An allopurinol adherence tool using plasma oxypurinol concentrations.

Area of Science:

• Pharmacology and Therapeutics
• Clinical Chemistry
• Gout Management

Background:

• Allopurinol is a common treatment for gout, but adherence can be challenging.
• Measuring steady-state oxypurinol plasma concentrations, the active metabolite of allopurinol, offers a potential method to assess adherence.
• Existing adherence assessment methods may have limitations in accuracy and practicality.

Purpose of the Study:

• To develop and validate an allopurinol adherence tool.
• The tool is based on steady-state oxypurinol plasma concentrations.
• To evaluate the tool's predictive performance for identifying patients with imperfect adherence.

Main Methods:

• Stochastic simulation of oxypurinol plasma concentrations using a pharmacokinetic model, considering factors like renal function, diuretic use, and ethnicity.
• Defined adherence thresholds based on the 20th percentile of peak and trough oxypurinol concentrations.
• Evaluated predictive performance using simulated low adherence data and real-world data from 146 individuals, calculating sensitivity, specificity, PPV, NPV, and ROC AUC.

Main Results:

• The developed tool demonstrated high sensitivity and specificity for both peak and trough oxypurinol concentrations.
• Positive and negative predictive values were robust, indicating reliable adherence assessment.
• External validation using the CKD-FIX study data confirmed the tool's predictive performance with a ROC AUC of 0.8113.

Conclusions:

• An allopurinol adherence tool utilizing plasma oxypurinol concentrations has been successfully developed and evaluated.
• The tool exhibits suitable predictive performance for adherence screening in clinical trials.
• The tool may also be beneficial for adherence assessment in certain clinical practice settings for gout management.