International consensus on allergen immunotherapy-II: Mechanisms, standardization, and pharmacoeconomics

This month, JACI presents the second portion of the comprehensive international consensus (ICON) statement on allergen immunotherapy. The ICON statement is an effort of the International Collaboration in Asthma, Allergy and Immunology (iCALL) that includes the European Academy of Allergy and Clinical Immunology (EAACI), the American Academy of Allergy, Asthma and Immunology (AAAAI), the American College of Allergy, Asthma and Immunology (ACAAI) and the World Allergy Organization (WAO). Jutel et al. review the evidence on how allergen immunotherapy (AIT) works and summarize what lies on the horizon (J Allergy Clin Immunol 2016; 137(2): 358-368).

A number of mechanisms underlie an allergic response to a substance such as grass pollen, house dust mites, or bee venom. Allergen immunotherapy involves slowly increasing exposure to an allergen over time, ideally resulting in a patient’s increased tolerance and clinical improvement. The literature indicates that administration of AIT leads to early decreases in the susceptibility of mast cells and basophils to respond to environmental proteins, even in the presence of elevated allergen-specific immunoglobulin (Ig)E. Desensitization is followed by allergen-specific T-regulatory (Treg) and B-regulatory (Breg) cell generation and regulation of allergen-specific IgE and IgG₄. In the longer term, changes in memory T- and B-cell compartments and shift in the balance of type 1 T-helper (Th1) and type 2 T-helper (Th2) cells result in sustained improvement.

There are a number of barriers to the use of AIT worldwide. One such barrier is a low awareness of its potential, in the context of patient welfare and improved pharmaco-economics. AIT is currently the only therapy with the capacity to alter the course of allergic disease. Further, standardization of the potency, consistency, and stability of allergen extracts used in AIT is essential, as is the standardization of the practices of regulatory agencies from different parts of the world. Potential facilitators for acceptance and increased use of AIT include validation and consensus on outcome measures for clinical trials; validated methods of assessing AIT’s impact; and post-marketing studies demonstrating the positive impact of AIT on the quality of life of its recipients.