Does early treatment of multiple sclerosis prevent the progression of disability later on?
Alisdair Coles, Wellcome Advanced Fellow Neurology, University of Cambridge
Amanda Cox, Research Fellow, Addenbrooke's Hospital Cambridge
Open Door - Spring 2002 pages 12-13
This is the critical question surrounding the treatment of MS.
For just over a decade now, a number of people with MS have been taking one or other of the beta interferons and we have some idea of their usefulness. But whilst they reduce the relapse rate in both the relapsing remitting (RRMS) and the progressive form of the disease, taking beta interferon does not prevent people with secondary progressive MS (SPMS) continuing to experience worsening disability.
Other drugs that act on the immune system have similarly failed to make an impact on progression. This may be because progression is due to the slow death of axons - the nerve fibres themselves - following the damage they have accumulated over years of inflammation.
One conclusion is that, once progression has started, no immune-acting drug will have a useful effect in preventing people with MS getting worse. So research is looking increasingly at treatments early on in the course of the illness. Already there have been two trials of beta interferon given to people with their first attack. Disappointingly however, they did not address the most important point: was the onset of progression delayed or prevented by taking beta interferon? A significant problem was that these trials lasted only two years, which is too short to answer this question.
In Cambridge, we are tackling this problem with an experimental drug called Campath-1H. This is an antibody that is injected intravenously once a day for five days. It need not be given again for another year. It seeks and kills off T-cells, the white blood cells that normally protect against infection. In MS, the T-cells mistakenly attack the myelin sheaths that surrounds nerve axons, resulting in inflammation and damage to the myelin.
Until recently Campath-1H had only been given to forty or so people with SPMS. From these patients, we learnt the same lesson as with beta interferon: there was a dramatic reduction in relapse rate, accompanied by an equally impressive effect on the number of lesions seen on MRI scans but half of our patients continued to worsen.
We believe that, if we treat patients early enough, we might be able to prevent the build-up of damage that leads to secondary progression. To test out this hypothesis, we have set up a clinical trial sponsored by the companies that make Campath-1H (Ilex-Millennium Partnership). The trial is starting in the Spring. Organised by Professor Compston and ourselves in Cambridge, there are also trial centres in Bristol, Liverpool and Newcastle. We are recruiting about 180 patients with "early aggressive" RRMS. By this we mean people:
- whose first attack must have been less than five years ago;
- who must have had at least three attacks in the last two years; and
- who are still able to walk without assistance.
Campath-1H infusion can cause a rash, temperature and headache but these side effects are brief and significantly reduced by administering intravenous steroids on the first three days of treatment. Because the immune system is damaged, there is an increased chance of infections for a few months after treatment. For mysterious reasons, one third of patients with MS develop Graves' disease after receiving Campath-1H. This is an autoimmune disease, like multiple sclerosis, that attacks the thyroid gland leading to an overactive thyroid. Tablets usually control this.
In order to compare Campath-1H with a "competitor", one third of the patients will be randomly chosen to receive beta interferon. Monitoring will be mainly done by clinical examinations every three months and everyone will have a MRI scan four times during the five years, looking in particular for signs of nerve damage and brain atrophy.
It will be about seven years before we have the final results of this study. This is a long time to wait, if you have MS. On the other hand, it is crucially important that we do not repeat the mistakes of previous trials and come up with a half-baked conclusion or address an issue (such as relapse rate) that is of secondary importance. What we all want to know is: can any treatment now reduce disability in the long-term? This trial of Campath versus beta interferon in early aggressive multiple sclerosis is our contribution to that debate.
For more information please contact:
Dr Amanda Cox, Research Fellow and Honorary Specialist Registrar in Neurology at Addenbrooke's Hospital Cambridge.