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The 2015 ECTRIMS meeting was held in Barcelona the first week of October.  This is one of the largest scientific meetings covering MS, and as usual, there were a large number of interesting presentations.

view of Barcelona

Clinical Highlights

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.  

Scientific Highlights: 

On the basic science side, B cells, genomics, and risk factors are hot areas.   The group from UCSF presented a nice comparison of B cells in the cerebrospinal fluid and in the blood.  They concluded that there is an increase in B cells in the spinal fluid in active MS, and that the characteristics of the B cells suggested an antigen driven response and movement from blood to spinal fluid.   Another presentation reported that T cells isolated from autopsy specimens were mostly the type of cells that provide help to B cells, again supporting the importance of B cells for MS. 

The number of genetic variations contributing to MS is now up to about 200, and efforts are in progress to synthesize the information and understand how the genetic variants combine to contribute to MS.  One approach was to take an in-depth look at the effects of a variant on immune function.  A second approach is to see which genetic variants vary in expression together, and try to cluster the variation into known cellular pathways. 

Risk factors for MS now include Epstein-Barr virus infection, smoking, low Vitamin D, and obesity.  Curiously, oral tobacco use seems to decrease MS risk, at least in Sweden.  Fatty acid intake may be important, but there is still no agreement on what types of fatty acids might benefit MS.  

J. William Lindsey, MD
University of Texas Multiple Sclerosis Research Group
Houston, Texas

copyright 2007-2018 John William Lindsey