Impact of early intervention with onabotulinumtoxinA treatment in adult patients with post-stroke lower limb spasticity: results from the double-blind, placebo-controlled, phase 3 REFLEX study.

The aim of this study in patients with post-stroke lower limb spasticity (PSLLS) was to evaluate the relationship between time of onabotulinumtoxinA treatment relative to stroke and efficacy outcomes. This was a phase 3, international, multicenter, randomized, 12-week, double-blind study, followed by a repeated treatment, open-label extension. Patients were aged 18-85 years with PSLLS (Modified Ashworth Scale [MAS] ≥ 3) of the ankle with the most recent stroke occurring ≥ 3 months before screening. Patients (double-blind phase) were randomized (n = 468) to onabotulinumtoxinA 300-400 U (300 U, mandatory ankle muscles (gastrocnemius, soleus, tibialis posterior); and ≤ 100 U, optional lower limb muscles (flexor digitorum longus, flexor hallucis longus, flexor digitorum brevis, extensor hallucis, and rectus femoris]) or placebo. Primary endpoint: MAS change from baseline (average score of weeks 4 and 6). Secondary endpoints: physician-assessed Clinical Global Impression of Change (CGI) average score of weeks 4 and 6 and physician-assessed Goal Attainment Scale (GAS; active and passive, weeks 8 and 12). When stratified by time since stroke (≤ 24 months, n = 153; > 24 months, n = 315, post hoc), patients treated ≤ 24 months post-stroke experienced greater improvements from baseline versus placebo in MAS (- 0.31 vs - 0.17), CGI (0.49 vs 0.12), and passive GAS scores (week 12, 0.37 vs 0.26). A ≥  - 1-point improvement in active (week 12; p = 0.04) and passive (week 8; p = 0.02) GAS scores versus placebo was achieved by more patients treated ≤ 24 months post-stroke; in patients treated > 24 months post-stroke, improvements were only observed in active scores (week 8; p = 0.04). OnabotulinumtoxinA 300-400 U was well tolerated, with no new safety findings.