Highlights from the 2015 ECTRIMS Meeting

Written by Susan Courtney, MSAA Senior Writer and Creative Director
Reviewed by Jack Burks, MD, MSAA Chief Medical Officer

The annual meeting of ECTRIMS (European Committee for Treatment and Research in Multiple Sclerosis) 31st congress took place on October 7-10, 2015 in Barcelona, Spain. Established in 1984, ECTRIMS is a European professional organization dedicated to understanding the cause and pathophysiology of MS and to the development of new treatments. Each year, ECTRIMS hosts the world’s largest annual international conference devoted to basic and clinical research in multiple sclerosis.

Hundreds of presentations were given along with more than 1,400 abstracts, so covering all of the topics would not be possible. This article summarizes just a few of the highlights from this recent conference that may be of particular interest to the MS community. Please note that we have not included details on the approved disease-modifying therapies. Many presented long-term data, with many “real world” experiences, showing continued safety and efficacy. No new or unexpected danger signals were identified.


Sun Exposure and Vitamin D

The EnvIMS study was conducted in Canada, Italy, Norway, Serbia and Sweden to analyze sun exposure during early life (prior to 15 years of age) to determine any association between sun exposure and an increased risk of MS. The results presented in this analysis only include data from the first three countries listed. Researchers analyzed questionnaires completed by individuals with MS and matched controls from each country. They found that MS risk was highest in individuals who during their early life experienced low levels of sun exposure in the summer, winter, and during weekends, along with higher levels of sun protection.

Another study looked at the Vitamin D level in people with relapsing-remitting MS (RRMS) and secondary-progressive MS (SPMS) to see if it may be associated with an increased risk of conversion from RRMS to SPMS. Vitamin D levels did not predict the three-year risk of conversion to SPMS. However, individuals with SPMS who did not have RRMS for a long duration, were found to have significantly lower Vitamin D levels than matched individuals with RRMS who did not progress to SPMS. These findings show a relationship between a low Vitamin D at the start of RRMS and early conversion to SPMS.

Fatty Acids

Researchers prospectively looked at the data from more than 81,000 women in the Nurses’ Health Study (1984-2004) and more than 95,000 women from the Nurses’ Health Study II (1991-2009). Their objective was to determine if an association may exist between the intake of dietary polyunsaturated fatty acids (PUFA) and the risk of developing MS. The researchers found that a higher intake of total PUFA, and particularly of linolenic acid and linoleic acid, was significantly associated with a lower risk of MS. The authors note that more studies are needed to confirm these findings, but also note that this may be another modifiable risk factor for MS.

Cancer Risk

A study in France looked at the lifetime cancer risk among individuals with MS compared to matched controls. Using a questionnaire, researchers looked at the responses from 902 individuals with MS and 903 controls. They found that the overall incidence of cancer was estimated to be 8.1 percent in the MS population and 16.6 percent in the control group. The authors concluded that people with MS have a significantly lower incidence of cancer and that the use of disease-modifying therapies (DMTs) did not increase this risk.


In a study of 254 individuals with relapsing MS who smoked (tobacco products) for more than five years, researchers compared magnetic resonance imaging (MRI) data between those who quit smoking and those who did not. Both groups continued to smoke during the first four years of the study, during which time baseline and four-year scans were performed. From years four to six, 148 continued to smoke while 106 stopped smoking. Compared to the individuals who continued to smoke, those who stopped experienced a significant decline in the rate of brain-volume loss. The authors believe this is the first study to look at brain-volume loss specifically in smokers with MS. They advise that people with MS who smoke should be actively counseled in an effort to quit smoking.

Clinically Isolated Syndrome

Treatment with Minocycline

Minocycline is an oral antibiotic that is inexpensive and has a known safety profile. In a Canadian Phase III double-blind study, 142 individuals with a first clinical demyelinating event, i.e., clinically isolated syndrome (CIS), were randomized to oral minocycline at 100 mg twice daily or an identical placebo. Treatment was continued for up to two years, or until MS was confirmed. Those receiving minocycline had a 44.6 percent lower risk of conversion to MS at six months, and a 37.6 percent lower risk at 12 months, versus individuals taking a placebo. The authors suggest that with the known safety and low cost of minocycline, this medication should be considered for the initial treatment of individuals with a first clinical demyelinating event, as well as for trials with combination therapies.

