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Inotersen treatment for patients with hereditary transthyretin amyloidosis
- Source :
- Dipòsit Digital de la UB, Universidad de Barcelona, Recercat. Dipósit de la Recerca de Catalunya, instname
- Publication Year :
- 2018
- Publisher :
- Massachusetts Medical Society, 2018.
-
Abstract
- BACKGROUND: Hereditary transthyretin amyloidosis is caused by pathogenic single-nucleotide variants in the gene encoding transthyretin ( TTR) that induce transthyretin misfolding and systemic deposition of amyloid. Progressive amyloid accumulation leads to multiorgan dysfunction and death. Inotersen, a 2'- O-methoxyethyl-modified antisense oligonucleotide, inhibits hepatic production of transthyretin. METHODS: We conducted an international, randomized, double-blind, placebo-controlled, 15-month, phase 3 trial of inotersen in adults with stage 1 (patient is ambulatory) or stage 2 (patient is ambulatory with assistance) hereditary transthyretin amyloidosis with polyneuropathy. Patients were randomly assigned, in a 2:1 ratio, to receive weekly subcutaneous injections of inotersen (300 mg) or placebo. The primary end points were the change in the modified Neuropathy Impairment Score+7 (mNIS+7; range, -22.3 to 346.3, with higher scores indicating poorer function; minimal clinically meaningful change, 2 points) and the change in the score on the patient-reported Norfolk Quality of Life-Diabetic Neuropathy (QOL-DN) questionnaire (range, -4 to 136, with higher scores indicating poorer quality of life). A decrease in scores indicated improvement. RESULTS: A total of 172 patients (112 in the inotersen group and 60 in the placebo group) received at least one dose of a trial regimen, and 139 (81%) completed the intervention period. Both primary efficacy assessments favored inotersen: the difference in the least-squares mean change from baseline to week 66 between the two groups (inotersen minus placebo) was -19.7 points (95% confidence interval [CI], -26.4 to -13.0; P
- Subjects :
- Tafamidis
endocrine system
medicine.medical_specialty
macromolecular substances
030204 cardiovascular system & hematology
03 medical and health sciences
chemistry.chemical_compound
Malalties del sistema nerviós
0302 clinical medicine
medicine
Malalties hereditàries
Adult
Aged
Aged, 80 and over
Amyloid Neuropathies, Familial
Disease Progression
Double-Blind Method
Female
Glomerulonephritis
Humans
Injections, Subcutaneous
Least-Squares Analysis
Male
Middle Aged
Oligonucleotides, Antisense
Polyneuropathies
Prealbumin
Quality of Life
Severity of Illness Index
Thrombocytopenia
RNAi Therapeutics
Medicine (all)
Peripheral neuropathies
biology
business.industry
Amyloidosis
nutritional and metabolic diseases
Nervous system Diseases
General Medicine
medicine.disease
nervous system diseases
Amyloid Neuropathy
Transthyretin
Neuropaties perifèriques
Multicenter study
chemistry
biology.protein
Cancer research
Medical genetics
Amiloïdosi
Amyloid cardiomyopathy
business
030217 neurology & neurosurgery
Genetic diseases
Subjects
Details
- Database :
- OpenAIRE
- Journal :
- Dipòsit Digital de la UB, Universidad de Barcelona, Recercat. Dipósit de la Recerca de Catalunya, instname
- Accession number :
- edsair.doi.dedup.....95fdbf6a28c8960b7f39722805188ea4