustained protection against HAE attacks and clinically meaningful improvements in health-related quality of life (HRQoL). HAE treatment goals include total disease control (attack-free) and normalization of life. Predicting treatment effect may aid shared decision-making and choice of long-term prophylaxis. Here, we report an attack-free probability model predicting garadacimab treatment effect beyond available Phase 3 clinical data and explore the relationship between HRQoL and attack-free duration. A generalized mixed-effect Poisson model was developed and validated with data from the garadacimab pivotal Phase 3 (VANGUARD) and Phase 3 open-label extension studies. Efficacy variables, including attack-free probabilities, were predicted for simulated populations of garadacimab-treated patients and assessed for goodness of fit. Analysis of covariance was used to assess the relationship between Angioedema Quality of Life questionnaire scores and attack-free duration. Model-predicted efficacy variables adequately reflected observed clinical data with high goodness of fit (Nakagawa-Schielzeth conditional R²: 74.3%). Following a 1-month attack-free period after garadacimab initiation, patients had a 60% cumulative probability of remaining attack-free up to Month 25 and 49% up to 5 years. HRQoL improved with increasing duration of attack-free periods, reaching minimal to no impairment after 6 months. This attack-free probability model suggests long-term effects of garadacimab over a 5-year treatment period. Patients treated with garadacimab have the potential to live attack-free for long periods of time, with substantial HRQoL improvements.",
  "abstract_shown": true,
  "affiliations": [
    "Division of Rheumatology and Clinical Immunology, Department of Medicine, Queen Mary Hospital, University of Hong Kong, Hong Kong, China.",
    "Section of Rheumatology, Allergy & Immunology, Department of Medicine, Yale University School of Medicine, New Haven, Connecticut, USA.",
    "University Hospital Frankfurt, Department for Children and Adolescents, Goethe University Frankfurt, Frankfurt, Germany.",
    "AARA Research Center, Dallas, Texas, USA.",
    "Midwest Immunology Clinic, Plymouth, Minnesota, USA.",
    "CSL Innovation GmbH, Marburg, Germany.",
    "CSL Behring, King of Prussia, Pennsylvania, USA.",
    "CSL Behring AG, Bern, Switzerland.",
    "CSL Vifor Pharma Management Ltd., Zurich, Switzerland.",
    "Charité - University Medical Center Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität Zu Berlin, Institute of Allergology, Berlin, Germany.",
    "Immunology and Allergology, Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Berlin, Germany."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 10,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Philip H Li",
      "orcid": "0000-0002-9155-9162"
    },
    {
      "affs": [
        1
      ],
      "name": "F Ida Hsu",
      "orcid": "0000-0003-2201-9442"
    },
    {
      "affs": [
        2
      ],
      "name": "Emel Aygören-Pürsün",
      "orcid": "0000-0001-7763-4982"
    },
    {
      "affs": [
        3
      ],
      "name": "William R Lumry",
      "orcid": "0000-0001-7608-5416"
    },
    {
      "affs": [
        4
      ],
      "name": "Jason Raasch",
      "orcid": "0009-0009-2619-7239"
    },
    {
      "affs": [
        5
      ],
      "name": "Ingo Pragst",
      "orcid": "0000-0002-1259-5422"
    },
    {
      "affs": [
        6
      ],
      "name": "Yinglei Li",
      "orcid": "0009-0006-5866-8160"
    },
    {
      "affs": [
        7
      ],
      "name": "Chiara Nenci",
      "orcid": "0000-0003-2319-2909"
    },
    {
      "affs": [
        8
      ],
      "name": "Marco Campioni",
      "orcid": "0000-0002-4373-1669"
    },
    {
      "affs": [
        9,
        10
      ],
      "name": "Markus Magerl",
      "orcid": "0000-0001-9218-5468"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/a85zyv3xrcyv4.bib",
  "cited_by": 0,
  "doi": "10.1111/cts.70737",
  "fulltext_url": "https://europepmc.org/articles/PMC13651541",
  "id": "a85zyv3xrcyv4",
  "issns": [
    "1752-8054",
    "1752-8062"
  ],
  "landing_url": "https://europepmc.org/article/MED/42852816",
  "language": "eng",
  "licence": "CC-BY-NC",
  "licence_label": "CC BY-NC",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2716|Coagulation, Bradykinin, Polyphosphates, and Angioedema"
    ]
  ],
  "openalex": "W7221085466",
  "pdf_url": "https://europepmc.org/articles/PMC13651541?pdf=render",
  "pmcid": "PMC13651541",
  "pmid": "42852816",
  "published": "2026-10-01",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/a85zyv3xrcyv4.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:18:10Z",
      "native_id": "MED:42852816",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42852816"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2716|Coagulation, Bradykinin, Polyphosphates, and Angioedema",
      "subfield": "human-genetics"
    }
  ],
  "title": "Garadacimab in Hereditary Angioedema: Modeling Suggests Sustained Improvements in Attack-Free Probability and Quality of Life Over 5 Years.",
  "title_text": "Garadacimab in Hereditary Angioedema: Modeling Suggests Sustained Improvements in Attack-Free Probability and Quality of Life Over 5 Years.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:18:10Z",
  "url": "https://research.draconitic.com/paper/a85zyv3xrcyv4",
  "venue": "Clinical and translational science",
  "versions": []
}