Camiel A Wijngaarde1, Marloes Stam1, Louise A M Otto1, Ruben P A van Eijk1, Inge Cuppen1, Esther S Veldhoen1, Leonard H van den Berg1, Renske I Wadman1, W Ludo van der Pol2. 1. From the Department of Neurology, UMC Utrecht Brain Center (C.A.W., M.S., L.A.M.O., R.P.A.v.E., I.C., L.H.v.d.B., R.I.W., W.L.v.d.P.), Biostatistics & Research Support, Julius Center for Health Sciences and Primary Care (R.P.A.v.E.), and Department of Pediatric Intensive Care (E.S.V.), University Medical Center Utrecht, Utrecht University, the Netherlands. 2. From the Department of Neurology, UMC Utrecht Brain Center (C.A.W., M.S., L.A.M.O., R.P.A.v.E., I.C., L.H.v.d.B., R.I.W., W.L.v.d.P.), Biostatistics & Research Support, Julius Center for Health Sciences and Primary Care (R.P.A.v.E.), and Department of Pediatric Intensive Care (E.S.V.), University Medical Center Utrecht, Utrecht University, the Netherlands. w.l.vanderpol@umcutrecht.nl.
Abstract
OBJECTIVE: To investigate probabilities of survival and its surrogate, that is, mechanical ventilation, in patients with spinal muscular atrophy (SMA). METHODS: We studied survival in a population-based cohort on clinical prevalence of genetically confirmed, treatment-naive patients with SMA, stratified for best acquired motor milestone (i.e., none: type 1a/b; head control in supine position or rolling: type 1c; sitting independently: type 2a; standing: type 2b; walking: type 3a/b; adult onset: type 4). We also assessed the need for mechanical ventilation as a surrogate endpoint for survival. RESULTS: We included 307 patients with a total follow-up of 7,141 person-years. Median survival was 9 days in SMA type 1a, 7.7 months in type 1b, and 17.0 years in type 1c. Patients with type 2a had endpoint-free survival probabilities of 74.2% and 61.5% at ages 40 and 60 years, respectively. Endpoint-free survival of SMA types 2b, 3, and 4 was relatively normal, at least within the first 60 years of life. Patients with SMA types 1c and 2a required mechanical ventilation more frequently and from younger ages compared to patients with milder SMA types. In our cohort, patients ventilated up to 12 h/d progressed not gradually, but abruptly, to ≥16 h/d. CONCLUSIONS: Shortened endpoint-free survival is an important characteristic of SMA types 1 and 2a, but not types 2b, 3, and 4. For SMA types 1c and 2a, the age at which initiation of mechanical ventilation is necessary may be a more suitable endpoint than the arbitrarily set 16 h/d.
OBJECTIVE: To investigate probabilities of survival and its surrogate, that is, mechanical ventilation, in patients with spinal muscular atrophy (SMA). METHODS: We studied survival in a population-based cohort on clinical prevalence of genetically confirmed, treatment-naive patients with SMA, stratified for best acquired motor milestone (i.e., none: type 1a/b; head control in supine position or rolling: type 1c; sitting independently: type 2a; standing: type 2b; walking: type 3a/b; adult onset: type 4). We also assessed the need for mechanical ventilation as a surrogate endpoint for survival. RESULTS: We included 307 patients with a total follow-up of 7,141 person-years. Median survival was 9 days in SMA type 1a, 7.7 months in type 1b, and 17.0 years in type 1c. Patients with type 2a had endpoint-free survival probabilities of 74.2% and 61.5% at ages 40 and 60 years, respectively. Endpoint-free survival of SMA types 2b, 3, and 4 was relatively normal, at least within the first 60 years of life. Patients with SMA types 1c and 2a required mechanical ventilation more frequently and from younger ages compared to patients with milder SMA types. In our cohort, patients ventilated up to 12 h/d progressed not gradually, but abruptly, to ≥16 h/d. CONCLUSIONS: Shortened endpoint-free survival is an important characteristic of SMA types 1 and 2a, but not types 2b, 3, and 4. For SMA types 1c and 2a, the age at which initiation of mechanical ventilation is necessary may be a more suitable endpoint than the arbitrarily set 16 h/d.
Authors: Jerry R Mendell; Samiah A Al-Zaidy; Kelly J Lehman; Markus McColly; Linda P Lowes; Lindsay N Alfano; Natalie F Reash; Megan A Iammarino; Kathleen R Church; Aaron Kleyn; Matthew N Meriggioli; Richard Shell Journal: JAMA Neurol Date: 2021-07-01 Impact factor: 18.302
Authors: Esther S Veldhoen; Camiel A Wijngaarde; Laura P Verweij-van den Oudenrijn; Fay-Lynn Asselman; Roelie M Wösten-van Asperen; Erik H J Hulzebos; Kors van der Ent; Inge Cuppen; Michael A Gaytant; Ruben P A van Eijk; W Ludo van der Pol Journal: Eur Respir J Date: 2020-11-19 Impact factor: 16.671
Authors: Esther S Veldhoen; Camiel A Wijngaarde; Erik H J Hulzebos; Roelie M Wösten-van Asperen; Renske I Wadman; Ruben P A van Eijk; Fay Lynn Asselman; Marloes Stam; Louise A M Otto; Inge Cuppen; Feline E V Scheijmans; Laura P Verweij-van den Oudenrijn; Bart Bartels; Michael A Gaytant; Cornelis K van der Ent; W Ludo van der Pol Journal: Orphanet J Rare Dis Date: 2022-02-21 Impact factor: 4.123