Long-term treatment effects of inotersen on health-related quality of life in patients with hATTR amyloidosis with polyneuropathy: Analysis of the open-label extension of the NEURO-TTR trial.
36-item Short-Form Health Survey
Norfolk Quality of Life---Diabetic Neuropathy
amyloidosis
inotersen
neuropathic pain
physical functioning
quality of life
transthyretin
Journal
Muscle & nerve
ISSN: 1097-4598
Titre abrégé: Muscle Nerve
Pays: United States
ID NLM: 7803146
Informations de publication
Date de publication:
10 2022
10 2022
Historique:
revised:
29
06
2022
received:
01
11
2021
accepted:
30
06
2022
pubmed:
9
7
2022
medline:
21
9
2022
entrez:
8
7
2022
Statut:
ppublish
Résumé
Hereditary transthyretin-mediated amyloidosis with polyneuropathy (hATTR-PN) progressively affects patients' functionality and compromises health-related quality of life (HRQL). The aim of this study was to quantify the projected long-term treatment effects of inotersen vs placebo on HRQL measures. The inotersen phase 2/3 randomized, double-blind, placebo-controlled trial NEURO-TTR (NCT01737398, 65 weeks) and its subsequent open-label extension (OLE; NCT02175004, 104 weeks) included 172 (112 inotersen and 60 placebo) patients. Placebo double-blind period and overall inotersen-inotersen (double-blind/OLE) treatment period (170 weeks) data were used to extrapolate the long-term placebo-placebo effect using mixed-effects models with repeated measures. Changes from baseline in the Norfolk Quality of Life-Diabetic Neuropathy (QoL-DN) and 36-Item Short Form Health Survey version 2 (SF-36v2) in hATTR-PN were estimated. Differences in changes were compared between the inotersen-inotersen and extrapolated placebo-placebo arms. Inotersen-inotersen patients maintained their HRQL with an observed change ranging from 10.3% improvement (Norfolk QoL-DN item "Pain kept you awake at night") to 11.6% deterioration (SF-36v2 Activities of Daily Living subdomain). The extrapolated placebo-placebo results suggest greater deterioration over time compared with inotersen-inotersen treatment on Norfolk QoL-DN total score (23.6; 95% confidence interval [CI], 8.9-38.3; P < .01), Activities of Daily Living (4.6; 95% CI, 2.0-7.3; P < .001), and "Pain kept you awake at night" (1.2; 95% CI, 0.4-1.9; P < .01). Similarly, greater deterioration was expected for the SF-36v2 Physical Component Summary (8.0; 95% CI, 3.2-12.8, P < .01), Bodily Pain (7.8; 95% CI, 2.0-13.5; P < .01), and Physical Functioning (10.6; 95% CI, 5.5-15.6; P < .0001). Long-term (>3 years) inotersen treatment was associated with slowing and, in some domains, halting of deterioration in key HRQL outcome measures, particularly physical functioning and pain.
Substances chimiques
Oligonucleotides
0
Prealbumin
0
Inotersen
0IEO0F56LV
Banques de données
ClinicalTrials.gov
['NCT01737398', 'NCT02175004']
Types de publication
Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
438-446Informations de copyright
© 2022 Wiley Periodicals LLC.
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