OnabotulinumtoxinA for the Treatment of Poststroke Distal Lower Limb Spasticity: A Randomized Trial

Background: Poststroke distal lower limb spasticity impairs mobility, limiting activities of daily living and requiring additional caregiver time. Objective: To evaluate the efficacy, safety, and sustained benefit of onabotulinumtoxinA in adults with poststroke lower limb spasticity (PSLLS). Design: A multicenter, randomized, double-blind, phase 3, placebo-controlled trial (NCT01575054). Setting: Sixty study centers across North America, Europe, Russia, the United Kingdom, and South Korea. Patients: Adult patients (18-65 years of age) with PSLLS (Modified Ashworth Scale [MAS] >= 3) of the ankle plantar flexors and the most recent stroke >= 3 months before study enrollment. Interventions: During the open-label phase, patients received <= 3 onabotulinumtoxinA treatments (>= 400 U) or placebo at approximately 12-week intervals. Treatments were into the ankle plantar flexors (onabotulinumtoxinA 300 U into ankle plantar flexors; >= 100 U, optional lower limb muscles). Main Outcome Measurements: The double-blind primary endpoint was MAS change from baseline (average score at weeks 4 and 6). Secondary measures included physician-assessed Clinical Global Impression of Change (CGI), MAS change from baseline in optional muscles, Goal Attainment Scale (GAS), and pain scale. Results: Of 468 patients enrolled, 450 (96%) completed the double-blind phase and 413 (88%) completed the study. Small improvements in MAS observed with onabotulinumtoxinA during the double-blind phase (onabotulinumtoxinA, -0.8; placebo, -0.6, P = .01) were further enhanced with additional treatments through week 6 of the third open-label treatment cycle (onabotulinumtoxinA/onabotulinumtoxinA, -1.2; placebo/onabotulinumtoxinA, -1.4). Small improvements in CGI observed during the double-blind phase (onabotulinumtoxinA, 0.9; placebo, 0.7, P = .01) were also further enhanced through week 6 of the third open-label treatment cycle (onabotulinumtoxinA/onabotulinumtoxinA, 1.6; placebo/onabotulinumtoxinA, 1.6). Physician- and patient-assessed GAS scores improved with each subsequent treatment. No new safety signals emerged. Conclusions: OnabotulinumtoxinA significantly improved ankle MAS, CGI, and GAS scores compared with placebo; improvements were consistent and increased with repeated treatments of onabotulinumtoxinA over 1 year in patients with PSLLS.