Background: The effectiveness of allopurinol in pts with gout depends on genetic factors (GF) [1]. How GF works on probability of the target serum uric acid (sUA) level achievement is not studied.

Objectives: To study the opportunity of the target sUA level achievement in pts with gout while taking allopurinol or febuxostat, depending on the polymorphism (rs2231142) of the ABCG2 gene.

Methods: The study included 82 pts with gout aged ≥18 yrs who did not take urate-lowering drugs (ULD) and had sUA level >360 µmol/l. Initially all patients were prescribed allopurinol 100 mg/day, than the dose was up-titrared to achieve the target sUA level (<360 µmol/l or <300 µmol/l in pts with chronic tophaceous gout). Maximum dosage was 900 mg/day; in pts with glomerular filtration rate (GFR) <60 ml/min/1.73 m ² - 300 mg/day. Pts who did not achieve the target sUA level while using allopurinol were prescribed febuxostat 80 mg/day, which, if necessary, was increased to 120 mg/day. Each patient was followed up until the target sUA level was achieved.

All pts underwent genotyping of the С>А (rs2231142) polymorphism of the ABCG2 gene. During the study we compared: the probability of achieving the target sUA level, the average values of the sUA level decline, the average doses of ULD in pts with different genotypes (CC, CA, AA) of the ABCG2 gene. Statistical analysis was carried out using the Statistica 12.0 software package, and descriptive statistics methods.

Results: The target sUA level was defined as <300 µmol/l in 45 (55%) of 82 pts, as <360 µmol/l in 37 (45%) pts. In 26 pts, the dose of allopurinol did not exceed 300 mg/day. In 28 (34%) pts on allopurinol therapy, the target level of sUA was achived. In 54 (66%) pts allopurinol was replaced with febuxostat, while in 22 (41%) of them, the level of sUA decreased and was below the target.

The CC genotype of the ABCG2 gene was found in 51 (62%) pts, the CA genotype in 30 (37%) pts, and the minor AA genotype in 1 (1%) pt. The opportunity of the target sUA level achievement during the allopurinol therapy in carriers of the homozygous CC genotype and CA or AA genotypes did not differ: 17 (33%) and 11 (35%) cases, respectively. It turned out that CA and AA pts required a significantly higher dose of allopurinol (365±102 mg/day) than CC pts (290±85 mg/day), p=0.002. Of 54 pts treated with febuxostat who did not achieve the target sUA level, 30 (56%) pts had the CC genotype and 24 (44%) pts had the CA genotype. The opportunity of the target sUA level achievement was comparable (p=0.22).

Conclusion: The opportunity of achieving the target sUA level in pts with gout taking allopurinol is not associated with the C>A polymorphism of the ABCG2 gene, but the presence of the CA and AA genotypes is associated with the need to prescribe large doses of allopurinol.

REFERENCES:

[1]Wen CC, Yee SW, Liang X et al. Genome-wide association study identifies ABCG2 (BCRP) as an allopurinol transporter and a determinant of drug response. Clin Pharmacol Ther. 2015 May;97(5):518-25. doi: 10.1002/cpt.89

Disclosure of Interests: Maxim Eliseev Speakers bureau: Berlin Chemie Menarini Group, Sobi, EGIS, CSC, MosFarma, Alium Group, Maria Chikina: None declared, Olga Sheliabina Speakers bureau: Berlin Chemie Menarini Group, Elena Cheremushkina: None declared