Safety of allergen immunotherapy: real-world evidence

Allergen immunotherapy (AIT) remains the only disease-modifying treatment for respiratory allergic diseases and the only intervention capable of preventing systemic sting reactions in patients with venom allergy (VA). This review summarizes recent real-world evidence on the safety of AIT.

Randomized controlled trials (RCTs) have consistently established the safety of licensed AIT products; however, real-world data are needed to comprehensively evaluate the frequency and severity of adverse events (AEs) and identify risk factors in routine practice. Safety data collection through registries and prospective or retrospective cohorts has confirmed that AIT is generally well tolerated across larger and heterogeneous populations, healthcare settings, and AIT practices. However, rare systemic reactions (SRs) and exceptionally fatal reactions (FRs) continue to occur. Careful pretreatment evaluation and close monitoring remain crucial, particularly during subcutaneous immunotherapy due to the higher risk of systemic reactions. Data on sublingual immunotherapy support a more favourable safety profile, with infrequent systemic reactions and no fatal reactions reported to date. In venom allergy, new evidence on clonal mast cell disorders, hereditary α-tryptasemia and detection of KIT p. D816V in peripheral blood is refining risk stratification.

Systemic and severe adverse events associated with AIT are infrequent. Careful risk stratification and evaluation before initiating immunotherapy can help identify high-risk patients and optimize the benefit-risk balance.