FC 111THE SOCIETAL IMPACT OF DELAYED DIALYSIS INITIATION ASSOCIATED WITH DAPAGLIFLOZIN BASED ON THE RESULTS OF DAPA-CKD
Authors: McEwan Phil , Darlington Oliver , Boyce Rebecca , Lambers Heerspink Hiddo , Wheeler David C , Garcia Sanchez Juan Jose 
Published: May 2021

Abstract

Background and Aims
Chronic kidney disease (CKD) continues to be a growing health concern worldwide, with an estimated global prevalence of 9.1% in 2017. End-stage kidney disease (ESKD) is commonly treated with dialysis and is associated with a significant societal and economic impact. Approximately 34 – 45% of employed CKD patients will leave employment by the time of dialysis initiation. As such, there could be significant benefits associated with delaying onset of dialysis. Current treatment for CKD consists of ACE-inhibitors and Angiotensin Receptor Blockers, which delay kidney replacement therapy by approximately 6 months. DAPA-CKD is a randomised, double-blind, placebo-controlled trial in which patients with estimated glomerular filtration rate (eGFR) between 25-75mL/min/1.73m2 and elevated urinary albumin excretion were assigned to dapagliflozin or placebo in addition to standard of care. The trial ended prematurely due to overwhelming efficacy and showed a 36% reduction in the incidence of ESKD for patients treated with dapagliflozin. This analysis of the DAPA-CKD study data aimed to look at the societal benefit of delaying initiation of dialysis based on outcomes observed in DAPA-CKD.

Method
The incidence of ESKD was predicted for patients treated with dapagliflozin compared to placebo over a 10-year time horizon using data from DAPA-CKD. Parametric survival models were derived from trial results and extrapolated, with Weibull distributions fitted for the incidence of ESKD and mortality. The mean time to ESKD was estimated for patients treated with dapagliflozin in addition to standard of care or standard of care alone, and 62% of patients reaching ESKD were assumed to be treated with dialysis, based on results of the DAPA-CKD clinical trial. The benefit of delaying dialysis initiation from a societal perspective was calculated using the average annual salary in the US and the proportion of working time lost due to dialysis. Inputs were derived based on published US data, and costs were discounted at 3% per annum.

Results
Treatment with dapagliflozin was estimated to delay the mean time to ESKD by approximately 2 years when compared to placebo. Patients in the placebo arm progressed to ESKD at a mean time of 7.8 years, compared to a mean time of 9.9 years in the dapagliflozin arm, without adjustment for patient survival. Over a 10-year time horizon, a cohort of 5,000 patients treated with dapagliflozin in addition to standard of care were estimated to experience 2,508 ESKD events, a reduction of 519 events in comparison with standard of care alone. Additionally, treatment with dapagliflozin in addition to standard of care was estimated to prevent 198 renal deaths compared to treatment with standard of care alone. Delays in dialysis initiation associated with dapagliflozin treatment was estimated to translate to 10-year reduction in societal costs of $29.2 million per 5,000 treated patients in a cohort of CKD patients eligible for treatment with dapagliflozin.

Conclusion
Dapagliflozin is associated with a significant reduction in the mean time to ESKD, therefore delaying the onset of dialysis initiation. In addition to improving patient outcomes, this delay in progression to ESKD could have notable economic benefits from a societal perspective.