Posted in Courses & Conferences on 13th Oct 2016


Conference details: 14-17 September, 2016; London, UK
News source: ECTRIMS congress organisers, and company press releases
First published online: 13/10/16

ECTRIMS and EAN join forces to formulate the first European MS treatment guidelines 

The Clinical Guideline on the pharmacological management of people with Multiple Sclerosis was developed jointly by ECTRIMS and European Academy of Neurology (EAN).

This is the largest European collaboration to consider therapeutic guidelines for MS and have been developed following the GRADE methodology that implies a sequential assessment of the quality of evidence, followed by judgment about the balance between desirable and undesirable effects, and subsequent decision about the strength of a recommendation. The main recommendations presented by Susana Otero (Multiple Sclerosis Center of Catalonia, Barcelona, Spain) are based on the latest evidence available worldwide and have been agreed by a large working group of key MS experts across Europe, as well as patient representatives from MS advocacy groups, such as EMSP and MSIF.

New guidelines for patients with clinically isolated syndrome

One of the key consensus statements which came out of the recent ECTRIMS/EAN meeting concerns patients with clinically isolated syndrome. These are patients that have had only one neurological incident and do not fulfil current diagnostic criteria for MS.

Based on the available evidence and mindful that MS is a progressive disease and delay in starting disease modifying treatments can have long-term consequences, the steering committee has recommended that CIS patients with visible abnormalities on MRI scans should receive disease modifying drugs (DMD) prior to diagnosis.

Consensus on treating patients with established MS

Research advances in recent decades mean that clinicians now have a large choice of effective drugs for the treatment of patient with confirmed MS. However, few of those drugs have been compared directly and the trial populations are too heterogeneous to draw direct comparisons.

The ECTRIMS/EAN steering group have therefore recommended that choosing the right drug for an individual patients with established MS should remain in the hands of the treating neurologist taking into account the patient’s history, their age, their level of disease activity, their comorbidities and, very importantly, their personal preferences.  Drug choices may also depend on availability within different healthcare systems and different licencing regulations across Europe.

The experts within the committee hope that on-going and future trials may provide further clarity and recommendations will be made as time goes on, when the evidence on which to base them becomes available.

Guidelines on monitoring the effectiveness of MS treatments

The steering group did agree that regardless of the drug chosen, regular monitoring should take place to investigate whether that treatment is having an impact on the disease.

The timing of monitoring will depend on many factors and will differ between countries but the ideal is for patients to have an MRI scan about 12 months after starting a drug treatment. If there is a poor treatment response, then the treatment strategy should be to move on to a more aggressive drug

Susana Otero, Multiple Sclerosis Center of Catalonia, Barcelona, Spain

Guidelines for treating patients with Primary Progressive MS (PPMS)

PPMS is diagnosed in around 10-15% of MS patients and currently has no disease modifying pharmacological treatment. Ocrelizumab, a potential treatment for PPMS, has recently be tested in a phase 3 clinical trial and results have been very encouraging, but the drug is currently still under review by the European Medicines Agency.

The ECTRIMS/EAN steering group has recommended that PPMS patients should receive Ocrelizumab and this consensus statement will be included in the published guideline – but only if the drug is licenced before the publication date, explains Otero.

ECF Satellite Symposium at ECTRIMS attended by 1600 MS professionals

The European Charcot Foundation welcomed more than 1600 MS professionals at its Satellite Symposium held during the congress.

The symposium “the role of B-cells in MS pathogenesis” chaired by Prof. Giancarlo Comi, addressed the following topics:

1.Why antibody therapy in MS (Prof. H.P. Hartung – Germany)

2.Update of the role of b-cells follicles in MS (Prof. R. Reynolds – UK)

3.Anti b-cells therapy in MS and related disorders (Prof. G. Comi – Italy)

Find out more about the European Charcot Foundation annual meeting in November at

Global research is focusing on better therapies for all stages of multiple sclerosis

The final late-breaking session session at ECTRIMS included news on the progress that is being made in determining the most effective drug treatments for the relapsing remitting stage of MS and in developing much-needed novel therapies for the secondary, progressive stage.

