147VP Efficacy and safety of Nusinersen in the treatment of spinal muscular atrophy in adolescents and adults

We aimed to explore the efficacy and safety of Nusinersen treatment in terms of motor function and electrophysiological indicators in Chinese adolescents and adults with SMA. The study included adolescent and adult SMA patients diagnosed at Huashan Hospital affiliated with Fudan University, The First Affiliated Hospital of Soochow University, and The First Affiliated Hospital of Anhui Medical University from October 2022 to December 2023, who received at least 4 doses of Nusinersen. Assessments of motor scales and pulmonary function, including the Hammersmith Functional Motor Scale Expanded (HFMSE), Revised Upper Limb Module (RULM), 6-Minute Walk Test (6MWT), and forced vital capacity (FVC%), were conducted the day before the 1st, 4th, 5th, and 6th treatments (V1, V4, V5, V6). Electrophysiological indicators, including compound muscle action potential (CMAP) and motor unit number index (MUNIX) for upper and lower limb nerves, were also collected to compare improvements in these metrics before and after treatment. A total of 54 patients were included in the study and divided into two groups: those able to walk independently (ambulatory group) and those unable to walk independently but able to sit independently (non-ambulatory group). The average age of the patients was 27.03 years (range 13-53 years), with 64.81% being male. Type II accounted for 16.67% (9/54), and Type III for 79.63% (43/54). Changes in HFMSE scores were statistically significant in both the non-ambulatory and ambulatory subgroups. In the ambulatory subgroup, HFMSE scores improved from baseline to V4 (mean +2.3 points, P=0.004), V5 (+3.0 points, P=0.004), and V6 (+4.2 points, P=0.005), with the ambulatory group showing more pronounced improvements compared to the non-ambulatory group. There was no statistically significant change in the average RULM score from baseline to V4, V5, and V6, but a positive trend was observed, with more marked improvements in the non-ambulatory group. The 6MWT showed significant improvement, with 33.33% (5/15), 66.67% (9/15), and 80.00% (12/15) of patients demonstrating clinically meaningful improvements at V4, V5, and V6, respectively. The CMAP and MUNIX values of upper and lower limb muscles showed a positive correlation with SMN2 copy numbers, motor function status, and baseline motor function scores. After treatment, the most significant increases were observed in the abductor digiti minimi (+0.92mV, P<0.001), trapezius (+0.86mV, P<0.001), and abductor pollicis brevis (+0.81mV, P<0.001) muscles, and lower limb muscles (tibialis anterior +0.44mV, P=0.017). The MUNIX results were similar to CMAP values, with upper limb improvements being superior to lower limbs. A CMAP value of the trapezius muscle ≥ 1.76 mV suggested that patients were more likely to respond to treatment by day 300 (sensitivity 84.6%, specificity 85.7%). With the extension of treatment duration, the incidence rate of adverse reactions remained stable, mainly presenting symptoms caused by post-lumbar puncture syndrome, and no patients were found to need medication discontinuation or change due to severe adverse reactions. Nusinersen improves motor function in SMA patients and is safe to use. CMAP values can serve as effective biomarkers to predict treatment prognosis, addressing the “ceiling effect” of RULM.