Clinical trials on a new combination therapy of Mitoxantrone (a chemotherapy drug) and Copaxone ( an already established MS Disease Modifying Drug) for use in relapsing-remitting multiple sclerosis, started in 2005. The initial trial, carried out at The Walton Centre in Liverpool was very encouraging leading to the setting up of a larger scale clincial trial in August 2006 in 10 centres across the UK to examine the combination further. To see if you are eligible to take part, visit http://www.mxga-mstrial.co.uk . 

Below you will be able to read all the latest news on the trials and also links to further pages where MSers give their personal accounts of their experiences whilst on the trials, and how the treatment affected their MS.

If you are a person with MS who has taken part in one of the Mitoxantrone and Copaxone combination trials and would like to share your experiences please feel free to send in your story to info@msrc.co.uk

• Alison's account of her experiences of the first Walton Centre trial.

The primary measure of outcome was the incidence of adverse events; secondary measures included number of Gd-enhanced lesions, confirmed relapses and EDSS changes.

Except age, baseline demographic characteristics were well matched in both treatment arms.

Both treatments were safe and well tolerated. M-GA induction produced an 89% greater reduction (relative risk (RR) = 0.11, 95% confidence interval (CI): 0.04-0.36, p Gd-enhancing lesions at months 6 and 9 and a 70% reduction (RR = 0.30, 95% CI: 0.11-0.86, p relapse rates were 0.16 and 0.32 in the M-GA and GA groups, respectively.

Short-term immunosuppression with mitoxantrone followed by daily GA for up to 15 months was found to be safe and effective, with an early and sustained decrease in MRI disease activity.

Barrow Neurological Institute, Phoenix, AZ, USA.

Source: Pubmed (30/04/08)

New data have demonstrated that relapsing-remitting multiple sclerosis (RRMS) patients treated with COPAXONE® (glatiramer acetate injection) following brief immunosuppression with mitoxantrone experienced a 90 percent reduction in magnetic resonance imaging (MRI)-monitored disease activity compared to their baseline. These benefits were achieved early on and were sustained throughout the 24-month study period. These long-term data were consistent with the 15-month initial results of this study, previously presented at an international meeting on multiple sclerosis (MS), which demonstrated that the induction treatment strategy was more effective than COPAXONE® alone on reducing relapses and MRI measures of disease activity (p=0.0147). Treatment with COPAXONE® after induction with mitoxantrone remained safe and effective throughout the treatment period.

These new findings were presented at the 59th Annual Meeting of the American Academy of Neurology (AAN) along with new confirming MRI findings from the 15-month study, which showed that the decreases in clinical and MRI markers of disease activity, were accompanied by favourable effects on disease burden and irreversible brain tissue damage as shown by significant decreases in the accumulation of lesion load, and significant reduction in the proportion of lesions evolving into chronic black holes.

"This combination therapy is emerging as a promising treatment option for patients who have active RRMS, or who are not responding optimally to traditional first-line therapies," said Tim Vollmer, M.D., Director, Neuroimmunology Program, Barrow Neurological Institute at St. Joseph's Hospital and Medical Center and the primary investigator in this study. "This study builds on earlier studies that demonstrate the effect of COPAXONE® on disease activity and inflammation in the central nervous system of RRMS patients," he added.

Data analysis surrounding the mode of action of this novel treatment strategy was also presented at the AAN, in which researchers attributed the benefit of the combination of therapies to the combined anti-inflammatory effect of COPAXONE® and mitoxantrone.

"These data shed new light on the concept of treating MS by first suppressing the auto-aggressive immune system with an immunosuppressant, and then favourably modifying its activity with an immunomodulator such as COPAXONE®," said Amit Bar-Or, M.D., FRCPC, assistant professor, Director of the Experimental Therapeutics at the Montreal Neurological Institute (MNI) and primary investigator of the immunological study.

Source: Teva Neuroscience (04/05/07)

The disclosure is another devastating blow to wheelchair-bound MS patient Vincent Smith.

Tragic Vincent (42) has already been refused life-enhancing injections of beta-interferon.

His devoted carer, Margaret Caldwell, told Sunday Life last night: "When we read about this new pioneering treatment I thought it would be fantastic for Vincent.

"I went on the internet to the neurological clinic in Liverpool and fed in all Vincent's details.