Alemtuzumab: using real world clinical data to find out how it compares to other MS drugs

One of the key presentations reported important results comparing alemtuzumab with beta interferon, fingolimod and natalizumab. All four drugs are licensed for the treatment of patients in the relapsing-remitting stage of MS, in which episodes of new neurological symptoms are followed by at least partial recovery.

Research over the last two decades has revolutionised therapy for MS patients and disease-modifying drugs are now often used as soon as a diagnosis is made in order to slow disease progression and delay the onset of disability.

New drugs have been developed regularly and individual treatments have been licensed when they have proved effective compared with placebo or one established treatment. A new drug does not need to be tested against all available treatments for MS, so the efficacy of already licensed drugs is difficult to compare. A comparison over different clinical trials is compromised by the fact that individual trials may differ significantly in their design and may be undertaken in very different groups of people.

The answer to this problem is to gather data on how all these drugs perform after they are approved for use in the clinic. MSBase ( is a registry that aims to collect clinical outcome data from people with MS in real-world clinical practice. By collecting sufficiently large amounts of such data, it is possible to statistically match the different patient populations and allows comparing the efficacy of different treatments in routine clinical practice.

Tomas Kalincik (University of Melbourne, Australia), on behalf of the MSBase collaboration, presented results from a study comparing the efficacy of alemtuzumab against three other treatments (fingolimod, beta interferon and natalizumab), all of which have been shown previously to reduce the frequency of MS relapses.

The real world data confirmed trial results and showed that alemtuzumab was better at suppressing relapses compared to beta interferon and fingolimod, and was similarly effective compared to natalizumab. Although patients treated with natalizumab showed slightly more clinical improvement than those treated with alemtuzumab, the rates of disability progression did not appear to differ significantly between the two drugs.

These findings demonstrate that real-world data obtained as part of clinical practice can be used to answer questions about the relative efficacy of treatments that would be difficult and prohibitively expensive to answer in dedicated treatment trials. This is important for people with MS, and the clinicians who advise them, to enable well-informed choices between treatments based on their relative efficacy and the risk of side effects.

More news about new treatments for secondary progressive MS

During the late break session, details were given about the EXPAND trial of the novel therapy siponimod (BAF312).

Many people with MS who have initially had relapses and remission eventually develop progressive disability that is not the result of relapses. This is known as secondary progressive MS (SPMS) and currently licensed treatments have only very moderate efficacy.

In the late breaking news session, Ludwig Kappos (University of Basel, Switzerland) reported the main results of EXPAND, which has included 1,651 patients with SPMS from 31 countries. SPMS patients, who were included only if they showed evidence of disability progression within the previous two years, were treated daily with either 2mg siponimod or a placebo (two patients were placed in the treatment group for every one patient in the placebo group).

The main outcome was confirmed MS progression over three months, measured using Expanded Disability Status Scale (EDSS) scores. When compared with placebo, siponimod reduced progression by 21% (HR 0.74), and this difference was statistically significant. At 6 months the reduction was 26%, and again this was statistically significant. Treatment effects were more noticeable in those who had had relapses, and treatment was associated with a reduction in the annualised relapse rate (which fell by about half compared with the placebo group).

The take home message from today is that EXPAND is the largest study to date to present data showing that a drug candidate for secondary progressive MS (siponimod) impacts on a clinical measure of disability progression. It is encouraging that we now have a potential treatment for SPMS that might be available for patients in the near future.

Prof. Xavier Montalban, President of the European Committee for Treatment and Research In Multiple Sclerosis

Refining the criteria used to diagnose MS at an early stage using MRI scan results

Presentation revealed the latest evidence-based thinking on how to use MRI scan results to diagnose MS with increasing accuracy.

Earlier this year, MAGNIMS, the European Collaborative Research Network that studies the use of MRI when diagnosing MS, published revised criteria for clinicians.

