IncobotulinumtoxinA Efficacy and Safety in Adults with Upper-Limb Spasticity Following Stroke: Results from the Open-Label Extension Period of a Phase 3 Study

Introduction: The objective of the study was to investigate the efficacy and safety of repeated incobotulinumtoxinA injections for the treatment of upper-limb post-stroke spasticity in adults. Methods: Adults 18–80 years of age with post-stroke upper-limb spasticity who completed the 12-week randomized, double-blind, placebo-controlled main period (MP) of a phase 3 trial (NCT01392300) were eligible to enrol in the 36-week open-label extension period (OLEX). The OLEX included three treatment cycles at fixed 12-week injection intervals; subjects were injected with 400 U incobotulinumtoxinA into the affected upper limb. Efficacy assessments included evaluation of muscle tone using the Ashworth Scale (AS) and the Global Impression of Change Scale (GICS) assessed by the investigator, subject, and caregiver. The incidence of adverse events (AEs) was monitored throughout the OLEX. Results: A total of 296 of 299 subjects (99.0%) who completed the MP received incobotulinumtoxinA in the OLEX, and 248 subjects completed the 36-week OLEX. The proportion of subjects with at least a 1-point improvement in AS score from each incobotulinumtoxinA treatment to the respective 4-week post-injection visit ranged by cycle from 52.3% to 59.2% for wrist flexors, 49.1% to 52.3% for elbow flexors, 59.8% to 64.5% for finger flexors, 35.5% to 41.2% for thumb flexors, and 37.4% to 39.9% for forearm pronators (P < 0.0001 for all). Over 90% of subjects were assessed by the investigator to be at least minimally improved (4 weeks post-injection) on the GICS during each injection cycle; 61.0% in the 1st cycle, 58.2% in the 2nd cycle, and 57.4% in the 3rd cycle were considered much improved or very much improved on the GICS. Three percent of subjects (9/296) reported treatment-related AEs; the most frequently reported were pain in the extremity (n = 2, 0.7%) and constipation (n = 2, 0.7%). Serious AEs were reported by 22 subjects (7.4%); however, none were considered treatment-related. Conclusions: Repeated injections of incobotulinumtoxinA for the treatment of post-stroke upper-limb spasticity led to significant improvements in muscle tone and investigator’s global impression of change. Treatment was well tolerated, with no serious treatment-related AEs. Funding: Merz Pharmaceuticals GmbH.