Definition, aims, and implementation of GA²LEN/HAEi Angioedema Centers of Reference and Excellence

GA²LEN, the Global Allergy and Asthma European Network, and HAE international (HAEi), the global umbrella organization for the world's hereditary angioedema (HAE) patient groups, have launched their joint ACARE (Angioedema Center of Reference and Excellence) program, within GA²LEN’s center of reference and excellence (CORE) initiative. Angioedema is a common, heterogeneous, often debilitating and chronic condition and is frequently a challenge for physicians and affected patients, especially patients suffering from recurrent attacks. Additionally, it can be a challenge for some patients to understand the underlying etiology of their angioedema (Table 1). GA²LEN’s CORE networks, such as UCARE for urticaria and ADCARE for atopic dermatitis, help to improve the management of difficult-to-treat conditions. Here, we describe the aims, requirements, provisions, application process, audit, and accreditation protocol for GA²LEN/HAEi ACAREs. ACAREs aim to provide excellence in angioedema management, increase the knowledge of angioedema through research and education, and promote advocacy activities that raise angioedema awareness. To become a certified ACARE, angioedema centers must fulfill 32 requirements, defined by specific provisions that will be assessed during an audit visit. The ACARE program will result in a strong network of angioedema specialists, promote angioedema research and awareness, and harmonize and improve angioedema management globally. ACAREs will expand access to modern angioedema medicines in countries where they are available and help to bring them to countries where they are not.¹

This document summarizes the aims of GA²LEN/HAEi Angioedema Centers of Reference and Excellence (ACAREs) and elaborates the requirements that ACAREs must fulfill to become certified. It also provides (see Appendix S1) background information on GA²LEN and HAEi, including HAEi member organizations and regional patient advocates, on why we need an Angioedema Center of Reference and Excellence (ACARE) program and network, and on the accreditation and certification process, governance and funding, and on the interaction with other GA²LEN networks of centers of reference and excellence. The protocols, aims, requirements, and provisions related to becoming a certified ACARE are based on (a) the experience of the GA²LEN UCARE network and (b) input from angioedema patients, general practitioners, and angioedema specialists.

What are the aims of GA²LEN/HAEi ACAREs? The aims of ACAREs are to set the global standard for excellence in comprehensive angioedema care through research, education, advocacy, and interaction among ACAREs. By serving as referral centers for the diagnosis and management of patients with angioedema, ACAREs will complement the local healthcare system. ACAREs aim to increase knowledge and awareness of angioedema.

What are the requirements for GA²LEN/HAEi ACAREs? ACAREs are required to demonstrate excellence in the management of angioedema, research activities, efforts in education, and advocacy activity. ACAREs need to fulfill 32 requirements, which are explained in the audit checklist (Figure 1A). This checklist includes specific deliverables for each requirement. For example, the requirement to know and follow international guidelines and consensus documents for angioedema (Requirement #16) entails that physicians and other ACARE healthcare professionals have read and understood the current versions of these guidelines and consensus documents and that their recommendations are implemented in their center.

These guidelines and consensus documents include, for example, the international WAO/EAACI guideline for HAE, the EAACI/GA²LEN/EDF/WAO guideline for urticaria, the International/Canadian hereditary angioedema guideline,^2-5 the international consensus on the diagnosis and management of pediatric patients with hereditary angioedema with C1 inhibitor deficiency, the international consensus on the use of genetics in the management of HAE,⁶ and the international consensus and practical guidelines on the gynecologic and obstetric management of female patients with hereditary angioedema caused by C1 inhibitor deficiency.⁷ The deliverables for this requirement are that (a) current guideline and consensus document versions are present (paper or electronic version) at the center, (b) ACARE staff can answer questions on the recommendations these documents provide, and (c) ACARE physicians can show, upon request, by use of a patient file, that patient management decisions are based on guideline recommendations (Figure 1B).

This publication marks our intent to start the implementation of the GA²LEN/HAEi ACARE initiative. Specialty centers for angioedema have started to apply to become ACAREs, and audits and certifications are ongoing (Figure 1B). We expect that most GA²LEN UCARE centers and many angioedema specialty centers will become ACAREs in the near future. We predict and hope that by 2022, GA²LEN/HAEi ACAREs will be established in every continent. This will result in a strong global network of angioedema specialists, promote angioedema research, and harmonize and improve angioedema management worldwide. GA²LEN and HAEi will measure the impact of ACAREs over time and document and report the benefits of this initiative. ACARE network activities and a current list of ACAREs are posted on the network's website (www.acare-network.com).

