Individuals treated with both lesinurad and a xanthine oxidase inhibitor (XOI) have exhibited increased rates of serum creatinine events compared with those treated only with an XOI, according to a study recently published in Rheumatology and Therapy. Higher rates of serum creatinine events correlated with decreasing estimated glomerular filtration rate.
The study researchers examined three phase 3, placebo-controlled combination clinical trials to estimate the number needed to treat and relative risks for renal lithiasis, renal failure, and increased serum creatinine. In total, 510 participants were treated with XOI and placebo, 509 with XOI and lesinurad 200 mg daily, and 508 with XOI and lesinurad 400 mg daily. Risks were examined and stratified by estimated glomerular filtration rate for each treatment group. Harm was defined as a relative risk > 1, whereas benefit was defined as a relative risk <1.
The incidence of increased serum creatinine was significantly higher among those treated with lesinurad 400 mg daily compared with those who received XOI alone, with a relative risk of 3.37 (95% CI, 1.79-6.35; P <.000). Lesinurad 200 mg daily was also associated with a higher incidence of increased serum creatinine, although it was not statistically significantly (relative risk, 1.85, 95% CI, 0.93-3.7; P =.081). However, the relative risk was<1.0 for renal failure and lithiasis in the lesinurad 200 mg group. After stratification by estimated glomerular filtration rate, a negative association was found between adverse events and renal function. However, there was a parallel decrease in relative risks, with a much higher increase in adverse events among placebo compared with the 200 mg group. Among those with normal estimated glomerular filtration rate, the relative risk was significant only for a 400 mg daily dose.
Limitations of this study include a small number of events, the exclusive use of publicly available data, and the fact that it is not a meta-analysis,
The study researchers conclude that “[the] rate of adverse renal events was similar in the placebo and lesinurad 200 mg groups, while the rates of renal failure and nephrolithiasis were numerically lower in the lesinurad 200 mg group than in the placebo group. The risk ratio of [serum creatinine] with lesinurad [vs] placebo decreased with worsening renal function.”
Perez-Ruiz F, Jansen TL, Tausche AK, et al. Reassessing the safety profile of lesinurad in combination with xanthine oxidase inhibitor therapy [published online February 14, 2019]. Rheumatol Ther. doi:10.1007/s40744-019-0143-9