Onasemnogene Abeparvovec in Type 1 Spinal Muscular Atrophy: A Systematic Review and Meta-Analysis

One of the latest approved therapies for spinal muscular atrophy (SMA) is onasemnogene abeparvovec, which transduces motor neurons with the survival of motor neuron gene. The aim of this meta-analysis was to estimate the effect of onasemnogene abeparvovec on motor function in participants with type 1 SMA. Medline, Web of Science, Scopus, and Cochrane Library were searched for studies published from inception to August 2022. Pre-post clinical trials and observational studies determining the effect of onasemnogene abeparvovec on the Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP-INTEND) score or motor milestones ( i.e ., head control, sit unassisted, feed orally, not use permanent ventilatory support, crawl, stand alone, and walk alone) in participants with type 1 SMA were included. Continuous outcomes ( i.e ., CHOP-INTEND score) were expressed as pre-post mean difference and 95% confidence interval (CI), while the proportion of participants who achieved >40, >50, and >58/60 points on the CHOP-INTEND and the achievement of the motor milestones were expressed as proportions and 95% CI. A random effects meta-analysis was conducted on each outcome, and the baseline CHOP-INTEND score was considered a covariate. Eleven studies were included in the systematic review, and four were included in the meta-analyses. Onasemnogene abeparvovec improved CHOP-INTEND scores by 11.06 (9.47 to 12.65) and 14.14 (12.42 to 15.86) points at 3 and 6 months postinfusion, respectively. Moreover, 87%, 51%, and 12% achieved CHOP-INTEND scores of >40, >50, and >58/60 points, respectively. However, this proportion increased to 100% in presymptomatic participants with greater baseline CHOP-INTEND. Motor milestones were also improved, especially in presymptomatic participants. Our systematic review not only showed a marked improvement in motor function in type 1 SMA but also showed that treatment in the presymptomatic stage improves the development of these children toward an evolution close to normal for their age.