Highlights from the 2016 ECTRIMS Annual Meeting

Epidemiology

(Research into possible causes and contributing factors)

The Microbiome

Multiple groups presented their research on the microbiome and its potential connection to MS. Over the past decade, studies have found that interactions between a person’s microbiome and his or her immune cells may contribute to the development and severity of many disease states, including MS. The microbiome refers to the many millions of bacteria that reside in a person’s body, with current research focusing mainly on the bacteria that live in the intestines. Specifically, researchers have hypothesized that imbalances in the number or types of different strains of bacteria could potentially cause the immune system to be inappropriately activated, possibly resulting in an autoimmune disease.

In one study, a group of pediatric MS researchers analyzed the microbiome of a small group of children or young adults with pediatric MS versus control subjects (children without MS). Although they were unable to find a characteristic bacteria “signature” that could identify the MS patients’ microbiomes compared to the controls, they did find that individuals with MS who had more types of bacteria in their microbiome had increased amounts of inflammatory immune cells in their blood, compared to those with fewer types of bacteria. This finding was reversed in the control group, where those who had more diversity of bacteria had a less-inflammatory profile. In another study, investigators from the MS Microbiome Consortium presented their work that demonstrated differences in the microbiome that correlated to whether a patient was treated with an MS medication or not, and if treated, whether they were on an oral or injectable MS therapy.

Diet

As part of a case-control study to assess risk factors in pediatric MS, 219 children or young adults with pediatric MS completed food questionnaires that looked at correlations between dietary components and the risk for MS relapse. While only a very slight increase in the risk of relapse was seen in patients with diets consisting of a higher fat content, researchers found that those individuals who had higher vegetable intake had 40-percent less risk for relapse versus those with low-vegetable intake. Though more work needs to be done to understand how diet might directly impact one’s MS course, this study suggests that a high-vegetable diet would be a favorable dietary intervention for people with MS.

BMI

A large study, consisting of more than 5,200 pediatric and adult MS patients and 15,000 controls from the United States and Sweden, found that people with a higher genetic risk for increased Body Mass Index (BMI) had a higher risk for getting MS. This association held true both in children and adults with MS. These findings lend support to the hypothesis that increased BMI may contribute to the risk for getting MS, though it is not clear how BMI might influence this risk.

Smoking

Many previous studies have shown a correlation between smoking, the risk of getting MS, and the risk of developing progressive MS. This year, researchers from Argentina presented their findings from a group of 183 individuals with MS. They found that those who smoked had almost twice the chance for residual disability after their first MS attack compared with non-smokers. This finding may be due to the development of more severe attacks in smokers or a decreased ability of a smoker’s nervous system to repair itself. This study underscores the importance of educating individuals with MS on the dangers of continuing to smoke after diagnosis, as it has become clear that smoking causes the course of one’s MS to be more severe than for a non-smoker.

Comorbidities

(Additional medical conditions)
Using a database comprised of data from their clinic’s electronic medical record, researchers from Ohio performed a three-year study that looked at the effect of additional medical conditions on MS in terms of walking speed, disability, and depression. They found that high blood pressure, diabetes, and obstructive pulmonary disease all had negative impacts on these MS outcomes, with high blood pressure being the most significant factor, given that it is independently associated with worsening in all three measures. This study suggests the importance of identifying and trying to control comorbidities in order to optimize outcomes in MS, though further work needs to be done to validate this.

Mortality

Early studies regarding mortality and MS have shown a decreased lifespan of about seven years for individuals with MS. Two studies were presented at ECTRIMS that found that differences in lifespan are thankfully diminishing over the years. The first study, from Denmark, looked at more than 14,000 people with MS who were followed since 1948. They found that the chance of death within 15 years of an MS diagnosis in more recent years has decreased significantly compared to 60 years ago. The second study, from Norway, also found a decreased mortality risk in recent years compared to previous years. These trends started even before MS medications were available, but it has continued since. This positive effect is most likely brought about by a combination of medications and improved treatment of complications.

Relapsing-Remitting MS

SOLAR Study

The results of the SOLAR study, the largest randomized trial of Vitamin D therapy in people with relapsing-remitting MS (RRMS) to date, were presented at ECTRIMS. The SOLAR study randomized 229 patients who were on high-dose interferon beta-1b therapy either to high-dose Vitamin D3 (14,000 IU daily) or placebo. Originally, the study was planned for a period of 96 weeks, but because of challenges with recruitment, the study length was changed to 48 weeks. The primary endpoint of the study was disease-activity-free (DAF) status at week 48. DAF was defined as having no relapses and no new MRI lesions or worsening of disability.

