Gains found over 4 years with Spinraza treatment in real world
New motor skills seen among SMA patients with long-term use
A real-world study of Spinraza (nusinersen) use in Switzerland among individuals with spinal muscular atrophy (SMA) found that, while patients tended to experience motor function benefits mostly in their first year of treatment, many continued to see gains or disease stabilization for four years.
Spinraza treatment had the largest effects when patients began using the approved therapy before the age of 2.5 years. Specifically, all children first treated in this age range gained new motor skills, according to the study data, which also showed that side effects of the medication were generally mild.
“Our data confirm that early initiation of treatment positively affects motor outcome in SMA,” the investigators wrote. However, they added that “patients who started the treatment late, also gained and/or stabilized motor function in our cohort [study group].”
The team also highlighted “the importance of close respiratory monitoring,” as some individuals began requiring ventilation support during the course of treatment.
Their study, “Real-world data on the effect of long-term treatment with nusinersen over >4 years in a cohort of Swiss patients with spinal muscular atrophy,” was published in the journal Clinical Neurology and Neurosurgery. Spinraza is marketed by Biogen, which was one of the funders of this study alongside the Swiss registry for neuromuscular disorders and other pharmaceutical companies.
SMA is chiefly caused by mutations in SMN1, the gene that contains the instructions to produce the survival motor neuron (SMN) protein. Another gene, SMN2, is a so-called backup gene for SMN1, but a slight difference in its DNA sequence results in only 10%-15% of working SMN.
Spinraza, which is given via intrathecal, or into-the-spinal canal, injection, works by increasing the amount of functional SMN protein generated from SMN2. It corrects the natural process, called alternative splicing, that leads to a shorter, less stable, and poorly working SMN protein from SMN2.
Long-term data on Spinraza treatment ‘scarce’
In clinical trials, Spinraza showed clinically meaningful benefits, including the achievement of motor milestones, improved motor function, and a lower risk of death among patients.
“However, long-term real-world data about the treatment effect of [Spinraza] are still scarce, and do not exist for longer than 4 years or concentrate on patient subgroups,” the research team noted. To learn more, the researchers followed 28 patients at Swiss regional neuromuscular centers for a median of 5.5 years.
“The present study describes prospectively collected data of children, adolescents and adults with SMA [types] 1-3 treated with [Spinraza] over 4.1-6.3 years,” the researchers wrote.
The team noted that “it is the first study to present real-world outcome data on motor function, respiratory and nutritional support, and the perceived changes of the condition by patient/caregiver over such a long period of treatment with nusinersen [Spinraza].”
Participants in the long-term study had begun experiencing SMA symptoms at a median age of 10 months. At the beginning of Spinraza treatment, their median age was 8.3 years.
“Over the four years [of] treatment, most gains were achieved in the first year followed by slower gain and stabilization,” the team wrote. Such improvements in motor function were seen with the Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP-INTEND), which measures muscle strength and function, the Hammersmith Functional Motor Scale Expanded — used to assess skills such as rolling, sitting, crawling, and standing — and the Revised Upper Limb Module of upper limb function.
“This contrasts with the well-described progressive course of the disease demonstrated in natural history cohorts,” the investigators wrote.
Early treament leads to greatest benefits, study finds
For further analysis, the investigators divided participants into subgroups based on the patients’ ages at the start of treatment.
The eight children who began treatment before age 2.5 saw the clearest gains in motor function.
“All patients acquired new motor abilities, and no patient lost any,” the researchers wrote, also noting that each child scored higher on at least one test of motor function. Two children unable to sit unassisted became able to walk with assistance, and three so-called sitters achieved independent walking.
A total of 14 participants started on Spinraza between the ages of 3.5 and 16. For these individuals, treatment began more than three years after their first motor symptoms. On motor abilities, eight participants remained stable, two gained a new ability — namely, head control, crawling, and climbing stairs — and four lost abilities, including rolling onto their side, sitting, and standing with assistance.
All six patients who began treatment after age 16 remained stable and no patient gained or lost a motor ability, the data showed. Three of these individuals could sit and three could walk before Spinraza treatment. All experienced gains on at least one motor assessment.
Three patients who began taking Spinraza before age 2.5 needed noninvasive ventilation and a feeding tube after starting treatment. Among those who were 3.5-16 years old at Spinraza start, four required noninvasive ventilation and/or nutritional support upon beginning the therapy; three started respiratory support and one nutritional and respiratory support during the study period. One child regained the ability to swallow, according to the researchers.
This study adds [to Spinraza data] that [after more than] 4 years of treatment, patients continued to perceive a benefit of the treatment or a stabilization of their condition.
One year into treatment, more than 80% of participants said they felt their condition had improved in the prior six months. The percentage was lower after four years, with 11 of the 21 patients who started Spinraza before age 16, and 3 of 5 initiating treatment later on, reporting minimal improvement
“In this study cohort, no patient died, and side effects were mild and transient,” the team wrote. However, three-quarters of participants experienced at least one adverse event, not including complications related to the spinal tap needed for administration. The most common side effect was the presence of proteins in the urine, with 15 participants experiencing 49 total events.
The small number of participants in each age group and the variability they showed before starting treatment limited the conclusions that the study could draw, the researchers noted.
Nonetheless, the team concluded, “this study adds that [after more than] 4 years of treatment, patients continued to perceive a benefit of the treatment or a stabilization of their condition.”
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