Real-world Efficacy of Tolvaptan Among Patients With ADPKD

Results of clinical trials among patients with autosomal dominant polycystic kidney disease (ADPKD) at risk of rapid progression demonstrated that tolvaptan led to a slower decline in kidney function compared with placebo. Ronald D. Perrone and colleagues conducted a study to assess the real-world effectiveness of tolvaptan by comparing annual rate of change in kidney function, as measured by estimated glomerular filtration rate (eGFR), in adults with ADPKD treated with and without tolvaptan.

The researchers reported results of the study during a poster session at the American Society of Nephrology Kidney Week 2023. The poster was titled Kidney Function Decline in Autosomal Dominant Polycystic Kidney Disease (ADPKD) Patients: Assessment of Real-world Effectiveness of Tolvaptan.

Using medical records of patients with ADPKD treated with tolvaptan for ≥2 years, 57 nephrologists in the United States completed a web-based survey (May 2019 to September 2022) to identify patients with ADPKD who were treated with tolvaptan (cases). A control group included a cohort of patients with ADPKD in Mayo class 1C to 1E who were not being treated with tolvaptan. Patients in the control group were identified from the CRISP, HALT-PKD (data provided by NIDDK CR, a program of the National Institute of Diabetes and Digestive and Kidney Diseases), and OVERTURE studies.

Mixed models were used to compare decline in kidney function between cases and controls, including treatment, time, and treatment-by-time interactions as fixed effects and patient-specific intercepts and slopes (for time) as random effects.

The surveys included data on 149 patients with ADPKD treated with tolvaptan. Of those, 110 were matched with controls for age, sex, and chronic kidney disease (CKD) stage. Among the 110 matched pairs, 60% were male, average age was 43 years, and 76% had CKD stage 3a or earlier.

At baseline, mean eGFR was 60 mL/min/1.73 m² among cases and 63 mL/min/1.73 m² among controls. The annual change in eGFR was –2.23 mL/min/1.73 m² among cases compared with –3.62 mL/min/1.73 m² among controls, with a statistically significant difference of 1.40 mL/min/1.73 m² per year (95% CI, 0.05-2.74; P=.042).

In a second analysis, matching cases and controls on baseline age, sex, and eGFR resulted in 98 matched pairs. In that subpopulation, there was an association between treatment with tolvaptan and a trend in reduction of decline rate by 1.18 mL/min/1.73 m² per year (95% CI, –0.22 to 2.50; P=.097).

In conclusion, the researchers said, “In the current analysis, tolvaptan showed real-world effectiveness in slowing decline in eGFR when compared with matched historical controls, consistent with its efficacy in clinical  trials.”

Source: Perrone RAD, Nunna S, Gandhi HK, Fernandes A, Garbinsky D, Zhou X. Kidney function decline in autosomal dominant polycystic kidney disease (ADPKD) patients: assessment of real-world effectiveness of tolvaptan. TH-PO421. Abstract of a poster presented at the American Society of Nephrology Kidney Week 2023; November 2, 2023; Philadelphia, Pennsylvania. Funding was provided by Otsuka Pharmaceutical Development & Commercialization, Inc.