Guiding Drug Provocation Testing for Ibuprofen Hypersensitivity in a Pediatric Population: Development of the I3A Risk-Stratification Tool

To create a risk stratification tool to help guide drug provocation testing (DPT) to ibuprofen, the gold standard testing for ibuprofen allergy.Prospectively recruited patients between the ages of 0 and 18 years (median age 5.9 years; IQR, 3.4–11.1 years) with symptoms of an ibuprofen hypersensitivity reaction who underwent DPT.DPT was performed via 2 steps, with patients receiving 10% of the target dose (10 mg/kg body weight, maximum 400 mg) followed by 90% of the target dose 30 minutes later if tolerated. The study used stepwise bidirectional multivariable logistic regression to calculate a predictive score for positive ibuprofen DPT based on significant univariable predictors. The optimal cutoff for this predictive score was determined using the Youden index. Patients with negative DPT were assessed for tolerance after reexposure via telephone follow-up.Eighteen (22.0%) patients had positive DPT. These patients were more likely to be aged 10 years and older and have their index reaction characterized by angioedema or anaphylaxis compared with patients having negative DPT. The I3A score (acronym for ibuprofen, 3As: angioedema, anaphylaxis, age, cutoff of 3) was created based on these increased odds ratios with the following point system assigned to each predictive variable: angioedema—2 points, anaphylaxis—1 point, and age 10 years and older—1 point. The optimal cutoff point total using the I3A score was found to be less than 3, which had the following test characteristics: sensitivity of 84.4%, specificity of 83.3%, negative predictive value of 94.7%, and positive predictive value of 60.0%. Of patients with negative DPT who were able to be contacted via telephone follow-up and had reexposure, 97.3% tolerated ibuprofen on reexposure.The I3A score was successfully able to distinguish low- and high-risk pediatric patients with ibuprofen allergy.Nonsteroidal anti-inflammatory drugs (NSAIDs) are a problematic drug allergy culprit in children, and ibuprofen accounts for the majority of NSAID hypersensitivity reactions. This study provides a risk stratification tool for patients with suspected ibuprofen allergy to determine who would be low risk for DPT. Further studies need to validate the findings, but this study provides a better understanding of risk when deciding to pursue ibuprofen DPT.