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

Clinical Parkinsonism & Related Disorders

卷:6

Robert A. Hauser¹  Michael A. Hast²  Jennifer Hui³  Erin Furr-Stimming⁴  Eric S. Molho⁵  Cynthia Comella⁶  Odinachi Oguh⁷  Georg Comes⁸  Daniel Truong⁹  Stuart H. Isaacson¹⁰  David Charles¹¹  Matthew Brodsky¹² 

[1] Corresponding author at: Neurological Sciences, Rush University Medical Center, 1747 Pleasant Valley Road NE, New Philadelphia, OH 22663, USA.;

[2] Science University, Portland, OR, USA;

[3] The Parkinson and Movement Disorder Institute, Fountain Valley, CA, USA;

[4] Albany Medical Center Neurosciences Institute, Albany, NY, USA;

[5] Cleveland Clinic Lou Ruvo Center for Brain Health, Las Vegas, NV, USA;

[6] Department of Neurological Sciences, Rush University Medical Center, Chicago, IL, USA;

[7] Department of Neurosciences, University of California, Riverside, Riverside, CA, USA;

[8] Oregon Health &

[9] Parkinson’s Disease and Movement Disorders Center of Boca Raton, Boca Raton, FL, USA;

[10] Parkinson’s Disease and Movement Disorders Center of Excellence, University of South Florida, Tampa, FL, USA;

[11] The University of Texas Health Science Center at Houston, McGovern Medical School, Houston, TX, USA;

[12] University of Southern California, Los Angeles, CA, USA;

关键词: Cervical dystonia;    Movement disorders;    Botulinum toxin;    BoNT;    IncobotulinumtoxinA;   

DOI  :  

来源: DOAJ

【 摘 要 】

IntroductionSome 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.

【 授权许可】

Unknown