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Safety and recommendations for outpatient nonsteroidal anti-inflammatory drug challenges

Published: November 16, 2021

While adverse reactions to nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly reported, only a minority are consistent with allergic hypersensitivity. Diagnosis of NSAID-induced hypersensitivity is based on clinical history in combination with drug challenge testing but can be difficult due to lack of standardized NSAID challenge protocols. Current drug challenge protocols for evaluation of NSAID hypersensitivity vary widely by physician and institution and can be prohibitively time and resource intensive. Unverified NSAID drug allergy labels often persist without confirmatory testing and can influence prescriber behavior and medication choices and adversely affect patient outcomes.

In a recent study published in The Journal of Allergy and Clinical Immunology: In Practice, Li et al report on a cohort of 249 individuals who underwent a total of 262 two-step outpatient NSAID challenge for any indication excluding aspirin exacerbated respiratory disease evaluation at two large academic centers in Boston, Massachusetts. The goal of this study was to describe the safety and outcomes of a simple, two-step NSAID drug challenge protocol implemented in outpatient settings.

The authors found that 85.5% of NSAID drug challenges performed were negative. Immediate reactions were induced in 11.5% of challenges, and delayed reactions were rare (3.1%). For immediate reactions, the majority that occurred after the second dose had symptom onset at more than 60 minutes after drug administration. One third of reactions required no treatment, and the remaining reactions were managed with oral antihistamines, leukotriene antagonists, oral corticosteroids, or albuterol. Only three individuals required treatment with intramuscular epinephrine and all responded rapidly and recovered. Importantly, subjective symptoms were reported in 13.7% of challenges; however, after shared decision making, all patients proceeded to complete the NSAID challenge with no objective signs of a reaction. Risk factors associated with a positive NSAID challenge included history of a recent prior reaction (within five years of drug challenge), a prior immediate reaction, history of cross-reactive NSAID hypersensitivity, and comorbid chronic spontaneous urticaria.

There is significant potential benefit related to NSAID allergy de-labeling and this study provides evidence for the overall low risk for severe reactions induced by NSAID challenge. The authors additionally offer practical recommendations for a two-step NSAID challenge protocol that can feasibly and safely be performed in an outpatient setting. NSAID drug challenges should be considered whenever possible, in order to facilitate drug allergy de-labeling in appropriate candidates.

The Journal of Allergy and Clinical Immunology: In Practice is an official journal of the AAAAI, focusing on practical information for the practicing clinician.

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