Highlights from the AAN and CMSC 2017 Annual Meetings
During the past few decades, advancements made in multiple sclerosis (MS) research have revolutionized the field. Thus far in 2017, the brisk pace has continued. The American Academy of Neurology (AAN) meeting in April 2017 in Boston, Massachusetts and the Consortium of MS Centers Conference (CMSC) in May 2017 in New Orleans, Louisiana were both venues for healthcare professionals and researchers to convene and report their latest progress. We’ve included some of the most interesting and cutting-edge ideas presented at these conferences in this update.
Ocrevus® (ocrelizumab) was approved by the United States Food and Drug Administration (FDA) in March 2017 for the treatment of relapsing forms of MS and primary-progressive MS. Ocrevus is a targeted antibody that works in a unique way among MS medications by removing the B cells from the blood. B cells are a type of immune cell that is now recognized as critical in MS-lesion formation.
Data presented highlighted the significant effects of Ocrevus in MS. A sub-analysis looking at the rate of No Evidence of Disease Activity (NEDA) in people with early MS (defined as having the first symptoms for less than two years with no previous MS treatments) in the relapsing-remitting MS trials OPERA I and OPERA II found a 76-percent increase in NEDA with Ocrevus treatment versus the Rebif® (interferon beta-1a) comparison group.1 Individuals with NEDA have no new MRI lesions, relapses, or signs of clinical progression. Essentially, their MS is stable by all measures.
Another sub-study highlighted the quick onset of action with Ocrevus. Researchers found that people receiving treatment already received a benefit within the first eight weeks, with a reduction in magnetic resonance imaging (MRI) activity and relapses. This is notable, especially for individuals with very active MS.2
Finally, the results of the year-three extension studies of Ocrevus in relapsing-remitting MS (RRMS) were presented. These studies found that individuals who started on Ocrevus continued to have exceedingly low relapse rates with good safety profiles during the third year of treatment. Furthermore, individuals who initially were randomized to the Rebif treatment group were found to have significantly decreased relapse rates when switched to Ocrevus during the extension study.3
The original Lemtrada® (alemtuzumab) trials in relapsing-remitting MS, CARE-MS I and CARE-MS II, showed a markedly significant decrease in clinical relapses and new MRI-lesion formation in people treated with Lemtrada versus those treated with Rebif. The vast majority of individuals in these trials have continued to follow up in the extension trials, providing at least six years of data.
Study investigators reported at the AAN meeting that Lemtrada-treated participants continued to have good MS-disease control many years after they were enrolled, and more than 50 percent of these individuals never required a re-dosing to treat recurrent disease activity. Furthermore, the rate of brain-volume loss was significantly decreased in those who were originally randomized to Lemtrada versus those in the Rebif comparison group. Brain-volume loss continued to remain low during the six-year follow-up period. Although extension studies are not generally regarded to have the same scientific stringency as the initial randomized studies, they provide important information regarding the long-term benefits and risks of a given treatment.4
Tecfidera® and Gilenya®
While a wide variety of MS treatment options are available, they generally have not been compared in head-to-head trials.5 Data collected in the “real world” setting of MS centers allows for some comparative evidence between drugs, but this does not come with the same rigor as a clinical trial.
Researchers from Cleveland presented one such study at AAN. They compared 390 people with MS on Tecfidera® (dimethyl fumarate, DMF) and 293 people with MS on Gilenya® (fingolimod). They found that individuals taking Tecfidera were more likely to discontinue the medication because of side effects. These individuals also had a higher likelihood of new lesions on brain MRI within the first 12 months of treatment and an increased worsening on their timed 25-foot walking tests. However, a similar proportion of people in both groups experienced new clinical relapses.
As noted earlier, readers should keep in mind that these findings were not from a rigorous comparison trial, but rather through data collected from individuals in a clinical setting. Individuals within the two treatment groups were not matched in terms of gender, age, time since diagnosis, or disease severity prior to initiation of treatment. Additionally, no one was “blinded,” so both the participants and the medical staff knew which medication was being taken. These details affect the ability to definitively compare the two medications to one another.
