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Vutrisiran and tafamidis are approved therapies for treating hereditary transthyretin-mediated (ATTRv/hATTR) amyloidosis with polyneuropathy, a rapidly progressive and fatal disease. To assist healthcare decision-makers, an indirect treatment comparison (ITC) was undertaken to explore the comparative efficacy of vutrisiran and tafamidis. Individual patient data (vutrisiran vs. placebo) and published results (tafamidis vs. placebo) from phase 3 randomized controlled trials were used in a Bucher analysis to assess differences in treatment effects between vutrisiran and tafamidis on: Neuropathy Impairment Score-Lower Limbs (NIS-LL), Norfolk Quality of Life-Diabetic Neuropathy (Norfolk QOL-DN) score, NIS-LL Response, and modified Body Mass Index (mBMI). Greater treatment effects were observed at 18 months with vutrisiran vs. tafamidis for all endpoints, with statistically significant improvements in polyneuropathy (relative mean change in NIS-LL: −5.3 [95% confidence interval (CI): −9.4, −1.2;  p  = 0.011]), health-related quality of life (HRQOL, relative mean change in Norfolk QOL-DN: −18.3 [95% CI: −28.6, −8.0;  p  &lt; 0.001]), and nutritional status (relative mean change in mBMI: 63.9 [95% CI: 10.1, 117.7;  p  = 0.020]). This analysis suggests vutrisiran has greater efficacy on multiple measures of polyneuropathy impairment and HRQOL compared to tafamidis in patients with ATTRv amyloidosis with polyneuropathy.

Indirect treatment comparison (ITC) of the efficacy of vutrisiran and tafamidis for hereditary transthyretin-mediated amyloidosis with polyneuropathy