A randomized, double-blind, placebo-controlled trial to evaluate the effect of nabiximols oromucosal spray on clinical measures of spasticity in patients with multiple sclerosis.
Bethoux et al.·Multiple Sclerosis and Related DisordersImpact 2.2
Nabiximols showed no significant benefit over placebo on the primary endpoint (MAS LLMT-6 change): treatment difference 0,04 (P=0,7152).
Summary
Phase III RCT (n=68, crossover, multicenter, double-blind) of nabiximols vs. placebo in MS-associated spasticity; primary endpoint MAS LLMT-6 not met: LS-mean difference 0,04 (p=0,7152). Secondary MAS LLMT-4 values also showed no significant group difference. Safety profile consistent with the known nabiximols profile.
P
PopulationAdults with multiple sclerosis and spasticity, n=68
I
InterventionNabiximols (THC:CBD) oral spray, adjunctive, up to 21 days per period
C
ControlPlacebo spray
O
OutcomeNo significant improvement in spastic muscle stiffness (MAS LLMT-6): LS-mean difference nabiximols vs. placebo = 0,04 (p = 0,7152)
Confidence in the evidence
Very lowLowModerateHigh
Moderate
The third of four GRADE levels, the effect estimate is probably reliable.
Downgraded for
Imprecision
Quality profile
Sample size★★★★★
BlindingDouble-blind
Effect sizeNo benefit
Citations / year★★★★★
Authors
Bethoux FA, Farrell R, Checketts D, Sahr N, Berwaerts J, Alexander JK, Skobieranda F
Spasticity is a common and potentially debilitating symptom of multiple sclerosis (MS) with a highly variable presentation. Understanding, quantifying, and managing MS-associated spasticity (MSS) is a challenge for research and in clinical practice. The tetrahydrocannabinol:cannabidiol oromucosal spray nabiximols has demonstrated beneficial effects in the treatment of MSS in clinical studies as well as real-world observational studies, and is approved for the treatment of MSS in 29 countries globally. Most randomized studies evaluated the efficacy of nabiximols using the change in average daily spasticity scores reported by patients using the spasticity Numeric Rating Scale as a primary endpoint. This study, RELEASE MSS1 (NCT04657666), was conducted using a prespecified primary endpoint of change in spastic muscle tone (Modified Ashworth Scale Lower Limb Muscle Tone-6 [MAS LLMT-6]) to corroborate the efficacy of nabiximols as adjunctive therapy observed with the patient-measured spasticity Numeric Rating Scale primary endpoint in the previous pivotal studies. This was a phase 3, multicenter, randomized, double-blind, placebo-controlled, 2-treatment, 2-period, crossover trial. Of 68 patients enrolled, 33 were assigned to nabiximols followed by placebo and 35 were assigned to placebo followed by nabiximols. Least squares mean changes in MAS LLMT-6 scores from baseline to day 21 were -0.23 for nabiximols and -0.26 for placebo; the least squares mean treatment difference in MAS LLMT-6 scores for nabiximols versus placebo was 0.04, which was not statistically significant (P = 0.7152). Mean changes in MAS LLMT-4 scores from baseline to day 21 also were not significantly different between the nabiximols and placebo groups. Safety results in this study were consistent with the known safety profile of nabiximols in patients with MSS. Despite the established efficacy of nabiximols in MSS observed using patient-reported measures, the primary endpoint was not met in this study.