TY - JOUR
T1 - Impact of Vutrisiran on Quality of Life and Physical Function in Patients with Hereditary Transthyretin-Mediated Amyloidosis with Polyneuropathy
AU - the HELIOS-A Collaborators Study Group
AU - Obici, Laura
AU - Ajroud-Driss, Senda
AU - Lin, Kon Ping
AU - Berk, John L.
AU - Gillmore, Julian D.
AU - Kale, Parag
AU - Koike, Haruki
AU - Danese, David
AU - Aldinc, Emre
AU - Chen, Chongshu
AU - Vest, John
AU - Adams, David
AU - Wixner, Jonas
AU - Backlund, Rolf
AU - Pilebro, Björn
AU - Anan, Intissar
AU - Edbom, Fredrik
AU - Ekman, Anna
AU - Arvidsson, Sandra
AU - Englund, Ulrika
AU - Söderberg, Karin
AU - Nordh, Erik
AU - Uneus, Erica
AU - Samuelsson, Kristin
AU - Nilzen, Anna
AU - Press, Rayomand
AU - Bilecen, Mirjam
AU - Coelho, Teresa
AU - Novais, Marta
AU - Rodrigues, Patricia
AU - Martins da Silva, Ana
AU - Cardoso, Inês
AU - Rodrigues, Carla
AU - Ramalho, Joana
AU - Martins, Helder
AU - Silva, Mónica
AU - Guimaraes, Nádia
AU - Perez, Javier
AU - Reis, Antonio Hipólito
AU - Monte, Julia
AU - Ferreira, Natalia
AU - Alves, Cristina
AU - Cardoso, Marcio
AU - Teixeira, Ricardo
AU - Conceição, Isabel
AU - Lamas, Filipa
AU - Oliveira Santos, Miguel
AU - Campos, Catarina
AU - de Azevedo Coutinho, Conceiçao
AU - Masri, Ahmad
N1 - Publisher Copyright:
© 2023, The Author(s).
PY - 2023/10
Y1 - 2023/10
N2 - 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. Trial Registration Number: ClinicalTrials.gov: NCT03759379.
AB - 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. Trial Registration Number: ClinicalTrials.gov: NCT03759379.
KW - ATTRv amyloidosis
KW - Nutritional status
KW - Physical function
KW - Polyneuropathy
KW - Quality of life
KW - RNA interference
KW - Vutrisiran
KW - hATTR amyloidosis
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U2 - 10.1007/s40120-023-00522-4
DO - 10.1007/s40120-023-00522-4
M3 - Article
AN - SCOPUS:85166317673
SN - 2193-8253
VL - 12
SP - 1759
EP - 1775
JO - Neurology and Therapy
JF - Neurology and Therapy
IS - 5
ER -