eprintid: 10175263 rev_number: 9 eprint_status: archive userid: 699 dir: disk0/10/17/52/63 datestamp: 2023-08-16 10:30:40 lastmod: 2024-10-30 18:18:11 status_changed: 2023-08-16 10:30:40 type: article metadata_visibility: show sword_depositor: 699 creators_name: Obici, L creators_name: Ajroud-Driss, S creators_name: Lin, KP creators_name: Berk, JL creators_name: Gillmore, JD creators_name: Kale, P creators_name: Koike, H creators_name: Danese, D creators_name: Aldinc, E creators_name: Chen, C creators_name: Vest, J creators_name: Adams, D creators_name: Wixner, J creators_name: Backlund, R creators_name: Pilebro, B creators_name: Anan, I creators_name: Edbom, F creators_name: Ekman, A creators_name: Arvidsson, S creators_name: Englund, U creators_name: Söderberg, K creators_name: Nordh, E creators_name: Uneus, E creators_name: Samuelsson, K creators_name: Nilzen, A creators_name: Press, R creators_name: Bilecen, M creators_name: Coelho, T creators_name: Novais, M creators_name: Rodrigues, P creators_name: Martins da Silva, A creators_name: Cardoso, I creators_name: Rodrigues, C creators_name: Ramalho, J creators_name: Martins, H creators_name: Silva, M creators_name: Guimaraes, N creators_name: Perez, J creators_name: Reis, AH creators_name: Monte, J creators_name: Ferreira, N creators_name: Alves, C creators_name: Cardoso, M creators_name: Teixeira, R creators_name: Conceição, I creators_name: Lamas, F creators_name: Oliveira Santos, M creators_name: Campos, C creators_name: de Azevedo Coutinho, C creators_name: Castro, J creators_name: Castro, I creators_name: Silva, D creators_name: Gonçalves, S creators_name: Di Buduo, E creators_name: Sforzini, C creators_name: Mussinelli, R creators_name: Rosti, V creators_name: Lozza, A creators_name: Racchi, A creators_name: Sabatelli, M creators_name: Luigetti, M creators_name: Bisogni, G creators_name: Romano, A creators_name: Guglielmino, V creators_name: Di Paolantonio, A creators_name: Bernardo, D creators_name: Vita, G creators_name: Mazzeo, A creators_name: Russo, M creators_name: Pareyson, D creators_name: Calabrese, D creators_name: Fenu, S creators_name: Saveri, P creators_name: Nienhuis, H creators_name: Bokhorst, G creators_name: Roos, C creators_name: Couperus, M creators_name: De Jong, G creators_name: Brunger, A creators_name: Drost, G creators_name: Lange, F creators_name: Colauto, A creators_name: Waddington-Cruz, M creators_name: Abreu, A creators_name: Pedrosa, RC creators_name: Gervais de Santa Rosa, R creators_name: Dias, M creators_name: Rakotondratafika, F creators_name: Echaniz-Laguna, A creators_name: Cauquil, C creators_name: Labeyrie, C creators_name: Beaudonnet, G creators_name: Boubrit, Y creators_name: Gaouar, A creators_name: Bourenane, H creators_name: Attarian, S creators_name: Yahia, EK creators_name: Verschueren, A creators_name: Grapperon, AM creators_name: Delmont, E title: Impact of Vutrisiran on Quality of Life and Physical Function in Patients with Hereditary Transthyretin-Mediated Amyloidosis with Polyneuropathy ispublished: inpress subjects: RFH divisions: UCL divisions: B02 divisions: C10 divisions: D17 divisions: G90 keywords: ATTRv amyloidosis, Nutritional status, Physical function, Polyneuropathy, Quality of life, RNA interference, Vutrisiran, hATTR amyloidosis note: © 2023 Springer Nature. This article is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/). abstract: INTRODUCTION: Hereditary transthyretin (ATTRv; v for variant) amyloidosis, also known as hATTR amyloidosis, is a progressive and fatal disease associated with rapid deterioration of physical function and patients' quality of life (QOL). Vutrisiran, a subcutaneously administered RNA interference (RNAi) therapeutic that reduces hepatic production of transthyretin, was assessed in patients with ATTRv amyloidosis with polyneuropathy in the pivotal HELIOS-A study. METHODS: The phase 3 open-label HELIOS-A study investigated the efficacy and safety of vutrisiran in patients with ATTRv amyloidosis