Injection-based safety of aqueous venom immunotherapy during venom extract shortage: impact of forced depot-to-aqueous switching.

BACKGROUND: Venom immunotherapy (VIT) is the only disease-modifying treatment for Hymenoptera venom allergy. Nationwide shortages of depot venom extracts necessitated transition to aqueous preparations, but real-world safety data on this switch remain limited. OBJECTIVE: To evaluate the injection-based safety of aqueous VIT and the impact of forced depot-to-aqueous switching on systemic reactions (SRs). METHODS: This retrospective single-center cohort included 31 aqueous VIT courses in 30 adults treated between January 2023 and January 2026. Patients initiated aqueous VIT or were compulsorily switched from depot preparations. SRs were assessed at treatment-course and injection levels. Predictors were evaluated using Firth penalized logistic regression. RESULTS: SRs occurred in 10/31 courses (32.3%) and in 28/504 injections (5.6%): 6.3% during buildup and 4.6% during maintenance. Most were mild to moderate, with no Grade 4-5 reactions. Comorbid disease independently predicted SRs (adjusted OR 5.87, 95% CI 1.07-38.42; p = 0.042). Forced switching showed higher odds of SRs but was not independently significant (adjusted OR 6.84, 95% CI 0.84-88.76; p = 0.072). CONCLUSIONS: Aqueous VIT remained feasible during the depot extract shortage despite a higher-than-previously-reported SR rate. Comorbid disease predicted SRs, while forced switching may identify patients requiring closer monitoring.