Progressive MS

MRI Differs between Types of MS

In a study to compare lesions in the brain and spinal cord of individuals with RRMS and primary-progressive MS (PPMS), 80 individuals (40 with RRMS and 40 with PPMS) underwent both brain and spinal-cord MRI scans. Participants were then categorized according to where they had lesions: brain only; spinal cord only; or brain and spinal cord. Lesions in the brain only were more common in individuals with RRMS, whereas lesions in the spinal cord only were more common for people with PPMS. Brain plus spinal cord lesions were similar between the two groups. Given the difference in the brain-only and spinal-cord-only groups, the authors believe that this supports the theory that PPMS is a distinct entity from the relapsing forms of MS. Additional analysis of the findings are planned.

Ocrelizumab Delays Disability Progression

Ocrelizumab is an investigational medicine for the long-term treatment of MS. This experimental medication has not only shown effectiveness with relapsing forms of MS, but has also shown positive study results in the Phase III ORATORIO study with primary-progressive multiple sclerosis (PPMS). This is the first medication to show positive effects on disability with this form of the disease, which affects approximately 10 percent of the MS population.

ORATORIO was a randomized, double-blind, and global multi-center trial that studied the effectiveness and safety of ocrelizumab compared to placebo in 732 people with PPMS. Every six months, two 300-mg infusions (for a total of 600 mgs) were given two weeks apart. Members of the treatment group were compared to a placebo group. The primary endpoint of this study was time to the onset of confirmed disability progression, defined as an increase in EDSS that is sustained for at least 12 weeks.

The Phase III ORATORIO study met its primary endpoint, showing that treatment with ocrelizumab significantly reduced the progression of clinical disability sustained for at least 12 weeks compared with placebo. Walking speed, as measured by the timed 25-foot walk, was improved by 29 percent. The incidence of adverse events associated with ocrelizumab was similar to placebo; the most common adverse events were mild-to-moderate infusion-related reactions. MRI hyper-intense T2 lesions were actually reduced by ocrelizumab, and brain-volume loss as viewed on MRI was reduced by 17.5 percent. In conclusion, this is the first study where a disease-modifying therapy has shown effectiveness in treating PPMS.

Research Trends

In this ECTRIMS presentation, the authors identify research trends in the treatment of progressive forms of MS. They reviewed trials in progress and future areas of research. The authors note both the importance and the challenges to finding effective therapies for this subgroup of the MS community.

As of May 2015, they had identified 33 trials that were in progress. Nearly 8,000 study participants are expected to be enrolled in these studies. The authors list the therapies being studied as follows:

  • Antioxidants (ibedenone)
  • Tyrosine kinase inhibitors (Masitinib)
  • Sphingosine receptor modulators (fingolimod, siponimod)
  • Immunomodulators (dimethyl fumarate, laquinimod)
  • Monoclonal antibodies (natalizumab, ocrelizumab, intrathecal rituximab)
  • Bone marrow/stem-cell therapy
  • Neuroprotective agents (amiloride, riluzole, fluoxetine)
  • Oxcarbazepine
  • Lithium
  • Phosphodiesterase inhibitors (ibudilast)
  • Hormone-based therapies (testosterone, ACTH, estriol, erythropoietin)
  • T-cell receptor peptide vaccine (NeuroVax)
  • Autologous T-cell immunotherapy (Tcelna)
  • MIS416 (a microparticulate immune response modifier)
  • Dopamine antagonists (domperidone)
  • Andrographolide (an anti-inflammatory herbal extract)
  • Caprylic triglycerides
  • Lipoic acid
  • MD1003 (highly concentrated biotin)
  • Sunphenon (green tea extract/epigallocatechin-gallate)

The authors conclude that the future is promising for the development of targeted disease-modifying therapies (DMTs) for the progressive MS population. They also state that strategies using novel trial designs, drug repurposing, and new models of collaboration may assist in identifying effective treatments that may be quickly implemented into treatment plans for individuals with this type of MS.

