Estimating Meaningful Differences in Measures of Neuropathic Impairment, Health-Related Quality of Life, and Nutritional Status in Patients With Hereditary Transthyretin Amyloidosis.

INTRODUCTION/AIMS: The degree of change in neuropathic impairment and quality of life (QoL) that is clinically meaningful to patients with hereditary transthyretin amyloidosis with polyneuropathy (ATTRv-PN) is not established. This study aimed to estimate the magnitude of treatment differences that are meaningful to patients in measures of neuropathy and QoL and to determine whether eplontersen achieved a meaningful improvement versus placebo.

METHODS

Data from the NEURO-TTRansform trial on patients with ATTRv-PN treated with eplontersen (n = 141) or historical placebo (n = 59) were used. Anchor-based approaches were used to estimate thresholds for meaningful differences in the modified Neuropathy Impairment Score +7 (mNIS+7) composite score, Norfolk QoL-Diabetic Neuropathy (Norfolk QoL-DN) total score, Neuropathy Symptoms and Change (NSC) total score, and modified body mass index (mBMI). Differences between the least squares means of the treatment groups were analyzed.

RESULTS

Meaningful improvement in mNIS+7 was estimated as -4.0 points and deterioration as 1.8 points. The estimated ranges of meaningful improvement and deterioration in Norfolk QoL-DN were -12.8 to -4.0 points, and 5.9 to 14.7 points, respectively. For NSC, ranges were -2.4 to -1.3 points for meaningful improvement, and 0.6 to 5.8 points for deterioration. The estimated meaningful improvement in mBMI was 9.8 kg/m × g/L and deterioration was -40.9 kg/m × g/L. Improvements in each measure with eplontersen versus placebo were greater than the estimates of meaningful differences.

DISCUSSION

Eplontersen demonstrated a clinically meaningful effect on neuropathic impairment, QoL, and nutritional status. Such estimates have implications for clinical practice and trials.