with polyneuropathy, compared with an external placebo group from the APOLLO study of the RNAi therapeutic patisiran. Measures of QOL and physical function were assessed. RESULTS: At month 18, vutrisiran improved Norfolk Quality of Life-Diabetic Neuropathy (Norfolk QOL-DN) total score (least squares mean difference [LSMD] in change from baseline [CFB]: –21.0; p = 1.84 × 10–10) and Norfolk QOL-DN domain scores, compared with external placebo. This benefit relative to external placebo was evident across all baseline polyneuropathy disability (PND) scores and most pronounced in patients with baseline PND scores I–II. Compared with external placebo, vutrisiran also demonstrated benefit in EuroQoL-Visual Analog Scale (EQ-VAS) score (LSMD in CFB: 13.7; nominal p = 2.21 × 10–7), 10-m walk test (LSMD in CFB: 0.239 m/s; p = 1.21 × 10–7), Rasch-built Overall Disability Score (LSMD in CFB: 8.4; p = 3.54 × 10–15), and modified body mass index (mBMI) (LSMD in CFB: 140.7; p = 4.16 × 10–15) at month 18. Overall, Norfolk QOL-DN, EQ-VAS, and mBMI improved from pretreatment baseline with vutrisiran, whereas all measures worsened from baseline in the external placebo group. At month 18, Karnofsky Performance Status was stable/improved from baseline in 58.2/13.1% with vutrisiran versus 34.7/8.1% with external placebo. CONCLUSION: Vutrisiran treatment provided significant clinical benefits in multiple measures of QOL and physical function in patients with ATTRv amyloidosis with polyneuropathy. Benefits were most pronounced in patients with earlier-stage disease, highlighting the importance of early diagnosis and treatment. date: 2023-07-01 date_type: published publisher: Springer Science and Business Media LLC official_url: https://doi.org/10.1007/s40120-023-00522-4 oa_status: green full_text_type: pub language: eng primo: open primo_central: open_green verified: verified_manual elements_id: 2043732 doi: 10.1007/s40120-023-00522-4 medium: Print-Electronic pii: 10.1007/s40120-023-00522-4 lyricists_name: Gillmore, Julian lyricists_name: Law, Steven lyricists_id: JGILL78 lyricists_id: SLAWX91 actors_name: Flynn, Bernadette actors_id: BFFLY94 actors_role: owner full_text_status: public publication: Neurology and Therapy event_location: New Zealand citation: Obici, L; Ajroud-Driss, S; Lin, KP; Berk, JL; Gillmore, JD; Kale, P; Koike, H; ... Delmont, E; + view all <#> Obici, L; Ajroud-Driss, S; Lin, KP; Berk, JL; Gillmore, JD; Kale, P; Koike, H; Danese, D; Aldinc, E; Chen, C; Vest, J; Adams, D; Wixner, J; Backlund, R; Pilebro, B; Anan, I; Edbom, F; Ekman, A; Arvidsson, S; Englund, U; Söderberg, K; Nordh, E; Uneus, E; Samuelsson, K; Nilzen, A; Press, R; Bilecen, M; Coelho, T; Novais, M; Rodrigues, P; Martins da Silva, A; Cardoso, I; Rodrigues, C; Ramalho, J; Martins, H; Silva, M; Guimaraes, N; Perez, J; Reis, AH; Monte, J; Ferreira, N; Alves, C; Cardoso, M; Teixeira, R; Conceição, I; Lamas, F; Oliveira Santos, M; Campos, C; de Azevedo Coutinho, C; Castro, J; Castro, I; Silva, D; Gonçalves, S; Di Buduo, E; Sforzini, C; Mussinelli, R; Rosti, V; Lozza, A; Racchi, A; Sabatelli, M; Luigetti, M; Bisogni, G; Romano, A; Guglielmino, V; Di Paolantonio, A; Bernardo, D; Vita, G; Mazzeo, A; Russo, M; Pareyson, D; Calabrese, D; Fenu, S; Saveri, P; Nienhuis, H; Bokhorst, G; Roos, C; Couperus, M; De Jong, G; Brunger, A; Drost, G; Lange, F; Colauto, A; Waddington-Cruz, M; Abreu, A; Pedrosa, RC; Gervais de Santa Rosa, R; Dias, M; Rakotondratafika, F; Echaniz-Laguna, A; Cauquil, C; Labeyrie, C; Beaudonnet, G; Boubrit, Y; Gaouar, A; Bourenane, H; Attarian, S; Yahia, EK; Verschueren, A; Grapperon, AM; Delmont, E; - view fewer <#> (2023) Impact of Vutrisiran on Quality of Life and Physical Function in Patients with Hereditary Transthyretin-Mediated Amyloidosis with Polyneuropathy. Neurology and Therapy 10.1007/s40120-023-00522-4 <https://doi.org/10.1007/s40120-023-00522-4>. (In press). Green open access document_url: https://discovery.ucl.ac.uk/id/eprint/10175263/1/s40120-023-00522-4.pdf