• Sativex is an oromucosal spray containing cannabis-based medicinal products which is indicated as add-on treatment for symptom improvement in patients with moderate to severe spasticity due to multiple sclerosis who have not responded adequately to other anti-spasticity medication. Physicians should assess patients after four weeks of use. Only patients who achieve significant clinical benefit should continue treatment.
• There are three key randomised controlled trials. In each trial, Sativex was compared with placebo in patients maintained on their current anti-spasticity agents. The primary end-point was mean percentage change from baseline on a patient-reported numeric rating scale (NRS) of spasticity. This outcome measure was devised for Sativex trials and has been accepted as a valid measure of spasticity.
• Analysis of two parallel group studies showed that there was a significant difference between Sativex and placebo in the proportion of patients who achieved a clinically significant response on the NRS (35% vs 24%). The difference of 11% is small but considered to be clinically relevant in a population of patients who are difficult to treat.
• Evaluation of Sativex is hindered by the lack of published information on the third study which was designed to identify responders with a four week trial period reflecting use in clinical practice. At the end of 4 weeks of treatment with Sativex, 42% of patients satisfactorily met the threshold (≥ 20% reduction in NRS score) for predicting patients expected to achieve a clinically significant response in the long term and were randomised to receive Sativex or placebo for 3 months. Analysis of secondary outcomes from this 3 month period showed a significant difference in favour of Sativex with improvements in spasm frequency, sleep disruption and the Barthel index. Using the EQ-5D tool, an increase in utility of 20% was reported for responders to Sativex from the start of the study.
• There are no robust long term efficacy data. The longest trial is four months duration.
• Adverse events such as dizziness, fatigue, somnolence, vertigo and disorientation were reported commonly during clinical trials.
• There has been no previous published cost-effectiveness analysis assessing Sativex for the treatment of spasticity due to MS. We developed a decision-analytic model to estimate the cost-effectiveness of Sativex plus oral medicines compared to standard treatment in a UK cohort of adults who have moderate to severe spasticity due to MS and have achieved insufficient benefits from oral anti-spasticity medicines.
• In the base case, there was little difference in quality-adjusted life years (QALYs) gained between Sativex plus oral anti-spasticity agents and oral anti-spasticity agents alone. There was a large difference in costs with Sativex costing more. This resulted in an incremental cost-effectiveness ratio (ICER) of £48,588 per year.
• A probabilistic sensitivity analysis which examined all of the uncertainties of the data simultaneously was undertaken. The probability of Sativex being cost-effective at a chosen threshold of £30,000 per QALY was estimated at 11.08%.
• The price of Sativex has a large impact on the ICER. For Sativex to be considered cost-effective at a threshold of £30,000 per QALY, the cost per prescription of three bottle should be £229 or less, a reduction of £146 (38.9%) compared with the current price of £375.