Your browser doesn't support javascript.
loading
Efficacy and safety of onasemnogene abeparvovec in children with spinal muscular atrophy type 1: real-world evidence from 6 infusion centres in the United Kingdom.
Gowda, Vasantha; Atherton, Mark; Murugan, Archana; Servais, Laurent; Sheehan, Jennie; Standing, Emma; Manzur, Adnan; Scoto, Mariacristina; Baranello, Giovanni; Munot, Pinki; McCullagh, Gary; Willis, Tracey; Tirupathi, Sandya; Horrocks, Iain; Dhawan, Anil; Eyre, Michael; Vanegas, Maria; Fernandez-Garcia, Miguel A; Wolfe, Amy; Pinches, Laura; Illingworth, Marjorie; Main, Marion; Abbott, Lianne; Smith, Hayley; Milton, Emily; D'Urso, Sarah; Vijayakumar, Kayal; Marco, Silvia Sanchez; Warner, Sinead; Reading, Emily; Douglas, Isobel; Muntoni, Francesco; Ong, Min; Majumdar, Anirban; Hughes, Imelda; Jungbluth, Heinz; Wraige, Elizabeth.
Afiliación
  • Gowda V; Children's Neurosciences, Evelina London Children's Hospital, Guy's and St Thomas' NHS Foundation Trust, London, United Kingdom.
  • Atherton M; Sheffield Children's NHS Foundation Trust, Sheffield, United Kingdom.
  • Murugan A; Department of Paediatric Neurology, University Hospital Bristol, Bristol, United Kingdom.
  • Servais L; MDUK Oxford Neuromuscular Centre and NIHR Oxford Biomedical Research Centre, University of Oxford, Oxford, United Kingdom.
  • Sheehan J; Division of Child Neurology, Centre de Référence des Maladies Neuromusculaires, Department of Pediatrics, University Hospital Liège and University of Liège, Avenue de l'Hôpital 1 4000 Liège, Belgium.
  • Standing E; Children's Neurosciences, Evelina London Children's Hospital, Guy's and St Thomas' NHS Foundation Trust, London, United Kingdom.
  • Manzur A; Children's Neurosciences, Evelina London Children's Hospital, Guy's and St Thomas' NHS Foundation Trust, London, United Kingdom.
  • Scoto M; Dubowitz Neuromuscular Centre, Great Ormond Street Hospital, London, United Kingdom.
  • Baranello G; Dubowitz Neuromuscular Centre, Great Ormond Street Hospital, London, United Kingdom.
  • Munot P; Dubowitz Neuromuscular Centre, Great Ormond Street Hospital, London, United Kingdom.
  • McCullagh G; NIHR Great Ormond Street Hospital Biomedical Research Centre and Great Ormond Street Hospital NHS Foundation Trust, London, United Kingdom.
  • Willis T; Dubowitz Neuromuscular Centre, Great Ormond Street Hospital, London, United Kingdom.
  • Tirupathi S; Royal Manchester Children's Hospital, Manchester, United Kingdom.
  • Horrocks I; Robert Jones and Agnes Hunt Orthopaedic Hospital NHS Foundation Trust, Oswestry, United Kingdom.
  • Dhawan A; Royal Belfast Hospital for Sick Children, Belfast, United Kingdom.
  • Eyre M; Royal Hospital for Children, Glasgow, United Kingdom.
  • Vanegas M; Paediatric Liver, GI and Nutrition Centre and MowatLabs, King's College Hospital, London, United Kingdom.
  • Fernandez-Garcia MA; School of Biomedical Engineering and Imaging Sciences, King's College London, London, United Kingdom.
  • Wolfe A; Children's Neurosciences, Evelina London Children's Hospital, Guy's and St Thomas' NHS Foundation Trust, London, United Kingdom.
  • Pinches L; Children's Neurosciences, Evelina London Children's Hospital, Guy's and St Thomas' NHS Foundation Trust, London, United Kingdom.
  • Illingworth M; Children's Neurosciences, Evelina London Children's Hospital, Guy's and St Thomas' NHS Foundation Trust, London, United Kingdom.
  • Main M; Children's Neurosciences, Evelina London Children's Hospital, Guy's and St Thomas' NHS Foundation Trust, London, United Kingdom.
  • Abbott L; University Hospital Southampton NHS Foundation Trust, Southampton, United Kingdom.
  • Smith H; Dubowitz Neuromuscular Centre, Great Ormond Street Hospital, London, United Kingdom.
  • Milton E; Dubowitz Neuromuscular Centre, Great Ormond Street Hospital, London, United Kingdom.
  • D'Urso S; Department of Paediatric Neurology, University Hospital Bristol, Bristol, United Kingdom.
  • Vijayakumar K; Department of Paediatric Neurology, University Hospital Bristol, Bristol, United Kingdom.
  • Marco SS; Sheffield Children's NHS Foundation Trust, Sheffield, United Kingdom.
  • Warner S; Chelsea and Westminster Hospital, London, United Kingdom.
  • Reading E; Paediatric Neurology Department, University Hospital of Wales, Cardiff, United Kingdom.
  • Douglas I; Royal Manchester Children's Hospital, Manchester, United Kingdom.
  • Muntoni F; Royal Manchester Children's Hospital, Manchester, United Kingdom.
  • Ong M; Royal Belfast Hospital for Sick Children, Belfast, United Kingdom.
  • Majumdar A; Dubowitz Neuromuscular Centre, Great Ormond Street Hospital, London, United Kingdom.
  • Hughes I; NIHR Great Ormond Street Hospital Biomedical Research Centre and Great Ormond Street Hospital NHS Foundation Trust, London, United Kingdom.
  • Jungbluth H; Sheffield Children's NHS Foundation Trust, Sheffield, United Kingdom.
  • Wraige E; Department of Paediatric Neurology, University Hospital Bristol, Bristol, United Kingdom.
Lancet Reg Health Eur ; 37: 100817, 2024 Feb.
Article en En | MEDLINE | ID: mdl-38169987
ABSTRACT

