Definition, aims, and implementation of GA<sup>2</sup>LEN/HAEi Angioedema Centers of Reference and Excellence
Authors: Marcus Maurer, Werner Aberer, Rosana Agondi, Mona Al‐Ahmad, Maryam Ali Al‐Nesf, Ignacio Ansotegui, Rand Arnaout, Luisa Karla Arruda, Riccardo Asero, Emel Aygören‐Pürsün, Aleena Banerji, Andrea Bauer, Moshe Ben‐Shoshan, Alejandro Berardi, Jonathan A. Bernstein, Stephen Betschel, Carsten Bindslev‐Jensen, Mojca Bizjak, Isabelle Boccon‐Gibod, Konrad Bork, Laurence Bouillet, Henrik Balle Boysen, Nicholas Brodszki, Sigurd Broesby‐Olsen, Paula Busse, Thomas Buttgereit, Anette Bygum, Teresa Caballero, Régis A. Campos, Mauro Cancian, Ivan Cherrez‐Ojeda, Danny M. Cohn, Célia Costa, Timothy Craig, Paulo Ricardo Criado, Roberta F. Criado, Dorottya Csuka, Joachim Dissemond, Aurélie Du‐Thanh, Luis Felipe Ensina, Ragıp Ertaş, José E. Fabiani, Claudio Fantini, Henriette Farkas, Silvia Mariel Ferrucci, Ignasi Figueras‐Nart, Natalia L. Fili, Daria Fomina, Atsushi Fukunaga, Asli Gelincik, Ana Giménez‐Arnau, Kiran Godse, Mark Gompels, Margarida Gonçalo, Maia Gotua, Richard Gower, Anete S. Grumach, Guillermo Guidos‐Fogelbach, Michihiro Hide, Natalia Ilina, Naoko Inomata, Thilo Jakob, Dario O. Josviack, Hye‐Ryun Kang, Allen Kaplan, Alicja Kasperska‐Zając, Constance Katelaris, Aharon Kessel, Andreas Kleinheinz, Emek Kocatürk, Mitja Košnik, Dorota Krasowska, Kanokvalai Kulthanan, M. Sendhil Kumaran, José Ignacio Larco Sousa, Hilary J. Longhurst, William Lumry, Andrew MacGinnitie, Markus Magerl, Michael P. Makris, Alejandro Malbrán, Alexander Marsland, Inmaculada Martinez‐Saguer, Iris V. Medina, Raisa Meshkova, Martin Metz, Iman Nasr, Jan Nicolay, Chikako Nishigori, Isao Ohsawa, Kemal Özyurt, Nikolaos G. Papadopoulos, Claudio A. S. Parisi, Jonathan Grant Peter, Wolfgang Pfützner, Todor Popov, Nieves Prior, German D. Ramon, Adam Reich, Avner Reshef, Marc A. Riedl, Bruce Ritchie, Heike Röckmann‐Helmbach, Michael Rudenko, Andaç Salman, Mario Sanchez‐Borges, Peter Schmid‐Grendelmeier, Faradiba S. Serpa, Esther Serra‐Baldrich, Farrukh R. Sheikh, William Smith, Angèle Soria, Petra Staubach, Urs C. Steiner, Marcin Stobiecki, Gordon Sussman, Anna Tagka, Simon Francis Thomsen, Regina Treudler, Solange Valle, Martijn van Doorn, Lilian Varga, Daniel O. Vázquez, Nicola Wagner, Liangchun Wang, Christina Weber‐Chrysochoou, Young‐Min Ye, Anna Zalewska‐Janowska, Andrea Zanichelli, Zuotao Zhao, Yuxiang Zhi, Torsten Zuberbier, Ricardo D. Zwiener, Anthony Castaldo
Journal: Allergy (2020)

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 HAE-1 HAE-2 Angioedema with or without wheals in patients with urticaria Anaphylaxis 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). The GA2LEN/HAEi ACARE is supported by its twin network, the GA2LEN UCARE network (www.ga2len-ucare.com). We thank Beate Schinzel for expert help with formatting and revising the manuscript as well as its submission. 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. 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