Natural history and survival in stage 1 Val30Met transthyretin familial amyloid polyneuropathy

Objectives: To assess natural history and treatment effect on survival among transthyretin-associated familial amyloid polyneuropathy (TTR-FAP) Val30Met patients. Methods: Multi-institutional, hospital-based study of TTR-FAP Val30Met patients prospectively followed-up until December 2016, grouped into untreated (n = 1,771), liver transplant (LTx) (n = 957) or tafamidis-treated (n = 432) cohorts. Standardized mortality ratios (SMR), Kaplan-Meier and Cox methods were used to estimate excess mortality, survival probabilities and adjusted hazard ratios (HR) for all-cause mortality, respectively. Results: Disease-modifying treatments decreased TTR-FAP excess mortality from ten to four (SMR 3.92, 95% CI 2.64–5.59). Median overall survival of untreated and LTx-treated cohorts was 11.61 (95% CI 11.14–11.87) and 24.73 years (95% CI 22.90-27.09), respectively, and was not reached in the tafamidis-treated cohort (maximum follow-up, 10 years). Both disease-modifying treatments improved survival. Am...