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. 2025 Jul 28;20(1):383.
doi: 10.1186/s13023-025-03739-8.

Unmet needs in hereditary angioedema: an international survey of physicians

Thomas Buttgereit  1   2 , Felix Aulenbacher  3   4 , Adil Adatia  5 , Carolina Vera Ayala  3   4 , Maryam Ali Al-Nesf  6 , Sabine Altrichter  7   8 , Mohamed Abuzakouk  9   10 , Mona Al-Ahmad  11 , Ramzy Mohammed Ali  6 , Alejandro Berardi  12 , Isabelle Boccon-Gibod  13 , Laurence Bouillet  14 , Luisa Brussino  15 , Marko Barešić  16 , Paula J Busse  17 , Stephen D Betschel  18 , Herberto Chong-Neto  19 , Oscar Calderón Llosa  20 , Timothy J Craig  21 , Anthony D Dorr  22 , Sérgio Duarte Dortas Junior  23 , Daria Fomina  24   25   26 , Henriette Farkas  27 , Jie Shen Fok  28   29   30 , Anete S Grumach  31 , Jens Greve  32 , Mar Guilarte  33 , Margarida Gonçalo  34 , Vesna Grivcheva-Panovska  35 , Michihiro Hide  36   37 , Roman Hakl  38   39 , Ankur Jindal  40 , Constance H Katelaris  41 , Shailajah Kamaleswaran  42 , Tamar Kinaciyan  43 , Elena Latysheva  44 , José Ignacio Larco Sousa  45 , Ramón Lleonart Bellfill  46 , Hassan Mobayed  6 , Martin Metz  3   4 , Iman Nasr  47 , Natasa T Mitrevska  48 , Stefania Nicola  15 , Claudio Alberto Salvador Parisi  49 , Grzegorz Porebski  50 , Jonny Peter  51   52 , Mariana Paes Leme Ferriani  53 , Nelson Rosario Filho  19 , Bülent Enis Şekerel  54 , Faradiba Sarquis Serpa  55 , Marcin Stobiecki  50 , Susanne Trainotti  56 , Anna Valerieva  57 , Chamard Wongsa  58 , Jane C Y Wong  59 , Esra Yucel  60   61 , Yinglei Li  62 , Chiara Nenci  63 , Marcus Maurer  3   4 , Markus Magerl #  3   4 , Philip H Li #  64
Affiliations

Unmet needs in hereditary angioedema: an international survey of physicians

Thomas Buttgereit et al. Orphanet J Rare Dis. .

Abstract

Background: Hereditary angioedema (HAE) is a rare and potentially life-threatening genetic disorder characterized by unpredictable attacks of angioedema. MENTALIST (UnMEt Needs in herediTAry angioedema-a gLobal physIcian perSpecTive) is the first international survey uncovering unmet needs and identifying barriers to optimal management in HAE following the latest update of the World Allergy Organization (WAO)/European Academy of Allergy and Clinical Immunology (EAACI) HAE guidelines.

Methods: This web-based survey comprised 24 questions on HAE management and unmet needs. HAE-expert physicians from the Angioedema Centers of Reference and Excellence network ranked unmet needs according to their own perspectives and their patients' perspectives, using a 10-point Likert scale ranging from 0 (not a challenge/unmet need at all) to 10 (huge challenge/unmet need).

Results: Of 64 respondents from 32 countries, most (91%) had > 5 years of experience in managing HAE. Overall, 48% of respondents (n = 31/64) reported that < 50% of their patients had achieved the WAO/EAACI HAE treatment goals of total disease control and "normalization" of life at the time of the survey. Implementation of consensus recommendations was found to be inconsistent across regions. Gaps in non-HAE-expert physician knowledge, treatment costs, and reimbursement for long-term prophylaxis were the highest-priority challenges according to the respondents. Burden of disease remains a challenge among patients, as reported by their physicians.

Conclusions: The MENTALIST findings highlight a need for removal of barriers to HAE treatment goals and propose a call to action to improve access to treatments, for greater provision of education for physicians and patients, critical collaboration with patient organizations and industry stakeholders and ultimately to optimize HAE care.

Keywords: Guidelines; Hereditary angioedema; Management; Treatment goals; Unmet needs.

