Efficacy and safety of two incobotulinumtoxinA injection intervals in cervical dystonia patients with inadequate benefit from standard injection intervals of botulinum toxin: Phase 4, open-label, randomized, noninferiority study. (2022)

• Record Type: Journal Article
• Authors: Comella, Cynthia; Hauser, Robert A.; Isaacson, Stuart H.; Truong, Daniel; Oguh, Odinachi; Hui, Jennifer; Molho, Eric S.; Brodsky, Matthew; Furr-Stimming, Erin; Comes, Georg; Hast, Michael A.; Charles, David
• Is Part Of: Clinical parkinsonism & related disorders. Volume 6(2022)
• Publication Date: 2022
• Subjects: Cervical dystonia -- Movement disorders -- Botulinum toxin -- BoNT -- IncobotulinumtoxinA; Parkinson's disease -- Periodicals; Movement disorders -- Periodicals; 616.833005
• DOI: 10.1016/j.prdoa.2022.100142
• Languages: English
• ISSNs: 2590-1125

Abstract

Highlights: Botulinum toxin treatment benefit for CD can wane before typical reinjection cycle. Shorter injection cycles of incobotulinumtoxinA are effective for treating CD. Shorter injection intervals have no unexpected AEs or loss of treatment effect. Abstract: Introduction Some patients with cervical dystonia (CD) receiving long-term botulinum neurotoxin (BoNT) therapy report early waning of treatment benefit before the typical 12-week reinjection interval. Methods: This phase 4, open-label, randomized, noninferiority study (CD Flex; NCT01486264) compared 2 incobotulinumtoxinA injection schedules (Short Flex: 8 ± 2 weeks; Long Flex: 14 ± 2 weeks) in CD patients. Previous BoNT-responsive subjects who reported acceptable clinical benefit lasting < 10 weeks were recruited. Efficacy and safety were evaluated after 8 injection cycles. The primary endpoint was change in Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) severity subscale 4 weeks after the eighth injection. Secondary endpoints included TWSTRS total and subscale scores. Immunogenicity was assessed in a subset of patients. Results: Two hundred eighty-two CD patients were randomized and treated (Short Flex, N = 142; Long Flex, N = 140), and 207 completed the study. Significant improvements in TWSTRS severity from study baseline to 4 weeks after cycle 8 were observed in both the Short Flex (4.1 points; P < 0.0001) and Long Flex (2.4 points; P = 0.002) groups; Short Flex was noninferior to Long Flex (LS mean difference = 1.4 points; 95% CI = [−2.9, 0.1] < Δ = 2.0). Key secondary endpoints favored Short Flex intervals. Adverse events (AEs) were comparable between groups. There was no secondary loss of treatment effect. Conclusion: Injection cycles < 10 weeks for incobotulinumtoxinA are effective (and noninferior to longer intervals) for treating CD patients with early waning of clinical benefit. Shorter injection intervals did not increase AEs or lead to loss of treatment effect.