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Published on: May 31, 2021
Comparative Safety and Treatment Persistence of Aeroallergen and Venom Immunotherapy: A Real-World Patient- and
Introduction:
Subcutaneous aeroallergen immunotherapy (SCIT) and venom immunotherapy (VIT) are established disease-modifying treatments, but treatment-related adverse reactions remain an important safety concern. Direct real-world comparisons of these modalities, particularly using injection-level analyses that account for repeated injections within patients, remain limited. This study aimed to compare adverse reactions and documented treatment discontinuation between SCIT and VIT at both the patient and injection levels.
Methods:
This retrospective single-center study included 172 adults receiving SCIT (n = 144) or VIT (n = 28) between January 2023 and December 2025. Adverse reactions were evaluated at the patient level and across 2,251 administered injections. Injection-level local and systemic reactions were compared using generalized estimating equation models accounting for repeated injections within patients.
Results:
At the patient level, local reactions (28.6% vs. 10.4%; p = 0.016) and systemic reactions (21.4% vs. 2.1%; p < 0.001) were more frequent with VIT than with SCIT. Four of the six VIT patients who experienced systemic reactions had a maximum severity grade of 3-4. At the injection level, local reaction frequencies were 95 versus 15 per 1,000 VIT and SCIT injections, respectively (odds ratio (OR) 4.33, 95% CI 1.36-13.76; p = 0.013), while systemic reaction frequencies were 95 versus 3 per 1,000 injections (OR 31.47, 95% CI 7.00-141.50; p < 0.001). Documented treatment discontinuation was numerically less frequent with VIT than with SCIT (3.6% vs. 13.9%), although the difference was not statistically significant (p = 0.205). Sensitization pattern was not associated with adverse reactions, and no exploratory biomarker association remained statistically significant after correction for multiple comparisons.
Conclusion:
VIT was associated with more frequent local and systemic reactions than SCIT, and higher-grade systemic reactions were observed among VIT recipients. Treatment persistence was numerically higher with VIT, although documented discontinuation did not differ significantly between modalities. Injection-level analyses complemented patient-level reporting by capturing repeated reaction episodes relative to treatment exposure.

