Predicting NSAID hypersensitivity: a risk score from a large cohort
Published online July 16, 2025
Nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most frequently implicated agents in drug hypersensitivity reactions (DHRs), with reported prevalence of up to 3.5% in adults. Being classified as “allergic to NSAID” can significantly complicate clinical management of acute and chronic pain. Moreover, in the context of acute cardiovascular diseases, contraindications to aspirin may delay or preclude its timely administration with severe consequences on patient survival. To investigate NSAID DHR, a drug provocation test (DPT), where NSAIDs are given in a controlled environment is essential. However, there remains a lack of reliable methods to determine which patients are at risk of reacting during a DPT to NSAIDs.
The primary objective of the study by Ghiordanescu et al., published in The Journal of Allergy and Clinical Immunology: In Practice, was to develop and validate a clinical risk score to predict a positive DPT to NSAIDs, and to assess its performance across different types of NSAID DHRs. The score was developed using a retrospective cohort of 1,035 patients evaluated for NSAID reactions at the Allergy Unit of the University Hospital of Montpellier, France, between February 2001 and December 2020. External validation was performed on a separate cohort from the University Hospital of Tours, France, between January 2019 and December 2024.
A predictive tool, the CA4TCH score, was generated to estimate the risk of a positive DPT to NSAIDs, based on the presence of specific clinical history elements. These consisted of the time between drug exposure and symptom onset (Chronology), Anaphylaxis or respiratory symptoms at the initial reaction, Aspirin as culprit, underlying Asthma, Atopy, Time from the reaction to the DPT, the number of culprit Chemical classes, and underlying chronic spontaneous urticaria (Hives). The score demonstrated good predictive performance, with a sensitivity of 78.4%, specificity of 70.4%, and a negative predictive value of 91.9%. It correctly identified 70.4% of the negative patients as “non-allergic”. Additionally, it correctly classified all positive subjects with profiles known to be associated with a high risk of NSAID DHR (NSAID-exacerbated respiratory and cutaneous disease). External validation confirmed these results.
CA4TCH supports personalized risk assessment at the time of patient evaluation and aligns with clinical expertise and guideline recommendations for managing NSAID DHR.
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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