In his presentation at ECTRIMS, Paolo Preziosa (Vita-Salute San Raffaele University, Milan, Italy) a young investigator within MAGNIMS, outlined results showing that their most recent techniques do indeed make it possible to diagnose MS earlier and more accurately in patients with very few clinical signs of the disease.

Using MRI data in MS diagnosis requires continual reassessment

MRI scans have been used routinely to help diagnose MS since 2001. Over the last 15 years there have been huge advances in the technology and so the criteria used to diagnose MS in patients on the basis of their scans results have had to change too.

One of the key goals is to use MRI imaging to detect changes within the brain and spinal cord of someone who has Clinically Isolated Syndrome (CIS). This term is used to describe someone who has experienced a single episode of neurological symptoms. This episode may have lasted only a few days, leaving clinicians with very little to go on when attempting to determine the underlying cause.

One of the key factors that MRI data is used to look for is whether the symptoms are caused by lesions in the nervous system that are ‘disseminated in time and space’. Using MRI technology to judge whether abnormalities in the grey matter particularly are associated with a subtle spread and progression of the disease is at the heart of the recent criteria.

Defining the criteria for a diagnosis of MS

Preziosa explained that the new criteria for MS diagnosis in patients with CIS specify that at least two of the following signs are visible on a detailed MRI scan:

  1. At least one lesion in the spinal cord
  2. Three or more lesions in the periventricular white matter in the brain
  3. At least one lesion in the infratentorial region, which includes the cerebellum
  4. At least one lesion in the cortical or juxtacortical region of the brain – so in or near the grey matter
  5. At least one lesion in an optic nerve

Preziosa emphasised that scoring cortical lesions (the grey matter) and lesions involving the white matter next to the cortex (called juxtacortical lesions) when assessing ‘dissemination in space’ was a key change to the current criteria and one that required detailed investigation within a clinical study.

The MAGNIMS study to test out the new criteria

During their work on the recent consensus statements, the MAGNIMS group set up a study involving 72 patients with CIS who were recruited from five European centres and followed up for over 2 years. One of the objectives was to reveal better the lesions present in the grey matter and in the adjacent white matter.

Finding lesions in or near the grey matter can be particularly difficult: Preziosa explained that patients in the study had a double inversion recovery MRI (DIR MRI) scan at study entry as this increases grey matter lesion detection compared to standard MRI.

After two years, 90% of those recruited to the study had developed MS, while 10% were found to have a separate neurological condition.

Encouragingly, the use of DIR MRI to detect lesions in the grey matter led to more patients being correctly diagnosed with MS right at the start of the study.

The group concludes that the changes that they have proposed to the diagnostic criteria for MS do indeed make it possible to diagnose MS in someone with very early clinical symptoms much more accurately.

These refinements in criteria seem to be small steps, but for patients with early stage MS, they are very significant. Being able to give someone an accurate diagnosis of MS enables disease-modifying treatments to be given as early as possible. Equally, if someone does not have MS, their clinical team can then move forward to finding out what is the cause of their symptoms.

Professor David Miller, Vice President & Chair of Scientific Committee of ECTRIMS

How optic nerve imaging can help monitor therapeutic effects in MS

Presentations revealed how imaging the retina and optic nerves can provide key information on disease progression in MS, including how effective treatment strategies are at slowing down those changes.

A comprehensive series of reviews, data and original reports explored and defined how researchers can use the visual system to better understand the disease process responsible for MS – including, how imaging of the optic nerve and retina can offer an interventional trial platform for proof of concept studies.

The importance of OCT imaging

Peter Calabresi (Director of the MS Center at Johns Hopkins, Baltimore, MD, USA), began the session by outlining the use and importance of Optical Coherence Tomography (OCT) as a non-invasive technique that is able to display and quantify retinal pathology. This standard imaging technology is widely available and is reproducible across different centers. In fact, it has been validated as a reliable indicator of disease progression in both longitudinal and cross-sectional datasets.

Using OCT to monitor drug response in MS

Raju Kapoor (University College, London, UK) described several clinical trials that have assessed the neuroprotective potential of various drugs by studying their effect on patients with optic neuritis. Using visual system imaging to monitor the impact of treatments on optic nerves themselves is a significant advance. However, more encouraging, is the potential of monitoring the response within the visual system could also provide information about the impact of the drug on lesions elsewhere in the central nervous system.