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Conflict of interest statement

Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: Not applicable. Competing interests: TB was a speaker for, and/or advisor for, and/or has received research funding from Almirall, Aquestive, BioCryst, CSL Behring, GSK, Hexal, KalVista Pharmaceuticals, Medac, Novartis, Pharming, Roche, Sanofi-Aventis, Swixx BioPharma, and Takeda. FA declares no conflict of interest in relation to this work. AA reports conference travel support and/or honoraria from BioCryst, Covis Pharma, CSL Behring, GSK, and Takeda; and clinical trial support from Astria, BioCryst, Ionis Pharmaceuticals, KalVista Pharmaceuticals, Octapharma, Pharvaris, and Takeda. CVA is a clinical trial/registry investigator for BioCryst, CSL Behring, Intellia, Novartis, Pharvaris, and Takeda. MAA-N declares no conflict of interest in relation to this work. SA declares no conflict of interest in relation to this manuscript. SA has conducted studies, and was an advisor and speaker, for ALK, Allakos, AstraZeneca, BioCryst, Blueprint, CSL Behring, Leo Pharma, Moxie, Novartis, Pharvaris, Sanofi, Takeda, and Thermo Fisher. MA declares no conflict of interest in relation to this work. MA-A received speaker and advisory board honoraria from AstraZeneca, GSK, and Sanofi. RMA declares no conflict of interest in relation to this work. AB has participated as a speaker for Takeda, and in advisory boards for CSL Behring and Pint Pharma. IB-G is or recently was a speaker, advisor, and engaged in research and educational projects for, and/or received research and consultancy grants from, BioCryst, CSL Behring, KalVista Pharmaceuticals, Novartis, Pharming, Pharvaris, and Takeda. LBo has consulted/served as speaker for, engaged in research and educational projects with, or accepted travel grants from BioCryst, Blueprint, CSL Behring, GSK, KalVista Pharmaceuticals, Novartis, Pharvaris, and Takeda. LBr declares no conflict of interest in relation to this work. MB has received travel and congress bursaries and lecture fees from Pharming and Takeda. PJB declares no conflict of interests in relation to this work. PB has received consultancy grants from BioCryst, CSL Behring, Intellia, and Takeda. SDB has received speaker/advisor fees and/or research funding from Astria, Canadian Blood Services, CSL Behring, Green Cross, Grifols, Ionis Pharmaceuticals, KalVista Pharmaceuticals, Novartis, Octapharma, Pharvaris, Sanofi, Takeda, and WSIB. HC-N has received grants for consultation from CSL Behring, Pint Pharma, and Takeda, and has received speaker grants from Takeda. OCL declares no conflict of interest in relation to this work. TC is a speaker for Astria Therapeutics, BioMarin, CSL Behring, Grifols, Regeneron, and Takeda; and has received research and consultancy grants from Astria, CSL Behring, BioCryst, BioMarin, GSK, Intellia, Ionis, KalVista Pharmaceuticals, Pharvaris, and Takeda. TC is a member of the US Hereditary Angioedema Association Medical Advisory Board and Director of the ACARE International Angioedema Center at Penn State University in Hershey, PA, USA. ADD has received honoraria from BioCryst, CSL Behring, and Takeda for advisory board and speaking services; has received reasonable expenses to attend meetings and conferences from BioCryst and Pharming; and has been a sub-investigator for clinical trials sponsored by BioCryst Pharmaceuticals, Ionis Pharmaceuticals, and KalVista Pharmaceuticals. SDDJr has received payment or honoraria from AstraZeneca, Chiesi, and Novartis. SDDJr received support for attending meetings and/or travel from CSL Behring, Sanofi, and Takeda. DF declares no conflict of interest in relation to this work. HF has received research grants from CSL Behring, Pharming, and Takeda; served as an advisor for BioCryst, CSL Behring, KalVista Pharmaceuticals, Intellia, Ionis Pharmaceuticals, ONO Pharmaceutical, Pharming, and Takeda; and participated in clinical trials/registries for BioCryst, CSL Behring, KalVista Pharmaceuticals, Pharming, Pharvaris, and Takeda. JSF has received speaker and/or consultancy fees for presentations and advisory board participation from CSL Behring, Menarini, Novartis, Takeda, and Viatris. ASG has received research funding from Brazilian Entity of Research (CNPq) and Takeda/Shire; and fees for educational activities or has acted as a consultant for Catalyst Pharmaceuticals, CSL Behring, KalVista Pharmaceuticals, MultiCare, Pharvaris, Pint Pharma, and Takeda. JG was a speaker and/or advisor for, and/or has received research funding from, BioCryst, CSL Behring, KalVista Pharmaceuticals, and Takeda. MGu has received honoraria for educational purposes from CSL Behring, Novartis, and Takeda; participated in advisory boards organized by CSL Behring, Novartis, and Takeda; and has received funding to attend conferences and educational events from CSL