Muscle Selection and Dosing in a Phase 3, Pivotal Study of AbobotulinumtoxinA Injection in Upper Limb Muscles in Children With Cerebral Palsy.

Autor:	Oleszek J; Department of Physical Medicine and Rehabilitation, University of Colorado and Children's Hospital Colorado, Aurora, IL, United States., Tilton A; LSUHSC and Children's Hospital New Orleans, New Orleans, LA, United States., Carranza Del Rio J; Hospital San José Celaya, Celaya, Mexico., Dursun N; Department of Physical Medicine and Rehabilitation, Faculty of Medicine, Kocaeli University, Izmit, Turkey., Bonikowski M; Mazovian Neuropsychiatry Center, Warsaw, Poland., Dabrowski E; Beaumont Health, Oakland University School of Medicine, Grosse Pointe, MI, United States., Page S; Ipsen, Slough, United Kingdom., Regnault B; Consultant to Ipsen, Boulogne-Billancourt, France., Thompson C; June Pharma Consultant to Ipsen, Boulogne-Billancourt, France., Delgado MR; Southwestern Medical Center, Scottish Rite Hospital for Children, University of Texas, Dallas, TX, United States.
Jazyk:	angličtina
Zdroj:	Frontiers in neurology [Front Neurol] 2021 Oct 29; Vol. 12, pp. 728615. Date of Electronic Publication: 2021 Oct 29 (Print Publication: 2021).
DOI:	10.3389/fneur.2021.728615
Abstrakt:	Background: Guidelines recommend botulinum toxin-A in pediatric upper limb spasticity as part of routine practice. Appropriate dosing is a prerequisite for treatment success and it is important that injectors have an understanding on how to tailor dosing within a safe and effective range. We report upper limb dosing data from a phase 3 study of abobotulinumtoxinA injections in children with cerebral palsy. Methods: This was a double-blind, repeat-treatment study (NCT02106351). In Cycle 1, children were randomized to abobotulinumtoxinA at 2 U/kg control dose or clinically relevant 8 U/kg or 16 U/kg doses. Doses were divided between the primary target muscle group (PTMG, wrist or elbow flexors) and additional muscles tailored to clinical presentation. During Cycles 2-4, children received doses of 8 U/kg or 16 U/kg and investigators could change the PTMG and other muscles to be injected. Injection of muscles in the other upper limb and lower limbs was also permitted in cycles 2-4, with the total body dose not to exceed 30 U/kg or 1,000 U (whichever was lower) in the case of upper and lower limb treatment. Results: 212 children were randomized, of which 210 received ≥1 abobotulinumtoxinA injection. Per protocol, the elbow and wrist flexors were the most commonly injected upper limb muscles. Across all 4 cycles, the brachialis was injected in 89.5% of children (dose range 0.8-6 U/kg), the brachioradialis in 83.8% (0.4-3 U/kg), the flexor carpi ulnaris in 82.4% (0.5-3 U/kg) and the flexor carpi radialis in 79.5% (0.5-4 U/kg). Other frequently injected upper limb muscles were the pronator teres(70.0%, 0.3-3 U/kg). adductor pollicis (54.3%, 0.3-1 U/kg), pronator quadratus (44.8%, 0.1-2 U/kg), flexor digitorum superficialis (39.0%, 0.5-4 U/kg), flexor digitorum profundus (28.6%, 0.5-2 U), flexor pollicis brevis/opponens pollicis (27.6%, 0.3-1 U/kg) and biceps (27.1%, 0.5-6 U/kg). AbobotulinumtoxinA was well-tolerated at these doses; muscular weakness was reported in 4.3% of children in the 8 U/kg group and 5.7% in the 16 U/kg group. Conclusions: These data provide information on the pattern of injected muscles and dose ranges used in this study, which were well-tolerated. Per protocol, most children received injections into the elbow and wrist flexors. However, there was a wide variety of other upper limb muscles injected as physicians tailored injection patterns to clinical need. Competing Interests: This study was funded by Ipsen. The authors employed or contracted by Ipsen SP, BR, and CT were involved in interpretation of the data; and in review, approval of, and decision to submit the manuscript. The funder had no other role in study conduct or preparation of this report. JO, AT, JC, ND, MB, ED, and MD were investigators in Ipsen-sponsored clinical trials and they or their institutions have received payment for participation. In addition, JO reports consultancy fees for Ipsen and Allergan. AT reports research support and educational grants from Ipsen and personal fees for consultancy from Ipsen. JC reports personal fees for consultancy and speaking from Ipsen. ND reports research support from Ipsen, Allergan, and Merz and personal fees for consultancy and speaking from Ipsen and Allergan. MB reports research support from Ipsen, Allergan, and Merz and personal fees for consultancy and speaking from Ipsen and Allergan. ED reports personal fees from Ipsen and Allergan for speaking, Solstice Neurosciences for consultancy and serves on a US speaker bureau. MD reports personal fees from Ipsen, Allergan and Kashiv Pharma for consultancy. (Copyright © 2021 Oleszek, Tilton, Carranza del Rio, Dursun, Bonikowski, Dabrowski, Page, Regnault, Thompson and Delgado.)
Databáze:	MEDLINE
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