This meta-analysis aims to evaluate the efficacy and safety of RNA inhibitor therapies in treating Hereditary transthyretin amyloidosis (hATTR) with polyneuropathy.

hATTR is a genetic disorder characterized by the misfolding and deposition of transthyretin (TTR) protein in various tissues. RNA interference (RNAi) therapies offer a promising approach by selectively targeting and reducing mutant TTR protein levels. While these therapies have shown efficacy in treating hATTR with polyneuropathy, variations in response and safety profiles across different TTR mutations emphasize the need for personalized treatment and close monitoring.

PubMed, EMBASE, and Cochrane databases were searched for clinical trials that fit our inclusion criteria. We performed a meta-analysis using RStudio to pool data. Proportional outcomes were summarized as pooled proportions with 95% confidence intervals (CIs), using a random-effects model. Continuous outcomes were calculated by pooling mean values with 95% CIs. Heterogeneity was assessed using the I² statistic and Cochran’s Q test. Subgroup analysis is performed based on individual RNAi drugs.

We included 5 trials involving 595 patients received Patisiran, Eplontersen, Inotersen, or Vutisiran. The mean change from baseline in mNIS+7 was -0.63 (95% CI: -3.44; 2.18), with the Patisiran subgroup being more effective. The mean change from baseline in Norfolk QOL-DN score was  −1.89 (95% CI: -3.09; -0.68). Serum TTR reduction from baseline was -77.17% (95% CI: -80.56; -73.79). Serious treatment-emergent adverse events were reported in 29.67% of the patients (95% CI: 22.54; 36.80).