For SMA children, early start to therapy may help with swallowing, eating
But new research is needed on how approved treatments affect swallowing ability
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- SMA can cause swallowing difficulties due to mouth and throat muscle weakness, affecting oral feeding in children.
- Better outcomes are seen when children are given disease-modifying therapies before symptoms start, a study found.
- The new review highlighted the lack of research on the impact of approved SMA therapies on swallowing ability.
Children with spinal muscular atrophy (SMA) who start on a disease-modifying therapy (DMT) — four have been approved in the last decade — before developing symptoms are usually able to feed by mouth, but SMA patients who already have swallowing difficulties before beginning treatment often continue to have them later on.
That’s according to a new review of available scientific literature, though the scientists stressed that even the most recent studies have significant limitations. The researchers urged further investigation into how newer available DMTs affect swallowing ability among people with SMA.
“Despite [current study] limitations, our findings suggest that the majority of presymptomatic patients treated with DMTs achieve good swallowing outcomes, with most patients able to achieve full oral nutrition,” the researchers wrote, noting that “this outcome is further supported by [newer] clinical and real-world data.”
Still, “standardised and validated assessments of swallowing … function are needed,” the team wrote.
The study, “Swallowing and feeding after disease-modifying treatment for spinal muscular atrophy: a systematic review of assessment modalities and outcomes,” was published in the Orphanet Journal of Rare Diseases. The work was funded by Roche, makers of the SMA disease-modifying treatment Evrysdi (risdiplam).
SMA is a genetic disorder that causes muscle weakness. This can affect the bulbar muscles — that is, the muscles of the mouth and throat — making it difficult for people with SMA to chew and swallow food.
“Progressive impairment of swallowing physiology and function has historically been reported amongst patients spanning the SMA severity spectrum. These deficits pose substantial risks to respiratory and nutritional health and are of great detriment to quality of life,” the researchers wrote.
Looking at studies to try to determine how DMTs affect swallowing
Disease-modifying therapies, or DMTs for short, are medications proven in clinical trials to slow the progression of SMA, helping patients maintain better motor function. Four DMTs for SMA have been approved in the U.S. since 2016: Spinraza (nusinersen), Zolgensma (onasemnogene abeparvovec-xioi), Itvisma (onasemnogene abeparvovec-brve), and Evrysdi.
Extensive research has shown that DMTs can help people with SMA preserve better overall motor function. But the impact of these therapies on swallowing ability has received less attention.
“Despite the significance of swallowing impairments, little is known regarding the effect of DMTs on feeding and swallowing in SMA,” the scientists wrote.
To determine what was currently known about how DMTs affect swallowing ability in SMA, an international team of researchers, including several scientists from Roche, conducted a review of the scientific literature. The team identified 72 studies that in some way evaluated swallowing function in SMA patients. However, most of these studies had limitations due to their design. For example, in nearly a third of studies, swallowing function was only measured after the DMT was started, making it impossible to draw comparisons from before treatment.
“These limitations significantly restrict our ability to draw conclusions regarding the effects of DMTs on bulbar outcomes,” the scientists wrote.
There was also a lot of variability from study to study in exactly how swallowing ability was measured. Only a few included formal clinical evaluations of bulbar muscle function.
“The heterogeneity [variability], and often questionable validity of the bulbar outcomes that were used, further convoluted the interpretation of results within and across investigations,” the scientists wrote.
The team said their results “highlight a lack of consensus within the medical community when it comes to the evaluation of bulbar integrity in SMA.” The scientists noted a need for “future investigations to systematically evaluate both physiological and functional aspects of bulbar integrity to allow stronger conclusions to be drawn regarding the effects of DMTs.”
Findings suggest early therapy is key to aid swallowing
With these limitations in mind, the available scientific literature does seem to support the idea that DMTs can help maintain swallowing ability in SMA patients — though outcomes were seen to vary based on when treatment was started.
Specifically, data suggest that if DMTs are started before obvious symptoms appear, children are usually able to feed entirely by mouth. But for patients who start DMTs after symptom onset, particularly those with SMA type 1, outcomes are more variable.
The studies showed that children who required nutritional assistance before starting a DMT often will still require some type of assistance after beginning treatment.
“The promising outcomes in patients treated prior to symptom onset are in strong contrast to bulbar outcomes amongst patients treated after symptoms have manifested,” the researchers wrote, noting that “there is wide variability in bulbar outcomes” for the latter group.
Patients treated with [disease-modifying therapies (DMTs)] prior to symptom onset typically have good feeding and swallowing outcomes. … Swallowing and feeding outcomes amongst patients treated with DMTs after symptom onset appear largely dependent on the level of impairment [before therapy].
These findings are broadly in line with data on how DMTs affect motor function in SMA: these medications can stop the disease from getting worse, but have limited ability to reverse damage that’s already occurred. Thus, the researchers noted, clinical outcomes are generally best when a child’s treatment is started as early as possible.
“Patients treated with DMTs prior to symptom onset typically have good feeding and swallowing outcomes. … Swallowing and feeding outcomes amongst patients treated with DMTs after symptom onset appear largely dependent on the level of impairment [before therapy],” the researchers concluded.
