Approximately 5–10% of asthmatics suffer of NSAID-exacerbated respiratory disease (NERD), with potential frequent severe reactions. The inability to use NSAIDs may thereby significantly impair their quality of life and impact care pathway by limiting therapeutic choices. In such context, to provide a safe therapeutic option is both challenging and of high interest for these patients.

To develop a safe algorithm for NSAID reintroduction in NERD patients, with or without biologic therapy, based on clinical history and comorbidities. To evaluate the recurrence of reactions when reintroducing an oxicam or a coxib using this algorithm.

A prospective study was conducted from June 2024 to January 2025, including 52 controlled moderate-to-severe asthmatic patients who experienced bronchospasm after administering at least two chemically distinct COX-1 NSAIDs. NERD diagnosis was based on clinical history, and in uncertain cases, aspirin provocation tests were performed. Cases with anaphylaxis underwent skin testing following EAACI recommendations. Patients were stratified into low risk (LR) and high risk (HR) for recurrence based on nasal polyposis, biologic therapy, advanced age, history of intensive care unit admission for NSAID-induced reactions, and hypersensitivity to paracetamol.

Fifteen NERD patients (53% female) underwent drug provocation tests (DPTs) with alternative NSAIDs. Five patients presented an additional history of paracetamol reaction, and eight with sulfite hypersensitivity. Eight patients were on biotherapy therapy for severe asthma. According to the algorithm, 3 LR patients tolerated piroxicam, and 12 HR patients tolerated celecoxib. All provocation tests were clinically well tolerated, with no decrease in FEV1>20%. In addition, no cross-reactivity was observed between oxicam/coxib, COX-1 NSAIDs, or paracetamol in NERD patients, regardless of biologic therapy status.

In our hands, the stratification algorithm and provocation tests demonstrated both safety and efficacy. All patients achieved an effective pain relief treatment with a marked improvement in quality of life.