TY - JOUR
T1 - IncobotulinumtoxinA Efficacy/Safety in Upper-Limb Spasticity in Pediatric Cerebral Palsy
T2 - Randomized Controlled Trial
AU - Dabrowski, Edward
AU - Chambers, Henry G.
AU - Gaebler-Spira, Deborah
AU - Banach, Marta
AU - Kaňovský, Petr
AU - Dersch, Hanna
AU - Althaus, Michael
AU - Geister, Thorin L.
AU - Heinen, Florian
N1 - Funding Information:
Conflict of Interest: The authors declare the following financial interests/personal relationships, which may be considered as potential competing interests: Edward Dabrowski participated in an advisory board and speaker bureau for Ipsen Biopharmaceuticals. Henry G. Chambers serves as a consultant for Orthopediatrics Corp, Allergan Corporation. Deborah Gaebler-Spira has no conflicts of interest. Marta Banach participated in the advisory board and speaker bureau for Merz Pharmaceuticals and served as a consultant and speaker for Ipsen, Allergan, Kedrion, and Shire. Petr Kaňovský received speaker's honoraria from Desitin, Ipsen Biopharmaceuticals, Merz Pharmaceuticals, and Medtronic. Hanna Dersch, Michael Althaus, and Thorin L. Geister are employees of Merz Pharmaceuticals GmbH. Florian Heinen received speaker's honoraria from Allergan plc, Desitin, Ipsen Biopharmaceuticals, Merz Pharmaceuticals, and Novartis and unrestricted educational grants from Allergan and Merz Pharmaceuticals.
Funding Information:
The authors wish to thank the patients, study investigators, DMC Chairperson Professor Dr. Bernard Dan, and DMC members Dr. Antigone Papavasiliou and Dr. Charles Fairhurst. This study was supported by Merz Pharmaceutical GmbH, Frankfurt am Main, Germany. Editorial support, under the direction of the authors, was provided by Dominic Singson, MD, and Claire Cairney, PhD, CMC Connect, McCann Health Medical Communications, and Sue Chambers, PhD, and Deirdre Elmhirst, PhD, Rx Communications, funded by Merz Pharmaceuticals GmbH, in accordance with Good Publication Practice (GPP3) guidelines.
Funding Information:
Funding: This study was supported by Merz Pharmaceuticals GmbH, Frankfurt am Main, Germany. Conflict of Interest: The authors declare the following financial interests/personal relationships, which may be considered as potential competing interests: Edward Dabrowski participated in an advisory board and speaker bureau for Ipsen Biopharmaceuticals. Henry G. Chambers serves as a consultant for Orthopediatrics Corp, Allergan Corporation. Deborah Gaebler-Spira has no conflicts of interest. Marta Banach participated in the advisory board and speaker bureau for Merz Pharmaceuticals and served as a consultant and speaker for Ipsen, Allergan, Kedrion, and Shire. Petr Ka?ovsk? received speaker's honoraria from Desitin, Ipsen Biopharmaceuticals, Merz Pharmaceuticals, and Medtronic. Hanna Dersch, Michael Althaus, and Thorin L. Geister are employees of Merz Pharmaceuticals GmbH. Florian Heinen received speaker's honoraria from Allergan plc, Desitin, Ipsen Biopharmaceuticals, Merz Pharmaceuticals, and Novartis and unrestricted educational grants from Allergan and Merz Pharmaceuticals.
Funding Information:
Funding: This study was supported by Merz Pharmaceuticals GmbH , Frankfurt am Main , Germany.