Behring, Novartis, Pharming, and Takeda. MGu is a clinical trial/registry investigator for BioCryst, CSL Behring, Novartis, Pharming, Pharvaris, and Takeda; and is a researcher from the VHIR program for promoting research activities. MGo has received honoraria for educational purposes or medical advice from AbbVie, AstraZeneca, Leo Pharma, Lilly, Novartis, Pfizer, Sanofi, and Takeda. VG-P has participated in clinical trials/registries for BioCryst, CSL Behring, KalVista Pharmaceuticals, Pharming, and Takeda. MH has received speaker/consultancy fees from BioCryst, CSL Behring, KalVista Pharmaceuticals, Pharvaris, and Takeda. RH has received speaker/consultancy fees and travel grants from, and/or participated in advisory boards for, CSL Behring, Pharming, Shire, and Takeda; and has served as a Principal Investigator for clinical trials sponsored by BioCryst Pharmaceuticals, CSL Behring, KalVista Pharmaceuticals, Pharming, and Pharvaris Netherlands. AJ declares no conflict of interest in relation to this work. CHK has received speaker/consultancy fees for presentations and advisory board participation from CSL Behring, KalVista Pharmaceuticals, Pharvaris, and Takeda. SK declares no conflict of interest in relation to this work. TK is or recently was a speaker and/or advisor for, and/or has received research funding from, BioCryst, Blueprint, CSL Behring, HAL Allergy, KalVista Pharmaceuticals, Kiniksa, Novartis, Pharvaris, Sanofi-Aventis, and Takeda/Shire. EL is or recently was a speaker and/or advisor for, and/or has received research funding from, CSL Behring, Generium, Novartis, Octapharma, and Takeda/Shire. JILS declares no conflict of interest in relation to this work. RLB has received speaker/consultancy fees from, and/or participated in advisory boards for, BioCryst, CSL Behring, Novartis, Pharming, and Takeda; and is/has been a clinical trial/registry investigator for BioCryst, Ionis, KalVista Pharmaceuticals, Pharvaris, and Takeda. HM declares no conflict of interest in relation to this work. MMet has received honoraria as a speaker and/or advisor from AbbVie, ALK-Abelló, Almirall, Amgen, Argenx, AstraZeneca, Bayer, Beiersdorf, Celldex, Celltrion, Escient, Galderma, GSK, Incyte, Jasper, Novartis, Pfizer, Pharvaris, Regeneron, Sanofi, Teva, Third Harmonic Bio, and Vifor. IN is or recently was a speaker for Sanofi and Takeda. NTM declares no conflict of interest in relation to this work. SN declares no conflict of interest in relation to this work. CASP declares no conflict of interest in relation to this work. GP has received speaker fees, and/or consultancy fees, and/or travel support from CSL Behring, Swixx BioPharma, and Takeda. JP is or recently was a speaker and/or advisor for, and/or has received research funding from, Astria, BioCryst, CSL Behring, Glenmark, Novartis, Pharming, Pharvaris, Sanofi/Regeneron, and Takeda. MPLF declares no conflict of interest in relation to this work. NRF declares no conflict of interest in relation to this work. BES declares no conflict of interest in relation to this work. FSS reports personal fees and other from AstraZeneca, CSL Behring, GSK, Novartis, and Takeda. MS has received grants and/or fees as a speaker from BioCryst, CSL Behring, KalVista Pharmaceuticals, Pharming, and Takeda; and is a clinical trial investigator for BioCryst, Ionis, Isis, KalVista Pharmaceuticals, and Pharvaris. ST was a speaker and/or advisor for CSL Behring and Takeda; and participated in clinical trials/registries for BioCryst, CSL Behring, Ionis Pharmaceuticals, and Takeda. AV has received honoraria for educational lectures, consultancy, sponsorship for educational meetings, and research projects from AstraZeneca, Astria Pharmaceuticals, Berlin-Chemie/Menarini Group, CSL Behring, Ewopharma, Ionis, KalVista Pharmaceuticals, Novartis, Organon, Pharming Group N. V., Pharvaris, Takeda/Shire, SOBI, Stallergenes Greer, and Teva. CW has received honoraria for scientific lectures from Abbott, AstraZeneca, GSK, Menarini, Novartis, Sanofi, and Takeda; and research support from Abbott and Sanofi. JCYW declares no conflict of interest in relation to this work. EY declares no conflict of interest in relation to this work. YL is a full-time employee of CSL Behring LLP and shareholder of CSL Limited. CN is a full-time employee of CSL Behring AG and shareholder of CSL Limited. MMau was a speaker and/or advisor for, and/or received research funding from, Astria, BioCryst, CSL Behring, KalVista Pharmaceuticals, Pharvaris, and Takeda. MMag has received financial support from CSL Behring for acting as a study center investigator during the conduct of the study and personal fees from BioCryst, CSL Behring, KalVista Pharmaceuticals, Novartis, Octapharma, Pharming Technologies, and Takeda/Shire. PHL was a speaker and/or advisor for, and/or has received research funding from, CSL Behring, KalVista Pharmaceuticals, Pharvaris, and Takeda.

