Evaluating the negative predictive value of provocation tests with nonsteroidal anti-inflammatory drugs

The nonsteroidal anti-inflammatory drugs (NSAIDs) hypersensitivity work-up is based on clinical history, skin tests, and drug provocation tests. The negative predictive value (NPV) of the latter is not established.

A cohort study was conducted in the Allergy Department in Montpellier to evaluate the NPV of the provocation test with NSAIDs in patients with clinical presentation suggestive of hypersensitivity, and negatively tested. Patients were contacted at least 6 months after the work-up. Patients who took NSAID and reacted were proposed a new allergy work-up, which included a provocation test with the culprit drug.

Among the 393 patients contacted, 279 (71.0%) were followed up. Two hundred and sixty (93.2%) patients had taken a NSAID at least once: 139 (53.5%) the same drug as the one tested and 215 (82.7%) an alternative (94, 33.7% taking both the tested NSAID and an alternative). Eight patients (3.1%) reported a reaction (five with the negatively tested NSAID and three with another NSAID). All the reactions occurred immediately after the first administration and were not severe. Among the five patients who reacted with the negatively tested NSAID, only three accepted a re-challenge, negative in two cases and positive in one, representing a NPV of 97.8% (95% CI: 95.4-100%). Three patients (3/215) reported a reaction when an alternative NSAID was taken, representing a NPV of 98.6% (95% CI: 97-100%).

The NPV of NSAIDs drug provocation test is high. This should reassure physicians who might hesitate to prescribe NSAIDs, especially in patients with negative allergic work-ups.