Major Allergen Content in Allergen Immunotherapy Products: The Limited Value of Numbers

Abstract

The prevalence of allergic disorders drastically increased over the last 50 years that today they can be considered epidemic. At present, allergen-specific immunotherapy (AIT) is the only therapy targeting the underlying cause of allergic disorders, and its superior evidence is based on accumulated data from clinical trials and observational studies demonstrating efficacy and safety. However, several aspects remain unsolved, such as harmonization and standardization of manufacturing and quantification procedures across manufacturers, homogeneous reporting of strength, and also the establishment of international reference standards for many allergens. This article discusses the issues related to the measurement of major allergen content in AIT extracts, raising the question of whether comparison of products by different manufacturers are appropriate as basis to choose among the different AIT products. Allergen standardization in immunotherapy products is critical to ensure quality and thereby safety and efficacy. However, lack of harmonization in manufacturing process, allergen quantification (methodologies and references), national regulatory differences, clinical practice, and labeling shows that the comparison of AIT products solely based on major allergen amounts is not rationale and, in fact, impossible. Moreover, further inherent characteristics of products and their clinical use such as their state of extract modification, addition of adjuvant or adjuvant-system, route of administration (sublingual/subcutaneous) and cumulative dose as per posology (including the volume per administration) need to be taken into account, when rating the information given for a specific product. Finally, only convincing clinical data can serve as the product-specific evaluation, or the basis for cross-product comparability, for individual products.

Preventive allergen immunotherapy with inhalant allergens in children

“…An optimized allergen: adjuvant ratio might improve the efficacy of lower allergen doses, risk–benefit ratio and allow rapid up‐dosing through various routes 45,111 . Currently, the needs for standardised AIT products and optimum calibration of their dose‐effect, allergen: adjuvant ratio and treatment routes remain unmet, as highlighted earlier 111,114,115 . Nevertheless, a personalised approach to these aspects has been envisioned 11,22 …”

“…45,111 Currently, the needs for standardised AIT products and optimum calibration of their dose-effect, allergen: adjuvant ratio and treatment routes remain unmet, as highlighted earlier. 111,114,115 Nevertheless, a personalised approach to these aspects has been envisioned. 11,22 Some randomised trials have investigated pAIT, but only a few are DBPCRCT.…”