[en] [en] BACKGROUND AND OBJECTIVES: Spinal muscular atrophy (SMA) is a progressive neuromuscular disorder associated with continuous motor function loss and complications, such as scoliosis and contractures. Understanding the natural history of SMA is key to demonstrating the long-term outcomes of SMA treatments. This study reviews the natural history of motor function, scoliosis, and contractures in patients with SMA.
METHODS: Electronic databases were searched from inception to June 27, 2022 (Embase, MEDLINE, and Evidence-Based Medicine Reviews). Observational studies, case-control studies, cross-sectional studies, and case series reporting on motor function (i.e., sitting, standing, and walking ability), scoliosis, and contracture outcomes in patients with types 1-3 SMA were included. Data on study design, baseline characteristics, and treatment outcomes were extracted. Data sets were generated from studies that reported Kaplan-Meier (KM) curves and pooled to generate overall KM curves.
RESULTS: Ninety-three publications were included, of which 68 reported on motor function. Of these, 10 reported KM curves (3 on the probability of sitting in patients with types 2 and 3 SMA and 8 on the probability of walking/ambulation in patients with type 3 SMA). The median time to loss of sitting (95% CI) was 14.5 years (14.1-31.5) for the type 2 SMA sitter population (their maximum ability was independent sitting). The median time to loss of ambulation (95% CI) was 13.4 years (12.5-14.5) for type 3a SMA (disease onset at age younger than 3 years) and 44.2 years (43.0-49.4) for type 3b SMA (disease onset at age 3 years or older). Studies including scoliosis and contracture outcomes mostly reported non-time-to-event data.
DISCUSSION: The results demonstrate that a high degree of motor function loss is inevitable, affecting patients of all ages. In addition, data suggest that untreated patients with types 2 and 3 SMA remain at risk of losing motor milestones during late adulthood, and patients with types 3a and 3b SMA are at risk of loss of ambulation over time. These findings support the importance of stabilization of motor function development even at older ages. Natural history data are key for the evaluation of SMA treatments as they contextualize the assessment of long-term outcomes.
Disciplines :
Pediatrics
Author, co-author :
Aponte Ribero, Valerie ; From F. Hoffmann-La Roche Ltd. (V.A.R., Y.M., K.G., C.S.S.), Basel, Switzerland, Mtech Access Limited (S.B., S.M.), Bicester, United Kingdom, SMA Europe (N.G.), Freiburg, Germany, SMA Schweiz (N.G.), Heimberg, Switzerland, Departments of Pediatrics and Neurology Neurosurgery (M.O.), McGill University, Montreal, Quebec, Canada, MDUK Oxford Neuromuscular Centre (L.S.), Department of Paediatrics, University of Oxford, United Kingdom, and Division of Child Neurology (L.S.), Centre de Rèfèrences des Maladies Neuromusculaires, Department of Pediatrics, University Hospital Liège and University of Liège, Belgium
Martí, Yasmina ; From F. Hoffmann-La Roche Ltd. (V.A.R., Y.M., K.G., C.S.S.), Basel, Switzerland, Mtech Access Limited (S.B., S.M.), Bicester, United Kingdom, SMA Europe (N.G.), Freiburg, Germany, SMA Schweiz (N.G.), Heimberg, Switzerland, Departments of Pediatrics and Neurology Neurosurgery (M.O.), McGill University, Montreal, Quebec, Canada, MDUK Oxford Neuromuscular Centre (L.S.), Department of Paediatrics, University of Oxford, United Kingdom, and Division of Child Neurology (L.S.), Centre de Rèfèrences des Maladies Neuromusculaires, Department of Pediatrics, University Hospital Liège and University of Liège, Belgium
