OBJECTIVES: Hereditary transthyretin (hATTR) amyloidosis is a rare, systemic, progressive, fatal disease characterized by the buildup of misfolded protein deposits in tissues and organs, leading to polyneuropathy and/or cardiomyopathy, often with autonomic neuropathy. The analysis described here examined the impact of treatment with inotersen compared to placebo for improving generic health-related quality of life (HRQoL) in patients with hATTR.

METHODS: The SF-36v2® Health Survey (SF-36v2) was administered at baseline, week 35, and week 66 to a sample of 172 adults with hATTR in the NEURO-TTR trial, a multicenter, multinational, double-blind trial (NCT01737398). Patients were randomized to receive inotersen or placebo (2:1 ratio). Changes in mean SF-36v2 scale and summary scores, as a function of treatment, were tested using mixed-effects models for repeated measures (MMRM). A responder analysis compared the percentage of patients whose score on each scale and summary measure got better (i.e., increased by at least the established minimally important change [MIC] threshold), got worse (i.e., decreased by at least the MIC threshold), or stayed the same using Fisher’s exact test.

RESULTS: MMRM yielded statistically significant treatment effects at week 66 on the majority of SF-36v2 subscales, with changes in mean scores significantly better for inotersen than placebo on physical functioning, role-physical, bodily pain, social functioning, and role-emotional subscales, in addition to the physical component summary (PCS), all p<0.05. The percentages of patients whose scores were same or meaningfully better at week 66 than at baseline was significantly higher for inotersen than for placebo for both PCS (70% vs. 48%) and mental component summary (MCS) scores (84% vs. 67%), both p <0.05.

CONCLUSIONS: Inotersen showed positive treatment effects relative to placebo at 66 weeks on several aspects of HRQoL, including physical, role, and social functioning, and pain. Thus, inotersen may be effective for improving HRQoL in patients with hATTR.