Figures

Fig. 1
Fig. 1
Physician perspectives: Ranking of challenges and unmet needs physicians face in treating patients with HAE-C1INH and HAE-nC1INH (overall population). Median values are represented by a solid line in the center of the box. Boxes indicate the IQR with whiskers extending to 1.5 × IQR. Outlier responses are reported as scatter points. The two scatter horizontal lines at 3.333 and 6.667 separate the three unmet need categories (Low: <3.333; medium: ≥3.333 to <6.667; high: ≥6.667). Abbreviations: C4 complement component 4, C1INH C1 inhibitor, HAE hereditary angioedema, HAE-C1INH HAE due to deficiency or dysfunction of C1 inhibitor, HAE-nC1INH HAE due to normal C1INH, IQR interquartile range, LTP long-term prophylaxis
Fig. 2
Fig. 2
Physician-reported patient perspectives: Ranking of challenges and unmet needs patients with HAE-C1INH and HAE-nC1INH report to their treating physicians (overall population). Median values are represented by a solid line in the center of the box. Boxes indicate the IQR with whiskers extending to 1.5 × IQR. Outlier responses are reported as scatter points. The two scatter horizontal lines at 3.333 and 6.667 separate the three unmet need categories (Low: <3.333; medium: ≥3.333 to <6.667; high: ≥6.667). *Including concerns about effectiveness of currently available treatments. Abbreviations: HAE hereditary angioedema, HAE-C1INH HAE due to deficiency or dysfunction of C1 inhibitor, HAE-nC1INH HAE due to normal C1 inhibitor, IQR interquartile range
Fig. 3
Fig. 3
Proportion of respondents who reported achieving HAE treatment goals of total control of the disease and “normalization” of life in their patients: data by a overall population and b region. Abbreviation: HAE hereditary angioedema
Fig. 4
Fig. 4
Ranking of barriers to achieving WAO/EAACI HAE treatment goals in patients with HAE-C1INH and HAE-nC1INH (overall population). Median values are represented by a solid line in the center of the box. Boxes indicate the IQR with whiskers extending to 1.5 × IQR. Outlier responses are reported as scatter points. The two scatter horizontal lines at 3.333 and 6.667 separate the three unmet need categories (Low: <3.333; medium: ≥3.333 to <6.667; high: ≥6.667). *Including concerns about effectiveness of currently available treatments. Abbreviations: EAACI European Academy of Allergy and Clinical Immunology, HAE hereditary angioedema, HAE-C1INH HAE due to deficiency or dysfunction of C1 inhibitor, HAE-nC1INH HAE due to normal C1 inhibitor, IQR interquartile range, WAO World Allergy Organization
See this image and copyright information in PMC

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