Pnd11 Efficacy and Safety of Brexanolone in the Treatment of Postpartum Depression: A Systematic Review and Meta-Analysis

Abstract

Objectives: AbobotulinumtoxinA (abo) and onabotulinumtoxinA (ona) were approved in pediatric upper limb (PUL) spasticity. The study objective was to evaluate efficacy and safety of abo and ona in PUL. Methods: An indirect treatment comparison (ITC) using Bucher's method was conducted based on a systematic literature review (SLR). The outcomes included change from baseline (CFB) at week 6 and 16 and responder rates (percentage of patients with at least 1-grade change) for Modified Ashworth Scale (MAS) or Ashworth Scale (AS) scores, and all-cause and treatment-related adverse events. At most, 4 studies were available per/outcome. A scenario analysis excluded one study with a different design, introducing substantial heterogeneity. Results: As identified through the SLR, 6 studies fitting specified criteria, were included in the ITC; only the abo trial and one ona trial were doubleblind. In the base-case, differences between abo and ona on MAS/AS CFB (DCFB) were not statistically significant (SS); treatments showed comparable efficacy and safety profiles with a numerical trend in favor of abo. In the sensitivity analysis for MAS/AS elbow, DCFB (95%CI) vs ona (week 6) was SS, at -0.68(-1.20,-0.16) for abo-8U/kg; -0.88(-1.42,-0.34) for abo-16U/kg, and at week 16 was -0.68(-1.17,-0.18) for abo-8U/ kg; -0.78(-1.31,-0.25) for abo-16U/kg. Responder rates for abo 8U/kg and 16U/kg, and ona (pooled doses 2U/kg-8U/kg) were 76.9%, 84.2%, and 74.7%, respectively, at week 6, and 58.4%, 66.3%, and 51.1%, at week 16; between-treatment differences were not SS. Relative risks of all-cause adverse events vs ona were 0.57(0.13,2.57) for abo 8U/ kg, and 0.47 (0.10,2.14) for abo 16U/kg. Conclusions: There was a numerical trend in favor of abo for efficacy and safety in base-case, and significant advantages of abo in the sensitivity analysis. Small study sample sizes and a lack of double-blind studies hinders definitive conclusions regarding comparative efficacy and safety between abo and ona in PUL.