RNAi Therapeutics for hATTR Amyloidosis: A Comprehensive Single Arm Meta-Analysis of Clinical Outcomes and Treatment Efficacy
Jorge Luis Vargas Rojas1, Mario S Lira Castañeda2, Bruno Mendoza Castillo3, Mishell Estefanía Llerena Vargas4, Sergio Morales Acosta5, Arath Josué Campos Muñoz6, Claudia Daniela Sanchez Serrano5, Karen Itzel Sanchez Ramirez7, Valentina Esguerra Romano8, Alejandra Gonzalez-Duarte Briseño9
1Universidad Autónoma de Bucaramanga, 2Facultad de Medicina y Nutrición, UJED, 3Benemérita Universidad Autónoma de Puebla, 4Universidad Tecnológica Equinoccial, 5Universidad de Guadalajara, 6Universidad Cuauhtémoc, 7Universidad Autónoma de Sinaloa, 8Fundación Universitaria Ciencias de la Salud, 9Department of Neurology at Grossman School of Medicine, NYU Langone Health Dysautonomia Center
Objective:
The primary objective of this single-arm meta-analysis is to comprehensively evaluate the efficacy and clinical outcomes of RNA interference (RNAi) therapies, specifically patisiran and vutrisiran, in the treatment of hereditary transthyretin amyloidosis (hATTR) with neurologic involvement.
Background:
New RNA interference (RNAi) therapies, particularly patisiran and vutrisiran, represent a groundbreaking approach in the management of Hereditary Transthyretin Amyloidosis (hATTR). By specifically targeting the genetic mechanisms that lead to the production of pathogenic TTR, these therapies have shown promise in reducing TTR levels and improving clinical outcomes.
Design/Methods:
We searched PubMed, Embase, and Cochrane for studies assessing patisiran and vutrisiran from mild to severe hereditary transthyretin amyloidosis with neurologic involvement. A linear mixed model using raw transformation computed weight of outcomes and confidence interval. Studies using proportion of events were analyzed with Inverse Variance (IV) R software version 4.2.1 and other studies were converted for consistency, following PRISMA guidelines.
Results:
This analysis included five studies, two randomized controlled trials (RCTs), three retrospective cohort studies with 363 patients in the intervention group aged between 18-85 years old, followed for 18 months. Neuropathy scores showed (mNIS+7) improvement achieved in 52.8% of patients (C.I. 45.83 - 59.83; p = 0.28), while 41.7% (C.I. 23.82 - 59.70; p = 0.08) improved their eNISLL scores. Norfolk Quality of life scores were improved in 54.5% of patients (C.I. 48.94 - 60.07; p = 0.37). Polyneuropathy disability staging was improved in 8.83% of patients (C.I. 5.56 - 13.75; p = 0.95). Orthostatic intolerance was improved in 28.8% of the patients (C.I. 22.20 - 35.57; p = 0.84).
Conclusions:
This meta-analysis demonstrates that RNA interference drugs significantly slow progression of disease, substantially improves neurologic symptoms and quality of life, with a favorable safety profile. These findings support its use as a valuable treatment option for hereditary transthyretin amyloidosis. Further research is needed to assess long-term outcomes and comparative effectiveness.
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