Sustained efficacy and safety of repeated incobotulinumtoxinA (Xeomin(®)) injections in blepharospasm

Abstract

IncobotulinumtoxinA (Xeomin(®), NT 201) is a purified botulinum toxin type A free from accessory (complexing) proteins. Previous studies evaluated single sets of incobotulinumtoxinA injections for the treatment of blepharospasm. Individualized injection intervals and other potential determinants of efficacy and safety need to be evaluated in a prospective, longitudinal study. Subjects with blepharospasm who completed a ≤ 20 weeks double-blind, placebo-controlled main period entered a ≤ 69 weeks open-label extension period (OLEX) and received ≤ 5 additional incobotulinumtoxinA treatments at flexible doses (≤ 50 U per eye) and flexible injection intervals (minimum of 6 weeks). Outcome measures included Jankovic Rating Scale (JRS) (sumscore, severity subscore and frequency subscore), Blepharospasm Disability Index, and adverse events. All 102 subjects who completed the main period entered the OLEX; 82 subjects completed the study, 56 received the maximum five injections. From each injection visit to a control visit 6 weeks later, investigator-rated JRS sumscores and subscores, and patient-rated Blepharospasm Disability Index were significantly improved (p ≤ 0.001 for all). All scores were still significantly improved at trial termination compared with the first injection visit (p < 0.05 for all). The most frequently reported adverse events were eyelid ptosis (31.4 %) and dry eye symptoms (17.6 %). The injection interval had no impact on the incidence of adverse events (post hoc analysis). No subject developed neutralizing antibodies during the study. Repeated incobotulinumtoxinA injections, administered at flexible doses and injection intervals from 6 to 20 weeks according to subjects' needs, provide sustained efficacy in the treatment of blepharospasm with no new or unexpected safety risks.

Figures

Fig. 1

Mean JRS sumscore (a), severity subscore (b), and frequency subscore (c) at injection visits, control visits 6 weeks following injection visits, and the TTV (ITT population). ITT intent-to-treat, JRS Jankovic Rating Scale, TTV trial termination visit ***p < 0.001, one-sample t test, for the change from the injection visit to the respective control visit 6 weeks later (calculated only for subjects who attended both the injection and the respective control visit). Error bars represent the standard deviation. The TTV took place between 6 and 20 weeks after the last injection visit

Fig. 2

BSDI mean score at injection visits, control visits 6 weeks following injection visits, and the TTV (ITT population). BSDI Blepharospasm Disability Index, ITT intent-to-treat, TTV trial termination visit **p = 0.001, ***p < 0.001, one-sample t test for the change from the injection visit to the respective control visit 6 weeks later. Error bars represent the standard deviation. The TTV took place between 6 and 20 weeks after the last injection visit