Dados do Trabalho

Título

Decline in functional capacity is associated with reduced ability to perform activities of daily living in patients with transthyretin cardiac amyloidosis: post hoc analysis of the APOLLO-B study.

Introdução e/ou Fundamento

A steady decline in functional capacity and health status (patients’ symptoms, function and quality of life) is a hallmark of transthyretin (ATTR) cardiac amyloidosis. In the Phase 3 APOLLO-B study (NCT03997383), patisiran preserved functional capacity, measured by 6-minute walk test (6MWT) distance, compared with placebo (median difference +14.7 m at Month 12). The association between functional capacity (6MWT) and patient-reported health status has not been previously described.

Objetivo

This post hoc analysis of APOLLO-B examined the association between declines in 6MWT and changes in participants’ health status, as measured by the Kansas City Cardiomyopathy Questionnaire (KCCQ).

Materiais e Métodos

In APOLLO-B, patients with ATTR cardiac amyloidosis were randomised (1:1) to receive patisiran or placebo in the 12-month, double-blind period. At Month 12, the association between change from baseline in 6MWT distance and individual items of the KCCQ was assessed with generalised estimating equations using adjacent-category logits. Results are reported as odds ratios (ORs) and corresponding 95% confidence intervals (CIs).

Resultados

When comparing the change from baseline in 6MWT at Month 12 between any two patients, those exhibiting 15 m greater walking preservation had lower odds of worsening ability to walk one block (OR [95% CI]: 0.88 [0.83, 0.93]), climb stairs (0.84 [0.80, 0.89]), hurry or jog (0.88 [0.83, 0.93]), dress themselves (0.85 [0.81, 0.90]), and perform yard/housework or carry groceries (0.89 [0.84, 0.93]). A greater proportion of patisiran-treated patients showed improvement in the 6MWT and KCCQ-Overall Summary score at Month 12 across a range of thresholds, compared with placebo, and a greater proportion of placebo-treated patients showed deterioration. Improvement in response to individual KCCQ questions consistently favoured treatment with patisiran over placebo; the greatest improvements were seen in quality of life, physically demanding activities and symptoms of shortness of breath and fatigue.

Conclusões

In patients with ATTR cardiac amyloidosis in the APOLLO-B study, incremental declines in 6MWT performance over 12 months were associated with increased odds of worsening ability to perform daily physical activities. The observed patisiran-related treatment difference in change from baseline in 6MWT was associated with broad impacts on the daily lives of patients.