Evaluating the Safety and effectivenesS in adult KorEaN patients treated with Tolvaptan for management of autosomal domInAnt poLycystic kidney disease (ESSENTIAL): final report

Abstract

Background: Tolvaptan, a selective vasopressin V2 receptor antagonist, was first approved by the Korean Ministry of Food and Drug Safety in 2015 as a treatment option for autosomal dominant polycystic kidney disease (ADPKD). To prescribe tolvaptan safely and effectively, we designed the phase 4 clinical trial among Korean ADPKD patients with chronic kidney disease stages 1 to 3. Methods: A total of 117 Korean patients aged 19 to 50 years with rapidly progressing ADPKD were enrolled in the study. Tolvaptan was prescribed for 24 months with the maximum tolerable dose up to 120 mg/day. The primary outcome was the incidence of treatment-emergent adverse events (TEAEs) including hepatic adverse events. The secondary outcomes were the annual mean percent change of total kidney volume (TKV) and the annual mean change of estimated glomerular filtration rate (eGFR). Results: A total of 489 TEAEs occurred in 106 patients (90.6%). A total of 17 cases of hepatic adverse events (14.5%) occurred during the study period and mostly within the first 18-month period. However, liver enzymes were normalized after drug discontinuation. Although it was not statistically significant, patients with a previous history of liver disease as well as those with mild elevation of liver enzyme showed a higher frequency of hepatic adverse events. Compared with the predicted value from the calculation, tolvaptan attenuated both TKV growth and eGFR decline rate. Conclusion: Although the incidence of hepatic adverse events was higher in Korean ADPKD patients compared to the previous studies, tolvaptan can be prescribed safely and effectively using meticulous titration and 1-month interval monitoring.