To evaluate the clinical efficacy and safety of intrathecal nusinersen combined with risdiplam in children with spinal muscular atrophy (SMA).

A total of 75 children with SMA were divided into a control group and an experimental group. The control group received intrathecal nusinersen (12 mg) at loading doses on days 0, 14, 28, and 63, followed by maintenance doses every 4 months for 12 months. The experimental group received additional oral risdiplam once daily, with the dose adjusted according to age and body weight, for 12 months. Clinical efficacy, motor function, pulmonary function, and adverse drug reactions were compared between the two groups.

Following treatment, the overall response rates in the experimental group and control group were 91.67% (33 cases/36 cases) and 82.05% (32 cases/39 cases), respectively, with no statistically significant difference between the two groups. (P>0.05). After treatment, the revised upper extremity module (RULM) scores in the experimental group and control group were 32.69±2.07 and 31.59±1.97, respectively; the Hammersmith Functional Motor Scale Expanded (HFMSE) scores for spinal muscular atrophy were 27.75±6.19 and 24.62±6.08, respectively; the 6-minute walking test (6MWT) results were (323.28±29.99) and (303.18±31.39) meters, respectively; the percentage of predicted forced vital capacity (FVC%pred) was (88.09±7.63)% and (83.85±7.79)%, respectively; the percentage of predicted forced expiratory volume in one second (FEV1%pred) was (97.54±8.69)% and (93.28±8.95)%, respectively; the percentage of predicted peak expiratory flow (PEF%pred) was (84.31±8.14)% and (79.64±8.05)%, respectively. In the PedsQL^TM-SMA Module, the scores for daily activities were 1.97±0.17 and 1.85±0.37, motor function scores were 2.14±0.35 and 2.03±0.28, fatigue/pain scores were 2.06±0.23 and 1.97±0.28, social interaction scores were 1.83±0.38 and 1.72±0.51, treatment worry scores were 1.94±0.23 and 1.85±0.37, and emotional functioning scores were 2.11±0.40 and 1.97±0.28, respectively. Serum neurofilament light chain (NfL) levels were (16.58±2.09) and (17.57±2.14) pg·mL^-1, and serum creatine kinase (CK) levels were (59.72±6.81) and (61.73±7.33) U·L^-1, respectively. Statistically significant differences were observed in the above indicators between the two groups (P<0.05). The overall incidence of adverse drug reactions in the experimental group and control group was 8.33% and 10.26%, respectively, with no statistically significant difference (P=0.775).

Intrathecal nusinersen combined with risdiplam significantly improves motor function in children with SMA compared with nusinersen alone, without increasing adverse drug reactions.