Understanding differences in allergen immunotherapy products and practices in North America and Europe

Information for Category 1 CME Credit Credit can now be obtained, free for a limited time, by reading the review articles in this issue. Please note the following instructions. Method of Physician Participation in Learning Process: The core material for these activities can be read in this issue of the Journal or online at the JACI Web site: www.jacionline.org . The accompanying tests may only be submitted online at www.jacionline.org . Fax or other copies will not be accepted. Date of Original Release: March 2019. Credit may be obtained for these courses until February 29, 2020. Copyright Statement: Copyright © 2019-2020. All rights reserved. Overall Purpose/Goal: To provide excellent reviews on key aspects of allergic disease to those who research, treat, or manage allergic disease. Target Audience: Physicians and researchers within the field of allergic disease. Accreditation/Provider Statements and Credit Designation: The American Academy of Allergy, Asthma u0026 Immunology (AAAAI) is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians. The AAAAI designates this journal-based CME activity for a maximum of 1.00 AMA PRA Category 1 Credit™ . Physicians should claim only the credit commensurate with the extent of their participation in the activity. List of Design Committee Members: Vera Mahler, MD, Robert E. Esch, PhD, Jorg Kleine-Tebbe, MD, William Lavery, MD, PhD, Greg Plunkett, PhD, Stefan Vieths, PhD, and David I. Bernstein, MD (authors); Zuhair K. Ballas, MD (editor) Disclosure of Significant Relationships with Relevant Commercial Companies/Organizations: V. Mahler reports personal fees (prior to current position) from ALK-Abello, Bencard/ATL, HAL, Novartis/Leti and other support from Allergopharma, Germany, and DBV, France, outside the submitted work and grants, personal fees, and other support from Novartis, Germany, and nonfinancial support from the European Academy of Allergy and Clinical Immunology outside the submitted work. J. Kleine-Tebbe reports personal fees from Allergopharma, ALK-Abello, Bencard/Allergy Therapeutics, Circassia, HAL, LETI, Lofarma, Merck (USA), and Stallergenes Greer for lecturing, conduct of studies or consultancy; personal fees from AllergenOnline (University of Nebraska), AstraZeneca, Dr. Pfleger, German Society of Allergology and Clinical Immunology, Glaxo, Novartis, Paraxel International, Sanofi, ThermoFisher for lecturing or consultancy; personal fees from Springer International and THIEME publishers outside the submitted work; and nonfinancial support from the American Academy of Allergy, Asthma u0026 Immunology, European Academy of Allergy and Clinical Immunology, and WHO/IUIS Allergen Nomenclature Subcommittee. S. Vieths reports personal fees from Arzteverband Deutscher Allergologen, the Swiss Society for Allergy and Immunology, Schattauer Allergologie Handbuch, Elsevier Nahrungsmittelallergien und Intoleranzen, Karger Food Allergy: Molecular Basis and Clinical Practice, and the American Academy of Asthma, Allergy u0026 Immunology; nonfinancial support from the German Research Foundation, the European Directorate for the Quality of Medicines and Health Care, the European Academy of Allergy and Clinical Immunology, the German Chemical Society (GDCh), AKM Allergiekongress, the International Union of Immunological Societies; and personal fees from University Hospital Giesen/Marburg, the University of Bonn, and Pharmacon; and nonfinancial support from the Spanish Society for Allergy and Clinical Immunology (SEAIC) outside the submitted work. D. I. Bernstein reports grants and personal fees from ALK-Abello and grants from Allergy Therapeutics, Merck, the American College of Allergy, and the American Academy of Allergy, Asthma u0026 Immunology outside the submitted work. Z. K. Ballas (editor) disclosed no relevant financial relationships. Activity Objectives: 1. To review the differences in allergen immunotherapy (manufacturing, regulatory requirements, and clinical administration) between the United States and Europe. 2. To understand the differences between European and American immunotherapy products and practices, including unique products available in each setting. 3. To describe the differing diagnostic and therapeutic approaches to allergen immunotherapy in Europe and the United States. Recognition of Commercial Support: This CME activity has not received external commercial support. List of CME Exam Authors: Ammara Ahmed, DO, Joan H. Dunlop, MD, Suzanne R. Kochis, MD, Jo Wilson, MD, and Robert A. Wood, MD. Disclosure of Significant Relationships with Relevant Commercial Companies/Organizations: The exam authors disclosed no relevant financial relationships. Allergen immunotherapy (AIT) is thought to be clinically effective and safe in treating allergic rhinitis, asthma, and stinging insect allergy in Europe and North America. However, there are intercontinental differences in AIT therapeutic products in terms of their application and regulation. In North America unmodified standardized and nonstandardized aqueous aeroallergen extracts are approved and used almost exclusively for subcutaneous immunotherapy, whereas more product options are available in Europe, including adsorbed allergens, chemically modified allergens, or both. Both liquid extracts and tablets are approved for sublingual immunotherapy in Europe. Nevertheless, within the European Union, there are major differences in AIT products approved and used in individual countries. There are major differences in the clinical approach to subcutaneous immunotherapy in polysensitized patients; in the United States mixed extracts containing multiple aeroallergens are used, whereas European allergists preferably administer separate injections of single allergen sources or homologous groups deemed to be clinically relevant. Moreover, the regulatory approach differs between the European Union and United States. In contrast to the United States, where common allergen standards exist based on biologic activity, no common standards exist in Europe. In terms of development of new investigational products, the United States has followed the European example for phase II and III studies; no formal US Food and Drug Administration guidance has been issued.