ECTRIMS 2015 Highlights and General Impressions, Part III

Continuing on our recap of ECTRIMS 2015, the topics that arguably made the biggest splash at this year’s meeting concerned new and repurposed treatments in the pipeline, as well as promising targets that have the potential to become viable therapies in the future, pending more research. Since balancing a drug’s efficacy with its safety and tolerability is of paramount importance to the person living with MS, a number of researchers presented results of long-term monitoring studies looking at safety outcomes for approved drugs as well as new tools for more effective monitoring. Finally, biomarkers are a hot topic in MS research, since they can potentially provide the key to more effective screening practices of individuals based on their predicted response to certain treatments and their predicted prognosis, i.e. how their disease will change over time. Read on for a summary of some of the highlights in these topics from the conference.

Professor Xavier Montalban, President ECTRIMS, presents the results from the ORATORIO clinical trial on ocrelizumab.

Professor Xavier Montalban, President ECTRIMS and Chair of ECTRIMS 2015, presents the results from the ORATORIO clinical trial on ocrelizumab. (Image Credits: Peter Schwarz-Lam)

 

New and repurposed treatments

  • B cells took centre stage at this year’s ECTRIMS. Ocrelizumab, an antibody shown to deplete disease-causing B cells, was featured in two high-profile studies. The results from OPERA I and II clinical trials, presented by Dr. Stephen Hauser (University of California SF, San Francisco, CA), showed that in participants with relapsing-remitting MS, ocrelizumab significantly reduced relapse rate, delayed disability progression and reduced the number of brain lesions compared to the first-line DMT beta-interferon-1a (Rebif). In a separate study in participants with primary progressive MS (ORATORIO), Dr. Xavier Montalban (Vall d’Hebron University Hospital, Barcelona, Spain) presented data showing that ocrelizumab significantly reduced the risk of disability progression compared to placebo, and also reduced the rate of brain volume loss and lesion growth.
  • An extension study of the CARE-MS I and II clinical trials for the second-line DMT alemtuzumab (Lemtrada), presented by Dr. Frederik Barkhorf (VU University Medical Centre, Amsterdam, Netherlands) showed that slowing down of brain volume loss was sustained in individuals with relapsing remitting MS over 5 years, despite most participants not needing continued treatment after 2 initial sets of infusions of alemtuzumab during the first year.
  • Results from an MS Scientific Research Foundation-funded clinical trial investigating the efficacy of minocycline, a tetracycline antibiotic used to treat acne and some inflammatory disorders, in reducing the risk of participants with clinically-isolated syndrome converting to MS, were presented by Dr. Luanne Metz (University of Calgary, Calgary, AB). The study showed that this inexpensive medication significantly reduced the risk of converting to MS compared to those individuals taking placebo.

 

Long-term monitoring studies

  • Despite being an effective treatment for relapsing remitting MS, natalizumab (Tysabri) is known to increase the risk of progressive multifocal leukoencephalopathy (PML), a dangerous infection of the brain, in some individuals. Dr. Lana Zhovtis Ryerson (NYU Langone Medical Center, New York, NY) presented preliminary data showing that an extended dose schedule with less frequent dosing of natalizumab maintained the efficacy of the drug while reducing the risk of PML thus far.
  • Two separate groups presented studies with head-to-head comparisons of natalizumab (Tysabri) and fingolimod (Gilenya) efficacy in relapsing remitting MS based on treatment registry data. Dr. N Koch-Henriksen (University of Aarhus, Aarhus, Denmark) and his team found no difference between the two drugs in their effect on reducing relapse rate. On the other hand, in a controlled interventional study led by Dr. David Laplaud (Centre hospitalier universitaire de Nantes, Nantes, France), participants on natalizumab performed better overall in terms of both clinical and imaging measures compared to those on fingolimod. These contradictory findings point to the need for further, long-term monitoring data to determine which individuals are likely to benefit most from either therapy.
  • New tools are needed to allow clinicians to identify patients who are at a high risk for serious side effects. Dr. Jodi Haartsen (Box Hill Hospital, Melbourne, Australia) presented data about the effectiveness of a multi-drug safety module called MS FIRST to track the incidence, timing and predictors of treatment safety outcomes, particularly low white blood cell counts in response to treatment.

