D1.398 - Safety Outcomes and Predictors of Clinically Significant Reactions in Positive Drug Provocation Tests: A 10-Year Tertiary-Center Cohort

Drug provocation tests (DPTs) are the reference standard for confirming drug hypersensitivity, yet positive tests may require urgent treatment even in controlled settings. We described the clinical profile, reaction patterns, and management needs of patients with positive DPTs and explored predictors of clinically significant reactions.

We retrospectively reviewed 10,635 DPTs performed in a tertiary allergy center (Jan 2015–Sep 2025). Patients with positive reactions were characterized for demographics, comorbidities, reaction onset and severity, and treatments. Moderate-to-severe reactions were defined as grade >1. Multivariable logistic regression assessed predictors of moderate-to-severe reactions.

Seventy-five positive reactions occurred in 66 adults (positivity rate 0.7%). Median age was 33.8 years (IQR 24.8–46.3) and 64.0% were female. Median time to onset was 120 min (IQR 60–180; range 5–360). Reactions were mild 52.0%, moderate 29.3%, and severe 18.7%. Pharmacologic intervention was required in 84.0%: antihistamines 76.0%, systemic corticosteroids 65.3%, short-acting bronchodilator 14.7%, and intramuscular epinephrine 14.7%; hospital admission occurred in 1.3%. Comorbidities were frequent, including asthma (44.0%), allergic rhinitis (38.7%), nasal polyps (28.0%), NSAID-exacerbated respiratory disease (NERD) (28.0%), and prior anaphylaxis (30.7%). In multivariable analysis, NERD independently predicted moderate-to-severe reactions (OR 7.10; 95% CI 1.58–31.84), and tests indicated by senior allergists were associated with higher risk than those indicated by fellows (OR 18.51; 95% CI 2.58–132.93).

In this study, conducted at a highly experienced center in DPT, the reaction rate was found to ve 0.7%. In a high-risk cohort, nearly one in five positive DPTs were severe and one in seven required epinephrine, underscoring the need for experienced centers with full emergency preparedness. Patients with NERD and other high-risk features warrant enhanced risk stratification and observation.