Subcutaneous intrathecal catheters allow for the reliable outpatient administration of nusinersen in patients with spinal muscular atrophy (SMA), according to a new study published in Muscle & Nerve. This ultimately results in meaningful improvements in arm function. However, it creates the risk of technical malfunction and iatrogenic infection.
Nusinersen, which is commercialized by Biogen as Spinraza®, is an antisense oligonucleotide for the treatment of SMA that must be administered intrathecally. This can be challenging, especially in patients with advanced disease who have spine deformities or fusions.
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Here, a team of researchers led by Kevin A. Strauss, MD, from the Clinic for Special Children in Strasburg, PA studied the safety and efficacy of subcutaneous intrathecal catheter administration of nusinersen in patients with advanced disease.
They analyzed the safety of the device in 17 patients who started nusinersen treatment between the ages of 2 and 32 years. The patients received 9 to 12 doses of nusinersen via a subcutaneous intrathecal catheter.
The results showed that 71% (12 of 17) of patients developed 14 treatment-related adverse events; these were related to the subcutaneous intrathecal catheter and not nusinersen. Device-related adverse events interfered with 2.5% of nusinersen doses. Four catheters needed to be revised surgically because they malfunctioned. One catheter had to be removed because of meningitis caused by Staphylococcus epidermidis.
The researchers also conducted a separate efficacy analysis in 11 patients with SMA, aged 11 to 25 years, with 3 copies of the SMN2 gene and a complex spine anatomy.
The mean performance on the 9-Hole Peg Test improved in both the dominant and nondominant hands in these patients, and the grip strength increased by almost half (44.9%). There were no significant changes in motor scales, muscle force, lung function, or SMA biomarkers. However, all participants reported at least 1 subjective improvement in endurance, purposeful hand use, arm strength, head control, and/or speech.
Carson VJ, Young M, Brigatti KW, et al. Nusinersen by subcutaneous intrathecal catheter for symptomatic spinal muscular atrophy patients with complex spine anatomy. Muscle Nerve. Published online October 4, 2021. doi:10.1002/mus.27425