Spinraza shows safety across real-world lab tests given young children
Most children with spinal muscular atrophy (SMA) treated with Spinraza (nusinersen) in a real-world setting had normal lab test results on measures of treatment safety, according to a new analysis.
“These data should provide useful information for clinicians to assess the safety of [Spinraza] therapy in the paediatric population,” the scientists, all with Children’s Hospital of Fudan University in Shanghai, China, wrote.
The real-world study, “Safety analysis of laboratory parameters in paediatric patients with spinal muscular atrophy treated with nusinersen,” was published in BMC Pediatrics.
Spinraza was approved to treat most SMA patients in China in early 2019
Spinraza is a therapy widely approved for SMA, a rare genetic disease with symptoms marked by progressive muscle weakness and atrophy (shrinkage). The treatment works by increasing the levels of SMN, a protein that is deficient in people with the neuromuscular condition.
Clinical trials have demonstrated that Spinraza’s use significantly improves motor function in infants and children with SMA.
A 2019 published safety analysis of seven clinical trials showed that the therapy was generally well tolerated and without serious side effects related to treatment. Abnormalities seen in lab tests, such as low platelet levels and elevated urinary protein, were mostly mild in severity.
But data from real-world safety studies, particularly those involving young children with SMA, are lacking, the researchers wrote.
This team analyzed detailed safety data from various lab tests collected from children with SMA treated with Spinraza at their university’s hospital between October 2019 and May 2022. The treatment was approved in China in February 2019.
Data covered a total of 46 children, given a median of four doses per patient, ranging from one to 10. Among this group, 12 children had SMA type 1, 23 had type 2, and 11 had type 3. Their mean age at disease onset was a little older than 1 year (13.4 months), and their mean age at the start of treatment was 4.7 years.
Blood, urine, and cerebrospinal fluid tests done before and during treatment
Various blood and urinary test results, including blood cell counts and markers of inflammation and liver and kidney injury, were collected before treatment (baseline measures) and before each Spinraza administration, which is given via intrathecal (into-the-spine) injection once every four months after a loading period.
White blood cell counts and levels of glucose and total protein from the cerebrospinal fluid (CSF), which surrounds the brain and spinal cord, also were investigated.
Among the markers of bodywide inflammation, white blood cell counts did not significantly change during Spinraza treatment, except for transient elevations in a few cases. C-reactive protein levels were normal in most patients, with three SMA type 2 patients showing temporary increases, suggesting mild infections.
Platelet counts for all children remained in the normal range while on Spinraza, with no significant changes, except for one patient with a low count at dose three, which normalized at the fourth dose.
Slight and transient elevations in activated partial thrombin time (APTT), a marker for blood clotting, were found in 14 patients during treatment, which normalized without intervention in seven children. Six patients had high APTT values at the last visit, while another had high APTT at the previous two visits. Regardless, APTT changes were not significant overall, the researchers noted.
While no child showed high values for the international normalized ratio (INR), a measure of the time it takes for blood to clot, significant INR increases per injection were reported during the observation period.
“Longer follow-up is needed to observe the trends in INR and APTT during [Spinraza] treatment,” the researchers wrote.
One patient had high creatinine levels, a sign of impaired kidney function, that returned to normal without intervention. Another had slightly high urea levels during treatment, but these levels also were high prior to Spinraza’s start. No patients had high cystatin C levels, another marker of kidney health.
No ‘persistent or significantly abnormal findings’ seen across tests
Ten children briefly showed blood in their urine, and seven had temporary increases in white blood cells in the urine, which returned to normal without antibiotics. Over time, however, there were significant changes in urea and cystatin C levels.
No significant elevations in tests of liver health markers were noted with Spinraza’s use, except for a few transient increases in two enzymes — alkaline phosphatase and gamma-glutamyl transferase — in some patients. Overall, statistical analysis showed no major changes in liver function tests throughout the treatment period.
White blood count and glucose and protein levels in the CSF of all other patients remained within the normal range, although glucose and protein levels rose significantly during treatment.
Other side effects related to Spinraza’s administration via spinal tap included headache in three (1.4%) of 213 procedures, back pain in four injections (1.9%), nausea in nine (4.2%), and vomiting in eight (3.8%). These events developed one to three days after the spinal tap, and patients recovered within one week without hospitalization.
“Our data showed that nusinersen [Spinraza] therapy is generally safe in children with SMA,” the scientists concluded. “Laboratory monitoring did not identify any persistent or significantly abnormal findings.”
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