Safety, tolerability and efficacy of widely available nusinersen program in children with Spinal Muscular Atrophy.

Objectives: Spinal Muscular Atrophy (SMA) is a devastating neuromuscular disorder characterized by a progressive loss of spinal motoneurons and leading to muscle weakness and atrophy. Nusinersen, the first disease-modifying treatment for SMA is increasingly used in patients beyond the criteria for the clinical trials. Little is known about its efficacy in older or more severely affected patients. In Poland, nusinersen is available for all SAM patients, regardless of age and functional status. Methods: All patients aged from 0 to 18 (mean 6.9) years included in the Polish SMA treatment program were prospectively followed according to the shared protocol. The data of patients who started treatment in 2019 were assessed one year later. Treatment was considered effective if patients remained stable or improved in the functional scales. Results: A total of 298 patients aged form 0 to 18 years were included in the analysis. After one year, 292 (98%) patients were on treatment. After one year, all patients improved or remained stable. The mean functional score increased by 8.9 points and 6.1 points in the CHOP-INTEND or HFMSE scale, respectively (p<0.001). The regression analysis revealed that the baseline functional status of patients was major determinant of treatment response. Treatment response did not depend on SMA type and the number of SMN2 gene copies. Conclusions: In the reported cohort, we found that nusinersen treatment is beneficial for SMA children regardless of their age, baseline functional status, and the number of SMN2 gene copies. Earlier treatment is associated with better response.
Keywords: Spinal muscular atrophy, nusinersen, children, real-world data