Safety, outcomes, and recommendations for two-step outpatient nonsteroidal anti-inflammatory drug challenges

ABSTRACT Background Nonsteroidal anti-inflammatory drug (NSAID) outpatient challenge protocols are not standardized, vary in clinical practice, and can be time and resource intensive to perform. Objective Investigate the safety and outcomes of two-step outpatient NSAID challenges for evaluation of patients with non-aspirin-exacerbated respiratory disease (AERD)-related NSAID hypersensitivity. Methods We conducted a retrospective study of patients with history of NSAID allergy who underwent outpatient NSAID challenges under allergist supervision. Individuals with AERD were excluded. Patient demographics, NSAID reaction history and drug challenge details and outcomes were collected. Results A total of 249 patients (mean age 51.6 years, 63.5% female) underwent 262 NSAID challenges. Of these, 224 (85.5%) challenges were negative. There were 30 challenges (11.5%) that resulted in an immediate reaction during the challenge procedure, and 8 (3.1%) that resulted in delayed reactions. Three individuals with immediate reactions required treatment with intramuscular epinephrine. Factors associated with a positive NSAID challenge included a prior reaction occurring within 5 years of drug challenge (Odds Ratio [OR] 3.66, 95% CI 1.67-8.44), history of a prior immediate reaction within 3 hours of NSAID ingestion (OR 2.45, 95% CI 1.12-5.57), history of cross-reactive NSAID hypersensitivity to multiple NSAIDs (OR 2.97, 95% CI 1.23-6.91), and presence of comorbid chronic spontaneous urticaria (OR 2.95, 95% CI 1.35-6.41). Conclusion Over 85% of two-step non-AERD NSAID drug challenges were negative for an immediate or delayed reaction, opening up patients for use of at least one clinically indicated NSAID. Challenge reactions were generally mild. Two-step NSAID challenge protocols can be safely performed in the outpatient setting.