Health impact of tafamidis in transthyretin amyloid cardiomyopathy patients: an analysis from the Tafamidis in Transthyretin Cardiomyopathy Clinical Trial (ATTR-ACT) and the open-label long-term extension studies

Mark H Rozenbaum, Andrea Garcia, Daniel Grima, Diana Tran, Rahul Bhambri, Michelle Stewart, Benjamin Li, Bart Heeg, Maarten Postma, Ahmad Masri, Mark H Rozenbaum, Andrea Garcia, Daniel Grima, Diana Tran, Rahul Bhambri, Michelle Stewart, Benjamin Li, Bart Heeg, Maarten Postma, Ahmad Masri

Abstract

Aim: The Tafamidis in Transthyretin Cardiomyopathy Clinical Trial (ATTR-ACT) showed that tafamidis reduced all-cause mortality and cardiovascular-related hospitalizations in patients with transthyretin amyloid cardiomyopathy (ATTR-CM). This study aimed to estimate the impact of tafamidis on survival and quality-adjusted life-years (QALYs).

Methods and results: A multi-state, cohort, Markov model was developed to simulate the disease course of ATTR-CM throughout a lifetime. For survival extrapolation, survival curves were fitted by treatment arm and New York Heart Association (NYHA) Class I/II (68% of patients) and NYHA Class III (32% of patients) cohorts using the individual patient-level data from both the ATTR-ACT and the corresponding long-term extension study. Univariate and multivariate sensitivity analyses were conducted. The predicted mean survival for the total population (NYHA Class I/II + III) was 6.73 years for tafamidis and 2.85 years for the standard of care (SoC), resulting in an incremental mean survival of 3.88 years [95% confidence interval (CI) 1.32-5.66]. Of the 6.73 life-years, patients on tafamidis spend, on average, 4.82 years in NYHA Class I/II, while patients on SoC spend an average of 1.60 life-years in these classes. The combination of longer survival in lower NYHA classes produced a QALY gain of 5.39 for tafamidis and 2.11 for SoC, resulting in 3.29 incremental QALYs (95% CI 1.21-4.74) in favour of tafamidis.

Conclusion: Based on the disease simulation model results, tafamidis is expected to more than double the life expectancy and QALYs of ATTR-CM patients compared to SoC. Longer-term follow-up data from the ATTR-ACT extension study will further inform these findings.

Clinical trials.gov identifier: NCT01994889 (date of registration: 26 November 2013).

Keywords: Cardiomyopathy; Mortality; Tafamidis; Transthyretin; Amyloidosis.

© The Author(s) 2021. Published by Oxford University Press on behalf of the European Society of Cardiology.

Figures

Figure 1
Figure 1
Model structure. NYHA, New York Heart Association Functional Classification.
Figure 2
Figure 2
Overview of observed and predicted survival for standard of care and tafamidis for (A) New York Heart Association I/II patients and (B) New York Heart Association III. NAR, number at risk; SoC, standard of care.
Figure 3
Figure 3
Predicted extrapolation and overall survival Kaplan–Meier for tafamidis and standard of care arms from Tafamidis in Transthyretin Cardiomyopathy Clinical Trial. SoC, standard of care.
Figure 4
Figure 4
Overview of (A) the mean and incremental mean survival and (B) quality-adjusted life-years by health state as predicted by the model. NYHA, New York Heart Association Functional Classification; QALYs, quality-adjusted life-years; SoC, standard of care.

