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Hope for all aspects of MS

A report from the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS)

Open Door - November 2009 pages 6-7

view of the auditorium during a presentation

Dusseldorf was the venue for the 2009 ECTRIMS conference. 4,913 health professionals from 86 countries attended including 275 from the UK. This meeting that started as a solely European event is now the largest MS meeting in the annual calendar.

The sessions covered all aspects of MS and what was particularly encouraging was that there is research and development going on in all areas - symptom management, genetics, imaging, primary progressive MS, relapsing remitting MS, and secondary progressive MS.

This article tries to pick out some of the key messages:


New drugs in development

Laquinimod

Having passed the safety and efficacy tests in phase II oral laquinimod is now being tested in two phase III trials. Both are large studies with in excess of 1,000 people with relapsing remitting MS in each, and both are now fully recruited. In one of the trials laquinimod is being compared with interferon beta 1a. Laquinimod is less potent than some of the other oral therapies being developed but as a consequence seems to have a lower level of risk.

Fingolimod

A study using fingolimod in primary progressive patients is now underway and includes UK sites. Side effects of fingolimod are being closely monitored and it is too early to fully understand the risks with this drug. Results involving 1,272 people with relapsing remitting MS were released shortly after the conference. These showed that fingolimod reduced relapse rates by 54- 60% and disability progression by 30-32% compared to placebo. The more serious side effects, fluid build up in the eye and skin cancer, that had been seen in previous studies did not occur in this trial.

Cladribine

The most advanced oral therapy in development terms has been submitted to the regulatory authorities in Europe. The 96 week data submitted shows a 55-58% reduction in relapses. The dose is related to body weight and at present it is unclear how many courses can be given safely. The current data has shown 8.7% of trial participants experienced serious adverse side effects including lymphopenia (reduction in white blood cells) and upper respiratory tract infections. It is likely that a chest x-ray and a test for tuberculosis will be mandatory prior to initiation of therapy.

Alemtuzumab (Campath)

The data for alemtuzumab is the most impressive in terms of impact on the disease and there is now four year follow up data for people from the trials, the majority of whom had only two years therapy comprising one week of infusions in each year. Alemtuzumab is 70% more effective in reducing relapse rate and disability progression than high dose interferon beta 1a. The side effects are, however, serious, although with close monitoring can be managed. It is yet to be determined how many cycles of treatment will be most effective. The current trial in early relapsing remitting MS is ongoing.

Lamotrigine

The UK trial reported was in secondary progressive MS and lamotrigine had no effect on the main outcome measure, central brain volume. There was also no effect on T2 lesion volume or relapse rate although the timed walk did improve.

Atorvastatin

A clinical trial reported using one of the statin drugs in relapsing remitting MS which failed to prove effective.

Dirucotide (MBP8298)

The Canadian study was the largest ever in secondary progressive MS but failed to show an effect.


Symptomatic therapy

  • Fatigue management requires people with MS to make choices said Prof Lauren Krupp, who emphasised the link between fatigue, depression, pain and sleep disturbance. She stressed the need to get these problems treated effectively to enable fatigue to be controlled and to minimise the impact on quality of life. Fatigue has no correlation with cognition or conventional MRI measures. Prof Krupp stated that exercise improves fatigue and cognitive behavioural therapy can also be effective.
  • Cognitive impairment can be a significant factor in MS and currently there is only one agent, donepezil (Aricept), that has any favourable trial data. The study is small and efforts are ongoing to repeat the investigation in a larger trial.
  • Slow release fampridine can be useful in the treatment of spasticity although there can be side effects.
  • Prof Kesselring looked at spasticity in detail and used a really helpful visual, Fig 1, to explain the impact of temperature on the speed of nerve messages (conduction velocity). It is evident from this that conduction within the nervous system is optimal when the temperature is around normal body temperature. Any increase or decrease and effectiveness falls. In MS, when there is reduced myelin the conduction rate is slower and thus the effect of temperature is even more significant.
    • graph showing peak speed of nerve messages when the body is its normal temperature

    Fig 1 - the effect of temperature on speed of nerve messages


Primary progressive MS

  • The mean age of onset of primary progressive MS is 40 years.
  • There are no apparent differences in the clinical aspects of primary progressive MS between men and women.
  • It now seems likely that primary progressive and relapsing remitting MS are not different diseases. Rather in primary progressive there are fewer lesions in the brain and more in the spinal cord. Significant MRI studies have been completed and there is more grey matter involvement in primary progressive MS, although the precise relationship between grey and white matter damage in the central nervous system remains unclear.
  • It appears that disability status as measured by EDSS is similar at the same age in primary progressive MS as in relapsing remitting. This poses the questions - are the early, relapsing stages of MS masked in primary progressive? And is this why individuals are diagnosed later and the disease appears to progress more rapidly?

Summing up

In summing up the meeting, Prof Compston drew attention to some of the major areas for future investigation:

  • Are there bio-markers which show which people will respond to treatment?
  • What happens when natalizumab (Tysabri) is stopped? Does disease activity return and is it at a higher level?
  • Progress has been made with reducing mortality when administering stem cell therapy but who is appropriate for therapy?
  • What is driving the apparent increase in MS in women?
  • Why is there a clustering of MS in people born in the summer months?
  • How important is the genetically linked vitamin D response?
  • What is the role of anti-infective agents, against for example Epstein Barr virus, and does stress pay a role?

Overall ECTRIMS was the showcase for a myriad of research studies. The key message remains treat MS early before axonal damage occurs.

MS remains a challenge both from the perspective of someone given a diagnosis and also from a research perspective. Treatment should be started early but there is now real optimism and living proof that active management from the outset can prevent the level of disability that may have been seen in the past.

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