Kidney Week

Abstract: TH-PO421

Kidney Function Decline in Autosomal Dominant Polycystic Kidney Disease (ADPKD) Patients: Assessment of Real-World Effectiveness of Tolvaptan

Session Information

• Genetic Diseases: Cystic - Therapeutic Investigations and Prognosis
  November 02, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Genetic Diseases of the Kidneys

• 1201 Genetic Diseases of the Kidneys: Cystic

Authors

• Perrone, Ronald D., Tufts Medical Center, Boston, Massachusetts, United States

Ronald D. Perrone,

• Nunna, Sasikiran, Otsuka Pharmaceutical Development and Commercialization Inc, Princeton, New Jersey, United States

Sasikiran Nunna,

• Gandhi, Hema Kannan, Otsuka Pharmaceutical Development and Commercialization Inc, Princeton, New Jersey, United States

Hema Kannan Gandhi,

• Fernandes, Ancilla, Otsuka Pharmaceutical Development and Commercialization Inc, Princeton, New Jersey, United States

Ancilla Fernandes,

• Garbinsky, Diana, RTI Health Solutions Research Triangle Park, Research Triangle Park, North Carolina, United States

Diana Garbinsky,

• Zhou, Xiaolei, RTI Health Solutions Research Triangle Park, Research Triangle Park, North Carolina, United States

Xiaolei Zhou,

Background

In clinical trials, tolvaptan led to a slower decline in kidney function (vs placebo) among ADPKD patients at risk of rapid progression. The objective of the current study is to evaluate real-world effectiveness of tolvaptan by comparing annual rate of change in kidney function, as measured by eGFR, in adult ADPKD patients treated with and without tolvaptan.

Methods

From May 2019 to September 2022, 57 US nephrologists completed a web-based survey using medical records of ADPKD patients treated with tolvaptan for ≥2 year (cases). A cohort of ADPKD patients in Mayo class 1C to 1E not treated with tolvaptan was obtained from CRISP, HALT-PKD (data provided by NIDDK CR, a program of the National Institute of Diabetes and Digestive and Kidney Diseases) and OVERTURE studies (controls). Cases and controls were matched 1:1 on baseline age, gender and chronic kidney disease (CKD) stage. Kidney function decline was compared between cases and controls using mixed models, which included treatment, time, and a treatment-by-time interaction as fixed effects and patient-specific intercepts and slopes (for time) as random effects.

Results

Of the 149 cases treated with tolvaptan, controls matched for age, sex and CKD stage were identified for 110 cases. Among these 110 matched pairs, the majority were male (60%), aged 43 (SD: 10.1) years on average, and 76% were in CKD stage 3a or earlier. Mean eGFR at baseline was 60 mL/min/1.73m² among cases and 63 mL/min/1.73m² among controls. The annual change in eGFR was -2.23 mL/min/1.73m² among cases vs -3.62 mL/min/1.73m² among controls with a statistically significant difference of 1.40 mL/min/1.73m² per year (95% CI: 0.05, 2.74, p =0.042). A second analysis, whereby cases and controls were matched on baseline age, gender and eGFR resulted in 98 matched pairs. In comparison of the 98 matched pairs tolvaptan was associated with a trend in reduction of decline rate by 1.18 mL/min/1.73m² per year (95% CI: -0.22, 2.58, p =0.097).

Conclusion

In the current analysis, tolvaptan showed real world effectiveness in slowing decline in eGFR when compared to matched historical controls, consistent with its efficacy in clinical trials.

Funding

• Commercial Support – Otsuka Pharmaceutical Development & Commercialization, Inc., Princeton, NJ, USA