 

New targets and biomarkers

  • MS Society-funded Postdoctoral fellow Dr. Soufiane Ghannam (Centre hospitalier de l’université de Montréal, QC) presented findings from his study on a molecule called DICAM, which he hypothesizes is involved in allowing disease-causing T cells to migrate across the blood brain barrier into the central nervous system. He demonstrated that pro-inflammatory T cells that are found in active brain lesions express DICAM, and that DICAM is regulated by certain signaling molecules called cytokines that are implicated in autoimmune disease. Dr. Ghannam’s presentation was awarded as one of three top oral presentations at ECTRIMS 2015.
MS Society-funded postdoctoral fellow Dr. Ghannam Soufiane receives his award for one of three top oral presentations. (Image Credits: Marco Ansaloni

MS Society-funded postdoctoral fellow Dr. Soufiane Ghannam (centre) receives his award for one of three top oral presentations from ECTRIMS President Prof. Xavier Montalban (left) and Vice-President Prof. David Miller (right). (Image Credits: Marco Ansaloni)

  • Researchers are continuously looking for novel molecular targets for developing new MS therapies, particularly in the area of repair. Dr. Thomas Scanlan (Oregon Health & Science University) and team are investigating a drug that mimics the remyelinating properties of thyroid hormone without its harmful effects when given in high doses. This “thyromimetic” drug, called sobetirome, was administered into the brains of mice, after which remyelination was measured is the brain tissue. The researchers found that sobetirome promoted the actions of myelin-producing cells and accelerated remyelination, paving the way for further studies of thyromimetics as potential remyelinating drugs.
  • The discovery of biomarkers is critical for giving researchers and clinicians the tools to predict who is at greatest risk of developing MS, and in people living with MS, how the disease will change over time. Dr. Maria Alba Mañé Martinez (Universitat Rovira i Virgili, Spain) and colleagues examined the levels of two proteins – called YKL-40 and GFAP – in the cerebral spinal fluid (CSF – the fluid that bathes the brain and spinal cord) in 280 participants with relapsing remitting MS. They found that high levels of these two proteins in the CSF of participants in the early stages of the disease was a strong predictor of a worse disability progression later on. This evidence suggests that YKL-40 and GFAP can potentially be used as biomarkers down the road to screen for individuals who may be candidates for more intensive treatment in order to stem disability progression.
  • Continuing with the biomarker theme, Dr. Signe Modvig (Copenhagen University Hospital Glostrup, Glostrup, Denmark) set out to identify clinically valuable biomarkers that can predict future MS disease and disability in individuals after a first demyelinating event (or clinically isolated syndrome – CIS). In a group of 86 participants with acute optic neuritis that were followed over a period of time, Dr. Modvig correlated the levels of a suite of biomarkers in the cerebral spinal fluid with different clinical indicators, including development of clinically definite MS, and long-term physical and cognitive disability. The results showed that two specific markers – called NFL and CHI3L1 –  were significant predictors long-term disability and conversion to MS following a first demyelinating event.

Questions or comments? Leave them below!

 

4 thoughts on “ECTRIMS 2015 Highlights and General Impressions, Part III

  1. Sandy Watts

    Thank you for the summary Dr Lee. Very comprehensive and very exciting. Was there any discussion of anti-lingo? Or are the current results of trial too new and too specific to 1 area? It is still in trial is it not? It seems to have gone rather quiet and I wonder if the results are not as positive as they hoped.

    Can you speak to that?
    Thank you

    Reply
    1. drkarenlee Post author

      Hi Sandy,

      There was in fact an update on Anti-LINGO-1 at the late-breaking news session. I have provided a brief summary of those findings in this blog post (scroll down to read the summary). The results are promising in that they suggest some evidence of protection against vision loss in people affected by optic neuritis, particularly in preventing the visual degradation in the unaffected eye.

      Dr. K

      Reply
  2. Karen

    With respect to the bio-markers, how easily can these be tested for? Would it it be a blood test? Spinal tap? Or is that the next step…..

    Reply
    1. drkarenlee Post author

      Hi Karen,

      That’s a great question. Both the blood and the cerebrospinal fluid (CSF) that’s obtained from spinal taps are potential sources of molecular biomarkers, although an important thing to consider is that they measure different components of the disease process and come with their own unique advantages and challenges. Since the CSF bathes the brain and spinal cord, it is in close proximity to inflammatory lesions and is the closest thing we have to a tissue sample (it is sometimes called a “liquid biopsy”). Certain MS-specific biomarkers can only be found in the CSF; however, spinal taps are relatively invasive and there are important safety concerns with this procedure. Blood, on the other hand, is much easier to collect and reflects the immune processes that occur in the periphery (outside of the brain and spinal cord). Despite recent advances in identifying new biomarkers for MS, there is still much work to be done in validating these potential candidates to make sure they correlate with different parts of the disease process and can reliably predict disease course and progression, as well as responses to treatment.

      For more information, I invite you to read this excellent (and free-to-access) review on biomarkers.

      Dr. K

      Reply

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