A placebo-controlled, parallel-group, randomized withdrawal study of subjects with symptoms of spasticity due to multiple sclerosis who are receiving long-term Sativex® (nabiximols)

• Published in: Multiple sclerosis Vol. 18; no. 2; pp. 219 - 228
• Main Authors: Notcutt, W, Langford, R, Davies, P, Ratcliffe, S, Potts, R
• Format: Journal Article
• Language: English
• Published: London, England SAGE Publications 01.02.2012; Sage Publications; Sage Publications Ltd
• Subjects: Aged; Biological and medical sciences; Cannabidiol; Cannabinoids - administration & dosage; Cannabinoids - adverse effects; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Dronabinol; Drug Combinations; Female; Humans; Kaplan-Meier Estimate; Male; Medical sciences; Middle Aged; Multiple sclerosis and variants. Guillain barré syndrome and other inflammatory polyneuropathies. Leukoencephalitis; Multiple Sclerosis, Chronic Progressive - complications; Multiple Sclerosis, Chronic Progressive - drug therapy; Multiple Sclerosis, Relapsing-Remitting - complications; Multiple Sclerosis, Relapsing-Remitting - drug therapy; Muscle Spasticity - diagnosis; Muscle Spasticity - drug therapy; Muscle Spasticity - etiology; Neurology; Placebos; Plant Extracts - administration & dosage; Plant Extracts - adverse effects; Substance Withdrawal Syndrome - diagnosis; cannabidiol; delta-9-tetrahydrocannabinol; multiple sclerosis; cannabinoids; Sativex; endocannabinoid system; nabiximols; spasticity; Human; Nervous system diseases; Multiple sclerosis; Spasticity; Muscle tonus alteration; Cannabinoid; Long term; Inflammatory disease; Striated muscle disease; Central nervous system disease; Placebo; Degenerative disease; Neurological disorder
• ISSN: 1352-4585; 1477-0970; 1477-0970
• DOI: 10.1177/1352458511419700

Background: Open-label studies are not ideal for providing robust evidence for long-term maintenance of efficacy of medicines, especially where medicines provide symptom relief and where long-term use of a placebo may be problematic and not ethical. Objective: To evaluate the maintenance of efficacy of Sativex in subjects who have gained long-term symptomatic relief of spasticity in multiple sclerosis (MS), and to assess the impact of sudden medicine withdrawal. Methods: An enriched enrolment randomized withdrawal study design was used. Eligible subjects with ongoing benefit from Sativex for at least 12 weeks entered this 5-week placebo-controlled, parallel-group, randomized withdrawal study. Each subjects’ previous effective and tolerated dose was continued. Results: A total of 18 subjects per group were enrolled. Demographics showed a mean duration of MS of 16.4 years, spasticity 12.7 years, mean duration of Sativex use of 3.6 years (median 3.4 years) and a mean daily dose of 8.25 sprays. Primary outcome of time to treatment failure was significantly in favour of Sativex (p = 0.013). Secondary endpoints showed significant changes in the Carer and Subject’s Global Impression of Change scales in favour of Sativex. Conclusions: Maintenance of Sativex efficacy in long-term symptomatic improvement of spasticity to a group of subjects with MS has been confirmed using this study design.