Data from two European trials — a real-life study in Italy, and a long-term Czech trial looking at impact on cognition — supported the efficacy of a widely approved cannabinoid spray in treating moderate to severe spasticity (muscular stiffness or involuntary spasms) in multiple sclerosis (MS) patients who failed to benefit from other spasticity treatments.
Sativex, developed by GW Pharmaceuticals, is a formulated extract of the cannabis sativa plant, whose principal components are delta-9-tetrahydrocannibinol (THC) and cannabidiol (CBD) in a 1:1 ratio. The medication is approved in about two dozen countries — mostly across Europe but also in Canada, Israel, and Australia — as an add-on treatment to other anti-spasticity medications, like baclofen and tizanidine. It is not approved for MS patients in the U.S.
An oromucosal spray, Sativex is absorbed through the lining of the mouth.
The observational, ongoing trial in Italy involved an initial 1,650 patients being treated at 30 MS centers, making it the largest study of Sativex use to date, Francesco Patti, MD, an associate professor of neurology at the University of Catania, Italy, said in a presentation Wednesday at the 34th congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS).
Progressive MS patients made up 80 percent of this early group, which had a mean age of 51, and a median expanded disability status scale (EDSS) score of 6.5, indicating considerable disability (the higher the EDSS score, the worse the patient’s disability level).
“Very few of our patients [entered] with less than 2.5 EDSS,” Patti said. “Results are mainly in patients with aggressive MS and more severe spasticity,” involving pain, considerable loss of mobility, disrupted sleep, and bladder problems.
Of note, the data is preliminary, and Patti said he expects a “complete analysis” of a large group to be available in a few months.
Hundreds of clinic visits were involved in the study, and almost 19 percent of patients stopped treatment, about half for lack of effectiveness, Patti said. Another one-third discontinued because of poor tolerability to Sativex. But no serious safety concerns were reported related to treatment, he said.
After one month of use, a response to the treatment was seen in 1,432 people, measured as at least a 20% improvement on the 0-10 Numeric Rating Scale (NRS) scores for spasticity (the higher the NRS, the worse the pain). A smaller number, 405, showed at least a 30% improvement, a degree of change considered clinically important.
A total of 593 patients were evaluated at six months, with most — 522 — continuing to show a 20% improvement over baseline, and 252 showing a 30% or greater benefit in spasticity scores. Essentially, benefits seen at one month were confirmed at six months, Patti said.
Patients also chose to use Sativex repeatedly, taking about “six to seven puffs a day,” he added.
In the cognition study conducted largely in the Czech Republic, researchers were “happy to see absolutely no negative impact,” said Jolana Marková, head of the neurology department at Thomayer Hospital in Prague, who presented the data at ECTRIMS.
The 50-week study she led — which also followed an initial treatment period to determine responders to Sativex treatment — involved about 190 patients, regardless of MS subtype, who were given either Sativex oromucosal spray or a placebo as an add-on to standard anti-spasticity medication. All participants had treatment-resistant spasticity related to their disease.
“Long-term treatment with Sativex was not associated with cognitive decline or significant changes in mood in this prone population sample,” Marková said. “Moreover, Sativex demonstrated again that it was efficacious and well tolerated … and no new safety concerns were identified.”
According to Marková and her research team, Sativex was superior as an add-on in treating resistant spasticity in MS patients, compared with adjusting first-line spasticity treatment for better efficacy alone.
Moderate to severe spasticity is estimated to affect about 30 percent of all MS patients.