This study did not find a difference in DAF status between the high-dose Vitamin D3 group and the placebo group. No difference was seen in the relapse rate. However, the study found a 32-percent decrease in the number of new lesions in the Vitamin D3 group versus the placebo group. The small study size may have possibly precluded more significant results. The finding of a decrease in new lesion formation, as seen on magnetic resonance imaging (MRI) in the Vitamin D3 group, is intriguing and deserves further study. However, as evidenced by the SOLAR study, in order to definitively answer the question of whether Vitamin D3 has a protective role in MS, it will be critical to design studies that are large enough and able to obtain full recruitment.

Treatment Early in the Clinical Course

Researchers from Sweden presented a series of 639 individuals who were diagnosed with MS from 2001 to 2007 and followed on average for 8.25 years. They found that for every year of delay in starting treatment, these individuals had a 6.7-percent greater risk in developing neurological disability. Put another way, people who started treatment three years after MS onset, had an almost two-and-a-half-times risk of developing disability compared to those who started treatment within one year from when their symptoms began. This study highlights the importance of recognizing MS symptoms as soon as possible and starting treatment shortly afterwards.

Progressive MS

Siponimod

The results of EXPAND, a Phase III international, randomized, and placebo-controlled trial of siponimod in people with secondary-progressive MS (SPMS), were presented at ECTRIMS. The trial randomized 1,651 individuals with SPMS to siponimod versus placebo in a 2:1 ratio (two-times as many patients were given siponimod versus placebo). The chemical composition of siponimod is closely related to an MS drug that is already available, Gilenya® (fingolimod), and is thought to work in the same way by trapping the immune cells in the lymph nodes so that they cannot enter the central nervous system to create lesions. The primary endpoint of the EXPAND trial was time to three-month confirmed disability progression (CDP). CDP was met when a participant developed an increase in his or her disability that was confirmed by a repeat exam three months later.

This trial was able to show a small, yet statistically significant, decrease in three-month CDP of 21 percent in those on the study drug compared to those on placebo. People in the siponimod arm also showed 23.4-percent less brain-volume loss as compared to placebo. However, no difference was seen in the two groups in changes in the timed 25-foot-walk. Relapses were decreased in the group taking siponimod. Overall, individuals in the treated group tolerated the drug well, though more serious adverse events and infections occurred in the siponimod group. The EXPAND trial is very important as it represents a potential treatment option for those with SPMS, given the fact that current MS treatments have not been shown to be effective in this form of MS.

Lipoic Acid

Another smaller, pilot trial also reported a positive result in SPMS. Researchers from Oregon conducted a two-year study that followed 27 individuals with MS who were given lipoic acid. Lipoic acid is a readily available anti-oxidant supplement thought to aid the function of mitochondria, which are cell structures that break down nutrients to create energy. In this study, 24 people with MS were given a placebo. After 96 weeks, the researchers found that the subjects in the lipoic acid group had significantly less brain-volume loss and were able to walk faster than the placebo group. Overall, the drug was well-tolerated, though stomach symptoms were higher in the lipoic acid group. Two participants in the lipoic acid arm had kidney issues during the trial; however, a kidney doctor thought this was unrelated to the lipoic acid treatment.

Accelerated brain-volume loss has been linked to worsening in progressive MS. The findings of this trial suggest that lipoic acid may offer neuroprotection by slowing down this process. Larger studies will need to be conducted to determine the effectiveness of lipoic acid, not only in slowing down brain loss as seen on MRI, but also to slow down the clinical progression of MS in patients.

Stem Cell Transplantation

Multiple small studies of stem cell transplantation in MS have been reported or are currently enrolling patients. Two main types of stem cell studies are being performed: hematopoietic stem cell transplants and mesenchymal stem cell transplants.

The first type, also called Autologous Hematopoietic Stem Cell Transplantation (AHSCT), is similar to a bone marrow transplant that cancer patients might receive. Stem cells are first harvested from the patient and saved, high doses of chemotherapy are given to destroy the patient’s immune system, and then shortly thereafter stem cells are transfused back into the patient. The stem cells referred to in these patients are the types of cells that will become white blood cells, which are part of the body’s immune system and work to fight disease and infection. AHSCT is often thought to bring about a “reset” of the immune system, back to its original purpose of guarding against infection and away from inappropriately attacking itself.

The second type of transplant, mesenchymal stem cell transplantation, refers to the transplantation of a patient’s own donor stem cells into the blood or spinal fluid, with the hope that they would ultimately become cells that work to repair and protect against the worsening of MS. These patients generally do not undergo high doses of chemotherapy beforehand. While the risk of mesenchymal stem cell transplants is thought overall to be lower, the mechanism by which these cells would bring about changes to a patient’s MS is less clear.

At ECTRIMS, multiple investigators provided updates on the progress of their research. A Polish group reported improvement in the quality of life of 57 individuals with MS two years following AHSCT, who were given the treatment after failing first- and second-line therapies. Participants also had improvement in disability scores over the course of the trial. Another group from Poland presented their data on 12 individuals with MS who had severe MS and were given mesenchymal stem cells directly into their spinal fluid. No major adverse events were reported and the disability levels of these patients remained stable or decreased a small amount. The field of stem cells in the treatment of MS is still in its infancy, though more trials are currently being planned and conducted that will give greater insight into their potential for use on a larger scale in the care of MS.

