Improvements in cardiac functional status and health-related quality of life in patients receiving early access tafamidis
M G Crespo-Leiro, N M Fine, M K Davis, V Marino, R Wang, T DamyAbstract
Introduction
The pivotal ATTR-ACT study was a 30-month, phase 3 trial of tafamidis in patients with transthyretin amyloid cardiomyopathy. The long-term extension (LTE) study enabled patients completing ATTR-ACT to access tafamidis treatment for ≥60 months. A protocol amendment introduced an independent cohort within the LTE study to allow early access to tafamidis treatment for naïve patients not previously enrolled in ATTR-ACT. With broad enrolment criteria, this cohort more closely represented the real-world ATTR-CM population than previous trial cohorts.
Purpose
Assess the effects of tafamidis on cardiac functional status and health-related quality of life in the independent early access cohort.
Methods
Patients enrolled in the early access cohort to receive open label tafamidis free acid 61 mg once daily for up to 60 months, until availability via prescription, or study discontinuation by the sponsor. New York Heart Association (NYHA) functional classification and Kansas City Cardiomyopathy Questionnaire Overall Summary (KCCQ-OS) score were assessed at visits throughout the study. Current analyses included all patients remaining in the study with an available NYHA or KCCQ-OS score at each visit. No imputation was made to account for patients who had left the study or did not have a score at that visit.
Results
1476 patients received ≥1 dose of tafamidis in the independent early access cohort. Patients had a mean (SD) age of 76.5 (7.8) years; the majority (88.8%) were male, and most (85.6%) had wild-type ATTR-CM. The median duration of treatment was 12.7 months and the longest was 54.5 months. At baseline, NYHA functional classification was 14.9%, 52.9%, 30.8%, and 1.3% across classes I, II, III, and IV respectively, and the mean (SD) KCCQ-OS score was 67.7 (23.4). Throughout the study, most continuing patients with data either maintained their NYHA class or demonstrated improvement. At Months 12, 24, 36, 48, and 54, the proportions of patients continuing in the study with no change from baseline in NYHA class were 69.8% (n=593/850), 64.3% (279/434), 61.0% (136/223), 73.7% (73/99), and 68.2% (30/44), respectively. The corresponding proportions with improvement from baseline were 15.4% (131/850), 18.9% (82/434), 19.3% (43/223), 15.2% (15/99), and 20.5% (9/44; Table). Mean (SD) change from baseline in KCCQ-OS score amongst patients continuing in the study with data was 0.4 (18.3) at Month 12, -1.3 (19.6) at Month 24, -1.3 (20.7) at Month 36, -1.6 (10.1) at Month 48, and -2.1 (19.5) at Month 54 (Figure). At every post-baseline Visit, ≥54.8% of patients with data had a stable or improved KCCQ-OS score, as indicated by a <5 point reduction or increase from baseline (Figure).
Conclusion
Findings in an all-comers population suggest tafamidis treatment is commonly associated with stabilisation or improvement in cardiac functional status and health-related quality of life in patients with ATTR-CM.For image description, please refer to the figure legend and surrounding text.For image description, please refer to the figure legend and surrounding text.