Dose response with onabotulinumtoxinA for post-stroke spasticity: a pooled data analysis.
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 (E(max)) model indicated a saturating dose-response relationship, with mean E(max) 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.
Yablon
Stuart A
SA
Baylor Institute for Rehabilitation, Dallas, Texas 75246, USA. doctory@earthlink.net
Brin
Mitchell F
MF
VanDenburgh
Amanda M
AM
Zhou
Jihao
J
Garabedian-Ruffalo
Susan M
SM
Abu-Shakra
Susan
S
Beddingfield
Frederick C
FC
D019274:Botulinum Toxins, Type A / Q000008:administration & dosage / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D004305:Dose-Response Relationship, Drug; D006801:Humans; D009128:Muscle Spasticity / Q000209:etiology / Q000628:therapy*; D020521:Stroke / Q000150:complications*; D016896:Treatment Outcome
D019274:Botulinum Toxins, Type A