MS Symptom and Wellness Strategies

Cognition over the Course

Not enough is known concerning the full extent of the effect of MS on cognitive function. Researchers in Spain conducted a study in patients that examined the cognitive function of 116 subjects, including people with early MS, people with progressive MS, and healthy controls. The researchers found differences in all areas tested between individuals with MS and controls. Those with progressive MS showed greater cognitive dysfunction than those with early MS. This work adds to what is already known about cognitive dysfunction in MS, namely that it can occur early in the course and that it is more severe in progressive MS. Future MS-treatment strategies need to target not only the physical disabilities that MS can cause, but also the cognitive changes as well.

Mental Health

Mindfulness is an approach aimed at reducing stress and suffering. It accomplishes this by teaching people to be more aware of their thoughts as well as their external environment on a moment-to-moment basis. This approach has been shown to be helpful in other chronic conditions.

Researchers from Spain conducted a mindfulness study in 58 individuals with RRMS. They assigned the participants to either a mindfulness group (31 patients), who received specific mindfulness instruction, or a control group (27 patients), who received standard (nonspecific) education. Both groups met weekly for eight weeks. After the eight weeks, people in the mindfulness group reported significant decreases in anxiety and depression, as well as increases in vitality, as compared to the control group. Both groups had significantly less fatigue than before the study, although no difference was seen between the two groups in terms of fatigue levels. This study provided support for mindfulness as an effective strategy for supporting mental health in individuals with MS.

Fatigue

Fatigue is the most common symptom reported by people with MS. Better treatments for fatigue are needed in order to optimize function and quality of life. A study out of the Netherlands tried to address this issue. The investigators studied 91 individuals with MS who were assigned to either 12 sessions in a Cognitive Behavioral Therapy (CBT) group or three sessions in a control group led by an MS nurse. While the CBT group received specific training, the control group received general psychoeducation about fatigue and its effects. CBT is a form of therapy that aims to provide coping strategies enabling a patient to problem-solve as well as to correct unconstructive patterns. Participants in this study were followed for 52 weeks afterwards and were given multiple questionnaires regarding fatigue to assess the effects of the intervention.

The study found that those who were enrolled in the CBT group had decreased fatigue compared to the control group. However, after the therapy sessions finished, the effect was diminished. Thus, this study would suggest that CBT does appear to be effective for MS fatigue, but it must be continued in order for the effects to be persistent.

Spasticity

Twenty people with MS who experienced significant spasticity (typically described by a patient as muscle tightness and cramping) were given Sativex®, an oral spray that is extracted from the cannabis plant and is composed of a standardized ratio of THC and CBD, the two major components of marijuana. After four weeks of Sativex treatment in the open-label study, nine of 20 participants were labeled as responders, with improvements in both patient- and physician-reported spasticity measures. This study did not have a control group. Marijuana derivatives such as Sativex may be good treatment options for people with MS who deal with spasticity, as risks from these substances are quite low and they have been shown in small trials, such as this one, to help reduce the troubling symptoms related to spasticity.

Pain

Italian researchers polled 374 individuals with MS regarding pain prevalence and type. Chronic pain was reported by 52 percent of the participants, with neuropathic (nerve) pain being the most common type. People with sensory symptoms and those with higher levels of disability were more likely to report having chronic pain. As this study demonstrated, chronic pain in MS is common yet not universal. When chronic pain is present, clinicians need to recognize the importance of addressing an MS patient’s pain in order to optimize his or her quality of life.

Sexual Dysfunction

Sexual dysfunction remains an under-recognized and under-treated problem for many people with MS. A total of 2,062 individuals with MS, 81 percent of whom were women, responded to questions regarding sexual function. Of the 2,062 participants, 43.7 percent were satisfied with their sexual function, while 54.5 percent reported a problem in at least one area, including lack of sexual interest and erectile dysfunction. Age, risk for depression, antidepressant use, and fatigue, all increased the risk for sexual dysfunction. This large poll of people with MS found sexual dysfunction to be a common issue. Communication between the patient and his or her care team on this topic is important.

We hope that this information is of interest and may be helpful to MSAA’s readers. However, with more than 1,500 abstracts presented at the meeting, covering all of the notable study results is not possible. To view webcasts, posters, and abstracts from the 2016 meeting, as well as meetings from previous years, please visit the ECTRIMS online library.

For general information 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.

Written by Michelle Fabian, MD
Attending Physician , Corinne Goldsmith Dickinson Center for MS 

Reviewed by Jack Burks, MD, MSAA Chief Medical Consultant
Edited by Susan Wells Courtney, MSAA Senior Writer