References

    1. Rapezzi C, Quarta CC, Riva L, Longhi S, Gallelli I, Lorenzini M. et al. Transthyretin-related amyloidoses and the heart: a clinical overview. Nat Rev Cardiol 2010;7:398–408.
    1. Arbustini E, Merlini G.. Early identification of transthyretin-related hereditary cardiac amyloidosis. JACC Cardiovasc Imaging 2014;7:511–514.
    1. Barrett CD, Alexander KM, Zhao H, Haddad F, Cheng P, Liao R. et al. Outcomes in patients with cardiac amyloidosis undergoing heart transplantation. JACC Heart Fail 2020;8:461–468.
    1. Ericzon B-G, Wilczek HE, Larsson M, Wijayatunga P, Stangou A, Pena JR. et al. Liver transplantation for hereditary transthyretin amyloidosis: after 20 years still the best therapeutic alternative? Transplantation 2015;99:1847–1854.
    1. Ruberg FL, Maurer MS, Judge DP, Zeldenrust S, Skinner M, Kim AY. et al. Prospective evaluation of the morbidity and mortality of wild-type and V122I mutant transthyretin amyloid cardiomyopathy: the Transthyretin Amyloidosis Cardiac Study (TRACS). American Heart Journal 2012;164:222–228.
    1. Grogan M, Scott CG, Kyle RA, Zeldenrust SR, Gertz MA, Lin G. et al. Natural history of wild-type transthyretin cardiac amyloidosis and risk stratification using a novel staging system. J Am Coll Cardiol 2016;68:1014–1020.
    1. Connors LH, Sam F, Skinner M, Salinaro F, Sun F, Ruberg FL. et al. Heart failure resulting from age-related cardiac amyloid disease associated with wild-type transthyretin: a prospective, observational cohort study. Circulation 2016;133:282–290.
    1. Maurer MS, Hanna M, Grogan M, Dispenzieri A, Witteles R, Drachman B. et al.; THAOS Investigators. Genotype and phenotype of transthyretin cardiac amyloidosis: THAOS (Transthyretin Amyloid Outcome Survey). J Am Coll Cardiol 2016;68:161–172.
    1. Grogan M, Dispenzieri A, Carlsson M, Stewart M, Schumacher J.. A Survival analysis of subjects with transthyretin amyloid cardiomyopathy from the Transthyretin Amyloidosis Outcomes Survey. J Card Fail 2017;23:S41.
    1. Pfizer. 2020. (20 January 2021).
    1. Pharmaceutical Safety and Environmental Health Bureau Ministry of Health LaW. Report on the Deliberation Results for Tafamidis Meglumine. 2019. (20 January 2021).
    1. Maurer MS, Bokhari S, Damy T, Dorbala S, Drachman BM, Fontana M. et al. Expert consensus recommendations for the suspicion and diagnosis of transthyretin cardiac amyloidosis. Circ Heart Fail 2019;12:e006075.
    1. Maurer MS, Schwartz JH, Gundapaneni B, Elliott PM, Merlini G, Waddington-Cruz M. et al. Tafamidis treatment for patients with transthyretin amyloid cardiomyopathy. N Engl J Med 2018;379:1007–1016.
    1. Elliott P, Drachman BM, Gottlieb SS, Hoffman JE, Hummel SL, Lenihan DJ, Ebede B. et al. Interim analysis of data from a long-term, extension trial of tafamidis meglumine in patients with transthyretin amyloid cardiomyopathy. Eur Heart J 2019;40:
    1. Damy T, Garcia‐Pavia P, Hanna M, Judge DP, Merlini G, Gundapaneni B. et al. Efficacy and safety of tafamidis doses in the Tafamidis in Transthyretin Cardiomyopathy Clinical Trial (ATTR‐ACT) and long‐term extension study. Eur J Heart Fail 2021;23:277–285.
    1. Goehler A, Geisler BP, Manne JM, Jahn B, Conrads-Frank A, Schnell-Inderst P. et al. Decision-analytic models to simulate health outcomes and costs in heart failure. Pharmacoeconomics 2011;29:753–769.
    1. Di Tanna GL, Bychenkova A, O'Neill F, Wirtz HS, Miller P, Ó Hartaigh B. et al. Evaluating cost-effectiveness models for pharmacologic interventions in adults with heart failure: a systematic literature review. PharmacoEconomics 2019;37:359–389.
    1. Göhler A, Geisler BP, Manne JM, Kosiborod M, Zhang Z, Weintraub WS. et al. Utility estimates for decision–analytic modeling in chronic heart failure—health states based on New York Heart Association classes and number of rehospitalizations. Value Health 2009;12:185–187.
    1. Madsen BK, Hansen JF, Stokholm KH, Brøns J, Husum D, Mortensen LS.. Chrome congestive heart failure: description and survival of 190 consecutive patients with a diagnosis of chronic congestive heart failure based on clinical signs and symptoms. Eur Heart J 1994;15:303–310.
    1. Chen J, Normand S-LT, Wang Y, Krumholz HM.. National and regional trends in heart failure hospitalization and mortality rates for Medicare beneficiaries, 1998-2008. JAMA 2011;306:1669–1678.
    1. Dunlay SM, Redfield MM, Weston SA, Therneau TM, Long KH, Shah ND. et al. Hospitalizations after heart failure diagnosis: a community perspective. J Am Coll Cardiol 2009;54:1695–1702.
    1. Long EF, Swain GW, Mangi AA.. Comparative survival and cost-effectiveness of advanced therapies for end-stage heart failure. Circ Heart Fail 2014;7:470–478.
