LAUSR

BACKGROUND Hereditary transthyretin amyloidosis (ATTRv) is a dominantly inherited, adult-onset, progressive and fatal disease caused by mutations in the transthyretin gene. Therapeutic agents approved for this disease include the TTR stabilizer tafamidis and the gene-silencing drugs patisiran and inotersen. Inotersen is an antisense oligonucleotide that suppresses the hepatic production of transthyretin. After EMA approval in 2018, an early access program was opened in Italy, and in this article, we present the long-term outcome of a cohort of Italian ATTRv patients that received inotersen within this program. METHODS This is a multicenter, observational, retrospective study of patients affected by ATTRv that started inotersen during the early access program. The primary endpoint was safety. Secondary endpoints included change from baseline in FAP score, PND, NIS, CADT, Norfolk QoL-DN, troponin, NT-proBNP, IVS thickness, and BMI. RESULTS In total, twenty-three patients were enrolled. No patient permanently discontinued the treatment because of thrombocytopenia and no cases of severe thrombocytopenia were observed. Five patients discontinued the treatment permanently because of voluntary withdrawal (two patients), renal failure after infective pyelonephritis, not related to inotersen, drug-related hypotension, and amyloid-negative crescentic glomerulonephritis. In seven patients, dosing frequency was reduced to every 2 weeks due to recurrent thrombocytopenia. Considering the FAP stage only two patients worsened while the other 21 patients remained stable until the last follow-up available. CONCLUSIONS The long-term safety profile of inotersen is favorable. Neurologic disease severity at baseline is the main factor associated with progression.