The presentations with the
largest impact at this meeting were the ones on ocrelizumab in relapsing and progressive MS. Ocrelizumab is a monoclonal
antibody which depletes B cells, one of the types of white blood cells. Rituximab is a similar drug which is already in use
for other diseases. The studies in relapsing MS had impressive results. Ocrelizumab was compared to Rebif, one
of the approved interferon treatments currently in use, in two independent studies, each including over 800 patients.
The relapse rate on ocrelizumab was decreased by 46% compared to Rebif. Worsening of disability as measured by the EDSS
was also decreased, and MRI measures of activity were markedly decreased. The obvious concern with this treatment strategy
is an increase in infections, but adverse events were minimal. There was a small increase in the number of upper respiratory
tract infections and in nasopharyngitis, but more serious infections were rare. Ocrelizumab looks like an effective
treatment with no evidence so far for limiting side effects.
There was also a study of ocrelizumab
in primary progressive MS. Patients were treated either with placebo or ocrelizumab for over two years, and the primary
outcome measure was change in disability as measured by the EDSS. There was a 24% reduction in the progression of disability
in the treated group. Secondary outcome measures showing a benefit were 25 foot timed walk, T2 lesion volume on MRI
and brain volume on MRI. As in the relapsing study, an increase in upper respiratory infections was observed.
There were also 11 cases of cancer in the treated group, compared to 2 in the placebo group. There were several different
types of cancer, so it is not clear whether this was just a random occurrence or somehow related to treatment. An increase
in cancer was not seen in the relapsing study which included much larger numbers of subjects. The benefit in progressive
MS is much less impressive than in relapsing MS, but this is the first phase III study with a positive outcome in primary
progressive MS. The study group was unusual in being relatively young (average age 44 years) and having 25% of subjects
with enhancing lesions on the baseline MRI. They have not done subgroup analyses to see whether older patients without
enhancing lesions also benefited.
Other noteworthy presentations included two comparisons
of natalizumab and fingolimod. Neither study was randomized, and one concluded that the two were similar in effectiveness,
while the other concluded that natalizumab was a little more effective. This is about what I would expect given what
is known about the two drugs. They are both very effective.
Dr. Metz presented the
results of their study of minocycline in early MS. Patients treated with minocycline after their first ever relapse
of MS were 44% less likely to have another relapse than patients on placebo. This is a pretty impressive result for
a drug that would cost a few hundred dollars a year. But I don’t think we are likely to see further studies to
verify this result.
Looking far in the future, Roland Martin gave a nice talk on possible
methods for inducing antigen specific tolerance. This approach would target just the parts of the immune system that
are causing MS, and if achieved, should have very few side effects.