DMTs have transformed SMA type 1 in Italy, nationwide study finds
Nearly 4 of every 5 infants with spinal muscular atrophy (SMA) type 1 born in Italy during the era of disease-modifying therapies (DMTs) are still alive, illustrating that such treatment has “radically changed the course of … type I SMA,” with “much higher survival,” according to a nationwide study with up to eight years of follow-up.
Among the children, most gained head control and the ability to sit independently.
An examination of SMA type 1 outcomes before DMTs were available, used for comparison, showed that 2 of every 3 affected infants had died, and more than twice as many needed breathing support.
“These findings strongly support the transformative impact of new therapies on the survival of type I SMA infants,” the researchers wrote. The data highlights “a new generation that is not only surviving longer but also experiencing significantly better motor, respiratory, and nutritional outcomes.”
The study,” Type I spinal muscular atrophy and disease modifying treatments: a nationwide study in children born since 2016,” was published in the journal eClinicalMedicine.
First DMTs approved for SMA in 2016, have changed disease course
SMA type 1 is the most common type of SMA, accounting for about 60% of cases. It’s also one of the most severe forms, with symptoms apparent at birth or developing within the first six months of life. Without treatment, children with SMA type 1 are generally unable to roll over or sit up unsupported, and most die before age 2, primarily due to respiratory failure.
The development of disease-modifying therapies, known as DMTs for short, has dramatically changed the course of SMA in all of its forms, however, perhaps most notably in type 1. Such treatments have resulted in marked improvements in motor function and survival — and in breathing and swallowing — among patients. The benefits of DMTs are particularly pronounced among children who start treatment before symptom onset.
While more than 200 studies have reported the benefits of DMTs in clinical trials and real-world settings, none have reported survival or long-term follow-up over four years in a large group of SMA type 1 patients, according to the team of researchers.
That led the team, from sites across Italy, to examine the outcomes of all symptomatic children with type 1 SMA born in the country since Jan. 1, 2016, when DMTs became available in that nation.
“To our knowledge, this is the first and only systematic, long-term, national-level data collection that includes all type I SMA infants diagnosed since 2016, when the first therapies became available, without any selection criteria,” the researchers wrote.
More than half of treated children gain head control, sit independently
A total of 241 infants with SMA type 1 were identified. Among them, 199 (about 83%) were still alive at the last follow-up. These children had a mean age of 4 years, ranging from about 6 weeks to 8 years. Among the 42, or about 17%, who didn’t survive, 17 had received DMTs, and 25 did not, with respiratory failure being the cause of death in all cases.
Motor milestones were achieved by 173 (about 87%) of the surviving patients, with 135 of these children gaining head control. Among these 135 youngsters, 130 were able to sit independently, 21 could stand, and three gained the ability to walk. All of those who could stand or walk didn’t need breathing support for more than 16 hours per day. The remaining 26 children, of whom 25 were treated, did not reach these developmental milestones.
Nine of the children still living (4.5%) required more than 16 hours of daily noninvasive breathing support, while 16 (8%) had a breathing tube implanted — called a tracheostomy — with continuous invasive ventilation. Five (2.5%) required a feeding tube via the nose, and 19 (9.5%) had a feeding tube planted into the abdomen.
The researchers then compared these findings with similar data from SMA type 1 patients born between 2010 and 2015, before DMTs were available.
Of the 140 evaluable patients, 97 (69%) died, a markedly higher proportion than after the advent of DMTs (17%). Likewise, 40 surviving patients (29%) required noninvasive ventilation for more than 16 hours a day or continuous invasive breathing support, higher than the 12.5% in total after DMTs.
Statistical calculations aligned with these outcomes, with significantly fewer infants dying and/or requiring breathing support after 2016. These results remained even when untreated patients born after 2016 were included in the post-2016 analysis.
Our results provide an overview of the ‘new natural history’ of type 1 SMA and draw a picture of a new generation of type 1 infants that is surviving longer and has better motor, respiratory and nutritional outcome[s].
The team also reported on six infants with SMA type 0, also called prenatal SMA, the rarest and most severe form of SMA, in which symptoms emerge before birth.
One of these children, treated with the DMT Spinraza (nusinersen) on day 30, was still alive at the last follow-up. Still, the infant never reached any motor milestones, needed more than 16 hours daily of noninvasive breathing support, and had an abdominal feeding tube placement. All five infants who died had been given breathing support, and one received Spinraza, while the families of the other four chose not to pursue treatment.
“Our results provide an overview of the ‘new natural history’ of type 1 SMA and draw a picture of a new generation of type 1 infants that is surviving longer and has better motor, respiratory and nutritional outcome[s],” the team concluded, noting that they “also observed a reduction in the number of infants requiring tube feeding … [once] seen as an inevitable choice” in many countries.
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