Can OCT scans predict disease progression?

In his introduction, Calabresi touched on a recent meta-analysis showing how well OCT retinal scans can accurately predict clinical outcomes five years later, mentioning an update on new data on predictions at 10 years. Alissa Rothman, a researcher in Calabresi’s group went into the study in more detail.

A total of 89 participants were included, most of them female patients with relapsing remitting MS who had a baseline expanded disability status scale (EDSS) of 2.8. Status OCT scans were performed on each patient at entry and follow up took place over a 10-year period. After using various models and adjusting for confounding factors such as age, sex and a history of optic neuritis, the total macular volume measured by the original OCT scans was found to accurately predict the EDSS scores at the ten-year follow up point.

In particular, the changes within the eye over the first 2-3 years seem to have the greatest predictive value.

Finally, Justin McKee (University of Oxford, UK) presented the results of the Amiloride Acute Optic Neuritis trial (the ACTION trial). Amiloride, a repurposed diuretic, which targets and blocks acid sensing ion channel 1 (ASIC1), is over-expressed in mouse models of MS and is present in post-mortem tissue from MS patients.

Previously, McKee explained, a cohort study in progressive MS had suggested that Amiloride may have a neuroprotective effect in MS. He then reported his group’s current study in which 48 patients with acute optic neuritis (within 28 days of onset) were given 10mg of Amiloride or a placebo. Treatment was continued for 5 months, then stopped for a month before outcomes were measured at 6 months and then again at 12 months.

Disappointingly, thickness of the retinal nerve fibre layer in the Amiloride treatment group was not significantly less than in the placebo group. The study included a number of secondary outcome measures, but no differences were observed between the groups here either.

Discussions following the presentation explored reasons for this negative result and many experts present focused on the therapeutic window in acute optic neuritis, which is very likely to be as little as 7 days. The potential of earlier treatment with Amiloride cannot be dismissed completely.

Research in this area of MS is now focusing on ways to understand the way in which immunomodulatory therapies work – we know they do, but we don’t understand fully how. Another major focus is to find out more about the mechanisms that lead to neuronal loss in MS so that we can develop new therapies to target MS progression that occurs without discernable inflammatory lesions.

Peter Calabresi, Director of the MS Center at Johns Hopkins, Baltimore, MD, USA

Lipoic acid shows great potential as a disease modifying treatment for secondary progressive MS

One of the parallel sessions reported promising early results on the potential benefits of lipoic acid in secondary progressive MS.

Lipoic acid is produced naturally in our own bodies and is found in many foods, and previous laboratory work has suggested that taking supplements of lipoic acid may help reduce some of the disabling effects of MS. Now this drug candidate is being tested in early stage human trial and can be added to the small number of drugs in development for secondary progressive MS.

Why could lipoic acid be so important?

Most people with MS initially have episodes of neurological symptoms that come and go. This stage of the disease is described as relapsing remitting MS and can last or months or even years. Eventually, however, most people develop deficits that progress over time and their disease is then termed secondary progressive MS.

Much of the progressive disability that occurs in secondary progressive MS is thought to be due to the loss of nerve cells and fibres. Treatments that could prevent or slow this loss could have the potential to prevent or slow disability progression.

Unfortunately, although we now have a range of treatments available for relapsing remitting MS, there are no licensed treatments for secondary progressive MS. As lipoic acid is inexpensive and readily available, and it is tolerated at high doses by MS patients, it is an attractive drug candidate.

Details of the lipoic acid study

In their double-blinded pilot treatment trial of lipoic acid, Chataway et al. studied 51 people with confirmed secondary progressive MS for 96 weeks. Lipoic acid, at a dose of 1200mg per day, was given to 27 patients, with a further 24 receiving a placebo. Participants were monitored using MRI scans to measure whole brain atrophy, atrophy of brain substructures and the spinal cord, atrophy of the retina and macular region in the eye, and by clinical assessment and questionnaires to determine impact on symptoms and quality of life.

