Nusinersen Exhibits Long-Term Safety and Efficacy Across Wide Spectrum of SMA Severity
Findings from a real-world study among 120 patients with SMA suggests that nusinersen administration is safe and well tolerated, with only 30% of the patients mostly experiencing mild adverse events.
Anna Kostera-Pruszczyk, MD, PhD
Newly published in the Orphanet Journal of Rare Diseases, a study showed that treatment with nusinersen (Spinraza; Biogen) resulted in continuous functional improvement and was well-tolerated in adults and older pediatric patients across a wide spectrum of spinal muscular atrophy (SMA) severity over a 30-month follow-up. These findings provide real-world evidence for the continued efficacy and safety of long-term treatment with nusinersen regardless of the type and severity of SMA.1
At months 14 and 30, increases of 3.9 points and 5.1 points, respectively (P <.001) in the mean Hammersmith Functional Motor Scale Expanded (HFMSE) score were reported. At the same times, the mean Revised Upper Limb Module (RULM) score increased by 0.79 points (P = .001) and 1.96 points (P <.001), respectively. Notably at months 14 and 26, the mean Children’s Hospital of Philadelphia Infant Test of Neuromuscular disorders (CHOP-INTEND) scores increased by 3.6 points and 5.6 points (both, P <.001), respectively. Furthermore, compared with the baseline at 14 and 30 months, the mean 6-minute walk test (6MWT) improved by 16.6 m and 27 m, respectively.
Senior author Anna Kostera-Pruszczyk, MD, PhD, professor and head of the department of neurology at the Medical University of Warsaw in Poland, and colleagues wrote, “Our study showed significant differences in the mean HFMSE score between baseline and subsequent time points of treatment in all 73 patients, including 6 with SMA2 and 67 with SMA3. When patients with SMA3, ambulant SMA3, and nonambulant SMA3 were evaluated separately, the differences in the mean score between baseline and subsequent time points were almost identical for all these groups.”
In total, the study included 130 adult and pediatric patients, older than 5 years old, treated with nusinersen between March 2019 and January 2022. All patients were treated with intrathecal loading doses of 12-mg nusinersen at days 1 (baseline), 14, 28, and 63, followed by maintenance doses every 4 months (month 6-month 30). HFMSE (score, 0–66), CHOP-INTEND (score, 0–66), RULM (score 0–37), and the 6MWT were utilized to assess patients’ according to functional ability or disease severity. In the final analysis, 120 treatment-naive patients were included with a total of 1023 intrathecal drug administrations via lumbar puncture (LP) of the treatment performed. The participants were followed for up to 30 months on nusinersen (mean, 14 [SD, 23] months). The subjective treatment outcomes were investigated using the Patients Global Impression–Improvement (PGI-I) scale at each follow-up visit.
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There were clinically meaningful improvements observed at month 14 and 30, in HFMSE (at least 3 points) in 62% and 71% of patients; in CHOP INTEND (at least 4 points) in 58% and 80% of patients; in RULM (at least 2 points) in 26.6% and in 43.5% of patients; and in 6MWT (at least 30-meter increase) with 26% and 50% of patients, respectively. In addition, there were improved PGI-I scores reported for 75% of treated patients at month 14 and 85% at month 30, with reports of worsening at 30 months.
Despite the procedure being generally well tolerated, post lumbar puncture syndrome (PLPS) was observed in 19% of the total LPs given (n = 1023) and most reported mild headache. Other adverse effects reported from the LP procedures included back pain (11%), nausea (4%), and vomiting (1%). There was only 1 patient who needed a single hospitalization for severe back pain following the LP. Notably, the LP given by CT or the C-arm fluoroscopy system (11%) was associated with a lower risk of PLPS compared with conventional intrathecal drug administration (22%) (P <.00001).1
“Our results demonstrated a significant potential for improvement also in older patients with SMA2 and SMA3 with a functional decline manifesting as a mean loss of 0.5 to 1 points in the HFMSE score per year. Interestingly, although the most dynamic improvement in our study was observed during the first 18 months of treatment, it remained significant until the end of follow-up. The rate of responders as assessed by the HFMSE score increased to 71% (20 out of 28 patients) at month 30,” Kostera-Pruszczyk et al noted.1
Considering the limitations, the size of adult patients with SMA1c and SMA2 samples were small. Also, since the CHOP-ATTEND test was not available and researchers used the CHOP-INTEND test instead, it was not validated in adults.2 In addition, the results for some of the tests performed were not accessible for all the time points because of the COVID-19 pandemic restrictions. At time of the pandemic, 31 doses were delayed, and the study did not involve a control group of untreated patients.
