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

Abstract

Introduction 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. Methods 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. Results 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. Conclusion 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.

Blood pressure measurements could be reduced in number during the drug provocation test

“…However, learned societies only set a frame for DPT performance and do not make specific recommendations about the type and rhythm of these measurements 1,3,4 . In our centre, data‐driven DPT is performed in 2–7 step dosing, depending on the drug classes, with time increments of 30 or 60 min (up to 3 h for certain nonsteroidal anti‐inflammatory drugs [NSAID]) 5–8 . The beta‐lactams (BL) pattern is generally applied to DPTs for other drugs.…”

“…Empirically, we considered the measurement of blood pressure (BP) and pulse as mandatory and required before starting the DPT, before every incremental dose and at any time during the DPT if symptoms of a DHR occurred. For patients with clinical histories of immediate non‐severe reactions, up to 25% of them may develop anaphylaxis during DPT 5–8 . A recent meta‐analysis of severe reactions during DPT 9 has found that the risk of anaphylactic reaction rises to one in each 345 DPT, and 22 DPT in patients reporting immediate reactions, and history of anaphylaxis, respectively.…”

“…Based on this and previous analyses of reactivity patterns and severity during DPT for different drug classes, we propose criteria to reduce the frequency of BP measurements during DPT, according to risk stratification based on patient clinical history and drug class. The risk of eliciting anaphylaxis during DPT is increased if the index clinical history is anaphylaxis, regardless of the drug class 5–8 . Moreover, patients with a history of anaphylaxis are also at risk for anaphylaxis during ST to BL 10 .…”

Advances and novel developments in drug hypersensitivity diagnosis

“…[50][51][52][53] Regarding NSAIDs, it was suggested to consider their absorption speed to determine steps for DPT. 54 The optimal total cumulative dose for DPT is also under debate.…”

“…If no reaction occurs, DPT is resumed at home with therapeutic doses for several days 50–53 . Regarding NSAIDs, it was suggested to consider their absorption speed to determine steps for DPT 54 …”