    1. U.S. Department of Health and Human Services. Adult Heart Allocation. Richmond, VA: Organ Procurement and Transplantation Network; 2019.
    1. Latimer N. NICE DSU Technical Support Document 14: Survival Analysis for Economic Evaluations Alongside Clinical Trials-Extrapolation with Patient-Level Data. Sheffield, UK: National Institute for Health and Clinical Excellence Decision Support Unit; 2011.
    1. Stensrud MJ, Hernán MA.. Why test for proportional hazards? JAMA 2020;323:1401–1402.
    1. R Core Team. R: A Language and Environment for Statistical Computing Computer Program, Version 3.5. 0. Vienna, Austria: R Core Team; 2018.
    1. Jackson C. flexsurv: A Platform for Parametric Survival Modeling in R. J Stat Softw 2019;70:1–33.
    1. Therneau TM, Lumley T.. Package ‘survival’. Survival Analysis Published on CRAN. 2014;2:3.
    1. Maurer MS, Elliott P, Merlini G, Shah SJ, Cruz MW, Flynn A. et al. Design and rationale of the phase 3 ATTR-ACT Clinical Trial (Tafamidis in Transthyretin Cardiomyopathy Clinical Trial). Circ Heart Fail 2017;10:e003815.
    1. Shaw JW, Johnson JA, Coons SJ.. US valuation of the EQ-5D health states: development and testing of the D1 valuation model. Med Care 2005;43:203–220.
    1. Efron B, Tibshirani RJ.. An Introduction to the Bootstrap. New York, NY: CRC Press; 1994.
    1. Burnham KP, Anderson DR.. Model Selection and Multimodel Inference: A Practical Information-Theoretic Approach (Vol. 2). New York, NY: Springer-Verlag; 2002.
    1. Burnham KP, Anderson DR.. Multimodel inference: understanding AIC and BIC in model selection. Sociol Methods Res 2004;33:261–304.
    1. Arias E, Xu J.. United States Life Tables, 2017. National Vital Statistics Report; vol 68 no 7. Hyattsville, MD: National Center for Health Statistics; 2019.
    1. Lane T, Fontana M, Martinez-Naharro A, Quarta CC, Whelan CJ, Petrie A. et al. Natural history, quality of life, and outcome in cardiac transthyretin amyloidosis. Circulation 2019;140:16–26.
    1. Ladefoged B, Dybro A, Povlsen JA, Vase H, Clemmensen TS, Poulsen SH.. Diagnostic delay in wild type transthyretin cardiac amyloidosis—a clinical challenge. Int J Cardiol 2020;304:138–143.
    1. Canepa M, Tini G, Musumeci B, Cappelli F, Milandri A, Mussinelli R. et al. Real-world versus trial patients with transthyretin amyloid cardiomyopathy. Eur J Heart Fail 2019;21:1479–1481.
    1. Sultan MB, Gundapaneni B, Schumacher J, Schwartz JH.. Treatment with tafamidis slows disease progression in early-stage transthyretin cardiomyopathy. Clin Med Insights Cardiol 2017;11:1179546817730322.
    1. Stewart M, Shaffer S, Murphy B, Loftus J, Alvir J, Cicchetti M. et al. Characterizing the high disease burden of transthyretin amyloidosis for patients and caregivers. Neurol Ther 2018;7:349–364.
    1. National Institute for Health and Clinical Excellence. Donepezil, Galantamine, Rivastigmine (Review) and Memantine for the Treatment of Alzheimer's Disease (Amended). London, UK: National Institute for Health and Clinical Excellence; 2007.
    1. U.S. Food and Drug Administration. FDA Approves New Treatments for Heart Disease Caused by a Serious Rare Disease, Transthyretin Mediated Amyloidosis. 2019. (21 January 2021).
    1. Kazi DS, Bellows BK, Baron SJ, Shen C, Cohen DJ, Spertus JA. et al. Cost-effectiveness of tafamidis therapy for transthyretin amyloid cardiomyopathy. Circulation 2020;141:1214–1224.
    1. Latimer NR, Abrams KR. NICE DSU Technical Support Document 16: Adjusting Survival Time Estimates in the Presence of Treatment Switching. Sheffield, UK: National Institute for Health and Clinical Excellence Decision Support Unit;2014.
    1. Nicod E, Annemans L, Bucsics A, Lee A, Upadhyaya S, Facey K.. HTA programme response to the challenges of dealing with orphan medicinal products: process evaluation in selected European countries. Health Policy 2019;123:140–151.
    1. Augustine EF, Adams HR, Mink JW.. Clinical trials in rare disease: challenges and opportunities. J Child Neurol 2013;28:1142–1150.
    1. Nestler-Parr S, Korchagina D, Toumi M, Pashos CL, Blanchette C, Molsen E. et al. Challenges in research and health technology assessment of rare disease technologies: report of the ISPOR rare disease special interest group. Value Health 2018;21:493–500.
    1. Caro JJ, Briggs AH, Siebert U, Kuntz KM; ISPOR-SMDM Modeling Good Research Practices Task Force-1. Modeling good research practices—overview: a report of the ISPOR-SMDM Modeling Good Research Practices Task Force. Med Decis Making 2012;32:667–677.

Source: PubMed

스폰서 및 공동 작업자

건강 상태

약물 개입

3
구독하다