Background:

Real-world data on the efficacy and safety of onasemnogene abeparvovec (OA) in spinal muscular atrophy (SMA) are needed, especially to overcome uncertainties around its use in older and heavier children. This study evaluated the efficacy and safety of OA in patients with SMA type 1 in the UK, including patients ≥2 years old and weighing ≥13.5 kg.

Methods:

This observational cohort study used data from patients with genetically confirmed SMA type 1 treated with OA between May 2021 and January 2023, at 6 infusion centres in the United Kingdom. Functional outcomes were assessed using age-appropriate functional scales. Safety analyses included review of liver function, platelet count, cardiac assessments, and steroid requirements.

Findings:

Ninety-nine patients (45 SMA therapy-naïve) were treated with OA (median age at infusion 10 [range, 0.6-89] months; median weight 7.86 [range, 3.2-20.2] kg; duration of follow-up 3-22 months). After OA infusion, mean ± SD change in CHOP-INTEND score was 11.0 ± 10.3 with increased score in 66/78 patients (84.6%); patients aged <6 months had a 13.9 points higher gain in CHOP-INTEND score than patients ≥2 years (95% CI, 6.8-21.0; P < 0.001). Asymptomatic thrombocytopenia (71/99 patients; 71.7%), asymptomatic troponin-I elevation (30/89 patients; 33.7%) and transaminitis (87/99 patients; 87.9%) were reported. No thrombotic microangiopathy was observed. Median steroid treatment duration was 97 (range, 28-548) days with dose doubled in 35/99 patients (35.4%). There were 22.5-fold increased odds of having a transaminase peak >100 U/L (95% CI, 2.3-223.7; P = 0.008) and 21.2-fold increased odds of steroid doubling, as per treatment protocol (95% CI, 2.2-209.2; P = 0.009) in patients weighing ≥13.5 kg versus <8.5 kg. Weight at infusion was positively correlated with steroid treatment duration (r = 0.43; P < 0.001). Worsening transaminitis, despite doubling of oral prednisolone, led to treatment with intravenous methylprednisolone in 5 children. Steroid-sparing immunosuppressants were used in 5 children to enable steroid weaning. Two deaths apparently unrelated to OA were reported.

Interpretation:

OA led to functional improvements and was well tolerated with no persistent clinical complications, including in older and heavier patients.

Funding:

Novartis Innovative Therapies AG provided a grant for independent medical writing services.
Palabras clave

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Tipo de estudio: Guideline / Observational_studies Idioma: En Revista: Lancet Reg Health Eur Año: 2024 Tipo del documento: Article País de afiliación: Reino Unido

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Tipo de estudio: Guideline / Observational_studies Idioma: En Revista: Lancet Reg Health Eur Año: 2024 Tipo del documento: Article País de afiliación: Reino Unido