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Nabiximols Effective and Well Tolerated for Patients Suffering From Refractory Spasticity in MS: Presented at ECTRIMS
By Chris Berrie
DÜSSELDORF, Germany -- September 14, 2009 -- The cannabinoid nabiximols is effective and well tolerated as an oromucosal spray for patients suffering from refractory spasticity because of multiple sclerosis (MS), according to research presented at the 25th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS).
In addition, nonresponders to nabiximols can be identified through a short therapeutic trial -- avoiding patient exposure to an ineffective treatment for prolonged periods of time, explained Judith Haas, MD, Principal Investigator for Germany, and Department of Neurology, Jewish Hospital, Berlin, Germany.
Muscle spasticity is a common problem for patients with MS, and can occur in up to 84% of patients, stated Dr. Haas. Much of the evidence for the benefits of cannabis is little more than anecdotal, she added, speaking here on September 11, so "a study was necessary to show that the efficacy is evidence based."
The objective of this study was to assess efficacy and safety of this nabiximols oromucosal spray in MS spasticity using an enriched study design. This started with a 4-week assessment treatment period (phase A) to identify patients who responded to nabiximols. The response threshold was set as a 20% or greater reduction in mean spasticity numerical rating scale (NRS) score.
Phase B was designed to run over 12 weeks, with the primary endpoint of mean change from baseline in spasticity NRS score.
In all, 572 patients with MS were enrolled in phase A. Upon completion of phase A, responders were randomised to placebo (n = 117) or to nabiximols (n = 124). Of these subjects, 115 and 109 completed phase B, respectively. In the treatment group, the mean dose of nabiximols was 8.3 sprays/day.
Baseline characteristics across the placebo and treatment groups were similar: mean age (48.1 vs 49.1 years, respectively); gender (female, 62% vs 58%); previous cannabis use in prior year (22% for each); duration of MS (11.8 vs 13.3 years) and of spasticity (6.7 vs 8.6 years); median Expanded Disability Status Scale (EDSS) score (6.0 vs 6.5); and spasticity NRS (3.92 vs 3.87).
The primary analysis of spasticity NRS observed significant benefit of active treatment over placebo (P = .0002). The secondary endpoint of spasm frequency also showed significant benefit for nabiximols over placebo (P < .005).
Secondary analyses that demonstrated significant treatment differences in favour of nabiximols over placebo were as follows: 30% responders (+0.23; P = .0003); sleep disruption NRS (-0.88; P < .0001); Bartel Activities of Daily Living index (+2.04; P = .0067); Subject Global Impression of Change (+1.70; P = .023); Clinical Global Impression of Change-impression of function (+2.40; P = .005); and Patient Global Impression of Change (+1.96; P = .005).
In phase A, adverse effects (AEs) were seen for 47% of the full patient population (268/572), with 92.5% of these being mild/moderate in severity, and with dizziness as the most common (14%).
Similarly, in phase B, AEs were experienced by 53% of the active treatment patients, with 89.0% as mild/moderate. Of note, no significant differences were seen between placebo and nabiximols treatment for the Beck Depression Inventory-II and for suicidal ideation.
With this formulation of nabiximols, concluded Dr. Haas, "the spasticity is influenced and ameliorated significantly, compared [with] the phase where the patients were treated with placebo. This positive outcome was also well supported by the secondary outcome measures."
The standardised formulation of nabiximols contains 2.7 mg delta(9)-tetrahydrocannabinol and 2.5 mg cannabinol per 100 mcL spray, with minor cannabinoids (5%-6%) and some other plant components.