Data-driven step doses for drug provocation tests to nonsteroidal anti-inflammatory drugs

Hypersensitivity to nonsteroidal anti-inflammatory drugs (NSAIDs) is of great concern because they are frequently encountered in daily clinical practice. Drug provocation tests (DPTs) are particularly needed for NSAIDs.

The aim of this retrospective study was to detect eliciting dose thresholds during NSAIDs DPT in order to suggest optimal step doses, using the survival analysis method. Our secondary objective was to describe subgroups at higher risk during DPT and evaluate the safety of our 30 minutes incremental 1-day protocol. The study comprised all the patients attended the Allergy of the University Hospital of Montpellier (France), between 1997 and 2017 for a suspicion of drug hypersensitivity reaction to NSAIDs.

Throughout the study period, 311 positive DPT were analyzed (accounting for 285 hypersensitive patients). We identified eliciting thresholds (dose and time), and we suggest the following steps for future DPT: for the rapid absorption group (acetylsalicylic acid, ibuprofen, ketoprofen, and tiaprofenic acid), every 30 minutes: 20%-30%-50% of daily therapeutic dose, for the moderate absorption group, every 30 minutes: for diclofenac 5%-15%-30%-50%, and for celecoxib, 20%-80%. For the slow absorption group, piroxicam, 25%-75%, was separated by a 3-hours interval. A surveillance period of 3 hours after the last dose is mandatory for patients.

Drug provocation test protocols for NSAID are empirical, driven by the knowledge on patterns of DHR, cross-reactivity between NSAID and pharmacological effects of these all drugs. This is the second experience in improving DPT protocols, after BL (B-lactam) antibiotics.