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. 2024 Nov 30:78:102967.
doi: 10.1016/j.eclinm.2024.102967. eCollection 2024 Dec.

Type I spinal muscular atrophy and disease modifying treatments: a nationwide study in children born since 2016

Maria Carmela Pera  1   2 , Giorgia Coratti  1   2 , Marika Pane  1   2 , Riccardo Masson  3 , Valeria Ada Sansone  4 , Adele D'Amico  5 , Michela Catteruccia  5 , Caterina Agosto  6 , Antonio Varone  7 , Claudio Bruno  8 , Sonia Messina  9 , Federica Ricci  10 , Irene Bruno  11 , Elena Procopio  12 , Antonella Pini  13 , Sabrina Siliquini  14 , Riccardo Zanin  3 , Emilio Albamonte  4 , Angela Berardinelli  15 , Chiara Mastella  16 , Giovanni Baranello  17   18 , Stefano Carlo Previtali  19 , Antonio Trabacca  20 , Chiara Bravetti  1   2 , Delio Gagliardi  21 , Massimiliano Filosto  22   23 , Roberto de Sanctis  1   2 , Richard Finkel  24 , Eugenio Mercuri  1   2 ; Italian SMA type I Study Group
Collaborators, Affiliations

Type I spinal muscular atrophy and disease modifying treatments: a nationwide study in children born since 2016

Maria Carmela Pera et al. EClinicalMedicine. .

Abstract

Background: The advent of disease-modifying treatments (DMT) has changed natural history in 5q Spinal muscular atrophy (SMA). The aim of this study was to report survival and functional aspects in all the Italian type I children born since 2016.

Methods: The study included all symptomatic children with type I SMA born since January 1st, 2016, when DMTs became available in Italy. All the Italian SMA referral centers provided data on survival and motor, respiratory, and nutritional status. To compare survival rate pre and post DMTs approval, we also included similar data from SMA I patients born between January 1st, 2010, and December 31st, 2015. A two-proportion z-test was conducted to compare the two cohorts. The significance level was set at p < .05.

Findings: 241 infants (98%) had type I SMA. Mean follow-up was 3.48 years (SD 2.33). Among type I patients, 42/241 did not survive (25 untreated), while 199 were alive at last follow-up (all treated; mean treatment age 0.6 years), with 25 needing >16 h/day ventilation or tracheostomy with continuous invasive ventilation. 130 of the 199 survivors (65%) achieved independent sitting, and 175 (87.9%) did not require tube feeding.

Interpretation: Our study provides a picture of the 'new natural history' of type I SMA, confirming the impact of the new therapies on the progression of type I with longer survival r and has better motor, respiratory and nutritional.

Funding: This research was partially funded by grants from the Italian Ministry of Health.

Keywords: Natural history; Spinal muscular atrophy; Survival; Therapy.

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Conflict of interest statement

Pera MC reports personal fees from BIOGEN S.R.L., ROCHE, NOVARTIS outside the submitted work. Coratti G reports personal fees from BIOGEN S.R.L., ROCHE, NOVARTIS outside the submitted work. Pane M reports personal fees from BIOGEN S.R.L., ROCHE, NOVARTIS outside the submitted work. Masson R reports personal fees from ROCHE, PTC and PFIZER outside the submitted work. Sansone V reports personal fees from BIOGEN S.R.L., ROCHE, NOVARTIS outside the submitted work. D’Amico A reports personal fees from BIOGEN S.R.L., ROCHE, GENZYME and NOVARTIS outside the submitted work. Catteruccia M has nothing to disclose. Agosto C has nothing to disclose. Varone A has nothing to disclose. Bruno C report personal fees from BIOGEN S.R.L., ROCHE, NOVARTIS outside the submitted work. Messina S report personal fees from BIOGEN S.R.L., ROCHE, NOVARTIS outside the submitted work. Ricci F report personal fees from BIOGEN S.R.L., ROCHE, NOVARTIS, PTC, SANOFI, PFIZER outside the submitted work. Bruno I reports personal fees from BIOGEN S.R.L., CHIESI, ASTRAZENECA, INOZYME, NOVARTIS outside the submitted work. Procopio E has nothing to disclose. Pini A report personal fees from BIOGEN S.R.L., ROCHE and NOVARTIS outside the submitted work. Siliquini S has nothing to disclose. Zanin R has nothing to disclose. Albamonte E reports personal fees from BIOGEN S.R.L., ROCHE, NOVARTIS outside the submitted work. Berardinelli A has nothing to disclose. Mastella C has nothing to disclose. Baranello G reports personal fees from BIOGEN S.R.L., ROCHE, NOVARTIS outside the submitted work. Previtali SC reports personal fees from LSC Lifescience, Esperare Foundation, Alia Therapeutics, Argenx, Wave outside the submitted work. Trabacca A has nothing to disclose. Bravetti C has nothing to disclose. Gagliardi D has nothing to disclose. Filosto M reports personal fees from Sanofi, Reata/Biogen, Amicus. De Sanctis R reports personal fees from BIOGEN S.R.L., ROCHE, NOVARTIS outside the submitted work. Finkel R reports personal fees from BIOGEN S.R.L., ROCHE, NOVARTIS, SCHOLAR ROCK, outside the submitted work. Mercuri E reports personal fees from BIOGEN S.R.L., ROCHE, AVEXIS, SCHOLAR ROCK and NOVARTIS outside the submitted work.

Figures

Fig. 1
Fig. 1
Percentage of survival status in SMA I. Key to figure: Panel A = whole cohort of SMA I, Panel B = whole cohort of treated SMA I, Panel C = whole cohort of untreated SMA I. NIV = non invasive ventilation, Tracheostomy = tracheostomy with continuous invasive ventilation.
Fig. 2
Fig. 2
SMA I percentage of survival status subdivided by year of birth and treatment status. Key to figure: NIV = non invasive ventilation, Tracheostomy = tracheostomy with continuous invasive ventilation.
Fig. 3
Fig. 3
SMA I percentage of survival status subdivided by years of follow-up. Key to figure: The bars represent the total number of patients at each year of follow-up, regardless of their survival or treatment status. The “n” values include all subjects, and treatment status can change over time, as some patients started treatment later during the follow-up period. Panel A: percentage of survival status subdivided by years of follow-up; Panel B: percentage of survival status subdivided by years of follow-up and SMN2 copy number. The individual with 4+ SMN2 copies did not reach 1 year of follow-up, therefore was excluded from the figure. NIV = non invasive ventilation, Tracheostomy = tracheostomy with continuous invasive ventilation.
Fig. 4
Fig. 4
SMA I percentage of nutritional status subdivided by year of birth and treatment status. Key to figure: NIV = non invasive ventilation, G-tube = gastrostomy tube, NGT = Nasogastric tube, Tracheo = tracheostomy with continuous invasive ventilation.
See this image and copyright information in PMC

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