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)

Rajiv Mundayat, Michelle Stewart, Jose Alvir, Sarah Short, Moh-Lim Ong, Denis Keohane, Denise Rill, Marla B Sultan, Rajiv Mundayat, Michelle Stewart, Jose Alvir, Sarah Short, Moh-Lim Ong, Denis Keohane, Denise Rill, Marla B Sultan

Abstract

Introduction: The effectiveness of tafamidis for the treatment of transthyretin familial amyloid polyneuropathy (TTR-FAP) was evaluated using data from the Transthyretin Amyloidosis Outcomes Survey (THAOS) registry.

Methods: Subjects receiving tafamidis (n = 252) were compared with untreated subjects in a non-randomized, matched cohort analysis. Subjects were matched with up to four untreated controls by genetic mutation, region of birth, and mean treatment propensity score.

Results: The matched, treated sample consisted predominantly of subjects with the Val30Met genotype (92.5%), from Portugal, and with a mean age of 40.4 years. Over the course of the 2-year follow-up period, subjects treated with tafamidis showed significantly less deterioration on the Neuropathy Impairment Score for Lower Limbs (p < 0.001) and its subscales (p < 0.023) compared with untreated subjects. There was significantly less deterioration among tafamidis-treated subjects compared with untreated subjects on the Norfolk Quality of Life scale (p < 0.001). There were no significant differences observed in functional (assessed by Karnofsky Performance Status Scale score) or nutritional (assessed by modified body mass index) status between the treated and untreated groups. The primary model which examined survival from baseline using the matched cohort was not able to yield estimates of the hazard ratio, as there were no deaths in the tafamidis-treated subjects.

Conclusion: These findings support the results from clinical trials and strengthen evidence of the effectiveness of tafamidis beyond conventional clinical trials.

Trial registration: ClinicalTrials.gov: NCT00628745 FUNDING: Pfizer.

Keywords: Familial amyloid polyneuropathy; Matched cohort analysis; Tafamidis; Transthyretin.

Figures

Fig. 1
Fig. 1
Eligible study population. THAOS Transthyretin Amyloidosis Outcomes Survey, TTR transthyretin
Fig. 2
Fig. 2
Treatment propensity scores for tafamidis-treated and matched control subjects, a before matching and b after matching
Fig. 3
Fig. 3
Slope estimates from repeated measures analysis model. mBMI modified body mass index, NCS Neurologic Composite Score, NIS-LL Neuropathy Impairment Score-Lower Limbs, TQoL Total Quality of Life

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