Cost-effectiveness of empagliflozin versus canagliflozin, dapagliflozin, or standard of care in patients with type 2 diabetes and established cardiovascular disease

Introduction Empagliflozin, a sodium-glucose co-transporter-2 (SGLT-2) inhibitor, is approved in the USA to reduce risk of cardiovascular (CV) death in adults with type 2 diabetes mellitus (T2DM) and established CV disease, based on EMPA-REG OUTCOME (Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients) trial results. Empagliflozin reduced major adverse CV event (MACE) by 14%, CV death by 38%, and hospitalization for heart failure (HHF) by 35% vs placebo, each on top of standard of care (SoC). SGLT-2 inhibitors canagliflozin and dapagliflozin have also been compared with placebo, all on top of SoC, in CV outcome trials. In the CANVAS (Canagliflozin Cardiovascular Assessment Study) Program, canagliflozin reduced MACE by 14% and HHF by 33%. Dapagliflozin reduced HHF by 27% in the DECLARE-TIMI 58 trial (Multicenter Trial to Evaluate the Effect of Dapagliflozin on the Incidence of Cardiovascular Events). This analysis estimated the cost-effectiveness of empagliflozin versus canagliflozin, dapagliflozin, or SoC, in US adults with T2DM and established CV disease.Research design and methods Individual patient-level discrete-event simulation was conducted to predict time-to-event for CV and renal outcomes, and specific adverse events over patients’ lifetimes. Occurrence of events in EMPA-REG OUTCOME was estimated based on event-free survival curves with time-dependent covariates. An HR for canagliflozin or dapagliflozin versus empagliflozin on each clinical event was estimated from published CANVAS, DECLARE-TIMI 58, and EMPA-REG OUTCOME data using indirect treatment comparison. Public sources provided US costs and utilities.Results The model predicted longer survival for empagliflozin versus canagliflozin, dapagliflozin, and SoC mainly due to direct reduction in CV death. Empagliflozin dominated canagliflozin, yielding more quality-adjusted life years (QALYs; 0.38) at a lower cost (−US$306). Compared with dapagliflozin and SoC, empagliflozin yielded 0.50 and 0.84 incremental QALYs at US$1517 and US$27 539 incremental costs, yielding incremental cost-effectiveness ratios of US$3054/QALY and US$32 848/QALY, respectively.Conclusions Empagliflozin was projected to dominate canagliflozin and be highly cost-effective compared with dapagliflozin and SoC using US healthcare costs

SC population^a characteristics and simulation validation.

<p>Abbreviations: CI, confidence interval; DM, diabetes mellitus; PPDM, prepregnancy diabetes mellitus; GDM, gestational diabetes mellitus; NHW, non-Hispanic white; NHB, non-Hispanic black.</p>a<p>Pregnant NHW and NHB women ages 15–44 in SC from January 2004-December 2008.</p>b<p>Assumes that prepregnancy BMI was underreported by 5% on the birth certificate.</p

Logistic regression equation predictor estimates.

<p>Results assume BMI is underreported by 5%.</p

US population simulation estimates of diabetes prevalence (95% CI) during pregnancy in non-Hispanic white and non-Hispanic black women ages 15–44.

<p>US population simulation estimates of diabetes prevalence (95% CI) during pregnancy in non-Hispanic white and non-Hispanic black women ages 15–44.</p

High level overview of methodology.

<p>SC ORS, SC Office of Research Statistics; NCHS, National Center for Health Statistics.</p

Economic evaluation of betibeglogene autotemcel (Beti-cel) gene addition therapy in transfusion-dependent β-thalassemia

Background: Standard of care (SoC) for transfusion-dependent β-thalassemia (TDT) requires lifelong, regular blood transfusions as well as chelation to reduce iron accumulation. Objective: This study investigates the cost-effectiveness of betibeglogene autotemcel (‘beti-cel’; LentiGlobin for β-thalassemia) one-time, gene addition therapy compared to lifelong SoC for TDT. Study design: Microsimulation model simulated the lifetime course of TDT based on a causal sequence in which transfusion requirements determine tissue iron levels, which in turn determine risk of iron overload complications that increase mortality. Clinical trial data informed beti-cel clinical parameters; effects of SoC on iron levels came from real-world studies; iron overload complication rates and mortality were based on published literature. Setting: USA; commercial payer perspective Participants: TDT patients age 2–50 Interventions: Beti-cel is compared to SoC. Main outcome measure: Incremental cost-effectiveness ratio (ICER) utilizing quality-adjusted life-years (QALYs) Results: The model predicts beti-cel adds 3.8 discounted life years (LYs) or 6.9 QALYs versus SoC. Discounted lifetime costs were $2.28 M for beti-cel ($572,107 if excluding beti-cel cost) and $2.04 M for SoC, with a resulting ICER of$34,833 per QALY gained. Conclusion: Beti-cel is cost-effective for TDT patients compared to SoC. This is due to longer survival and cost offset of lifelong SoC