Real-life safety of venom immunotherapy in children and adults: latent class analysis from the Adverse Events Registry

Background Venom Immunotherapy (VIT) safety remains a key consideration in daily clinical practice. Currently, there is considerable variation in the reported frequency of adverse events (AE) during VIT, and risk factors have not been fully elucidated. Furthermore, no previous study has used Latent Class Analysis (LCA) to assess the real-life safety of VIT across different patient profiles. Methods LCA was performed on data from 212 adults and 165 children undergoing 398 VIT treatments using different protocols and products across 8 European countries, retrieved from the Adverse Events Registry (ADER). Associations between identified profiles and the frequency of local and systemic AE were evaluated using logistic regression. Results Three latent classes were identified; each class encompassed different characteristics of patients’ demographics, treatment protocols and products. Class 1: 135 patients undergoing premedicated VIT treatment without adjuvants, through ultrarush up-dosing regimens associated with a “moderate-risk” regarding AE frequency but with more severe systemic AE recorded in this class; Class 2: 138 younger patients (median age: 13.6 years old) receiving premedicated VIT, without adjuvants, using rush up-dosing associated with a “higher-risk” profile for experiencing frequent AEs [OR = 6.523, 95% CI = (3.211 –13.253); p < 0.001] and systemic AEs [OR = 4.149, 95% CI = (1.765–9.754); p = 0.001]. Honeybee (HB) venom and female sex were associated with SAE and AE, respectively, in this class, whereas each one-year increase in age was associated with 3.6% reduction in odds for AE [OR = 0.964, 95% CI (0.931–0.999), p = 0.045]. Class 3: the oldest group of patients ( n = 104), receiving mostly HB-VIT with adjuvants, through conventional and cluster up-dosing protocols without premedication, associated with a “low-risk” of AE. In the overall study population, VIT with HBV, female sex and rush updosing protocol were associated with higher odds for AE. Conclusion VIT is generally well-tolerated in real-life clinical practice both in children and adults, although systemic AEs were recorded in 17.2% of cases. A high-risk profile for frequent AEs was identified in our study, with younger age, honeybee venom and female sex independently associated with higher odds of AE. These associations, together with rush updosing, were also confirmed in the overall population.