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
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...
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| Language: | English |
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Elsevier
2022-01-01
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| Series: | Clinical Parkinsonism & Related Disorders |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2590112522000135 |
| _version_ | 1818204845411139584 |
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| author | Cynthia Comella Robert A. Hauser Stuart H. Isaacson Daniel Truong Odinachi Oguh Jennifer Hui Eric S. Molho Matthew Brodsky Erin Furr-Stimming Georg Comes Michael A. Hast David Charles |
| author_facet | Cynthia Comella Robert A. Hauser Stuart H. Isaacson Daniel Truong Odinachi Oguh Jennifer Hui Eric S. Molho Matthew Brodsky Erin Furr-Stimming Georg Comes Michael A. Hast David Charles |
| author_sort | Cynthia Comella |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-12T03:47:43Z |
| format | Article |
| id | doaj.art-3fa867ffb3694c2dbb3fcc82e13d78bd |
| institution | Directory Open Access Journal |
| issn | 2590-1125 |
| language | English |
| last_indexed | 2024-12-12T03:47:43Z |
| publishDate | 2022-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Clinical Parkinsonism & Related Disorders |
| spelling | doaj.art-3fa867ffb3694c2dbb3fcc82e13d78bd2022-12-22T00:39:29ZengElsevierClinical Parkinsonism & Related Disorders2590-11252022-01-016100142Efficacy 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 studyCynthia Comella0Robert A. Hauser1Stuart H. Isaacson2Daniel Truong3Odinachi Oguh4Jennifer Hui5Eric S. Molho6Matthew Brodsky7Erin Furr-Stimming8Georg Comes9Michael A. Hast10David Charles11Department of Neurological Sciences, Rush University Medical Center, Chicago, IL, USA; Corresponding author at: Neurological Sciences, Rush University Medical Center, 1747 Pleasant Valley Road NE, New Philadelphia, OH 22663, USA.Parkinson’s Disease and Movement Disorders Center of Excellence, University of South Florida, Tampa, FL, USAParkinson’s Disease and Movement Disorders Center of Boca Raton, Boca Raton, FL, USADepartment of Neurosciences, University of California, Riverside, Riverside, CA, USA; The Parkinson and Movement Disorder Institute, Fountain Valley, CA, USACleveland Clinic Lou Ruvo Center for Brain Health, Las Vegas, NV, USAUniversity of Southern California, Los Angeles, CA, USAAlbany Medical Center Neurosciences Institute, Albany, NY, USAOregon Health & Science University, Portland, OR, USAThe University of Texas Health Science Center at Houston, McGovern Medical School, Houston, TX, USAMerz Pharmaceuticals GmbH, Frankfurt am Main, GermanyMerz Pharmaceuticals, LLC, Raleigh, NC, USADepartment of Neurology, Vanderbilt University Medical Center, Nashville, TN, USAIntroductionSome 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.http://www.sciencedirect.com/science/article/pii/S2590112522000135Cervical dystoniaMovement disordersBotulinum toxinBoNTIncobotulinumtoxinA |
| spellingShingle | Cynthia Comella Robert A. Hauser Stuart H. Isaacson Daniel Truong Odinachi Oguh Jennifer Hui Eric S. Molho Matthew Brodsky Erin Furr-Stimming Georg Comes Michael A. Hast David Charles 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 Cervical dystonia Movement disorders Botulinum toxin BoNT IncobotulinumtoxinA |
| title | 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | 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 |
| topic | Cervical dystonia Movement disorders Botulinum toxin BoNT IncobotulinumtoxinA |
| url | http://www.sciencedirect.com/science/article/pii/S2590112522000135 |
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