Abstract Details

Title RNAi Therapeutics for hATTR Amyloidosis: A Comprehensive Single Arm Meta-Analysis of Clinical Outcomes and Treatment Efficacy

Topic General Neurology

Presentation(s) P9 - Poster Session 9 (11:45 AM-12:45 PM)

Poster/Presentation
Number 2-005

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.

Authors/Disclosures
Mario S. Lira Castañeda, MD PRESENTER	Mr. Lira Castañeda has nothing to disclose.
Jorge L. Vargas Rojas	Mr. Vargas Rojas has nothing to disclose.
Bruno Mendoza, MD	Mr. Mendoza has nothing to disclose.
MISHELL E. LLERENA VARGAS, MD	Dr. LLERENA VARGAS has nothing to disclose.
Sergio Morales Acosta, MBBS	Dr. Morales Acosta has nothing to disclose.
Arath J. Campos Muñoz, MD	Dr. Campos Muñoz has nothing to disclose.
Claudia Sanchez, MD	Dr. Sanchez has nothing to disclose.
Karen I. Sanchez Ramirez, MD	Dr. Sanchez Ramirez has nothing to disclose.
Valentina Esguerra Romano, MD	Miss Esguerra Romano has nothing to disclose.
Maria Alejandra Gonzalez Duarte, MD, FAAN (NYU Dysautonomia Center)	Dr. Gonzalez Duarte has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Alnylam. Dr. Gonzalez Duarte has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Astra Zeneca. Dr. Gonzalez Duarte has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Alnylam . The institution of Dr. Gonzalez Duarte has received research support from Pfizer.

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