Promising results: lipoic acid prevents brain atrophy

At the end of the trial, MRI scans revealed a lower rate of whole brain atrophy in the lipoic acid treatment group compared to the placebo group. The rate of brain volume decline over time in those who took lipoic acid supplements was 0.22% per year and 0.65% per year in those who took the placebo. This is a 66% reduction, which is statically significant (p=0.004).

Lipoic acid treatments were well tolerated

The rate of serious adverse events was very similar between both groups. People in the lipoic acid group reported a higher rate of stomach upsets (an adverse effect) and a lower rate of falls (a benefit).

A very positive sign was also that more than 80% of the participants took the tablets regularly throughout the study period and only five participants withdrew during the course of the trial.

Taking lipoic acid forward in clinical trials

The study group recognises that this trial is a pilot. However, the strength of the response seen in patients with secondary progressive MS was sufficiently promising to warrant a larger trial to confirm the possible neuroprotective effects of lipoic acid and to further explore both the clinical benefits and the potential adverse effects.

The MS-STAT trial of high dose simvastatin has also shown a reduction in the rate of brain volume loss, and the EXPAND trial of siponimod, which will be presented at ECTRIMS tomorrow, has shown a beneficial effect on disability progression. Add in this study on lipoic acid and we are beginning to see several promising treatments emerge for secondary progressive MS.

Prof. Xavier Montalban, President of the European Committee for Treatment and Research In Multiple Sclerosis

Real world data from Biogen affirms efficacy of Tecfidera and 9 year safety profile

Further data show benefits of patient coaching in reducing discontinuation rates

Data presented from both real-world and clinical settings demonstrated that dimethyl fumarate delivered consistent1 and sustained efficacy2 among patients with relapsing-remitting multiple sclerosis (RRMS), and adds to its safety profile for up to nine years of treatment.3

Real world findings demonstrate efficacy of dimethyl fumarate versus other MS therapies

Retrospective results from the worldwide MSBase registry show that dimethyl fumarate reduced the risk of first relapse versus interferons by 26% (n=420 matched pairs; HR 0.74; 95% CI 0.57, 0.97; p=0.027), glatiramer acetate by 28% (n=382; 0.72; 0.54, 0.95; p=0.022) and teriflunomide by 34% (n=256; 0.66; 0.45, 0.99; p=0.042). In the primary analysis, no significant difference was found versus fingolimod-treated patients (n=415; 1.03; 0.73, 1.46; reference = FTY).1 Time to first relapse was measured using binomial propensity score matching.

The MSBase registry is one of the largest sources of real-world data and includes nearly 40,000 MS patients across 72 countries. Our analysis shows that dimethyl fumarate significantly reduced the risk of first relapse compared to platform therapies and teriflunomide, and had comparable efficacy to fingolimod

H. Butzkueven, Associate Professor in the Department of Medicine, University of Melbourne and one of the investigators for the study

As a secondary endpoint, the study also demonstrated similar and consistently lower annualised relapse rates (ARR) for dimethyl fumarate-treated patients versus those treated with interferons (0.23 [95% CI 0.19, 0.27] vs 0.26 [0.24, 0.29]), glatiramer acetate (0.24 [0.19, 0.28] vs 0.26 [0.23, 0.29]) and teriflunomide (0.17 [0.13, 0.22] vs 0.27 [0.22, 0.33]). ARR for dimethyl fumarate-treated patients was found to be similar but higher versus fingolimod-treated patients (0.22 [0.18, 0.27] vs 0.19 [0.17, 0.23]).1

Positive ARR findings were also reported in a second real-world study analysing data from over 3,500 dimethyl fumarate-treated patients from a US Commercial Claims Database. An average reduction in ARR of -0.11 (0.41 vs 0.30; p<0.05) was demonstrated in the year following initiation of dimethyl fumarate versus the year before initiation.4

