Muscle spasticity is a common clinical problem in about 60% of patients with multiple sclerosis (MS) often leading to considerable distress.
Methods: A 15 week, multi-centre, double blind, randomized, placebo controlled parallel group study was undertaken to evaluate the efficacy of standardised whole plant cannabis medicine (Sativex®) in patients with MS. After a 7 day baseline period, 337 subjects were randomised to receive either Sativex or placebo. The endpoints included change in mean spasticity NRS score, spasticity NRS at clinic visits, Modified Ashworth Scale, timed 10 metre walk, Barthel activities of daily living, carer global impression of change (CGIC), quality of life questionnaires, EQ-5D and MSQoL-54, sleep quality, review of pain, tremor and fatigue, spasm severity and bladder symptoms.
Results: For the primary endpoint, the mean NRS spasticity scores showed a statistically significant treatment difference of -0.46 points in favour of Sativex in the per protocol (PP) population (p=0.035; 95% Cl: -0.88, -0.03). The intention to treat (ITT) population showed a trend in favour of Sativex with a treatment difference of -0.23 points (p=0.219; 95%Cl: -0.59, 0.14). In the PP population 36% of patients achieved at least a 30% improvement in spasticity NRS with an odds ratio of 1.74 (95% Cl: 0.005, 0.266). This trend was also observed in the ITT population with an odds ratio of 1.34 in favour of Sativex. These findings were supported by the CGIC assessment which was strongly in favour of Sativex (Odds ratio 1.25, p=0.270; 95% Cl: 0.84, 1.85).
The following secondary endpoints showed trends in favour of Sativex: spasticity and sleep assessments at clinic visits, Modified Ashworth Scale; timed 10-metre walk, quality of life questionnaire EQ-5D, sleep quality, review of pain, tremor, spasm severity and bladder symptoms.
When the data from this and a previous study were pooled, a statistically significant difference in spasticity in favour of Sativex was seen in the ITT population (-0.34, 95% Cl: -0.64, -0.04, p=0.027).
Conclusions: The patients randomized in this study exhibited severe levels of spasticity despite ongoing treatment with the best available anti-spasticity treatments. In the PP population the reduction in symptoms of spasticity in the Sativex-treated group was statistically significant. This did not extend to the ITT populations but in this, and other secondary endpoints, the outcomes were in favour of Sativex.