Batson, Sarah ; From F. Hoffmann-La Roche Ltd. (V.A.R., Y.M., K.G., C.S.S.), Basel, Switzerland, Mtech Access Limited (S.B., S.M.), Bicester, United Kingdom, SMA Europe (N.G.), Freiburg, Germany, SMA Schweiz (N.G.), Heimberg, Switzerland, Departments of Pediatrics and Neurology Neurosurgery (M.O.), McGill University, Montreal, Quebec, Canada, MDUK Oxford Neuromuscular Centre (L.S.), Department of Paediatrics, University of Oxford, United Kingdom, and Division of Child Neurology (L.S.), Centre de Rèfèrences des Maladies Neuromusculaires, Department of Pediatrics, University Hospital Liège and University of Liège, Belgium
Mitchell, Stephen; From F. Hoffmann-La Roche Ltd. (V.A.R., Y.M., K.G., C.S.S.), Basel, Switzerland, Mtech Access Limited (S.B., S.M.), Bicester, United Kingdom, SMA Europe (N.G.), Freiburg, Germany, SMA Schweiz (N.G.), Heimberg, Switzerland, Departments of Pediatrics and Neurology Neurosurgery (M.O.), McGill University, Montreal, Quebec, Canada, MDUK Oxford Neuromuscular Centre (L.S.), Department of Paediatrics, University of Oxford, United Kingdom, and Division of Child Neurology (L.S.), Centre de Rèfèrences des Maladies Neuromusculaires, Department of Pediatrics, University Hospital Liège and University of Liège, Belgium
Gorni, Ksenija ; From F. Hoffmann-La Roche Ltd. (V.A.R., Y.M., K.G., C.S.S.), Basel, Switzerland, Mtech Access Limited (S.B., S.M.), Bicester, United Kingdom, SMA Europe (N.G.), Freiburg, Germany, SMA Schweiz (N.G.), Heimberg, Switzerland, Departments of Pediatrics and Neurology Neurosurgery (M.O.), McGill University, Montreal, Quebec, Canada, MDUK Oxford Neuromuscular Centre (L.S.), Department of Paediatrics, University of Oxford, United Kingdom, and Division of Child Neurology (L.S.), Centre de Rèfèrences des Maladies Neuromusculaires, Department of Pediatrics, University Hospital Liège and University of Liège, Belgium
Gusset, Nicole; From F. Hoffmann-La Roche Ltd. (V.A.R., Y.M., K.G., C.S.S.), Basel, Switzerland, Mtech Access Limited (S.B., S.M.), Bicester, United Kingdom, SMA Europe (N.G.), Freiburg, Germany, SMA Schweiz (N.G.), Heimberg, Switzerland, Departments of Pediatrics and Neurology Neurosurgery (M.O.), McGill University, Montreal, Quebec, Canada, MDUK Oxford Neuromuscular Centre (L.S.), Department of Paediatrics, University of Oxford, United Kingdom, and Division of Child Neurology (L.S.), Centre de Rèfèrences des Maladies Neuromusculaires, Department of Pediatrics, University Hospital Liège and University of Liège, Belgium
Oskoui, Maryam; From F. Hoffmann-La Roche Ltd. (V.A.R., Y.M., K.G., C.S.S.), Basel, Switzerland, Mtech Access Limited (S.B., S.M.), Bicester, United Kingdom, SMA Europe (N.G.), Freiburg, Germany, SMA Schweiz (N.G.), Heimberg, Switzerland, Departments of Pediatrics and Neurology Neurosurgery (M.O.), McGill University, Montreal, Quebec, Canada, MDUK Oxford Neuromuscular Centre (L.S.), Department of Paediatrics, University of Oxford, United Kingdom, and Division of Child Neurology (L.S.), Centre de Rèfèrences des Maladies Neuromusculaires, Department of Pediatrics, University Hospital Liège and University of Liège, Belgium
Servais, Laurent ; Université de Liège - ULiège > Département des sciences cliniques
Sutherland, C Simone ; From F. Hoffmann-La Roche Ltd. (V.A.R., Y.M., K.G., C.S.S.), Basel, Switzerland, Mtech Access Limited (S.B., S.M.), Bicester, United Kingdom, SMA Europe (N.G.), Freiburg, Germany, SMA Schweiz (N.G.), Heimberg, Switzerland, Departments of Pediatrics and Neurology Neurosurgery (M.O.), McGill University, Montreal, Quebec, Canada, MDUK Oxford Neuromuscular Centre (L.S.), Department of Paediatrics, University of Oxford, United Kingdom, and Division of Child Neurology (L.S.), Centre de Rèfèrences des Maladies Neuromusculaires, Department of Pediatrics, University Hospital Liège and University of Liège, Belgium. simone.sutherland@roche.com
Language :
English
Title :
Systematic Literature Review of the Natural History of Spinal Muscular Atrophy: Motor Function, Scoliosis, and Contractures.
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