D1.92 - Optimizing Aspirin Oral Provocation Testing in Suspected NSAID Hypersensitivity: A Real-World Protocol Analysis

NSAID hypersensitivity is frequently related to COX-1 inhibition. Aspirin is central to the diagnostic work-up, as a negative aspirin oral provocation test (A-OPT) excludes COX-1-mediated hypersensitivity, while a positive test confirms the diagnosis; however, safety and protocol standardization remain concerns. Objectives: To evaluate the safety and diagnostic utility of A-OPT in patients with suspected NSAID-HS, and to review aspirin provocation protocols used in clinical practice.

We reviewed clinical data of patients with suspected NSAID-HS who underwent A-OPT at our Department between January 2020-December 2025. Demographic and clinical data, including index reactions, test outcomes, and A-OPT protocols were assessed.

A total of 161 patients were included (mean age 49.97±15.35 years; 63% female). Index reactions were immediate in 77% and non-immediate in 9.3%. Suspected HS involved a single NSAID in 68.3% of patients and multiple NSAIDs in 27.9%; aspirin was implicated in 42%.

A-OPT was positive in 34 patients (21.5%), at cumulative doses ranging from 250 to 1000 mg. Most reactions were cutaneous (91.2%); 3 cases met criteria for anaphylaxis. Only one positive A-OPT was observed in 60-minutes interval protocols.  

When aspirin was not implicated in the index reaction, initiating the diagnostic work-up with A-OPT reduced the number of provocation tests required, both in patients with suspected HS to a single NSAID (n = 51; p<0.001) and to multiple NSAIDs (n = 21; p = 0.004).

A negative A-OPT (n = 122) excluded COX-1–mediated NSAID-HS. In 28% of patients also supported an IgE-mediated mechanism, allowing less restrictive avoidance recommendations. One patient showed exclusive A-OPT positivity while tolerating other NSAIDs, but the underlying mechanism could not be established. No significant association was found between test positivity and comorbidities. All protocols were safely applied despite variability in dose-escalation schemes; three life-threatening reactions occurred and were promptly managed. 

A-OPT is a safe and highly informative diagnostic tool. Its use as a first-line test improves diagnostic efficiency by reducing the need for multiple provocation particularly when aspirin is not implicated in the index reaction. These findings support the routine use of A-OPT in the diagnostic work-up of suspected NSAID hypersensitivity.