Abstract Details

Title Efficacy and Safety of RNA Interference Therapies/Protein Stabilizers for Transthyretin Amyloidosis with Polyneuropathy: A Systematic Review and Meta-analysis

Topic General Neurology

Presentation(s) P11 - Poster Session 11 (11:45 AM-12:45 PM)

Poster/Presentation
Number 7-008

Objective

This systematic review and meta-analysis aimed to evaluate and compare the efficacy and safety of RNA interference (RNAi) therapies and protein stabilizers in patients with transthyretin amyloidosis with polyneuropathy (ATTR-PN), synthesizing evidence from randomized controlled trials to inform clinical decision-making and identify differences between these two therapeutic mechanisms.

Background Transthyretin amyloidosis with polyneuropathy (ATTR-PN) is a progressive hereditary disorder caused by misfolded transthyretin deposition, leading to severe neuropathy and multisystem failure. Two therapeutic strategies exist: RNA interference therapies suppressing transthyretin production and stabilizers preventing tetramer dissociation. Comprehensive comparative evidence across clinical outcomes remains limited, necessitating systematic synthesis to inform treatment selection.

Design/Methods This systematic review followed PRISMA 2020 guidelines. Four electronic databases were searched through August 2025 for randomized controlled trials evaluating RNAi therapies or transthyretin stabilizers versus placebo in ATTR-PN patients. Primary outcomes included neuropathy impairment (mNIS+7) and quality of life (Norfolk QOL-DN). Secondary outcomes were modified BMI, disability (R-ODS), gait speed (10-MWT), and treatment discontinuation due to adverse events. Study quality was assessed using Cochrane RoB 2.0. Random-effects models pooled mean differences for continuous outcomes and risk ratios for dichotomous outcomes with 95% confidence intervals.

Results Four RCTs involving 716 patients (499 intervention, 217 placebo) were included. Interventions significantly improved neuropathy impairment (mNIS+7: MD −26.93, 95% CI −32.77 – −21.09, P<0.0001). Quality of life improved substantially (Norfolk QOL-DN: MD −18.47, 95% CI −22.78 – −14.16, P<0.0001). Gait speed increased (MD 0.28 m/s, 95% CI 0.20–0.36, P<0.0001), modified BMI improved (MD 112.60, 95% CI 79.02–146.18, P<0.0001), and disability scores decreased (R-ODS: MD 8.63, 95% CI 7.19–10.07, P<0.0001). Treatment discontinuations were reduced 63% versus placebo (RR 0.37, 95% CI 0.14–0.97, P=0.04).

Conclusions Transthyretin-targeting therapies improve neuropathy, quality of life, and functional outcomes, with RNAi showing greater efficacy. Head-to-head trials are needed to better define comparative risk-benefit profiles.

Authors/Disclosures
Krutika Katageri, MD PRESENTER	Dr. Katageri has nothing to disclose.
Fahad Amin, MBBS	Mr. Amin has nothing to disclose.
Rohama Rehman, MBBS	Dr. Rehman has nothing to disclose.
Fatima Rasool	Miss Rasool has nothing to disclose.
Hafiza Maheen Fatima, MBBS	Ms. Fatima has nothing to disclose.

��ɫ��

��ɫ��