Background: Muscle spasticity is common in multiple sclerosis (MS), occurring in more than 60% of patients. Objective: To compare Sativex with placebo in relieving symptoms of spasticity due to MS. Methods: A 15-week, multicenter, double-blind, randomized, placebo-controlled, parallel-group study in 337 subjects with MS spasticity not fully relieved with current anti-spasticity therapy. Results: The primary endpoint was a spasticity 0–10 numeric rating scale (NRS). Intention-to-treat (ITT) analysis showed a non-significant improvement in NRS score, in favor of Sativex. The per protocol (PP) population (79% of subjects) change in NRS score and responder analyses (≥30% improvement from baseline) were both significantly superior for Sativex, compared with placebo: −1·3 versus −0·8 points (change from baseline, p=0·035); and 36% versus 24% (responders, p=0·040). These were supported by the time to response (ITT: p=0·068; PP: p=0·025) analyses, carer global impression of change assessment (p=0·013) and timed 10-meter walk (p=0·042). Among the subjects who achieved a ≥30% response in spasticity with Sativex, 98, 94 and 73% reported improvements of 10, 20 and 30%, respectively, at least once during the first 4 weeks of treatment. Sativex was generally well tolerated, with most adverse events reported being mild-to-moderate in severity. Discussion and conclusions: The 0–10 NRS and responder PP analyses demonstrated that Sativex treatment resulted in a significant reduction in treatment-resistant spasticity, in subjects with advanced MS and severe spasticity. The response observed within the first 4 weeks of treatment appears to be a useful aid to prediction of responder/non-responder status.

Background/Objectives: Calf muscle hypertonicity following stroke may impair walking rehabilitation. The aim of this study was to assess botulinum toxin (Dysport^®) in post-stroke calf spasticity. Methods: A prospective, multicentre, double-blind, placebo-controlled, dose-ranging study was performed to evaluate dysport at 500, 1,000 or 1,500 units in 234 stroke patients. They were assessed at 4-week intervals over 12 weeks. Results: The primary outcome measure, 2-min walking distance and stepping rate increased significantly in each group (p < 0.05, paired test), but there was no significant difference between groups (including placebo). Following dysport treatment, there were small but significant (p = 0.0002–0.0188) improvements in calf spasticity, limb pain, and a reduction in the use of walking aids, compared to placebo. Investigators’ and patients’ assessments of overall benefit suggested an advantage for dysport over placebo, but this was not significant. Sixty-eight patients reported 130 adverse events, with similar numbers in each group. The few severe events recorded were not considered to be treatment-related. Conclusion: Dysport resulted in a significant reduction in muscle tone, limb pain and dependence on walking aids. The greatest benefits were in patients receiving dysport 1,500 units, but 1,000 units also had significant effects. Dysport 500 units resulted in some improvements. Since few adverse events were reported, this therapy is considered safe and may be a useful treatment in post-stroke rehabilitation of the leg. Possible reasons why functional improvements in gait parameters were not observed are also discussed.