Dose response with onabotulinumtoxinA for post-stroke spasticity: A pooled data analysis

• Published in: Movement disorders 2011-02, Vol.26 (2), p.209-215
• Main Authors: Yablon, Stuart A., Brin, Mitchell F., VanDenburgh, Amanda M., Zhou, Jihao, Garabedian-Ruffalo, Susan M., Abu-Shakra, Susan, Beddingfield III, Frederick C.
• Format: Article
• Language: English
• Subjects: Ashworth Scale; Biological and medical sciences; Botulinum Toxins, Type A - administration & dosage; Botulinum Toxins, Type A - therapeutic use; Clinical Trials as Topic; dose response; Dose-Response Relationship, Drug; Humans; Medical sciences; Muscle Spasticity - etiology; Muscle Spasticity - therapy; Neurology; onabotulinumtoxinA; spasticity; Stroke - complications; Treatment Outcome; Vascular diseases and vascular malformations of the nervous system
• ISSN: 0885-3185; 1531-8257
• DOI: 10.1002/mds.23426

Clinical trials demonstrate that onabotulinumtoxinA reduces upper limb post‐stroke spasticity, with therapeutic response influenced by injected dose. Individual studies provide limited insight regarding muscle group‐specific dose–response relationships. Our objective was to characterize dose–response relationships between onabotulinumtoxinA and muscle tone in specific upper limb muscles. Individual patient data from seven multicenter, randomized, double‐blind, placebo‐controlled trials were pooled. Of 544 post‐stroke patients enrolled, 362 received onabotulinumtoxinA and 182 received placebo, injected into the flexor carpi radialis (FCR), flexor carpi ulnaris (FCU), flexor digitorum superficialis (FDS), flexor digitorum profundus (FDP), and/or biceps brachii (BB). Ashworth Scale score change at week 6 (AshworthCBL) was the primary outcome measure for muscle tone. For a broader analysis of response, AshworthCBL/onabotulinumtoxinA dosage relationships were characterized using three techniques: (1) AshworthCBL plotted as a function of onabotulinumtoxinA dose in Units (U) [dose–response curve]; (2) mean AshworthCBL per onabotulinumtoxinA dose depicting the responses seen with specific dose injection clusters/groups for each specific muscle group; and (3) onabotulinumtoxinA dose estimated to produce a mean 1‐point decrease in AshworthCBL as an indicator of clinically meaningful benefit of treatment. Increasing onabotulinumtoxinA doses produced greater AshworthCBLs (muscle tone improvements). The maximal week 6 response (Emax) model indicated a saturating dose–response relationship, with mean Emax AshworthCBL values of ‐1.48, ‐1.48, ‐0.63, ‐0.77, and ‐0.61 in the FCR, FCU, FDS, FDP, and BB, respectively. OnabotulinumtoxinA doses estimated to produce a mean 1‐point decrease in AshworthCBL were: 22.5U, 18.4U, 66.3U, 42.5U in the FCR, FCU, FDS, and FDP, respectively, and not determinable in the BB. These analyses demonstrate a saturating effect of greater muscle tone improvements with increasing onabotulinumtoxinA doses in post‐stroke spasticity patients. These findings suggest potentially effective onabotulinumtoxinA doses in selected muscle groups in this study population. © 2010 Movement Disorder Society.