Publisher Copyright:
© 2021 The Authors
PY - 2021/10
Y1 - 2021/10
N2 - Background: This randomized phase 3 study with double-blind main period (MP) and open-label extension (OLEX; NCT02002884) assessed incobotulinumtoxinA safety and efficacy for pediatric upper-limb spasticity treatment in ambulant/nonambulant (Gross Motor Function Classification System [GMFCS] I-V) patients, with the option of combined upper- and lower-limb treatment. Methods: Patients were aged two to 17 years with unilateral or bilateral spastic cerebral palsy (CP) and Ashworth Scale (AS) score ≥2 in treatment-selected clinical patterns. In the MP, patients were randomized (2:1:1) to incobotulinumtoxinA 8, 6, or 2 U/kg body weight (maximum 200, 150, 50 U/upper limb), with optional lower-limb injections in one of five topographical distributions (total body dose ≤16 to 20 U/kg, maximum 400 to 500 U, depending on body weight and GMFCS level). In the OLEX, patients received three further treatment cycles, at the highest MP doses (8 U/kg/upper limb group). Outcomes included AS, Global Impression of Change Scale (GICS), and adverse events (AEs). Results: AS scores improved from baseline to week 4 in all MP dose groups (n = 350); patients in the incobotulinumtoxinA 8 U/kg group had significantly greater spasticity improvements versus the 2 U/kg group (least-squares mean [standard error] for upper-limb main clinical target pattern −1.15 [0.06] versus −0.93 [0.08]; P = 0.017). Investigator's, child/adolescent's, and parent/caregiver's GICS scores showed improvements in all groups. Treatment benefits were sustained over further treatment cycles. AE incidence did not increase with dose or repeated treatment across GMFCS levels. Conclusions: Data provide evidence for sustained efficacy and safety of multipattern incobotulinumtoxinA treatment in children and adolescents with upper-limb spasticity.
AB - Background: This randomized phase 3 study with double-blind main period (MP) and open-label extension (OLEX; NCT02002884) assessed incobotulinumtoxinA safety and efficacy for pediatric upper-limb spasticity treatment in ambulant/nonambulant (Gross Motor Function Classification System [GMFCS] I-V) patients, with the option of combined upper- and lower-limb treatment. Methods: Patients were aged two to 17 years with unilateral or bilateral spastic cerebral palsy (CP) and Ashworth Scale (AS) score ≥2 in treatment-selected clinical patterns. In the MP, patients were randomized (2:1:1) to incobotulinumtoxinA 8, 6, or 2 U/kg body weight (maximum 200, 150, 50 U/upper limb), with optional lower-limb injections in one of five topographical distributions (total body dose ≤16 to 20 U/kg, maximum 400 to 500 U, depending on body weight and GMFCS level). In the OLEX, patients received three further treatment cycles, at the highest MP doses (8 U/kg/upper limb group). Outcomes included AS, Global Impression of Change Scale (GICS), and adverse events (AEs). Results: AS scores improved from baseline to week 4 in all MP dose groups (n = 350); patients in the incobotulinumtoxinA 8 U/kg group had significantly greater spasticity improvements versus the 2 U/kg group (least-squares mean [standard error] for upper-limb main clinical target pattern −1.15 [0.06] versus −0.93 [0.08]; P = 0.017). Investigator's, child/adolescent's, and parent/caregiver's GICS scores showed improvements in all groups. Treatment benefits were sustained over further treatment cycles. AE incidence did not increase with dose or repeated treatment across GMFCS levels. Conclusions: Data provide evidence for sustained efficacy and safety of multipattern incobotulinumtoxinA treatment in children and adolescents with upper-limb spasticity.
KW - Botulinum neurotoxin A
KW - Cerebral palsy
KW - IncobotulinumtoxinA
KW - Multipattern treatment
KW - Pediatric
KW - Spasticity
UR - http://www.scopus.com/inward/record.url?scp=85111603014&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85111603014&partnerID=8YFLogxK
U2 - 10.1016/j.pediatrneurol.2021.05.014
DO - 10.1016/j.pediatrneurol.2021.05.014
M3 - Article
C2 - 34339951
AN - SCOPUS:85111603014
VL - 123
SP - 10
EP - 20
JO - Pediatric Neurology
JF - Pediatric Neurology
SN - 0887-8994
ER -