CONFLICT OF INTEREST

Dr Maurer reports grants and personal fees from Allakos, personal fees from Aralaz, grants and personal fees from AstraZeneca, grants and personal fees from BioCryst, grants from Blueprint, grants and personal fees from CSL Behring, grants and personal fees from FAES, grants and personal fees from Genentech, grants from Kalvista, grants from Lilly, grants from Menarini, grants and personal fees from Novartis, grants from Leo Pharma, grants from Moxie, grants from Pharming, personal fees from Pharvaris, grants and personal fees from Roche, from Sanofi, grants and personal fees from Shire/Takeda, grants and personal fees from UCB, grants and personal fees from Uriach, outside the submitted work. Dr Aberer reports other from Takeda, other from CSL Behring, outside the submitted work. Dr Ansotegui reports personal fees from Mundipharma, personal fees from Roxall, personal fees from Sanofi, personal fees from MSD, personal fees from Faes Farma, personal fees from Hikma, personal fees from Astra Zeneca, personal fees from Stallergens, outside the submitted work. Dr Aygören-Pürsün reports personal fees from Adverum, grants and personal fees from BioCryst, grants and personal fees from CSL Behring, grants and personal fees from Kalvista, personal fees from Pharming, grants and personal fees from Shire/Takeda, during the conduct of the study. Dr Banerji reports grants from Takeda, BioCryst, personal fees from Takeda, BioCryst, CSL, Pharming, Pharvaris, Kalvista, outside the submitted work. Dr Aberer reports other from Takeda, other from CSL Behring, outside the submitted work. Dr Bernstein reports grants and personal fees from Shire/Takeda, grants and personal fees from CSL Behring, grants and personal fees from BioCryst, grants and personal fees from Kalvista, grants from IONIS, grants and personal fees from Novartis/Genentech, grants and personal fees from Astra Zeneca, grants and personal fees from Sanofi Regeneron, from HAEA MAB, during the conduct of the study. Dr Betschel reports personal fees from CSL Behring, personal fees from Takeda/Shire, during the conduct of the study; personal fees from Octapharma, grants from Green Cross, personal fees from Novartis, personal fees from CADTH, outside the submitted work; and Chair of the Canadian Hereditary Angioedema Network. Dr Bork reports personal fees from CSL, personal fees from Shire, outside the submitted work. Dr Busse reports personal fees from CSL Behring, grants and personal fees from Shire, personal fees from Pharming, personal fees from Pearl Therapeutics, personal fees from BioCryst, personal fees from CVS Health, personal fees from Novartis, personal fees from Law offices of Levin, Riback, Adelman and Flangel, outside the submitted work. Dr Bygum reports grants and other from CSL Behring, grants and other from Shire/TAKEDA, other from ViroPharma, from HAE Scandinavia, outside the submitted work. Dr Caballero reports personal fees and other from BioCryst, personal fees, non-financial support and other from CSL-Behring, personal fees from Merck, personal fees and other from Novartis, personal fees from Octapharma, personal fees, non-financial support and other from Shire HGT, personal fees and other from Pharming NV, outside the submitted work. Dr Campos reports and Personal fees for consulting and lectures from Takeda. Dr Cancian served for Scientific Advisory Boards, and received travel grants, for/from CSL Behring and Shire-Takeda. His Institution (Department of Medicine, University of Padua, Italy) received grants from CSL Behring and Shire-Takeda. Dr Cohn reports personal fees from Takeda, personal fees from Pharming, personal fees from CSL, personal fees from BioCryst, outside the submitted work. Dr Craig reports grants, personal fees and other from CSL Behring, grants and personal fees from Dyax, grants, personal fees and other from Takeda, grants and personal fees from BioCryst, grants and personal fees from Pharming, personal fees from Grifols, grants and non-financial support from GSK, grants and non-financial support from Regeneron, grants and non-financial support from Novartis/Genetech, outside the submitted work; and On the Medical Advisory Board for HAE-A of America, AAAAI Board, ALA Mid Atlantic Board. 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Dr Gompels reports other from Speaker at Novartis Urticaria conference 2019, outside the submitted work; and A member of the Immunology Clinical reference group. Dr Gower reports grants, personal fees, research grants and other from Takeda/Shire/Dyax, research grants and other from BioCryst Pharmaceuticals, other from CSL Behring, other from Pharming, other from Fresenius kabi, outside the submitted work. Dr Grumach reports grants, personal fees and other from Shire/Takeda, personal fees and other from CSL Behring, outside the submitted work. Dr Hide reports grants and personal fees from Shire/Takeda, Mitsubishi-Tanabe, Taiho-yakuhin, personal fees from CSL-Behring, BioCryst, Novartis, Teikoku-Seiyaku,Eizai, Kaken, Kyowahakkou-Kirin, grants from Glaxo-Smith-Klein, outside the submitted work. 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Dr Stobiecki reports personal fees from lectures given for CSL Behring, Takeda (Shire), personal fees from conducting clinical trials as a principal investigator for BioCryst, personal fees from consultant work for: BioCryst, CSL Behring, Takeda (Shire), Pharming, outside the submitted work. Dr Sussman reports grants and personal fees from Research grants from pharmaceutical companies. Novartis, Genentech, Amgen, Sanofi, CSL behring, Leo, Kedrion, Green Cross, DBV, Aimune. Ð'dConsulting and honararia from Novartis, Novo, CSL Behring, Amgen., during the conduct of the study; grants from Novartis Pharmaceutical, grants from Genentech, grants from CSL behring, grants from Amgen, grants from Leo, grants from DBV, grants from Aimune, grants from Sanofi, non-financial support from Novartis, non-financial support from Novo, non-financial support from Pediapharm, non-financial support from Sanofi, grants from Kedrion, outside the submitted work. 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Other authors declare that they have no conflicts of interest.