First-Generation TTR Silencing Therapies in Hereditary Transthyretin Amyloidosis With Polyneuropathy: Real-World Insights From a German Single-Referral Center.

BACKGROUND: Hereditary transthyretin (ATTRv) amyloidosis is a rare, genetically heterogeneous disease leading to an unstable configuration of transthyretin (TTR) and hence irregular deposition of TTR amyloid fibrils. The disease predominantly affects the peripheral nervous system, resulting in a progressive sensorimotor polyneuropathy (ATTRv-PN), but can also involve the cardiac and other organ systems. The TTR mRNA silencers patisiran and inotersen effectively reduce serum TTR levels, thereby improving neurologic disability and quality of life in patients with ATTRv-PN. This real-world study investigated long-term efficacy and tolerability of both compounds in patients with ATTRv-PN.

METHODS: This retrospective study from a German single-referral center assessed the effects of treatment with patisiran or inotersen on clinical parameters of 35 patients with ATTRv-PN treated at the Amyloidosis Center of Heidelberg University Hospital for up to 6 years after therapy start. The study included analyses of serum TTR levels, NT-proBNP, creatinine and modified body mass index (mBMI), and reported side effects throughout the observational period.

RESULTS: Both silencers stably reduced serum TTR levels by 81.1% (p = 0.0039, patisiran) and 82.8% (p = 0.0039, inotersen), respectively, after 8 to 15 months compared to mean baseline. NT-proBNP, creatinine, and mBMI values remained stable during treatment. With patisiran, a lower rate of reported adverse effects was observed. Grade 1 thrombocytopenia was reported primarily for inotersen-treated patients.

CONCLUSIONS: Our findings confirm long-term treatment with TTR silencers in a real-world setting is safe, consistently reducing serum TTR levels, stabilizing neurologic symptoms, cardiac and renal functions, and nutritional parameters.