The MSBase registry data also found that approximately twice as many dimethyl fumarate-treated patients discontinued treatment after six months of continuous therapy relative to fingolimod (HR 2.39; 95% CI 1.78, 3.20) and interferons (HR 1.40; 95% CI 1.07, 1.83).1 No difference was found versus glatiramer acetate (HR 1.18; 95% CI 0.89, 1.56) or teriflunomide (HR 0.95; 95% CI 0.66, 1.37).1

The use of patient coaching to reduce discontinuation rates was demonstrated in a retrospective real-world study. In patients treated with dimethyl fumarate, rates were reduced in coached patients by up to 48% versus controls (5.7%, 17.1% and 29.2% of coached patients [n=4750] stopped therapy after 3, 12 and 24 months, versus 10.4%, 25.2% and 56.4% of controls [n=3266], respectively).5

Reasons for therapy discontinuation differed between coached and control patients, with partly manageable side effects found to be the main reason for discontinuation for controls. These results could indicate the potential for patient coaching to play an essential role in overcoming such side effects for dimethyl fumarate patients.5

Additional real-world data presented by Biogen demonstrated that the safety profile of dimethyl fumarate remained consistent over nine years,3 and its overall benefit-risk remained favourable.6 These data also further substantiate current guidance for monitoring absolute lymphocyte counts (ALC) to mitigate the risk of moderate to severe prolonged lymphopenia during treatment with dimethyl fumarate.6

Data from ENDORSE further clarify benefits of dimethyl fumarate for newly-diagnosed patients

New 7-year data from the ENDORSE study, an extension to the DEFINE and CONFIRM clinical trials, demonstrated that ARR remained low at 7 years for both treatment groups (0.13 [95% CI 0.10–0.18] with dimethyl fumarate; 0.16 [95% CI 0.11–0.24] for patients switched from placebo). Switch patients experienced a 61% relative reduction in ARR following the switch to dimethyl fumarate after 2 years on placebo (ARR 0.26 [95% CI 0.18–0.37] vs 0.10 [0.07–0.15]; p<0.0001).2 These findings illustrate the potential of dimethyl fumarate to provide positive clinical outcomes over the long-term for people with relapsing remitting MS.

In addition, estimated 24-week confirmed disability progression (CDP) was 18.0% (95% CI 12.0–26.4) in the dimethyl fumarate group versus 26.4% (95% CI 17.4–38.7) in the switch group, representing a 41% risk reduction (95% CI 0.32–1.10, p=0.0979).2


  1. Spelman T, et al.Comparative analysis of MS outcomes in dimethyl fumarate-treated patients relative to propensity matched fingolimod, interferon, glatiramer acetate, or teriflunomide. P1157. The 32ndCongress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS), London, England, 14–19 September 2016.
  1. Gold R, et al.Seven-year follow-up of the efficacy of delayed-release dimethyl fumarate in newly diagnosed patients with relapsing-remitting multiple sclerosis: integrated analysis of DEFINE, CONFIRM, and ENDORSE. P631. The 32ndCongress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS), London, England, 14–19 September 2016.
  1. Fox RJ, et al.Absolute lymphocyte count and lymphocyte subset profiles during long-term treatment with delayed-release dimethyl fumarate in patients with relapsing-remitting multiple sclerosis. P716. The 32ndCongress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS), London, England, 14–19 September 2016.
  1. Boster A, et al.Annual relapse rates in multiple sclerosis patients treated with different disease-modify therapies – findings from a real world setting. EP1481. The 32ndCongress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS), London, England, 14–19 September 2016.
  1. Begus-Nahrmann Y, et al.The potential of individualized patient coaching to optimize treatment with delayed-release dimethyl fumarate: a retrospective analysis of patients with multiple sclerosis treated in a real-world setting. P1214. The 32ndCongress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS), London, England, 14–19 September 2016.
  1. Buckle G, et al.Effect of delayed-release dimethyl fumarate on lymphocyte subsets in patients with relapsing multiple sclerosis: a retrospective, multicentre, observational study (REALIZE). EP1495. The 32ndCongress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS), London, England, 14–19 September 2016.

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