Why carry out this study?
|
Tafamidis has been shown to be effective in delaying disease progression among patients with transthyretin amyloidosis with polyneuropathy (ATTR-PN), but very little is known on whether it impacts mortality. |
This report represents the first evaluation of the effect of tafamidis on mortality in Val30Met and non-Val30Met patients with ATTR-PN that uses data from clinical trials where patients received up to 8.5 years of treatment. |
What was learned from the study?
|
Over the course of 8–9 years, there were very few deaths among patients with ATTR-PN treated with tafamidis. |
This finding is potentially significant given the severely shortened life span of patients with ATTR-PN and suggests that tafamidis may confer a survival benefit. |
Notwithstanding study limitations, the current analysis offers an important evaluation of patients treated with tafamidis in clinical trials. |
Introduction
Methods
Study Design and Patients
Statistical Analysis
Results
Patient Population and Baseline Characteristics
Val30Met | Non-Val30Met | ||
---|---|---|---|
Tafamidis-to-tafamidisa (n = 38) | Placebo-to-tafamidisb (n = 37) | Tafamidis (n = 18) | |
Study completion | |||
Yes | 31 (81.6%) | 27 (73.0%) | 7 (38.9%) |
No | 5 (13.2%) | 8 (21.6%) | 9 (50.0%) |
Ongoing | 2 (5.3%) | 2 (5.4%) | 2 (11.1%) |
Primary reason for discontinuation | |||
Adverse event | 2 (5.3%) | 1 (2.7%) | 2 (11.1%) |
Patient withdrew consent | 1 (2.6%) | 3 (8.1%) | 3 (16.7%) |
Liver transplant | 0 (0.0%) | 0 (0.0%) | 0 (0.0%) |
Patient died | 2 (5.3%) | 1 (2.7%) | 4 (22.2%) |
Other | 0 (0.0%) | 3 (8.1%) | 0 (0.0%) |
Characteristics | Val30Met | Non-Val30Met | |
---|---|---|---|
Tafamidis-to-tafamidisa (n = 65) | Placebo-to-tafamidisb (n = 63) | Tafamidis (n = 21) | |
Gender, n (%) | |||
Female | 33 (50.8) | 37 (58.7) | 8 (38.1) |
Male | 32 (49.2) | 26 (41.3) | 13 (61.9) |
Race, n (%) | |||
Caucasian | 57 (87.7) | 55 (87.3) | 19 (90.5) |
Latin American | 6 (9.2) | 7 (11.1) | |
Asian | 1 (4.8) | ||
African–Caribbean | 1 (4.8) | ||
Not available | 2 (3.1) | 1 (1.6) | |
Age, years | |||
Mean (SD) | 40.0 (12.7) | 38.1 (12.8) | 63.1 (9.9) |
Median (range) | 36.0 (25–74) | 34.0 (22–71) | 64.3 (44–77) |
mBMI, mean (SD), [g/L] × [kg/m2] | 1006.4 (164.5) | 1010.7 (211.1) | 1052.5 (206.7) |
Symptom duration, mean (SD), years | 3.9 (4.0) | 2.9 (2.7) | 5.4 (5.1) |
NIS-LL (range, 0–88), mean (SD) | 8.4 (11.3) | 11.1 (13.4) | 27.6 (24.7) |
Norfolk QOL-DN (TQOL) (range, −2 to 138), mean (SD) | 27.4 (24.0) | 30.5 (26.7) | 47.8 (35.1) |
Patient Deaths
Study | Patient | Genotype/treatment | Cause of death | Relationship to study drug |
---|---|---|---|---|
18-month double-blind study in Val30Met patients | 54-year-old female | Val30Met/tafamidis | Cardiac tamponade | Unrelated |
41-year-old female | Val30Met/placebo | Hepatic failure | Unrelated | |
63-year-old female | Val30Met/placebo | Sepsis | Unrelated | |
35-year-old female | Val30Met/placebo | Unknown cause | Unrelated | |
10-year open-label extension study | 66-year-old male | Val30Met/T–T | Cardiac failure | Unrelated |
72-year-old male | Val30Met/T–T | Lymphomaa | Unrelated | |
71-year-old male | Val30Met/P–T | Ileus | Unrelated | |
72-year-old female | Non-Val30Met/tafamidis | Cardiac arrest | Unrelated | |
76-year-old female | Non-Val30Met/tafamidis | Sepsis | Unrelated | |
61-year-old male | Non-Val30Met/tafamidis | Complications following heart transplant | Unrelated | |
76-year-old female | Non-Val30Met/tafamidis | Amyloidosis | Unrelated |