Linear Projection of Estimated Glomerular Filtration Rate Decline with Canagliflozin and Implications for Dialysis Utilization and Cost in Diabetic Nephropathy

Abstract

Introduction Diabetes is a common cause of end-stage kidney disease leading to dialysis or kidney transplantation. Estimated glomerular filtration rate (eGFR) measures kidney function, and differences in the rate (slope) of eGFR decline can be used to assess treatment effects on kidney function over time. In the CREDENCE trial, the sodium glucose co-transporter 2 inhibitor canagliflozin slowed the rate of eGFR decline by 60% compared to placebo in patients with diabetes and chronic kidney disease. This analysis utilized eGFR slopes from CREDENCE to estimate the difference in time to dialysis by treatment arm and estimated the economic value of that delay. Methods A linear decline in eGFR and maintenance of stable therapy were assumed for the canagliflozin and placebo arms in CREDENCE. Mean eGFR over time was calculated using acute (baseline to week 3) and chronic (week 3 onward) slopes. Reaching eGFR of 10 ml/min/1.73 m 2 was assumed to represent the need for chronic dialysis. The difference in time to dialysis between treatments was calculated. Based on the average duration of dialysis, annual dialysis costs were determined, discounting 2020 US dollars at an inflation rate of 4%. Results Following the acute and chronic eGFR slopes, the projected time to dialysis was 22.85 years for canagliflozin and 9.90 years for placebo. Based on 95% confidence intervals from CREDENCE, the model-estimated difference in time to dialysis was 9.27–17.48 years. With a mean baseline participant age of 63 years, the delay in dialysis with canagliflozin would be associated with a reduction in dialysis costs of approximately $170,000 per patient in 2020 dollars. Conclusion Using clinical trial data, canagliflozin treatment was projected to delay dialysis by approximately 13 years, which could translate to a substantial cost savings. More precise estimates should be investigated with considerations for nonlinear eGFR slope trajectory, competing risks, and patient characteristics. Trial Registration ClinicalTrials.gov identifier, NCT02065791. Electronic supplementary material The online version of this article (10.1007/s13300-020-00953-4) contains supplementary material, which is available to authorized users.

Modeling Chronic Kidney Disease in Type 2 Diabetes Mellitus: A Systematic Literature Review of Models, Data Sources, and Derivation Cohorts

“…One approach adopted in the literature to reduce complexity is to focus on the CKD outcomes associated with the largest clinical-and economic-burden, usually ESKD [8]. Examples include prediction of ESKD from four readily available, not kidneyrelated clinical characteristics as in the BRAVO risk engine [64], or a simple linear projection of eGFR slopes using a threshold for dialysis initiation as assumed by Durkin and Blais [146]. The latter approach in particular is straightforward to implement and communicate and may suffice to provide an early approximation of intervention effects on the incidence of highburden events such as ESKD.…”

Canagliflozin: from glycemic control to improvement of cardiovascular and renal prognosis in patients with type 2 diabetes mellitus. Resolution of Advisory Board

“…В исследовании CREDENCE ежегодное снижение рСКФ на канаглифлозине (-1,85 мл/мин/1,73 м 2 в год) было в 2,5 раза меньше, чем на плацебо (-4,59 мл/мин/1,73 м 2 в год) [32]. Используя данные изменения рСКФ из исследования CREDENCE, была построена математическая модель, показавшая, что при условии длительного приема канаглифлозин позволяет на 13 лет отсрочить наступление терминальной стадии ХБП (рСКФ 10 мл/мин/1,73 м 2 ), требующей проведения гемодиализа [33].…”

“…Наибольший риск, связанный с приемом препарата, представляют грибковые генитальные инфекции, частота развития которых была небольшой: 3,7-4,2% у мужчин и 10,4-11,4% у женщин. Стоит отметить, что в 98% случаев имело место лишь однократное развитие генитального кандидоза, и в >99% не требовалось отмены препарата [33]. Данный риск является управляемым и предотвращаемым.…”

Gliflozins position update in the treatment algorithms for patients with type 2 diabetes mellitus and chronic kidney disease: new pathogenetic mechanisms and data from subanalyses of the large randomised control trails

“…Иллюстрацией важности включения препаратов с доказанными кардио-и нефропротективными эффектами в схемы лечения соответствующих популяций пациентов c СД 2 может являться анализ M. Durkin и соавт. [50]. На основании темпов снижения рСКФ в популяции исследования CREDENCE была построена линейная модель ожидаемых различий во времени наступления необходимости проведения постоянного диализа (предполагалось как снижение рСКФ <10/мл/мин/1,73 м 2 ).…”