@article{discovery10175263,
           month = {July},
            note = {{\copyright} 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/).},
       publisher = {Springer Science and Business Media LLC},
           title = {Impact of Vutrisiran on Quality of Life and Physical Function in Patients with Hereditary Transthyretin-Mediated Amyloidosis with Polyneuropathy},
            year = {2023},
         journal = {Neurology and Therapy},
        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 {$\times$} 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 {$\times$} 10-7), 10-m walk test (LSMD in CFB: 0.239 m/s; p = 1.21 {$\times$} 10-7), Rasch-built Overall Disability Score (LSMD in CFB: 8.4; p = 3.54 {$\times$} 10-15), and modified body mass index (mBMI) (LSMD in CFB: 140.7; p = 4.16 {$\times$} 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.},
          author = {Obici, L and Ajroud-Driss, S and Lin, KP and Berk, JL and Gillmore, JD and Kale, P and Koike, H and Danese, D and Aldinc, E and Chen, C and Vest, J and Adams, D and Wixner, J and Backlund, R and Pilebro, B and Anan, I and Edbom, F and Ekman, A and Arvidsson, S and Englund, U and S{\"o}derberg, K and Nordh, E and Uneus, E and Samuelsson, K and Nilzen, A and Press, R and Bilecen, M and Coelho, T and Novais, M and Rodrigues, P and Martins da Silva, A and Cardoso, I and Rodrigues, C and Ramalho, J and Martins, H and Silva, M and Guimaraes, N and Perez, J and Reis, AH and Monte, J and Ferreira, N and Alves, C and Cardoso, M and Teixeira, R and Concei{\cc}{\~a}o, I and Lamas, F and Oliveira Santos, M and Campos, C and de Azevedo Coutinho, C and Castro, J and Castro, I and Silva, D and Gon{\cc}alves, S and Di Buduo, E and Sforzini, C and Mussinelli, R and Rosti, V and Lozza, A and Racchi, A and Sabatelli, M and Luigetti, M and Bisogni, G and Romano, A and Guglielmino, V and Di Paolantonio, A and Bernardo, D and Vita, G and Mazzeo, A and Russo, M and Pareyson, D and Calabrese, D and Fenu, S and Saveri, P and Nienhuis, H and Bokhorst, G and Roos, C and Couperus, M and De Jong, G and Brunger, A and Drost, G and Lange, F and Colauto, A and Waddington-Cruz, M and Abreu, A and Pedrosa, RC and Gervais de Santa Rosa, R and Dias, M and Rakotondratafika, F and Echaniz-Laguna, A and Cauquil, C and Labeyrie, C and Beaudonnet, G and Boubrit, Y and Gaouar, A and Bourenane, H and Attarian, S and Yahia, EK and Verschueren, A and Grapperon, AM and Delmont, E},
             url = {https://doi.org/10.1007/s40120-023-00522-4},
        keywords = {ATTRv amyloidosis, Nutritional status, Physical function, Polyneuropathy, Quality of life, RNA interference, Vutrisiran, hATTR amyloidosis}
}