Evolución del tratamiento en la atrofia muscular espinal: perspectivas del registro SMArtCARE

Real world treatments for 5q-spinal muscular atrophy (SMA) have evolved rapidly following the sequential approval of three disease-modifying treatments (DMT): nusinersen, onasemnogene abeparvovec (OA) and risdiplam. The aim of this study was to accurately map the sequence and timing of SMA treatments using the SMArtCARE registry, a disease-specific registry for patients with SMA across 84 participating centers in Germany, Austria, and Switzerland. All patients registered in SMArtCARE were included in the analysis. Patients were grouped based on their treatment regimen: those who remained on the first DMT versus those who switched DMT. The impact of clinical and genetic factors on treatment decisions were evaluated, including age at initiation of treatment, SMN2 copy number, motor function status, the need for ventilator support or tube feeding, and the presence of scoliosis. A total of 2,140 patients were included. Of these, 1,294 patients (60.5%) initiated treatment with nusinersen, 514 patients (24.0%) with risdiplam, 243 patients (11.4%) with OA. Overall, 1,366 patients (63.8%) remained on the first DMT. Most treatments switches occurred shortly after approval of a new DMT. Notably, most patients who switched, showed no change in motor milestone status between the start of the first and the second DMT. In this large real-world cohort, we present the first comprehensive analysis of SMA treatment patterns across all age groups and disease severities. While most patients remained on the first DMT, switches were mainly observed after DMT approvals. Decisions to switch appear multifactorial and are not directly related to motor function effectiveness.