Declines in lung function are steeper and quicker in children with spinal muscular atrophy (SMA) type 2 than non-ambulatory children with SMA type 3, matching changes seen in motor abilities in these two patient groups over time, an eight-year study of untreated children in a global SMA registry reported.
Rates of decline, however, slowed and differences eased around age 13, its researchers reported. These findings are intended to better distinguish SMA patients by disease type, aiding in measures of the long-term effectiveness of disease-modifying therapies on lung health.
The study, “Respiratory trajectories in type 2 and non-ambulant 3 Spinal muscular atrophy in the iSMAC cohort study,” was published in the journal Neurology.
Progressive difficulty breathing is the most common non-neurological symptom and leading cause of mortality in SMA.
Although evaluating respiratory function has gained interest in children with SMA type 1, due to available treatments that improve these patients’ motor function and life expectancy, few studies have assessed the long-term respiratory progression in SMA types 2 and 3.
“The correlation between with respiratory and motor function in these milder subtypes is particularly interesting in light of the new therapeutic options” — Spinraza (nusinersen), Zolgensma, and Evrysdi (risdiplam) — now available, the researchers wrote.
An international team of scientists looked for relevant data among records of pediatric patients taking part in the International SMA Consortium (iSMAc) between June 2010 and September 2018. iSMAc, a worldwide registry, includes both treated and untreated (natural history) SMA patients; investigators focused on those not using any disease-modifying treatment to better establish its natural progression.
Of 437 patients whose records were included, 348 were type 2 (average age of 6.9 at first visit) and 89 were non-ambulatory type 3 (average age at first visit, 11.1). Among those with type 2 disease, 278 could sit (sitters), 32 could not (unable to sit up without support), and 38 did not have a defined status.
Loss of respiratory function, as measured by forced vital capacity (FVC, a standard measure of lung health), followed different paths between the two SMA types, and between individuals of the same type with different motor function.
Overall, type 2 children experienced a steady decline in respiratory function of 4.2% per year between the ages of 5 and 13. Sitters, however, had a slower rate of decline than non-sitters (4.1% vs. 6.0%, respectively).
In contrast, type 3 youths tended to gain in respiratory function between the ages of 5 and 8 (an 11.8% FVC increase, on average), after which they experienced an average decline of 6.3% up to age 13.
From age 13 on, rates of decline leveled off and became nearly equal: 1.0% per year on average in type 2 and 0.9% per year in type 3.
Researchers couldn’t offer an explanation for the initial FVC gain among type 3 patients, and cautioned against drawing firm conclusions given this study’s small sample population.
On average, type 2 children were more likely to need non-invasive ventilation (NIV) than type 3 children (46% vs. 11%), and at a younger age (a median of 5 vs. 15.1 years).
The need for NIV among type 2 patients corresponded to their motor abilities, with 61% of non-sitters needing such ventilation compared with 38% of sitters.
Scoliosis, a sideways curvature of the spine, was frequently found in children with both these SMA types, but did not appear to significant effect respiratory function, even among those who needed surgery.
“The data provided by this study will be important when interpreting the long-term real world respiratory outcome of patients who are now being treated with disease modifying therapies,” the researchers concluded.
Still, these findings should be confirmed in larger studies, they added, “to establish more precisely thresholds of motor function scores associated with different levels of respiratory function.”