Biotin Pilot Study

As noted in MSAA’s article on the highlights of this year’s American Academy of Neurology’s (AAN’s) 67th Annual Meeting, biotin is a B vitamin, although it is sometimes referred to as Vitamin H. It is involved in key steps of energy metabolism and fatty acid synthesis. Among other actions, biotin activates an enzyme in myelin synthesis. Using this hypothesis and building upon data from a small, open-label pilot study, MD1003, a high-dose biotin preparation of 300 mg/day, was studied in a Phase III trial of patients diagnosed with SPMS or PPMS. Please note that this dose is hundreds of times higher than what can typically be purchased as a supplement of this vitamin.

In the abstract presented at ECTRIMS, the authors noted that biotin significantly improved MS-related disability and decreased the risk of progression in patients with progressive MS. They also note that these effects were more pronounced in individuals with SPMS, although this could be a result of not having enough people with PPMS in the study. Study participants who were also treated with fampridine experienced a decreased risk of progression and benefits in general wellbeing.

Also noted in MSAA’s earlier article, these results suggest a possible therapeutic effect of high-dose biotin in progressive MS and merit further study. Though this trial gives initial support for its potential use, a larger trial will need to be done to truly understand whether biotin is an effective treatment in progressive MS. Noting that the dose of biotin studied would require taking hundreds of commercially-available pills of this vitamin, it is not recommended that patients begin such a regimen at the present time. Studies also need to determine if any toxic effects could result from taking such high doses of this vitamin, although none were reported in the trials.

Other Experimental Treatments

Stem Cells

MS stem cell collaborative groups in Europe have clinical trials underway. A Polish experiment showed positive four-year results on relapses (86 percent with no relapses), MRI (78 percent with no new T2 lesions), and disease progression (82 percent stable). A Seattle group has been doing MS stem cell research for 20 years. The most recent three-year study showed 90 percent of treated patients were free of progression, 87 percent were relapse-free, and 21 percent had no relapses, progression, or MRI changes.


Ocrelizumab is showing effectiveness in treating both relapsing forms of MS as well as PPMS (as noted earlier). In this report, ocrelizumab met both the primary and major secondary endpoints in the Phase III, OPERA I and OPERA II studies.
The total combined enrollment for both studies was 1,656, which included individuals with relapsing forms of MS who either had relapsing-remitting MS or secondary-progressive MS with relapses. Taking place at 307 sites in 40 countries, individuals received either 600 mg of ocrelizumab via intravenous (IV) infusion every six months, or the approved 44-mcg dose of Rebif® (interferon beta-1a), given via subcutaneous injection three-times weekly. Significant reductions resulted in annualized relapse rate (ARR) over a two-year period, progression of clinical disability, as measured by the Expanded Disability Status Scale (EDSS) and number of lesions in the brain (areas of disease activity) as measured by MRI.


Daclizumab (with the brand name, (Zinbryta™) is being studied in RRMS and SPMS. It is a genetically engineered monoclonal antibody that binds to CD25, a receptor on T cells that is thought to become activated in response to MS. Daclizumab is believed to work by selectively targeting these activated T cells without causing general T-cell depletion. It is approved by the FDA for use in rheumatoid arthritis and other autoimmune diseases. Daclizumab high yield process (DAC HYP) is administered subcutaneously once every four weeks, rather than via intravenous infusion.

In abstracts presented at ECTRIMS, DAC HYP was shown to be more effective in patients at risk for high disease activity, as well as for those with less active disease, compared to individuals taking interferon beta-1a (Avonex®). Over the course of three years, DAC HYP was also associated with less brain-volume loss with RRMS, compared to individuals taking interferon beta-1a. The safety and tolerability profile has been well characterized in clinical studies for periods up to six years. Showing a positive benefit/risk profile, DAC HYP represents a potential effective treatment option for individuals with RRMS.

