Highlights from the 2014 Joint ACTRIMS-ECTRIMS Meeting

Written by Margaret M. McCormick, RN, BSN, MSCN
Reviewed by Jack Burks, MD, MSAA Chief Medical Officer
Edited by Susan Wells Courtney

Every three years, two international organizations come together to share, discuss, and debate the most recent basic and clinical research findings in the area of multiple sclerosis (MS). The joint meeting, alternately hosted in North America and Europe, took place in Boston, Massachusetts September 10th through 13th.

This is the sixth triennial joint conference of ACTRIMS (Americas Committee for Treatment and Research in Multiple Sclerosis) and ECTRIMS (European Committee for Treatment and Research in Multiple Sclerosis). ECTRIMS, established in 1984, is the European professional organization dedicated to understanding the cause and pathophysiology of MS and to the development of new treatments. ACTRIMS, established in 1995, is the North American counterpart to ECTRIMS, and provides a forum to exchange information, debate current issues, and discuss advances related to basic and clinical issues in research in MS and other demyelinating diseases.

This summary of the ACTRIMS-ECTRIMS Sixth Triennial Joint Meeting highlights focuses on topics of particular interest to those directly affected by MS and MS healthcare professionals. While we would like to include more information, only a fraction of the more than 1,700 scientific papers and almost 200 presentations could be addressed in this article.

Experimental Therapies

Lemtrada® (alemtuzumab, formerly Campath), is given intravenously each day for five days and again one year later, daily for three days. Lemtrada has been submitted to the United States Food and Drug Administration (FDA) for approval; a decision is expected in late 2014.

The majority of patients treated with Lemtrada (alemtuzumab) in the CARE-MS I study (a Phase III comparison of alemtuzumab and Rebif in treatment-naïve patients) were free of new brain lesions and magnetic resonance imaging (MRI) activity at year three. Although the majority of the patients did not receive treatment after the first two yearly courses of Lemtrada, most continued to experience a slowed yearly rate of brain volume loss over three years.

For a summary of research conducted to support approval for relapsing-remitting MS (RRMS), please see MSAA’s MS Research Update 2014.

Laquinimod is an oral medication taken once daily under investigation for the treatment of RRMS. In the Phase III BRAVO trial, treatment with laquinimod resulted in a significant reduction in brain atrophy (reduction) in both grey matter and white matter, compared to placebo. Using pooled data from the ALLEGRO and BRAVO trials, researchers determined that laquinimod demonstrated significant benefits in relapse, disability, walking, and MRI outcomes in patients with RRMS with Expanded Disability Status Scores (EDSS) of more than 3 (where an individual is able to walk but experiences moderate difficulty in one functional system [FS] or mild difficulty in another area).

For a summary of research conducted to support approval for RRMS, please see MSAA’s MS Research Update 2014.

Daclizumab (also known as Zenapax®) is given by intravenous (IV) infusion every four weeks and is also studied when given in subcutaneous injections. It is under investigation for the treatment of both RRMS and secondary-progressive MS (SPMS). Primary results were reported for the DECIDE study in which 1,841 RRMS patients were randomized to treatment with either Avonex (interferon beta-1a) 30 mcg every week or daclizumab HYP (high-yield process) 150 mg every four weeks, both delivered by subcutaneous injection (under the skin).

Treatment with daclizumab resulted in a 45-percent reduction in annualized relapse rate (ARR), a 54-percent reduction in new and newly enlarging T2 lesions, and a 65-percent reduction in new gadolinium-enhancing lesions. Risks associated with daclizumab treatment included infections, rash dermatitis, and liver enzyme abnormalities.

For a summary of research conducted to support approval for RRMS and SPMS, please see MSAA’s MS Research Update 2014.

