Five-year disease-modifying therapeutic experience of 102 Chinese pediatric 5q-spinal muscular atrophy: a retrospective analysis

Abstract 5q-Spinal Muscular Atrophy (SMA) is a fatal autosomal recessive disease characterised by the progressive muscle weakness and atrophy. In this retrospective study, we described the long-term clinical outcomes of novel disease-modifying therapies (DMTs) for 5q-SMA, drawing on experience from southern China. This is a single-center large cohort which enrolled 102 pediatric patients confirmed with 5q-SMA at Guangzhou women and children’s medical center from 2019 to 2024. 102 patients were included, 24 were classified as SMA type 1, 56 with type 2 and 22 with type 3. 100% of the patients received nusinersen, with 31 (30.3%) patients starting risdiplam and 2 patients transitioning to zolgensma therapy. Over the five-year treatment and follow-up period (2019–2024), the survival rate reached 97.08 %. One child with SMA type 1 and two with SMA type 2 died while receiving nusinersen monotherapy. Compared with baseline, the enrolled SMA patients exhibited statistically significant motor-function gains. Nevertheless, type 1 patients experienced weight loss, while linear growth was compromised in both type 1 and type 2 patients after treatment. Serum insulin-like growth factor-1 (IGF-1) levels rose modestly in types 1 and 2, but the increase did not reach statistical significance. Respiratory tract infections, malnutrition, scoliosis and fracture are the main complications and potential life-threatening risk factors during DMTs. Moreover, longer diagnostic to treatment intervals were significantly and inversely associated with motor function gains and directly associated with higher complication rates. This retrospective study confirms the effectiveness of nusinersen and risdiplam for 5q-SMA, and highlights the critical importance of early initiation of DMTs.