Evaluation of Mortality During Long-Term Treatment with Tafamidis for Transthyretin Amyloidosis with Polyneuropathy: Clinical Trial Results up to 8.5 Years

Giampaolo Merlini, Teresa Coelho, Márcia Waddington Cruz, Huihua Li, Michelle Stewart, Ben Ebede, Giampaolo Merlini, Teresa Coelho, Márcia Waddington Cruz, Huihua Li, Michelle Stewart, Ben Ebede

Abstract

Introduction: The effects of tafamidis on mortality in Val30Met and non-Val30Met patients with transthyretin amyloidosis with polyneuropathy (ATTR-PN) were evaluated.

Methods: The analyses were based on cumulative data from the Val30Met patients in the 18-month double-blind registration study and its 12-month open-label extension study, the non-Val30Met patients of the 12-month open-label study, and both patient groups in the ongoing 10-year extension study. Kaplan-Meier analyses of time to death from first treatment dose were performed. For the Val30Met group, two treatment groups were analyzed: those who received tafamidis in both the parent and extension studies (T-T) and those who received placebo in the parent study and switched to tafamidis in the extension studies (P-T).

Results: Kaplan-Meier estimates (95% confidence interval [CI]) were available up to 9 years for the Val30Met group, at which time 85.9% (53.1-96.4) and 91.1% (77.9-96.6) of the patients in the T-T and P-T groups, respectively, were alive. For the non-Val30Met group, estimates were available up to 8 years from the first dose, and the percentage of patients alive was 75.9% (47.7-90.2).

Conclusion: Long-term tafamidis treatment may confer survival benefit in patients with ATTR-PN.

Trial registration: ClinicalTrials.gov identifier: NCT00409175, NCT00791492, NCT00630864, and NCT00925002.

Keywords: Amyloidosis; Mortality; Polyneuropathy; Tafamidis; Transthyretin; Val30Met.

Figures

Fig. 1
Fig. 1
Kaplan–Meier curves of patient survival while on study medication from first dose of treatment for Val30Met (a) and non-Val30Met (b) patients (full safety population, N = 128 and N = 21, respectively). Patients were censored at the last telephone contact (last visit date + 30 days) for those who concluded the study (completed or discontinued participation in the study) or at the cut-off of January 3, 2017, for ongoing patients. Val30Met patients from the parent study who were randomized to placebo and discontinued participation in that study were included in the P–T treatment, while those randomized to tafamidis and discontinued were included in the T–T treatment group. P–T, placebo treatment in the parent study followed by tafamidis treatment in the open-label extension studies (n = 63); T–T, tafamidis treatment in both the parent and open-label extension studies (n = 65)

