Abstract Details

Title Neurological Efficacy and Safety of RNA Therapeutics in Hereditary Transthyretin Amyloidosis (hATTR): A Systematic Review and Meta-analysis

Topic Neuromuscular and Clinical Neurophysiology (EMG)

Presentation(s) P6 - Poster Session 6 (5:00 PM-6:00 PM)

Poster/Presentation
Number 9-006

Objective To evaluate the neurological efficacy and safety of RNA therapeutics in hATTR patients.

Background Hereditary transthyretin amyloidosis (hATTR) is a progressive disease caused by mutations in the transthyretin (TTR) gene. These mutations result in misfolded TTR proteins that deposit as amyloid in peripheral nerves, heart, and gastrointestinal tract. Recently, RNA-based therapies like small interfering RNAs (siRNAs) and antisense oligonucleotides (ASOs) have been approved for treating hATTR.

Design/Methods A comprehensive search on Medline, Cochrane Library, and ClinicalTrials.gov was conducted from inception to August 14, 2024. Primary outcomes included changes in Norfolk Quality of Life-Diabetic Neuropathy (Norfolk QoL-DN) score, modified Neuropathy Impairment Score+7 (mNIS+7), and modified body mass index (mBMI). Safety endpoints encompassed adverse events, serious adverse events, and all-cause mortality. Continuous and dichotomous outcomes were analyzed using mean differences (MD) and risk ratios (RR), respectively, with 95% confidence intervals (CI), under a random-effects model.

Results Four randomized controlled trials involving 842 participants (568 receiving RNA therapeutics; 274 receiving a placebo) were included. Compared to placebo, RNA therapeutics demonstrated significant improvements in Norfolk QoL-DN (MD: -18.79; 95% CI: -22.32 to -15.25; p<0.00001; I²=28%) and mNIS+7 scores (MD: -26.90; 95% CI: -31.67 to -22.13; p<0.00001; I²=61%). RNA therapeutics also exhibited better preservation of mBMI (MD: 114.98; 95% CI: 90.64–139.32; p<0.00001; I²=59%). No significant differences were observed in the risk of adverse events (RR: 0.89; 95% CI: 0.69–1.15; p=0.36; I²=34%), serious adverse events (RR: 0.70; 95% CI: 0.31–1.58; p=0.39; I²=20%), and all-cause mortality (RR: 0.70; 95% CI: 0.31–1.58; p=0.39; I²=20%).

Conclusions RNA therapeutics effectively slow neurological progression and improve quality of life in hATTR patients, with a favorable safety profile comparable to placebo. Subgroup analyses indicated superior efficacy of siRNAs over ASOs. These findings support the use of RNA therapeutics as an effective and well-tolerated treatment option for hATTR.

Authors/Disclosures
Hassan Ijaz, MBBS PRESENTER	Mr. Ijaz has nothing to disclose.
Maha Sajjad	Maha Sajjad has nothing to disclose.
Huzaifa S. Nawaz, MBBS	Dr. Nawaz has nothing to disclose.
Sajjad U. Hasan, MBBS	Dr. Hasan has nothing to disclose.
Rabia Ashraf, MBBS	Dr. Ashraf has nothing to disclose.
Riya Bhagwan, MBBS	Dr. Bhagwan has nothing to disclose.
Ayesha Ejaz, MBBS	Miss Ejaz has nothing to disclose.
Hifza Qadeer ud din, MBBS	Miss Qadeer ud din has nothing to disclose.
Abbas Hussain, student	Mr. Hussain has nothing to disclose.
Arshad Ali, MBBS	Dr. Ali has nothing to disclose.
Hafiz Sohail Ashraf, MD	Dr. Ashraf has nothing to disclose.

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