Mauricio R Delgado1, Ann Tilton2, Barry Russman3, Oscar Benavides4, Marcin Bonikowski5, Jorge Carranza6, Edward Dabrowski7, Nigar Dursun8, Mark Gormley9, Marek Jozwiak10, Dennis Matthews11, Iwona Maciag-Tymecka12, Ece Unlu13, Emmanuel Pham14, Anissa Tse14, Philippe Picaut14. 1. Texas Scottish Rite Hospital for Children, Dallas, Texas; University of Texas Southwestern Medical Center, Dallas, Texas; mauricio.delgado@tsrh.org. 2. Louisiana State University Health Center and Children's Hospital New Orleans, New Orleans, Louisiana; 3. Shriner's Hospital for Children, Portland, Oregon; 4. Centro de Rehabilitacion Infantil, Mexico City, Mexico; 5. Non-public Healthcare Unit Mazovian Neurorehabilitation and Psychiatry Center in Zagorze, Wiazowna, Poland; 6. Hospital San José Celaya, Celaya, Guanajuato, Mexico; 7. Children's Hospital of Michigan, Detroit, Michigan; 8. Kocaeli University Medical Faculty, Izmit, Turkey; 9. Gillette Children's Specialty Healthcare, St Paul, Minnesota; 10. Department of Pediatric Orthopedics and Traumatology K. Marcinkowski University of Medical Sciences, Poznan, Poland; 11. Children's Hospital Colorado, Aurora, Colorado; 12. Rehabilitation Center KROK PO KROKU, Gdansk, Poland; 13. Yildirim Beyazit Training and Research Hospital, Ankara, Turkey; and. 14. Ipsen, Les Ulis, France.
Abstract
BACKGROUND: Although botulinum toxin is a well-established treatment of focal spasticity in cerebral palsy, most trials have been small, and few have simultaneously assessed measures of muscle tone and clinical benefit. METHODS: Global, randomized, controlled study to assess the efficacy and safety of abobotulinumtoxinA versus placebo in cerebral palsy children with dynamic equinus foot deformity. Patients were randomized (1:1:1) to abobotulinumtoxinA 10 U/kg/leg, 15 U/kg/leg, or placebo injections into the gastrocnemius-soleus complex (1 or both legs injected). In the primary hierarchical analysis, demonstration of benefit for each dose required superiority to placebo on the primary (change in Modified Ashworth Scale from baseline to week 4) and first key secondary (Physician's Global Assessment at week 4) end points. RESULTS:Two hundred and forty-one patients were randomized, and 226 completed the study; the intention to treat population included 235 patients (98%). At week 4, Modified Ashworth Scale scores significantly improved with abobotulinumtoxinA; mean (95% confidence interval) treatment differences versus placebo were -0.49 (-0.75 to -0.23; P = .0002) for 15 U/kg/leg and -0.38 (-0.64 to -0.13; P = .003) for 10 U/kg/leg. The Physician's Global Assessment treatment differences versus placebo of 0.77 (0.45 to 1.10) for 15 U/kg/leg and 0.82 (0.50 to 1.14) for 10 U/kg/leg were also significant (both Ps < .0001). The most common treatment-related adverse event was muscular weakness (10 U/Kg/leg = 2; placebo = 1). CONCLUSIONS:AbobotulinumtoxinA improves muscle tone in children with dynamic equinus resulting in an improved overall clinical impression and is well tolerated.
RCT Entities:
BACKGROUND: Although botulinum toxin is a well-established treatment of focal spasticity in cerebral palsy, most trials have been small, and few have simultaneously assessed measures of muscle tone and clinical benefit. METHODS: Global, randomized, controlled study to assess the efficacy and safety of abobotulinumtoxinA versus placebo in cerebral palsychildren with dynamic equinus foot deformity. Patients were randomized (1:1:1) to abobotulinumtoxinA 10 U/kg/leg, 15 U/kg/leg, or placebo injections into the gastrocnemius-soleus complex (1 or both legs injected). In the primary hierarchical analysis, demonstration of benefit for each dose required superiority to placebo on the primary (change in Modified Ashworth Scale from baseline to week 4) and first key secondary (Physician's Global Assessment at week 4) end points. RESULTS: Two hundred and forty-one patients were randomized, and 226 completed the study; the intention to treat population included 235 patients (98%). At week 4, Modified Ashworth Scale scores significantly improved with abobotulinumtoxinA; mean (95% confidence interval) treatment differences versus placebo were -0.49 (-0.75 to -0.23; P = .0002) for 15 U/kg/leg and -0.38 (-0.64 to -0.13; P = .003) for 10 U/kg/leg. The Physician's Global Assessment treatment differences versus placebo of 0.77 (0.45 to 1.10) for 15 U/kg/leg and 0.82 (0.50 to 1.14) for 10 U/kg/leg were also significant (both Ps < .0001). The most common treatment-related adverse event was muscular weakness (10 U/Kg/leg = 2; placebo = 1). CONCLUSIONS: AbobotulinumtoxinA improves muscle tone in children with dynamic equinus resulting in an improved overall clinical impression and is well tolerated.
Authors: Mauricio R Delgado; Marcin Bonikowski; Jorge Carranza; Edward Dabrowski; Dennis Matthews; Barry Russman; Ann Tilton; Juan Carlos Velez; Anne-Sophie Grandoulier; Philippe Picaut Journal: J Child Neurol Date: 2017-09-15 Impact factor: 1.987
Authors: Ann Tilton; Barry Russman; Resa Aydin; Umit Dincer; Raul G Escobar; Sehim Kutlay; Zbigniew Lipczyk; Juan Carlos Velez; Anne-Sophie Grandoulier; Anissa Tse; Philippe Picaut; Mauricio R Delgado Journal: J Child Neurol Date: 2017-01-09 Impact factor: 1.987
Authors: Malgorzata Field; Andrew Splevins; Philippe Picaut; Marcel van der Schans; Jan Langenberg; Daan Noort; Keith Foster Journal: Toxins (Basel) Date: 2018-12-13 Impact factor: 4.546