Allergen challenge tests in allergen im- munotherapy: State of the art

Introduction: Treatment effects in aller-gen immunotherapy (AIT) studies are based on symptomatic improvement, and evalua-tions of naturally exposed patients do often show weak efficacy. Allergen challenge tests, such as conjunctival (CAC), nasal (NAC), or bronchial (BAC) challenge tests, or chal-lenges in allergen exposure chambers (AEC) are accepted by regulators for AIT phase II studies only. Methods: This review aims to describe different allergen challenge test methods, summarizes safety and limitations for each, and discusses their potential for use in AIT trials. Results: Organ-specific al-lergen challenges provide information about individual reactivity, reaction threshold, and organ-specific efficacy of AIT. AECs, targeting all affected organs simultaneously, were de-veloped to investigate disease mechanisms and treatment effects under controlled and reproducible conditions. Conclusion: A high level of standardization is existing for NAC only; in CAC and BAC, the toolbox is limited to subjective symptom scoring with no vali-dated objective parameters identified yet. AECs are complex and heterogenous; corre-lation of systems and comparability of study data is required. All challenge methods are safe when conducted by experienced staff.

Automated summary

Different allergen challenge test methods including CAC, NAC, BAC, and AEC have their own safety and limitations. NAC is the only method with a high level of standardization, while subjective symptom scoring is the only evaluation method for CAC and BAC. AEC is a complex and heterogeneous method that requires validation of system correlation and comparability of study data. Only experienced staff can ensure the safety of all challenge methods.