#2-31E. Personalizing Allopurinol Safety: A Prognostic Model for SCAR Risk (LR, 2025)

When initiating allopurinol for gout, how do we accurately balance the need for effective urate-lowering therapy with the risk of devastating, potentially fatal severe cutaneous adverse reactions (SCARs)? This retrospective new-user cohort study, utilizing large linked UK primary care and hospital data (CPRD Aurum/GOLD), developed and externally validated a prognostic model to estimate the 100-day risk of allopurinol-induced SCARs. The model incorporates readily available clinical factors such as age, ethnicity, chronic kidney disease (CKD) stage, and initial allopurinol dose. The core finding emphasizes that initial allopurinol doses of 300 mg or higher and increasing severity of CKD stage are strong independent predictors of SCAR risk, providing crucial data for safer prescribing. However, clinicians must note that due to the extreme rarity of the outcome, the external validation cohort had only 16 events, resulting in wide confidence intervals that warrant cautious interpretation of performance metrics for specific high-risk individuals. For patients where routine HLA-B*58:01 genetic screening is not cost-effective or recommended, this model provides an individualized risk estimate, supporting evidence-based shared decision-making and potentially preventing life-threatening adverse events by informing the choice between allopurinol and alternative urate-lowering drugs.

Citation: Cipolletta E, Nakafero G, Rozza D, et al. Development and validation of a prognostic model for predicting the risk of allopurinol-induced severe cutaneous adverse reactions: a retrospective new-user cohort study using linked primary care, hospitalisation, and mortality data. Lancet Rheumatol. 2025. DOI: https://doi.org/10.1016/ S2665-9913(25)00165-1

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