Background
Spasticity is a common symptom for people with multiple sclerosis (MS), and increases in prevalence and severity throughout the disease course. Worsening spasticity is associated with impaired mobility and other symptoms and negatively impacts quality of life, increasing health resource utilization and costs. Nabiximols oromucosal spray, containing mainly tetrahydrocannabinol (THC) and cannabidiol (CBD), and also other CBD and non-CBD components is approved in >25 countries outside of the US as add-on therapy in people with moderate-to-severe MS spasticity who do not respond adequately to other antispasticity medications.
Objectives
To evaluate the efficacy and safety of nabiximols spray as add-on therapy to antispasticity treatment in people with moderate to severe treatment-resistant MS spasticity.Methods
The review was undertaken following principles published by the Centre for Reviews and Dissemination. A comprehensive search of Medline, Embase, and Cochrane Library databases was conducted. Randomised controlled trials (RCTs) and non-randomised trials investigating the effect of adding nabiximols to standard antispasticity treatment in people with moderate-to-severe MS spasticity were included. Evaluated outcomes included proportion of patients with improvement (≥30%) in Numeric Rating Scale (NRS) spasticity, mean change in NRS spasticity, quality of life, adverse events. When appropriate data were pooled using meta-analysis.Results
A total of 7 RCTs with 1,570 participants were eligible for inclusion. Studies scored low risk of bias. Of these studies, data from 4 studies (468 participants) evaluated nabiximols within the approved dose, 1–12 sprays/day: 2 (n=347) were appropriate for pooling (after a 4-week single-blind period, almost half of the enrolled participants met early response criterion [improvement of ≥20%, label condition] and were randomised). Of these early responders, a greater proportion of patients were clinically relevant responders (≥30% NRS improvement) with nabiximols than placebo at the end of a 12-week double-blind period (pooled: 75% vs 45%, RR 0.55 [0.33, 0.92]), with a statistically significant reduction in mean NRS spasticity (NRS 0-10) from baseline compared with placebo (pooled: mean difference -1.30 [-2.33, -0.27]). Adverse events were generally mild-to-moderate in severity, transient and rarely required treatment discontinuation. One systematic review of non-randomised studies was identified which reported results in line with those from RCTs.Conclusions
Add-on nabiximols provides clinically relevant improvement of MS spasticity in patients who do not respond adequately to antispasticity medications both in clinical trial and daily practice settings.