Blanka Stiburkova (1,2), Lenka Hasikova (1), Josef Bartl (2)
Affiliation(s):
1. Institute of Rheumatology, Prague, Czech Republic and Department of Rheumatology, First Faculty of Medicine, Charles University, Prague, Czech Republic
2. Department of Pediatrics and Inherited Metabolic Disorders, Charles University, First Faculty of Medicine and General University Hospital in Prague, Prague, Czech Republic
Background: Gout is the most prevalent inflammatory arthritis worldwide. The xanthine oxidase inhibitor allopurinol is the most frequently administrated drug for the treatment of gout. Poor allopurinol adherence is a major challenge in gout management and may lead to more severe disease outcomes and increased gout-related healthcare costs.
Objectives: Our study aimed to evaluate adherence to allopurinol using urinary oxypurinol in a cohort of patients with gout and primary hyperuricemia.
Methods: 220 patients with primary hyperuricemia or gout from the Institute of Rheumatology were selected on the base of daily dosage of allopurinol and positive claimed to be taking allopurinol at clinical follow-ups. Biological materials were collected in the Bank of Biological Materials of the Institute of Rheumatology. Data, including demographics, serum uric acid level (SUA), estimated glomerular filtration rate, urinary oxypurinol, xanthine, and hypoxanthine concentrations were analyzed. Family history of gout, age of disease onset, and details of gout therapy and co-medication were recorded. We have also determined the presence of allelic variant p.Q141K in ABCG2 gene by Sanger sequencing of all coding regions. High-performance liquid chromatography determination of oxypurinol, xanthine, and hypoxanthine in urine was performed on an Alliance 2695 and a 2998 photodiode array detector.
Results: In 58 patients (26.4%) we have not detected any oxypurinol in urine. Thus patients with undetectable oxypurinol were younger (p < 0.0001), had a higher SUA (p < 0.0001), fractional excretion of uric acid (p = 0.0314), a lower allopurinol dosage (p = 0.02) and an earlier onset of disease (p = 0.0076) compared with those with detectable oxypurinol in urine. In patients with undetectable oxypurinol in urine, there was also a higher proportion of patients with primary hyperuricemia (p =0.012), compared to patients with detectable oxypurinol. There were no significant differences between these two groups of patients in sex, disease duration, presence of tophi, familial occurrence, eGFR, use of co-medication, or the presence of allelic variant p.Q141K in the ABCG2 gene. The level of urinary oxypurinol positively correlated with the dosage of allopurinol.
Conclusions: Urine oxypurinol is a useful measure of adherence, and has potential for future application in clinical practice. It is an objective and quantifiable indicator of adherence, thus enabling timely intervention and additional education for non-adherent patients.
Funded by: Ministry of Education, Youth, and Sports BBMRICZ LM2023033, and Ministry of Health, Czech Republic (CZ), NU22-01-00465