Generic Disease-Modifying Therapies

A nine-month randomized, double-blind trial of 794 people with RRMS, called “GATE,” demonstrated that generic glatiramer acetate was equivalent to Copaxone® and superior to placebo in both safety and efficacy. The concept of generic versions of MS disease-modifying therapies is relatively new to the MS community, as the original drugs were protected by law to have a certain period of exclusivity. As these time periods expire, other pharmaceutical companies may look to provide similar drugs. MSAA published an online article on this topic titled, “The Issues Surrounding Generic Versions of MS Drugs.”

Pregnancy and Breastfeeding


Because DMTs are not tested in pregnant women, information about the potential risks of fetal exposure is not available to guide decision-making by women who are pregnant or wish to become pregnant. Gathering as much information as possible on this important question is critical to women with MS during child-bearing years. Although women are advised to use birth control and to discontinue DMTs when they wish to become pregnant, fetuses are exposed during unexpected pregnancies or with the intentional use of DMTs during pregnancy. The outcomes of these pregnancies are monitored during clinical trials and through pregnancy registries following product approval.

While the data presented at the meeting on pregnancy were encouraging, as a limited number of women who became pregnant on DMTs did not see abnormalities in their babies, individuals with MS need to be strongly cautioned. These data were on small numbers of women and do not suggest that getting pregnant is considered safe while taking DMTs. The recommendations of the FDA and MS experts still stand for women on DMTs to take preventative measures to avoid pregnancy.


In a German study of 201 women, women with MS who breastfed their newborn infants for two months exclusively did not experience more post-partum relapses than those who bottle-fed or used supplemental feedings.

A 10-year study of all pregnancies in a hospital in Spain found no difference in the course of MS disease between women who chose to breastfeed and women who chose artificial feeding and restarted their treatment sooner.

Risk Factors and MS

MS is a disease marked by feelings of loss of control due to the unpredictable nature of the disease. While still unpredictable, it is encouraging to discover that there are lifestyle factors under one’s control that have the potential to modify the course of the disease. Research is ongoing around what are known as modifiable risk factors, which include smoking, exercise, body weight, salt intake, and Vitamin D levels.


The risk of developing anti-natalizumab antibodies (which decrease the effectiveness of Tysabri) was 2.4 to 2.7-times higher in smokers than in non-smokers, with a trend toward increasing risk with increasing intensity of smoking.

People with MS with the HLA-DRB1*15:01 gene who smoked had a higher annualized relapse rate (ARR) during treatment with interferon-beta than those who did not smoke.

Thirty-two genes are expressed differently in MS patients who smoke and those who do not smoke. Smoking was found to increase the genes involved in the pro-inflammatory process in people with MS.


In a study of 70 RRMS patients over a period of one year, higher salt intake was associated with a 2.75 to 3.95-times higher relapse rate as compared with those in the low-intake group. Higher salt intake was also associated with a 3.4-fold higher chance of developing a new MRI lesion. Similar findings were documented in a subsequent study of 52 patients.


A relationship was found between the interaction of infectious mononucleosis (IM) and adolescent obesity and the risk of developing MS. A possible explanation, according to the study authors, is that an obese state both impacts the cellular immune response to infections such as IM and causes a state of chronic immune-mediated inflammation. Women with a higher weight in adolescence and higher body mass index (BMI) in early adulthood were younger at the time of their diagnosis with MS.

Vitamin D

Vitamin D levels were lower in those with progressive MS than RRMS in a retrospective study of 181 people with MS. (A retrospective study is one that reviews data previously collected for another reason.) A relationship was also found between Vitamin D levels and the degree of disability in a subgroup of people with RRMS.

As Vitamin D levels decreased, the number of new, active lesions increased in a study population of individuals with RRMS from the BEYOND study (a study that compared treatment of two different doses of Betaseron with Copaxone). This relationship was present even in the population that was considered to have adequate levels of Vitamin D.

Vitamin D level was only associated with the risk of relapse in those patients carrying at least one copy of HLA-DRB1 or HLA-DRB3, the strongest genetic risk factor for MS in a group of children diagnosed with MS or with clinically isolated syndrome (CIS). This latter syndrome refers to individuals who show certain symptoms of MS, but do not have enough evidence of the disease to confirm a diagnosis of MS.

