Efficacy of nabiximols oromucosal spray on spasticity in people with multiple sclerosis: Treatment effects on Spasticity Numeric Rating Scale, muscle spasm count, and spastic muscle tone in two randomized clinical trials.
Nicholas et al.·Multiple Sclerosis and Related DisordersImpact 2.2
Nabiximols led to significant improvements in spasticity versus placebo across all measured parameters (Spasticity NRS, Spasm Count, MAS) over 12 weeks.
Summary
Two enriched-responder RCTs (GWSP0604, SAVANT) with pooled analysis of nabiximols oral spray in MS spasticity; mean NRS improvement versus placebo -0,36 to -0,89 (GWSP0604) and -0,52 to -1,96 (SAVANT); spasm reduction 19–35% vs. placebo; significant MAS improvement with nabiximols, especially in 6 key muscle groups of the lower extremity (-0,16 to -0,37), sustained over 12 weeks.
P
PopulationAdults with multiple sclerosis and spasticity (responder-enriched sample, ≥20% NRS improvement during run-in phase); two RCTs (GWSP0604 and SAVANT), pooled analysis
I
InterventionNabiximols oromucosal spray (THC/CBD), titrated over 12 weeks
C
ControlPlacebo spray
O
OutcomeSignificantly greater reduction in mean daily Spasticity NRS score for nabiximols vs. placebo (difference -0,36 to -0,89 in GWSP0604; -0,52 to -1,96 in SAVANT); spasm count reduction 19–35% versus placebo; improved Modified Ashworth Scale (MAS) score in favor of nabiximols, especially lower extremities (-0,16 to -0,37)
Confidence in the evidence
Very lowLowModerateHigh
High
The highest of four GRADE levels, the effect estimate is very reliable.
Quality profile
Sample size★★★★★
BlindingDouble-blind
Effect sizeClear benefit
Citations / year★★★★★
Authors
Nicholas J, Lublin F, Klineova S, Berwaerts J, Chinnapongse R, Checketts D, Javaid S, Steinerman JR
To provide a comprehensive assessment of the treatment effects of nabiximols oromucosal spray on multiple sclerosis spasticity in two clinical trials, GWSP0604 and SAVANT. Both studies enriched for responders before randomization, defined by a ≥20% improvement in Spasticity 0-10 numeric rating scale (NRS) score. Additionally, SAVANT used randomized re-titration following washout. Spasticity NRS outcomes, spasm count, and modified Ashworth scale (MAS) scores were analyzed. Mean change from baseline in average daily Spasticity NRS scores was significantly larger for nabiximols than placebo at all postbaseline timepoints, ranging from -0.36 to -0.89 in GWSP0604 and -0.52 to -1.96 in SAVANT. Percent reduction in geometric mean change from baseline in average daily spasm count for nabiximols ranged from 19-35% versus placebo. A treatment difference favoring nabiximols was observed in overall MAS scores during the randomized part of each study. Treatment effect was larger for combinations of lower limb muscle groups (ranging between -0.16 and -0.37). Nabiximols leads to improvement in spasticity that was sustained over the 12-week treatment period as measured by average daily Spasticity NRS scores, daily spasm counts, and MAS scores for combinations of muscle groups, especially the combination of the 6 key muscle groups in the lower limbs in NRS responders to nabiximols treatment.