References

    1. Planté-Bordeneuve V, Kerschen P. Transthyretin familial amyloid polyneuropathy. Handb Clin Neurol. 2013;115:643–658. doi: 10.1016/B978-0-444-52902-2.00038-2.
    1. Hund E. Familial amyloidotic polyneuropathy: current and emerging treatment options for transthyretin-mediated amyloidosis. Appl Clin Genet. 2012;5:37–41. doi: 10.2147/TACG.S19903.
    1. Koike H, Tanaka F, Hashimoto R, Tomita M, Kawagashira Y, Iijima M, et al. Natural history of transthyretin Val30Met familial amyloid polyneuropathy: analysis of late-onset cases from non-endemic areas. J Neurol Neurosurg Psychiatry. 2012;83:152–158. doi: 10.1136/jnnp-2011-301299.
    1. Ando Y, Coelho T, Berk JL, Waddington Cruz M, Ericzon BG, Ikeda S, et al. Guideline of transthyretin-related hereditary amyloidosis for clinicians. Orphanet J Rare Dis. 2013;8:31. doi: 10.1186/1750-1172-8-31.
    1. Rowczenio DM, Noor I, Gillmore JD, Lachmann HJ, Whelan C, Hawkins PN, et al. Online registry for mutations in hereditary amyloidosis including nomenclature recommendations. Hum Mutat. 2014;35:E2403–E2412. doi: 10.1002/humu.22619.
    1. Rowczenio D, Wechalekar A. Mutations in hereditary amyloidosis, 2015. Available from: . Accessed 11 Feb 2020.
    1. Okamoto S, Wixner J, Obayashi K, Ando Y, Ericzon BG, Friman S, et al. Liver transplantation for familial amyloidotic polyneuropathy: impact on Swedish patients’ survival. Liver Transpl. 2009;15:1229–1235. doi: 10.1002/lt.21817.
    1. Swiecicki PL, Zhen DB, Mauermann ML, Kyle RA, Zeldenrust SR, Grogan M, et al. Hereditary ATTR amyloidosis: a single-institution experience with 266 patients. Amyloid. 2015;22:123–131. doi: 10.3109/13506129.2015.1019610.
    1. Mariani LL, Lozeron P, Théaudin M, Mincheva Z, Signate A, Ducot B, et al. Genotype-phenotype correlation and course of transthyretin familial amyloid polyneuropathies in France. Ann Neurol. 2015;78:901–916. doi: 10.1002/ana.24519.
    1. Coelho T, Inês M, Conceição I, Soares M, de Carvalho M, Costa J. Natural history and survival in stage 1 Val30Met transthyretin familial amyloid polyneuropathy. Neurology. 2018;91:e1999–e2009. doi: 10.1212/WNL.0000000000006543.
    1. Sattianayagam PT, Hahn AF, Whelan CJ, Gibbs SD, Pinney JH, Stangou AJ, et al. Cardiac phenotype and clinical outcome of familial amyloid polyneuropathy associated with transthyretin alanine 60 variant. Eur Heart J. 2012;33:1120–1127. doi: 10.1093/eurheartj/ehr383.
    1. Ericzon BG, 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. doi: 10.1097/TP.0000000000000574.
    1. Parman Y, Adams D, Obici L, Galán L, Guergueltcheva V, Suhr OB, et al. Sixty years of transthyretin familial amyloid polyneuropathy (TTR-FAP) in Europe: where are we now? A European network approach to defining the epidemiology and management patterns for TTR-FAP. Curr Opin Neurol. 2016;29(Suppl 1):S3–S13. doi: 10.1097/WCO.0000000000000288.
    1. Suhr OB, Larsson M, Ericzon BG, Wilczek HE, FAPWTR’s Investigators Survival after transplantation in patients with mutations other than Val30Met: extracts from the FAP World Transplant Registry. Transplantation. 2016;100:373–381. doi: 10.1097/TP.0000000000001021.
    1. Waddington Cruz M, Benson MD. A review of tafamidis for the treatment of transthyretin-related amyloidosis. Neurol Ther. 2015;4:61–79. doi: 10.1007/s40120-015-0031-3.
    1. Coelho T, Merlini G, Bulawa CE, Fleming JA, Judge DP, Kelly JW, et al. Mechanism of action and clinical application of tafamidis in hereditary transthyretin amyloidosis. Neurol Ther. 2016;5:1–25. doi: 10.1007/s40120-016-0040-x.
    1. Coelho T, Maia LF, Martins da Silva A, Waddington-Cruz M, Planté-Bordeneuve V, Lozeron P, et al. Tafamidis for transthyretin familial amyloid polyneuropathy: a randomized, controlled trial. Neurology. 2012;79:785–792. doi: 10.1212/WNL.0b013e3182661eb1.
    1. Merlini G, Planté-Bordeneuve V, Judge DP, Schmidt H, Obici L, Perlini S, et al. Effects of tafamidis on transthyretin stabilization and clinical outcomes in patients with non-Val30Met transthyretin amyloidosis. J Cardiovasc Transl Res. 2013;6:1011–1020. doi: 10.1007/s12265-013-9512-x.
    1. Coelho T, Maia LF, da Martins Silva A, Waddington Cruz M, Planté-Bordeneuve V, Suhr OB, et al. Long-term effects of tafamidis for the treatment of transthyretin familial amyloid polyneuropathy. J Neurol. 2013;260:2802–2814. doi: 10.1007/s00415-013-7051-7.
    1. Waddington Cruz M, Amass L, Keohane D, Schwartz J, Li H, Gundapaneni B. Early intervention with tafamidis provides long term (5.5-year) delay of neurologic progression in transthyretin hereditary amyloid polyneuropathy. Amyloid. 2016;23:178–183. doi: 10.1080/13506129.2016.1207163.
    1. Barroso FA, Judge DP, Ebede B, Li H, Stewart M, Amass L, et al. Long-term safety and efficacy of tafamidis for the treatment of hereditary transthyretin amyloid polyneuropathy: results up to 6 years. Amyloid. 2017;24:194–204. doi: 10.1080/13506129.2017.1357545.
    1. Gundapaneni BK, Sultan MB, Keohane DJ, Schwartz JH. Tafamidis delays neurological progression comparably across Val30Met and non-Val30Met genotypes in transthyretin familial amyloid polyneuropathy. Eur J Neurol. 2018;25:464–468. doi: 10.1111/ene.13510.
    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. doi: 10.1056/NEJMoa1805689.
    1. Mundayat R, Stewart M, Alvir J, Short S, Ong ML, Keohane D, et al. Positive effectiveness of tafamidis in delaying disease progression in transthyretin familial amyloid polyneuropathy up to 2 years: an analysis from the transthyretin amyloidosis outcomes survey (THAOS) Neurol Ther. 2018;7:87–101. doi: 10.1007/s40120-018-0097-9.
    1. Koike H, Hashimoto R, Tomita M, Kawagashira Y, Iijima M, Tanaka F, et al. Diagnosis of sporadic transthyretin Val30Met familial amyloid polyneuropathy: a practical analysis. Amyloid. 2011;18:53–62. doi: 10.3109/13506129.2011.565524.
    1. Adams D, Theaudin M, Cauquil C, Algalarrondo V, Slama M. FAP neuropathy and emerging treatments. Curr Neurol Neurosci Rep. 2014;14:435. doi: 10.1007/s11910-013-0435-3.
    1. Conceição I, Gonzalez-Duarte A, Obici L, Schmidt HH, Simoneau D, Ong ML, et al. “Red-flag” symptom clusters in transthyretin familial amyloid polyneuropathy. J Peripher Nerv Syst. 2016;21:5–9. doi: 10.1111/jns.12153.

Source: PubMed

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