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      Cost-Effectiveness of Canagliflozin Added to Standard of Care for Treating Diabetic Kidney Disease (DKD) in Patients with Type 2 Diabetes Mellitus (T2DM) in England: Estimates Using the CREDEM-DKD Model

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          Abstract

          Introduction

          On the basis of reductions in diabetic kidney disease (DKD) progression and major adverse cardiovascular events observed in the landmark CREDENCE trial, canagliflozin 100 mg received an extension to its EU marketing authorisation in July 2020 to include the treatment of DKD in people with type 2 diabetes mellitus (T2DM) making it the first pharmacological therapy to receive regulatory authorisation for treatment of DKD since the RENAAL and IDNT trials in nearly 20 years. Efficient allocation of limited healthcare resources requires evaluation not only of clinical safety and efficacy but also economic consequences. The study aim was to estimate the cost-effectiveness of canagliflozin when added to current standard of care (SoC) versus SoC alone from the perspective of the NHS in England.

          Methods

          A microsimulation model was developed using patient-level data from CREDENCE, including risk equations for the key clinical outcomes of start of dialysis, hospitalisation for heart failure, nonfatal myocardial infarction, nonfatal stroke, and all-cause mortality. DKD progression was modelled using estimated glomerular filtration rate and urinary albumin-to-creatinine ratio evolution equations. Risk for kidney transplant was sourced from UK-specific sources given the near absence of events in CREDENCE. Patient characteristics and treatment effects were sourced from CREDENCE. Unit costs (£2019) and disutility weights were sourced from the literature and discounted at 3.5% annually. The time horizon was 10 years in the base case, and sensitivity analysis was performed.

          Results

          Canagliflozin was associated with sizable gains in life-years and quality-adjusted life-year (QALYs) over 10 years, with gains increasing with simulation duration. Cost offsets associated with reductions in cardiovascular and renal complications were sufficient to achieve overall net cost savings. The findings were generally confirmed in the sensitivity analyses.

          Conclusion

          Model results suggest that adding canagliflozin 100 mg to SoC can improve patient outcomes while reducing overall net costs from the NHS perspective in England.

          Trial Registration

          ClinicalTrials.gov identifier, NCT02065791.

          Electronic supplementary material

          The online version of this article (10.1007/s13300-020-00968-x) contains supplementary material, which is available to authorized users.

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          Most cited references32

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          Canagliflozin and Cardiovascular and Renal Events in Type 2 Diabetes

          Background Canagliflozin is a sodium-glucose cotransporter 2 inhibitor that reduces glycemia as well as blood pressure, body weight, and albuminuria in people with diabetes. We report the effects of treatment with canagliflozin on cardiovascular, renal, and safety outcomes. Methods The CANVAS Program integrated data from two trials involving a total of 10,142 participants with type 2 diabetes and high cardiovascular risk. Participants in each trial were randomly assigned to receive canagliflozin or placebo and were followed for a mean of 188.2 weeks. The primary outcome was a composite of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke. Results The mean age of the participants was 63.3 years, 35.8% were women, the mean duration of diabetes was 13.5 years, and 65.6% had a history of cardiovascular disease. The rate of the primary outcome was lower with canagliflozin than with placebo (occurring in 26.9 vs. 31.5 participants per 1000 patient-years; hazard ratio, 0.86; 95% confidence interval [CI], 0.75 to 0.97; P<0.001 for noninferiority; P=0.02 for superiority). Although on the basis of the prespecified hypothesis testing sequence the renal outcomes are not viewed as statistically significant, the results showed a possible benefit of canagliflozin with respect to the progression of albuminuria (hazard ratio, 0.73; 95% CI, 0.67 to 0.79) and the composite outcome of a sustained 40% reduction in the estimated glomerular filtration rate, the need for renal-replacement therapy, or death from renal causes (hazard ratio, 0.60; 95% CI, 0.47 to 0.77). Adverse reactions were consistent with the previously reported risks associated with canagliflozin except for an increased risk of amputation (6.3 vs. 3.4 participants per 1000 patient-years; hazard ratio, 1.97; 95% CI, 1.41 to 2.75); amputations were primarily at the level of the toe or metatarsal. Conclusions In two trials involving patients with type 2 diabetes and an elevated risk of cardiovascular disease, patients treated with canagliflozin had a lower risk of cardiovascular events than those who received placebo but a greater risk of amputation, primarily at the level of the toe or metatarsal. (Funded by Janssen Research and Development; CANVAS and CANVAS-R ClinicalTrials.gov numbers, NCT01032629 and NCT01989754 , respectively.).
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            Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy

            Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium-glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes.
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              K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification.

              (2002)
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                Author and article information

                Contributors
                mw@ihe.se
                Journal
                Diabetes Ther
                Diabetes Ther
                Diabetes Therapy
                Springer Healthcare (Cheshire )
                1869-6953
                1869-6961
                2 December 2020
                2 December 2020
                January 2021
                : 12
                : 1
                : 313-328
                Affiliations
                [1 ]GRID grid.416779.a, ISNI 0000 0001 0707 6559, The Swedish Institute for Health Economics, ; Lund, Sweden
                [2 ]Mundibiopharma Limited, Cambridge, UK
                [3 ]GRID grid.488312.4, ISNI 0000 0004 0383 8714, Napp Pharmaceuticals Limited, ; Cambridge, UK
                [4 ]GRID grid.497530.c, ISNI 0000 0004 0389 4927, Janssen Global Services, LLC, ; Raritan, NJ USA
                [5 ]Costello Medical Consulting Limited, London, UK
                Article
                968
                10.1007/s13300-020-00968-x
                7843731
                33263893
                6c142928-c57f-4c49-b2fc-1f84ca0deefb
                © The Author(s) 2020

                Open Access This article is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License, which permits any non-commercial use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc/4.0/.

                History
                : 8 October 2020
                : 6 November 2020
                Categories
                Original Research
                Custom metadata
                © The Author(s) 2021

                Endocrinology & Diabetes
                albuminuria,canagliflozin,chronic kidney disease (ckd),cost-effectiveness,credence,diabetes,diabetic kidney disease (dkd),diabetic nephropathy,dialysis

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