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.

The risk of composite outcome was significantly lower among SGLT2 inhibitor therapy users compared to IBT users (Hazard ratio (HR):0.778, p=0.001, 95% confidence interval (CI):0.671-0.904). When individual outcomes were considered SGLT2 inhibitor users had a lower risk of stroke (HR:0.831, p=0.028, 95%CI:0.704-0.981) and MI (HR:0.704, p=0.024, 95%CI:0.519-0.955) compared to IBT users. However, the difference in the risk of all-cause mortality was non-significant between two groups (HR:1.605, p=0.433, 95%CI:0.492-5.238). Among patients with co-morbid HF, the risk of HF-related ER visits was significantly lower for SGLT2 inhibitor therapy users (HR:0.629, p,0.001, 95% CI:0.507-0.779) compared to IBT users, but the association was not significant for HF-related hospitalizations (HR:0.770, p=0.109, 95%CI:0.560-1.060). Conclusions: SGLT2 inhibitor therapy use was associated with a lower risk of stroke, MI, and HF-related ER visits compared to IBT use.