Cannabis MS Treatment Doubts In Review Of Sativex

There is no strong evidence to back the use of cannabis extract in the treatment of multiple sclerosis (MS), it was claimed.

A review of evidence on the first licensed preparation, Sativex, said there were "limitations" which made it difficult to identify the place of the product in clinical practice.

Sativex, in the form of a mouth spray, contains the principal extracts - dronabinol and cannabidiol - found in the leaf and flower of the cannabis plant, and is the first cannabinoid preparation to be licensed for use in the treatment of muscle spasms in MS.

The review, in the December issue of Drug and Therapeutics Bulletin (DTB), published by BMJ Journals, says MS is estimated to affect around 60,000 people in England and Wales, and around one in every 1,000 people will develop the condition in the UK.

An increase in muscle tone, or spasticity, is a common symptom of the condition, causing involuntary spasms, immobility, disturbed sleep, and pain.

Complex combinations of drugs are sometimes needed to manage spasticity, but they do not work that well and have a range of unpleasant side-effects, the DTB says.

Sativex is intended for use as a second-line treatment in patients in whom these other options have failed. But the review said the trial data on which the success of Sativex is based are limited.

Overall, the trials, on which the drug's approval was based, did show a small difference in the numbers of patients in whom symptoms abated compared with those taking a dummy (placebo) preparation, it said.

But in many of these studies, Sativex was used for relatively short periods - from six weeks to four months. And none included an active ingredient with which the effects of Sativex could be compared.

Two of the trials included doses that exceeded the 12 daily sprays for which the preparation is licensed, it said, and one trial did not have sufficient numbers of participants to validate the results.

A third trial, which was properly designed, and did have sufficient numbers of participants, did not find any significant difference in symptom relief between those who took Sativex and those who did not, it said.

The preparation is also expensive, it added, and costs around 10 times as much as other drugs used for the secondary treatment of MS muscle spasms.

The review says the strength of the evidence is insufficient to warrant its routine use. "We believe that such limitations make it difficult to identify the place of this product in clinical practice," it concludes.

GW Pharmaceuticals, the drug's maker, said: "We are disappointed with the conclusions drawn and strongly believe these comments give a misleading view of the drug."

A spokesman said the drug had been licensed in the UK by the Medicines and Healthcare Products Regulatory Agency (MHRA) in 2010.

Dr Stephen Wright, the company's research and development director, said: "The writers appear to have misunderstood important elements of the design of Sativex clinical trials and provide a flawed assessment of Sativex data.

"Furthermore, the article contradicts the opinion of 22 separate national authorities in Europe and around the world that have granted approval for Sativex and recognise the important benefits it provides to MS patients with spasticity."

The company said the review "fails to focus on clinical trials data which form the basis for Sativex' approval and which guide its use in clinical practice."

A spokesman said: "The key Phase III data on Sativex is robust and compelling, showed highly statistically significant results for the primary and all key secondary endpoints, and is entirely consistent with the dosing recommended in the product label."

He said the DTB "significantly overstates the price of daily Sativex treatment", adding: "Follow-up of all patients prescribed Sativex in the UK, covering more than 12,000 patient years, shows that the average daily dose in long-term clinical use is four sprays per day, a daily cost of £5.50. This is half the cost assumed by the DTB."

Ed Holloway, head of care and services research at the MS Society, said: "The MHRA has already looked at the evidence surrounding Sativex and has decided it is a safe and effective treatment for spasticity - otherwise it would not have been licensed.

"The MS Society believes the MHRA is the right organisation to be making that decision and this latest paper does not provide any new evidence; it simply looks at the same evidence the MHRA has already reviewed via a rigorous process.

"As such, we do not believe this work should call into question the MHRA's decision. Sativex works for some people and we want everyone with MS to have all possible treatment options available to them to combat the symptoms of the condition."

http://www.huffingtonpost.co.uk 13/12/2012