"We were hoping he might even get on a clinical trial programme, but the minute I keyed in his address I was informed it did not apply to Northern Ireland. "If anyone deserves a break it's Vincent, but this is just one more major setback."

The revolutionary new treatment, using a cocktail comprised of chemotherapy drug Mitoxantrone and MS anti-relapse drug copaxone, has been a remarkable success.

A trial on 27 MS patients over the last year was so successful that the disease modifying therapy is now being offered across 10 centres in Britain.

The combination of the two drugs has so far been used in only the most severe cases, but patients treated with the cocktail showed signs their attacks were happening 90pc less.

Consultant neuro-surgeon Dr Mike Boggild, who led the trials, said the treatment effectively halted degeneration in its tracks.

More than 4,000 people are registered as MS in Northern Ireland. Robert McConnell of the MS Society said: "We've been inundated with calls about this.

"We know Mike Boggild and he has been to Northern Ireland. But the truth is, there is a long way to go before this can be prescribed clinically.

"Reports have been hyped by newspapers, but it can't yet be taken as gospel until clinical trials are done."

Vincent, a former electronics engineer, lives in bleak one-room surroundings in south Belfast. He was diagnosed with MS in when in his early 20s. He had been receiving beta-interferon on the NHS for six years but it was withdrawn last year on the grounds that he could no longer walk "with or without assistance, persistent for at least six months".

He is now dependent on supplies of LDN tablets, which, although not fully clinically tested, he is able to buy privately from a pharmacist in the Republic.

"The system has forgotten Vincent and it seems he will now be denied access to new drugs, even though he's at an advanced stage of the disorder," added Margaret.

"It's enough to make you weep - but I'm afraid tears won't help."

Source: Sunday Life © 2006 Independent News and Media (NI)

The treatment regime, consisting of a limited course of mitoxantrone (an immunosuppressant normally used to treat cancer) followed by long-term glatiramer acetate (Copaxone - one of two classes of disease modifying drugs for use in relapsing-remitting multiple sclerosis), has proven so successful in this early trial that a full controlled study is now being initiated at 10 centres across the UK to examine the combination further. Investigators are now looking to enrol suitable patients with MS.

In this 'open' trial the combination was found to provide a rapid and sustained suppression of relapses in MS patients experiencing frequent, recurrent and disabling attacks (90% reduction in annualised relapse rate maintained, to date, for a mean of 36 months). It was also shown to improve, or at least stabilise, existing levels of disability in the 27 patients who had extremely active forms of the disease. Follow up in early patients now extends to over 5 years.

The patients treated with this new protocol, developed by a research team at the Walton Centre for Neurology and Neurosurgery in Liverpool, had all been diagnosed with Relapsing Remitting MS for less than 5 years and showed clear signs that their disease was likely to progress quickly producing early and severe disability.

Dr Mike Boggild, Consultant Neurologist at the Walton Centre and principal investigator of this research commented: "This novel treatment regime has proved remarkably effective in a group of patients with early MS and a poor prognosis. Though there are certain risks, associated particularly with the use of Mitoxantrone, we have been able to limit these by using this agent for just a short 'induction' period and, balanced against the high risk of early disability for these patients, the outcomes we have seen appear to justify this approach. The effect is so striking that we suspect the two drugs may be acting synergistically"

Karen Ayres, 28 from Warrington is a patient who has benefited from the new treatment protocol. She said: "Lying paralysed in hospital, I truly believed that I would never get the chance to travel again, let alone go back to university to study. Without mitoxantrone and Copaxone treatment, I simply don't think it would have been possible - it is not an exaggeration to say that I feel as though the treatment has given me my life back. I have been able to take up my beloved backpacking again and I am currently studying for a PhD. MS really doesn't spell the end of your life"

Mitoxantrone, the first immunosuppressant to be approved by the United States Food and Drug Administration (FDA) for use in MS, has previously been shown in randomised controlled studies in the US to reduce relapses in MS, but due to its potential toxicity its use is limited. Previous attempts to extend its effectiveness with subsequent use of interferon-beta have been disappointing, so researchers at the Walton Centre decided to use the alternative class of disease modifying drug, glatiramer acetate (Copaxone).

Source: News-Medical.Net ©2006 News-Medical.Net