Gut Microbiomes

Gut microbiomes (bacteria) affect immune cells in the bowels. These cells can affect immunity throughout the body, including in MS patients. This article shows that Aubagio® (teriflunomide) can change gut immunity to increase “good immune cells.” These cells “down regulate” the reactive immune cells that damage the brain in MS. This may be an added explanation as to why the drug has a positive effect in MS patients. This work was done in a mouse model of MS (EAE). Other DMTs may also affect the gut microbiomes in a way to increase their positive affect on MS. The main point is that gut bacteria may affect MS in a positive (or negative) way.

MS Symptoms

Cognition and Information Processing

Cognitive impairment is common in MS and trials have shown that first-line disease-modifying therapies (DMTs) have had positive effects on cognitive measures. In another study, newly diagnosed individuals and healthy controls were given either interferon beta-1a, interferon beta-1b, or glatiramer acetate, to compare their effects on cognitive status in MS. Researchers found that the number of cognitively impaired patients decreased at month 12, and then remained stable at month 18 and month 24. No difference was found between the three treatment arms. These results indicate that DMTs significantly improve cognitive function after one year of starting treatment with either an interferon or glatiramer acetate, and no difference was found between these different treatments.

An 11-year follow-up of the BENEFIT study (BENEFIT 11), showed that individuals given Betaseron in early MS (those with clinically isolated syndrome, or CIS) experienced an improved cognitive performance early in the trial. That improvement persisted for 11 years compared to patients whose treatment was delayed for up to two years. This indicates that early treatment was important in improving cognition in the long term as well as improving the physical aspects of MS.

In a separate two-year observational study, 63 individuals with MS who were already taking natalizumab (Tysabri) were given a baseline assessment on cognition at the start of this study. Participants were divided into two groups: those who had already been taking Tysabri for more than two years, and those who had been taking Tysabri for two years or less. After an additional two years in the observational study, regardless of how long participants were taking Tysabri previously, significant improvements were seen at the group level in executive function, verbal memory, and working memory. Over a two-year period, no patient experienced a sustained worsening of cognitive function. According to the authors, the results of this study suggest that Tysabri preserves cognitive function, including the ability to learn, for four years and beyond of continuous therapy.

The authors of a small study note that while cognitive rehabilitation for an individual has been shown to be effective, no studies have been conducted in a group setting that addresses several cognitive symptoms. Researchers looked to determine the effectiveness of an integrative group-based cognitive rehabilitation program (REHACOP) on improving a range of cognitive symptoms in individuals with MS. Three one-hour sessions were conducted weekly for three months, focusing on attention, learning and memory, executive function, language, and social cognition. Extensive neuropsychological assessment was performed at baseline and after the completion of the three-month program. Compared to the control group, the individuals receiving REHACOP showed significant improvements in several of the cognitive domains. These results suggest that an integrative approach in a group format may be an effective approach to improving cognitive issues for individuals with MS.

Another study found that individuals with MS who smoke cannabis exhibit slower information-processing speed in comparison to individuals with MS who do not smoke cannabis. Additionally, when viewed on an MRI, the pattern of cerebral activity in the brain associated with information processing is also different between those with MS who smoke cannabis and those who do not. Individuals who smoke cannabis had less activation on both sides of the thalami (an area of the brain that relays sensory information), and increased activation in the anterior cingulate (an area of the brain that regulates certain autonomic and endocrine functions, and is also involved in emotional learning, vocalizations, and other functions).

Sleep Patterns and Fatigue

Researchers studied sleep patterns in people with MS who also experience fatigue. They found that these individuals required more time to fall asleep and more time to reach REM sleep, which can result in less time available for these important sleep periods. The authors note that reduced REM sleep may directly contribute to daytime symptoms in MS, including fatigue.

