Impact of baseline polyneuropathy severity on patisiran treatment outcomes in the APOLLO trial
Publication Details
Amyloid
September 2022
Author(s)
Dianna Quan1, Laura Obici2, John L Berk3, Yukio Ando4, Emre Aldinc5, Matthew T White5, David Adams6
Affiliations
1Department of Neurology, University of Colorado Anschutz, Aurora, CO, USA; 2Amyloidosis Research and Treatment Centre, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy; 3Amyloidosis Center, Boston Medical Center, Boston, MA, USA; 4Department of Neurology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan; 5Alnylam Pharmaceuticals, Cambridge, MA, USA; 6Neurology Department, APHP, CHU Bicêtre, Université Paris-Saclay, U1195, INSERM, Neurology Department, AP-HP, CHU Bicêtre, Le Kremlin Bicêtre, France
Abstract
Objective:
Assess how baseline polyneuropathy severity impacts response to patisiran regarding neurologic impairment and quality of life (QOL) in patients with hereditary transthyretin-mediated amyloidosis (ATTRv amyloidosis).
Methods:
This post hoc analysis grouped patients from the Phase 3 APOLLO study (n = 225) by baseline Neuropathy Impairment Score (NIS) into quartiles: 6–<31; 31–<57; 57–<85.5; 85.5–141.6. Neurologic impairment (modified NIS+7 [mNIS+7], NIS total score), disability (Rasch-built Overall Disability Scale [R-ODS]), gait speed (10-meter walk test [10-MWT]), grip strength, and QOL (Norfolk Quality of Life-Diabetic Neuropathy [Norfolk QOL-DN] questionnaire) were assessed.
Results:
Across all baseline NIS quartiles, patisiran improved several clinical markers of disease compared with placebo at 18 months. Patients in lower NIS quartiles, treated with patisiran earlier in the disease course, maintained better scores in mNIS+7, NIS total score, R-ODS, 10-MWT, grip strength, and Norfolk QOL-DN versus those in higher NIS quartiles, while placebo-treated patients experienced worsening of all functional measures after 18 months across all quartiles.
Conclusions:
Patisiran treatment improved neurologic function and QOL across a wide range of baseline polyneuropathy severities versus placebo. Timing of treatment initiation in patients with ATTRv amyloidosis remains critical for the preservation of function. (ClinicalTrials.gov number, NCT01960348)
PMID
36120830
DOI
10.1080/13506129.2022.2118043
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