Contributions
Abstract: P1862
Type: Poster
Abstract Category: Late breaking news
Aims: To evaluate the efficacy of Sativex (tetrahydrocannabinol [THC]:cannabidiol [CBD] oromucosal spray) as add-on compared to further optimized standard antispastic therapy with oral baclofen and/or tizanidine and/or dantrolene (alone or combined) in multiple sclerosis (MS) patients with moderate to severe spasticity who have not gained adequate relief through 2 optimized standard antispastic drugs. Secondarily, to evaluate the effect of Sativex on spasticity, associated symptoms and tolerability.
Methods: European, prospective multicenter, parallel group, randomized, double-blind, placebo controlled study, with a first single-blind, non-randomized Sativex trial phase (4 weeks (wks) period, Phase A) to identify initial responders (Minimal Clinically Important Diff., MCID, defined as ≥20% improvement in the 0-10 NRS MS spasticity score (NRS-SS)), followed by a 1 to 4 wks washout period between trial phase and randomized phase, where initial responders were required to return to a ≥80% of their baseline NRS-SS score for qualifying for a 12 wks placebo controlled randomized phase (Phase B). Both phases included up-titration; all antispastic medication doses could be adjusted throughout the study.Primary endpoint: % of MS spasticity responders after 12 wks of randomized treatment. Response (Clinically Important Diff, CID) defined as NRS-SS improvement of ≥30% from Phase B start. Secondary variables: other measurements of spasticity and associated symptoms, tolerability.
Results: 191 patients enrolled at 15 sites (14 CZ, 1 AT) in the trial Phase A. 70% female, mean age 51y, mean EDSS = 5.9, mean NRS-SS = 6.4. 70.5% (n=134) were initial responders after 4 wks trial period. 79.1% (n=106) returned to initial NRS-SS in the wash-out period and were randomized (n=53 Sativex, n=53 placebo). After 12 wks the CID responder rate was 77.4% vs 32.1% in favour of Sativex (ITT, p< 0.0001, OR = 7.1, CI:2.9-16.7), with first line medications adjustments in both groups. Mean Sativex dose: 7.3 sprays/d (wk 12). At 12 wk there were also significant improvements in favour of Sativex in the mean changes from phase B start in: NRS-SS:-3.5 vs -1.6 (ITT; p< 0.0001), pain NRS:-3.2 vs -1.8 (ITT; p=0.0013), and mod. Ashworth scale:-0.3 vs -0.06 (ITT; p=0.0007). 22.6 and 13.2% of patients reported AEs, all mild or moderate but 1 placebo. No related SAEs.
Conclusions: Adding Sativex is more efficacious to improve resistant MS spasticity than only readjusting first line antispastic drugs.
Disclosure: Study funded by Almirall S.A., Barcelona, Spain
Abstract: P1862
Type: Poster
Abstract Category: Late breaking news
Aims: To evaluate the efficacy of Sativex (tetrahydrocannabinol [THC]:cannabidiol [CBD] oromucosal spray) as add-on compared to further optimized standard antispastic therapy with oral baclofen and/or tizanidine and/or dantrolene (alone or combined) in multiple sclerosis (MS) patients with moderate to severe spasticity who have not gained adequate relief through 2 optimized standard antispastic drugs. Secondarily, to evaluate the effect of Sativex on spasticity, associated symptoms and tolerability.
Methods: European, prospective multicenter, parallel group, randomized, double-blind, placebo controlled study, with a first single-blind, non-randomized Sativex trial phase (4 weeks (wks) period, Phase A) to identify initial responders (Minimal Clinically Important Diff., MCID, defined as ≥20% improvement in the 0-10 NRS MS spasticity score (NRS-SS)), followed by a 1 to 4 wks washout period between trial phase and randomized phase, where initial responders were required to return to a ≥80% of their baseline NRS-SS score for qualifying for a 12 wks placebo controlled randomized phase (Phase B). Both phases included up-titration; all antispastic medication doses could be adjusted throughout the study.Primary endpoint: % of MS spasticity responders after 12 wks of randomized treatment. Response (Clinically Important Diff, CID) defined as NRS-SS improvement of ≥30% from Phase B start. Secondary variables: other measurements of spasticity and associated symptoms, tolerability.
Results: 191 patients enrolled at 15 sites (14 CZ, 1 AT) in the trial Phase A. 70% female, mean age 51y, mean EDSS = 5.9, mean NRS-SS = 6.4. 70.5% (n=134) were initial responders after 4 wks trial period. 79.1% (n=106) returned to initial NRS-SS in the wash-out period and were randomized (n=53 Sativex, n=53 placebo). After 12 wks the CID responder rate was 77.4% vs 32.1% in favour of Sativex (ITT, p< 0.0001, OR = 7.1, CI:2.9-16.7), with first line medications adjustments in both groups. Mean Sativex dose: 7.3 sprays/d (wk 12). At 12 wk there were also significant improvements in favour of Sativex in the mean changes from phase B start in: NRS-SS:-3.5 vs -1.6 (ITT; p< 0.0001), pain NRS:-3.2 vs -1.8 (ITT; p=0.0013), and mod. Ashworth scale:-0.3 vs -0.06 (ITT; p=0.0007). 22.6 and 13.2% of patients reported AEs, all mild or moderate but 1 placebo. No related SAEs.
Conclusions: Adding Sativex is more efficacious to improve resistant MS spasticity than only readjusting first line antispastic drugs.
Disclosure: Study funded by Almirall S.A., Barcelona, Spain