Walking, Fatigue, and Balance

Fampridine is the active ingredient in Ampyra™ (dalfampridine), an oral, timed-release medication developed to improve the conduction of impulses between damaged nerves of the central nervous system (CNS). It was approved in 2010 by the United States Food and Drug Administration (FDA) to improve walking in individuals with MS. A non-randomized prospective study of 30 individuals with different types of MS found that in addition to walking speed, fampridine has the potential to improve physical and cognitive fatigue, mood, and quality of life. The authors point out that further placebo-controlled studies are needed to precisely identify fampridine’s benefits beyond its effects on walking.

A small study sought to identify the effectiveness of different assistive devices on gait and walking for individuals with MS who have problems with walking. The researchers found that the study participants experienced greater improvements while using either a single-point cane or a trekking pole, versus a four-point cane. One factor contributing to this better performance is thought to be the more positive psychosocial impact that these first two devices provide, versus the four-point cane, which may have a negative psychological impact for individuals with MS. The authors suggest that the single-point cane and trekking pole are good first-line options for people with MS who have difficulty in walking.

In an effort to identify an effective, safe, and fun method of improving balance problems in MS, researchers looked at the Nintendo® Wii Fit™ games as a possible activity to be added to conventional treatments. In this small pilot study, six individuals with MS who experience balance problems participated in a balance exercise program that included several Wii Fit games (appropriate for one’s abilities) for 16 supervised sessions of 45 minutes each. Significant improvements were observed in one-leg stance for both the right and left legs. More importantly, functional MRI demonstrated objective evidence of increased connectivity in the areas of the brain that are associated with balance. While more studies are needed, the authors conclude that the Nintendo Wii Fit games may be an enjoyable and effective method for improving balance when added to one’s conventional treatment plan.


Nabiximols are a cannabinoid-based preparation that is given via nose spray. It is approved in parts of Europe and Canada for the treatment of spasticity in MS. In this Italian study, changes in spasticity-related measures were analyzed for one year in 120 patients suffering from moderate to severe spasticity; most with progressive disease. Of the 120 participants, 96 percent (115) completed the first month of treatment; and of these 115, 84 (73 percent) were considered to be responders to the therapy. This latter group of responders experienced a significant improvement in spasticity, which persisted one year after starting therapy. Drop-out rate was considered low (at 15.8 percent) and was largely due to side effects, which included confusion, fatigue, and vertigo.

MS in Women

Oral Contraceptives

Oral hormonal contraceptives may have an impact on the clinical course of MS. An exploratory, retrospective study was conducted with 141 women with MS, 75 of whom were not taking oral contraceptives and 66 of whom were taking oral contraceptives. This study showed that those in the latter group experienced a less severe disease course, based on the MS Severity Score (MSSS) and disability progression as measured by the Expanded Disability Status Scale (EDSS). However, results were mixed as no difference was observed in the annual relapse rate (ARR).

Epidural Analgesia

MS affects many women during their childbearing years and studies have been conducted to see what factors may increase the risk of post-partum relapses. Researchers looked retrospectively at the analyzed data of 389 women following their pregnancies and at least three months post-partum. According to the study, 156 women out of the 389 received epidural analgesia during delivery. Researchers found that those who received an epidural did not have an increased risk of a post-partum relapse, even if they experienced a relapse during pregnancy. These results suggest that epidural analgesia may be used safely in women with MS.

Mental Health

Risk of Suicide

A large Swedish study looked at nearly 30,000 individuals with MS to compare suicide rates with matched individuals without MS. The authors concluded that both women and men with MS are at a higher risk of both attempted and completed suicide, finding that women are at a higher risk of attempting suicide, while men are at a higher risk of completing suicide. The authors theorize that the stress and perceived prognosis associated with MS may cause this increased risk. Additionally, people with a higher education are usually less-likely to attempt or complete suicide, however, this is not true for individuals with MS. These findings may assist the medical community in taking a more proactive role in identifying people with MS who may be at a higher risk of suicide and recommending counseling as well as other urgent programs to patients and their families.