Other Topics


Optical coherence tomography (OCT), a non-invasive imaging test that uses light waves to take cross-section pictures of the retina, might help determine brain atrophy (reduction) without the need for a brain MRI. Researchers found that certain changes in the retina accurately reflected grey matter atrophy in the whole brain, especially in those with progressive MS.

Parasitic Infections and MS

Parasite infection was found to be protective against MS disease activity in a group of 12 parasite-infected MS patients. Compared to individuals with MS who were not infected, parasite-infected MS patients experienced a significantly lower number of relapses, a lower change in EDSS scores, and fewer brain lesions on MRI. Conversely, when treated with anti-parasitic drugs, the parasite-infected group experienced worsening of their disease.

Adherence to MS Medications

In a group of German people with MS who completed an anonymous online survey of medication-adherence behavior, 35 percent reported problems with adherence. Patients who had realistic expectations of the benefits of adherence, good self-management skills, and reliable sources of information, were more adherent. An individualized program of patient counseling (PCP) resulted in increased adherence related to better management of adverse events.

Gut Microbial Environment

Studies have related gut dysbiosis (an imbalance in the microorganisms in the gut resulting from too few good bacteria and/or too many harmful bacteria) with development or severity of many conditions, including Crohn’s disease, type I diabetes, obesity, and autism. The Corinne Goldsmith Dickinson Center for Multiple Sclerosis at Mount Sinai Hospital in New York City and University of California San Francisco MS Center are collaborating to study whether gut dysbiosis may have an impact on MS.

Iron Deposits

Neurodegeneration (injury to nerves) is associated with the accumulation of iron in the oligodendrocytes (cells that produce and repair myelin), and appears to contribute to disability in MS. Researchers studied the brains of individuals who died from complications associated with MS and found that iron was primarily stored in the oligodendrocytes.


Signs of remyelination (myelin repair) may be present even in cases of profound axonal (nerve) damage. Examination of biopsied brain tissue from patients with early MS (obtained to exclude diseases such as infection or cancer) revealed that signs of remyelination are sometimes present, despite the fact that these lesions were mainly demyelinated (where myelin is no longer present).

Although remyelination occurs in MS, it is often not sufficient to prevent irreversible damage and progressive disability. Researchers are beginning to understand the steps in the remyelination process. Oligodendrocyte progenitor cells (OPC) have been identified as one of the main cell types responsible for remyelination. These cells can now be identified through the use of certain markers, allowing the process to be studied in-depth.

MS Treatment with Myelin Peptide Skin Patches

MS treatments that could more specifically inhibit the inflammatory activity of the immune system could potentially represent an improvement over current medications that have a more global effect. To that end, researchers tested a myelin peptide infused skin patch in two different doses compared to a placebo, to determine whether it could help stop the inflammatory response that can result in damage to the brain.

The patches strongly suppressed the inflammatory response and also resulted in a positive clinical effect. Compared to the placebo group, patients in the treated group had positive responses with respect to the number of brain lesions, annual relapse rate (ARR), number of individuals who were relapse-free, disability, and EDSS scores. There were no serious adverse events. Redness and itching in the local area of the patch was observed in 20 percent of the individuals in the treatment group.

Stem Cells

Results of a Phase I safety study of stem cell transplantation were reported. Twenty-four individuals with RRMS or SPMS who had EDSS scores of 3.0 to 6.5 received a single IV infusion of mesenchymal stem cells that were derived from their own bone marrow.

No significant safety issues resulted; no serious or severe adverse events occurred; and there were minimal infusion-related side effects. The trial was not designed to test efficacy and there was no evidence of either disease activation or improvement with respect to brain lesions or any other measures tested. The safety study was successful, but before Phase II trials are considered, many questions need to be addressed. These include issues of cell dose, route of administration, number of infusions, and whether cells are derived from the patient or a disease-free donor.