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ECTRIMS 2018: Updates on Progressive MS

Which subgroups of progressive MS should be treated?

Dr. Xavier Montalban, professor at the University of Toronto, presented an overview of treatments in progressive multiple sclerosis (PMS), beginning the talk with why drugs in PMS fail.  Firstly, the pathological processes involved in PMS compared to relapsing-remitting MS are different, therefore novel treatments to target the processes in PMS are needed. Second, the patient population that is recruited for the clinical trials are not appropriate to identify the benefits of treatment. Finally, the current outcomes used in clinical trials to determine effects of treatments are not sensitive measures. Based on the evidence collected from PMS clinical trials, there tends to be a better response in people with PMS with prior relapses, rapidly evolving disease, active baseline imaging, younger individuals, shorter disease duration, treatment naïve and lower disability score. For clinical trials in progressive MS to be effective, key questions needs to be answered:

In active PMS, is persistence of relapses or worsening of disease the definition of treatment failure?

In PMS that is not-active, is disability worsening or appearance of relapses the definition of treatment failure?

How long should treatments be administered to evaluate treatment efficacy?

What measures should define an effective treatment?

Neuroprotection in progressive MS

pill-1884775_1920Dr. Robert Fox, from the Cleveland Clinic, presented an overview of the PMS drugs. Ocrelizumab is the only drug for PMS that is approved in many countries. Ocrelizumab is conditionally approved in Canada for treating adults with primary progressive MS. A new study, called ORATORIO-HAND, will measure the effects of ocrelizumab in older and more disabled patients. Results from Siponimod clinical trial show that individuals with less active disease are more likely to respond to treatment. Opicinumab shows benefits in recovery for individuals with acute inflammatory disease, however, effects from this drug were modest. Biotin MD 1003 effects on patients with PMS is modest but promising. Surprisingly, there was faster atrophy with MD1003, potentially due to fluid shift in the brain, and speaks to the limitation of using brain atrophy as an outcome measure. Speaking of outcome measures, Dr. Fox also talked about the outcomes measures to keep in consideration. Firstly, brain atrophy (or volume) is a noisy measure, meaning that it doesn’t always present results that are associated with treatment. Secondly, serum neurofilament light chain (see below for more info on this) is a potential biomarker that is gaining momentum in MS and may be useful in progressive MS as well. Finally, improvement in hand function has been well-correlated with treatments although inconsistent results are seen between different methods used to measure hand function. Dr. Fox concludes by mentioning that lessons from recent clinical trials need to be used to guide future research in PMS. Using sensitive outcome measures and careful trial design are important to clearly understand treatment effects in PMS.

Neurofilament as a biomarker for progressive MS: Does it work?

blood-1813410_1920An emerging biomarker, which is a measurable indicator of a biological process that can be used as a predictor of health or disease, is Neurofilament light chain (NfL). Every time I attend a conference in the past year, I hear about this biomarker. In fact, check out my posts from the ECTRIMS/ACTRIMS last year and AAN conference from this year to see what was discovered about NfL in MS. At #ECTRIMS2018, NfL came up again and this time, it was to determine whether NfL could be a biomarker for monitoring neuronal damage, disease activity and treatment response in individuals with PMS. Dr. Ludwig Kappos from the  Neurologic Clinic and Policlinic, Departments of Medicine, Clinical Research, Biomedicine and Biomedical Engineering, University Hospital and University of Basel, presented research comparing blood NfL levels in individuals with primary progressive MS (PPMS) that participated in the INFORMS trial (to test fingolimod) and individuals with secondary progressive MS (SPMS) that participated in EXPAND trial (to test Siponimod). The results revealed that in both groups of individuals with PPMS and SPMS, NfL was associated with brain atrophy suggesting that it may be a biomarker that could be used in progressive forms of MS.

IB-MS: A potential and novel treatment for progressive forms of MS. 

With 14 treatments approved in Canada for relapsing-remitting MS and only one therapy that is conditionally approved for adults with PPMS, there is a need to have more treatment options for people diagnosed with PMS.  Dr. E. Ciampi, researcher from Pontificia Universidad Católica de Chile, compared the efficacy and safety of IB-MS, a drug extracted from a medicinial plant, versus mock drug on individuals with PMS. 43 individuals with inactive clinical or radiological PMS that were older than 18 years and with an EDSS score of less than 8 were randomized to receive either IB-MS (140 mg) orally twice a day or a mock (placebo) drug. The primary outcome of the study was to determine if IB-MS was effective in reducing brain atrophy over a period of 24 months. Unfortunately, the results revealed no difference in brain volume change between the two groups. However, individuals treated with IB-MS had a lower EDSS score and reduced disability progression score at 24 months compared to the placebo group. Adverse effects by individuals that were administered IB-MS were mild rash, inflammation due to herpes virus, and acute coronary syndrome. Outcomes on progression and disability provide hope for IB-MS as a potential treatment for people with inactive PMS. A larger, multicenter study is needed to confirm these effects.

Enjoyed learning about these advances in progressive MS? Leave a comment below.

Categories Research

National vice-president, research, past MS researcher, and PhD in Cellular and Molecular Medicine from University of Ottawa. Leads the MS Society's research program to find the cure for MS and improve the quality of life for people affected by the disease.

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