Psychiatric Disorders in MS

A large Canadian study looked at nearly 47,000 people with MS over the course of 10 years to determine the incidence and prevalence of psychiatric disorders, specifically depression, anxiety, bipolar disorder, and schizophrenia. Compared to matched controls, the incidence and prevalence of these disorders were all higher in the MS population. The authors note that these data suggest a non-specific effect of MS on these types of disorders and implies the need for psychiatric support to be included in treatment plans, in addition to illness-specific strategies.


Disease-Modifying Therapies

Researchers looked at using Tecfidera™ (dimethyl fumarate) for the treatment of children with RRMS who either experience a suboptimal response to conventional first-line therapies or who are not able to tolerate the side effects. Of the 13 children treated, three discontinued due to side effects. Nine children were followed for at least 12 months; they experienced either stabilized or improved EDSS scores while on treatment for one year or more. The authors suggest that this oral medication may be safe and well-tolerated for children with relapsing forms of MS, but results from ongoing formal studies are needed to confirm these findings. Tecfidera is not FDA-approved for pediatric MS at this time.

A report was presented about a 13-year-old girl who was diagnosed with highly aggressive MS when she was 12. She was initially given Rebif® (interferon beta-1a), but continued to experience relapses and MRI activity. Ten months after diagnosis, she received Lemtrada® (alemtuzumab), which is approved for highly active MS in adults, but is not FDA-approved for pediatric MS at this time. After receiving a first cycle of Lemtrada, the 13-year-old girl stopped experiencing relapses and no inflammatory activity was seen on MRI scans. The treatment was well-tolerated. The authors propose that Lemtrada may be considered as a therapeutic option for pediatric MS cases with high inflammatory activity.

The Betapaedic study is designed to measure the safety and tolerability of interferon beta-1b (Betaseron®) in the treatment of pediatric patients with RRMS. It is an observational study and does not have a control group. Participants include 67 children with MS, between the ages of 12 and 16, and who had not received previous disease-modifying therapy (DMT). After one year of treatment, 64.2 percent had no relapses, 83.6 percent had no change in disease status, and 50.7 percent were both relapse-free and progression-free. However, MRI scans indicated new T2 lesions in 49.3 percent of the patients and gadolinium-enhancing lesions in 29.9 percent of the patients, relative to baseline. No new or unexpected adverse events were reported and further follow-up will provide additional information. Betaseron is not FDA-approved for Pediatric MS at this time.

At 15 MS centers in Brazil, Gilenya® (fingolimod) was given to 30 young individuals with MS before the age of 21 (ranging in age from 14 to 20), all of whom had very active MS. The goal of the study was to report on the short-term safety and efficacy of this treatment in young patients. Researchers found that fingolimod was both safe and effective for this population. No major adverse events were reported and degree of disability did not progress in any of the participants. Three of the patients (10 percent) experienced a new relapse and new lesions on MRI; fingolimod was discontinued in two of these cases. The authors conclude that fingolimod is a good therapeutic option for individuals before the age of 21. However, they also note that the observational period was relatively short and much longer follow-up is needed to further support the data on efficacy and long-term safety. Gilenya is not FDA-approved for pediatric MS at this time.

Activity Levels, Depression, and Fatigue

Researchers in Canada looked at the activity levels of children with MS, compared to children with acquired demyelinating syndromes (about one-fifth of whom will eventually be diagnosed with MS) and healthy controls. They found that children with MS were less likely to participate in vigorous physical activities than the other two groups observed. Those who participate in vigorous physical activities experience fewer symptoms of depression and fatigue — both of which are common in children with MS. The investigators suggest that more studies be conducted, focusing on interventions that would encourage more participation in these types of activities that could potentially improve the symptoms of depression and fatigue.

For more information about MS or to speak with a trained Client Services Specialist, please call MSAA’s Helpline at (800) 532-7667, extension 154. Questions to MSAA’s Client Services department may also be emailed to MSquestions@mymsaa.org.