There were three major clinical
trials that reported initial results at this meeting. The first was the TRANSFORMS trial which compared
fingolimod with Avonex. Fingolimod is an oral medication that interferes with the movement of white blood
cells. It had impressive results in a previous phase II study. This was a phase III
study that enrolled about 1280 patients. Fingolimod reduced the relapse rate by about 50% compared to Avonex.
It also had some side effects. The most concerning were two deaths in the high dose group from virus
infections. At this point fingolimod looks like a very effective treatment for relapsing MS, but safety
concerns may limit its use.
The CLARITY trial tested cladribine, a chemotherapy drug,
against placebo in relapsing MS. They followed 1300 patients for 2 years. The number
of relapses was decreased by over 50%. Side effects were more frequent in the cladribine group, but there
weren’t any that were particularly alarming. This appears to be an effective therapy, but the side
effects and long term effectiveness need further study.
The third major trial was the rituximab
in primary progressive MS study. Preliminary results from this were presented at WCTRIMS in Montreal earlier
this year. This presentation had some more details. The study overall was negative,
but patients younger than 51 years or with enhancing lesions on MRI did better on treatment. This is an
encouraging first step to effective treatment for progressive disease.
Biogen presented an
update on Tysabri and PML. There have now been 6 cases of PML since Tysabri was reintroduced in July 2006.
Three of these patients had previous chemotherapy treatment for immunosuppression. One of the cases
was fatal, and the others had additional deficits. There have now been over 25,000 people treated for at
least 12 months with Tysabri, so the rate seems to be somewhere around 1 per 5000 people per year. I will
continue to monitor this. The page titled Tysabri update on this website has a link to the most up-to-date
information from Biogen.
There was an interesting presentation on the use of deep-brain stimulation to treat severe tremor
in MS. This is already an established treatment for Parkinson’s disease. The patients
they treated all had disabling tremor. The tremor and their function both improved. This
is an interesting option for treatment for people who are disabled by tremor rather than weakness.
There
were several reports of small groups of patients treated with aggressive immunosuppression. These included
studies with high dose chemotherapy followed by bone marrow transplant, alemtuzumab (a monoclonal antibody that eliminates
most white blood cells), and cyclophosphamide. The rationale of this approach is to suppress the immune
system and prevent autoimmune demyelination. These treatments all appear very effective in stopping clinical
relapses and enhancing lesions on MRI scans over the first year or two of followup. They all have worrisome
side effects and their longer term effectiveness is unknown.
In a related report, a group from Italy
reported on the occurrence of leukemia after mitoxantrone treatment. Mitoxantrone is a chemotherapy drug
which I am using in people with severe MS. Leukemia is a known complication of this, and we previously
thought the risk was about 1 in 1000. The Italian study found 21 cases in 2,854 mitoxantrone-treated patients.
This means the risk is closer to 1 in 100. I usually use this treatment in people with severe MS, so the
risk may be acceptable. Other chemotherapy drugs may have less troublesome side effects.
