VANCOUVER, BC—For patients with post-stroke lower limb spasticity, repeated injections of onabotulinumtoxinA over 1 year resulted in sustained benefit, final results from a Phase 3 trial presented at the 68th Annual AAN Meeting have found.
Improvements in the Modified Ashworth Scale (MAS) and Clinical Global Impression of Change (CGI) scores observed during the double-blind phase continued during the open-label phase, during which physician- and patient-rated improvements in function tended to increase with repeated treatments, said Theodore H. Wein, MD, of McGill University Department of Neurology and Neurosurgery, Montreal General Hospital, Montreal, Quebec, Canada.
The multicenter trial randomly assigned patients to a 12-week double-blind phase of placebo or onabotulinumtoxinA 300U in the mandatory ankle muscles, with an additional ≤100U in optional muscles, followed by an open-label phase, during which patients could receive up to 3 onabotulinumtoxinA treatments at 12, 24, and 36–42 weeks. The primary endpoint was average change at Week 4 for MAS; key secondary endpoints were CGI and Goal Attainment Scale (GAS).
Of the 468 patients enrolled, 450 (96%) completed the double-blind phase and 413 (88%), the open-label phase. A total of 364 patients (78%) received 3 open-label treatments. Baseline demographics and disease characteristics were similar between groups. Mean age was 57.0 years in the placebo arm and 56.0 years in the onabotulinumtoxinA arm; 66.0% and 63.5% were men and 63.8% and 68.7% had moderate stroke severity, respectively.
“During the double-blind phase, the mean MAS change from baseline for the average of Weeks 4 and 6 was significantly greater with onabotulinumtoxinA vs. placebo, -0.8 vs. -0.6 (P=0.01),” Dr. Wein said. Further improvements in ankle MAS were observed with repeated treatments during the open-label phase.
Results also showed CGI score improvements in the double-blind phase by physician for the average of Weeks 4 and 6 that was significantly higher for onabotulinumtoxinA vs placebo, 0.9 vs.. 0.7 (P=0.01), which continued throughout the open-label phase to Week 60. Additionally, with each subsequent treatment, physician- and patient-assessed GAS scores and percentage of responders improved.
The mandatory ankle muscles injected were the gastrocnemius medial and lateral heads, the soleus, and the tibialis posterior. Optional lower limb muscles were the flexor digitorum longus and brevis, the flexor hallucis longus, the extensor hallucis, and the rectus femoris.
No new safety signals were identified, and the majority of the treatment-emergent adverse events in the double-blind phase were mild or moderate in severity. These included pain in extremity, nasopharyngitis, arthralgia, fall, back pain, and injection site pain. During the open-label phase, the incidence of events decreated with successive treatment cycles, he concluded.
Disclosure: Dr. Wein and other study coauthors received funds from Allergan plc for consultancy, research, and speaking.