Background Large scale randomized studies are underway to assess whether compared to placebo, each XO-inhibitor, allopurinol or febuxostat, can prevent renal function loss. This evidence is needed and will confirm their nephroprotective potential. However, neither study will answer a key question: Does the renal protective effect of allopurinol differ from that of febuxostat?
Objectives To assess the comparative effectiveness of allopurinol vs. febuxostat for preventing incident renal disease in elderly.
Methods In a retrospective cohort study using Medicare claims data, we included patients newly treated with allopurinol or febuxostat (baseline period of 183 days without either medication). We used 1:5 propensity-matched Cox regression analyses to compare the hazard ratio (HR) of incident renal disease with allopurinol use and allopurinol dose vs. febuxostat (reference category). Sensitivity analyses included multivariable-adjusted regression models.
Results There were 31,465 new allopurinol or febuxostat treatment episodes in 26,443 patients; 8,570 ended in incident renal disease. Crude rates of incident renal disease per 100,000 person-days were 53 with allopurinol vs. 93 with febuxostat. Crude rates of incident renal disease per 100,000 person-days were lower with higher daily dose: allopurinol <200, 200–299 and ≥300 mg/day with 65, 48 and 43; and febuxostat 40 mg and 80 mg/day with 93 and 89, respectively. In propensity-matched analyses, compared to febuxostat use, allopurinol use was associated with lower HR of incident renal disease, 0.61 (95% confidence interval (CI): 0.49, 0.77). Compared to febuxostat 40 mg/day, allopurinol doses <200, 200–299 and ≥300 mg/day were associated with lower HR of incident renal disease, 0.75 (95% CI: 0.65, 0.86), 0.61 (95% CI: 0.52, 0.73) and 0.48 (95% CI: 0.41, 0.55), respectively. Sensitivity analyses using multivariable-adjusted regression confirmed these findings.
Conclusions Allopurinol was more effective than febuxostat in preventing incident renal disease in elderly patients. Future studies need to examine the mechanism of this renal benefit of allopurinol.
Disclosure of Interest J. Singh Grant/research support from: Savient, Takeda, Consultant for: Savient, Takeda, Regeneron, Merz, Iroko, Bioiberica, Crealta and Allergan pharmaceuticals, WebMD, UBM LLC and the American College of Rheumatology, J. Cleveland: None declared