Children With SMA Type 1 See Increase in Life Expectancy With Treatment

Spinal muscular atrophy (SMA) type 1 life expectancy has increased among infants from 2016 due to disease-modifying treatments (DMTs), leading to better motor, respiratory, and nutritional outcomes, according to a study published in eClinicalMedicine.

Researchers conducted a nationwide study of all 33 Italian SMA referral centers to describe survival and functional aspects of children with SMA type 1 born since 2016, the year DMTs became available in Italy. An analysis of similar data was conducted from data collected between 2010 and 2015 to compare survival rates before and after the availability of DMTs.

All included infants had genetic confirmation of an SMN1 gene mutation and severe hypotonia with onset before the age of 6 months. Infants who showed antenatal signs of disease (type 0) were classified separately. Asymptomatic patients identified through newborn screening were not included due to lack of widespread availability during the study period. A 2-proportion z-test was employed for statistical analysis.

A total of 247 infants with SMA born after 2016 were included in the study (type 1, 98%; mean follow-up, 3.48 years [SD, 2.33]), with SMN2 copies available for 242 infants:

• 1 copy: n=7; 2.89%
• 2 copies: n=212; 87.6%
• 3 copies: n=22; 9.1%
• 4 copies; n=1; 0.4%

Only 1 of the 6 infants with SMA type 0 born after 2016 was alive at the last follow-up. The surviving infant was treated with nusinersen at 30 days of life and required more than 16 hours of daily non-invasive ventilation (NIV) and required placement of a gastrostomy tube (GTube); the infant did not reach any motor milestones such as head control, independent sitting, standing, or walking.

Of the 241 infants with SMA type 1 born after 2016, 199 (82.5%) were still alive at the last follow-up (mean age, 4.04 years [SD, 2.1]. Of the 42 infants who did not survive, 17 received DMTs and 25 did not undergo any DMT treatment. Cause of death in all patients who did not survive was related to respiratory failure.

Of the 199 surviving infants with SMA type 1, 16 had a tracheostomy with continuous invasive ventilation, and 9 required more than 16 hours of NIV daily. Only 1 surviving infant was not treated. A total of 19 surviving infants had a GTube, and 5 required a nasogastric tube (NGT). Of the surviving infants, 26 did not achieve any motor milestones.

A total of 135 of the remaining 173 surviving infants gained head control, 130 of those 135 gained the ability to stand, and 3 of the 135 gained the ability to walk. None of the infants who gained the ability to stand or walk required a tracheostomy with continuous invasive ventilation or more than 16 hours of daily NIV.

Of the 140 infants with SMA type 1 born from 2010 through 2015, 97 (69%) had passed away (mean age, 1.12 years [SD, 1.8]), while 40 infants (29%) are surviving with more than 16 hours of daily NIV or tracheostomy with continuous invasive ventilation.

Comparison of the 2 cohorts of treated infants (pre-2016 vs post-2016) showed a significantly lower proportion of infants who passed away (z=–10.14; P <.001) and who require more than 16 hours of NIV daily or continuous invasive ventilation via tracheostomy (z=–4.55; P <.001) in the post-2016 cohort. Cumulative z-test showed a markedly lower combined proportion of infants who passed away or required more than 16 hours of NIV daily or continuous invasive ventilation in the post-2016 group (27% vs 97%; z=–13.22; P<.001). Similar results were observed after the addition of untreated patients in the post-2016 cohort.

Study limitations included a limited number of näive patients receiving gene therapy only.

“Further follow up will allow to obtain long term data for infants treated with the individual drugs and to establish possible differences between individual therapies and possible combinations or associations that are becoming increasingly frequent,” the researchers wrote.

They concluded, “In conclusion our results provide an overview of the ‘new natural history’ of type I SMA and draw a picture of a new generation of type I infants that is surviving longer and has better motor, respiratory and nutritional outcomes.”

Some of the study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.