Comparison between tafamidis and liver transplantation as first-line therapy for hereditary transthyretin amyloidosis

Abstract

Background

By stabilizing transthyretin, tafamidis delays progression of amyloidosis due to transthyretin variant (ATTRv) and replaced liver transplantation (LT) as the first-line therapy. No study compared these two therapeutic strategies.

Methods

In a monocentric retrospective cohort analysis, patients with ATTRv amyloidosis treated with either tafamidis or LT were compared using a propensity score and a competing risk analysis for three endpoints: all-cause mortality, cardiac worsening (heart failure or cardiovascular death) and neurological worsening (worsening in PolyNeuropathy Disability score).

Results

345 patients treated with tafamidis (n = 129) or LT (n = 216) were analyzed, and 144 patients were matched (72 patients in each group, median age 54 years, 60% carrying the V30M mutation, 81% of stage I, 69% with cardiac involvement, median follow-up: 68 months). Patients treated with tafamidis had longer survival than LT patients (HR: 0.35; p = .032). Conversely, they also presented a 3.0-fold higher risk of cardiac worsening and a 7.1-fold higher risk of neurological worsening (p = .0071 and p < .0001 respectively).

Conclusions

ATTRv amyloidosis patients treated with tafamidis would present a better survival but also a faster deterioration of their cardiac and neurological statuses as compared with LT. Further studies are needed to clarify the therapeutic strategy in ATTRv amyloidosis.

Keywords:

• tafamidis
• transthyretin
• cardiac amyloidosis
• liver transplantation
• polyneuropathy

Acknowledgements

We thank the patients who were followed and treated in the NNERF since the early 90s. We thank the data managers that were involved in the study in each hospital of the NNERF, especially Sophie-Nathalie Marchal (Bicêtre), Vincent Karam (Paul Brousse), Pierre Marc Lallemand, and Cathy Ladeveze (Antoine Béclère), and Fatima Ouderg (Bichat). We thank the medical-surgical team of the Hepato-Biliary Centre of the Paul Brousse Hospital. Finally, we thank Eric Duong, who reviewed our manuscript for style and language. Eric Duong was financially compensated for his contribution.

Authors contributions

VA, DA and MS led the study conceptualization, development of the research question.

AB, PS, and VA led the development of advanced statistical analyses. PS and PML collected the data. VA and PS wrote the first draft of the paper. DA declared the database to the French authorities. CQ, EP, IK, AR, FR, AEL, and DS contributed to the discussion on protocol development and provided critical feedback on drafts of the manuscript. All authors had full access to all the study data, and VA had final responsibility for submission and is the guarantor. The corresponding author (VA) attests that all listed authors meet authorship criteria and that no others meeting the criteria have been omitted.

Disclosure statement

The author(s) received no specific funding for this work.

Out of this work, VA and MS declare having links of interest with Pfizer (consulting fees, research scholardship); VA, DA and MS declare having links of interest with Pfizer and with Alnylam (for both, consulting fees, and research scholardship).

Additional information

Funding

The author(s) reported there is no funding associated with the work featured in this article.