TeriPRO was an open-label study of 545 individuals with MS who were started on Aubagio® (teriflunomide) and followed for 48 weeks.6 The goal of the study was to evaluate for patient-reported outcomes. A total of 58 percent of people in the study were switched from another MS therapy. At 48 weeks, 68 percent of people were satisfied with Aubagio as a treatment. The relapse rate in this study was reported to be very low, with one relapse reported for every eight individuals in the study.
Ampyra® (dalfampridine) is FDA-approved for individuals with MS who are experiencing gait issues. It works by blocking potassium channels and allowing for more efficient conduction of the nerve impulses from the brain to the spinal cord, resulting in the ability to walk quicker or farther in about 40 percent of those taking the medication.
Researchers in Italy conducted a study in which they tested Ampyra in people with MS-related cognitive dysfunction to see if they could find a benefit in this realm. A total of 120 people with MS were enrolled into the study – 50 percent into the Ampyra group and 50 percent into a placebo group. Results showed that people in the Ampyra group performed better on cognitive testing than the placebo group, with 76 percent of the treated group showing at least a 20-percent improvement compared to 44 percent of the controls. As might be expected, this benefit was not sustained after Ampyra was discontinued.
Although researchers did find improved cognitive function with this medication, the participants did not find that it translated to improved quality of life.7 Based on the findings in this study, Ampyra may be a useful treatment for patients with cognitive dysfunction.
What Matters to MS Patients
“MyMSTeam” is an online social network of 75,000 people with MS. More than 1,100 people from this group responded to a survey regarding their MS symptoms, their definition of MS progression, and factors that impact MS medication choices. As in previous studies, fatigue was the most common symptom reported (82 percent), followed by gait issues (64 percent), and problems with balance (64 percent). Respondents reported that they most often define MS disability progression by losing the ability to walk and exercise (42 percent), the inability to do daily functions (25 percent), or the inability to be independent (22 percent).
In terms of choices of medications, almost half (47 percent) found their doctor’s opinion to be the most important factor in choosing a medication. Interestingly, for those on an oral disease-modifying therapy (DMT), only 40 percent reported the doctor’s opinion as the most important factor, while 36 percent said that the method of administration was the most important factor. For people taking injections, 53 percent reported the doctor’s opinion to be most important. Surveys such as this are valuable for health professionals. They allow for greater understanding of the experience of a person with MS, which will allow for treatment strategies that align more closely to a person’s needs.8
Modifiable Lifestyle Factors
To optimize health and functioning in people with MS, all aspects of health must be considered. Researchers conducted a survey of 7,400 people with MS enrolled in the NARCOMS study to evaluate the impact of lifestyle factors on overall health and wellness in people with MS.9 Lifestyle factors included diet, body-mass index, leisure-time physical activity, and smoking status. Correlations were then drawn between suboptimal lifestyle factors, e.g., smoking, poor diet, and low physical activity, and a person’s risk for depression, fatigue, or cognitive dysfunction. Interestingly, the study authors found that 43 percent of the respondents met criteria for having optimal health habits.
Suboptimal habits were reported as follows: 36 percent in the area of diet, 17 percent for body-mass index, 4 percent in terms of leisure-time physical activity, and 0.5 percent for smoking status. When disease duration and level of disability were accounted for, people with two or more sub-optimal health habits were found to be at greater risk for depression, fatigue, and cognitive issues, versus those with one or none of these habits. This study highlights the importance for doctors and other care providers to continue to encourage people with MS to adopt the healthiest lifestyle possible. Doing so may help to minimize their risk for depression, fatigue, and cognition – all of which are common symptoms in MS.
Community-Based Wellness Programs
The concept of wellness encompasses not only physical wellbeing, but also includes emotional, social, and spiritual wellness. Wellness is critical to optimizing quality of life. The promotion of wellness, in addition to standard medical therapies, should be a priority among MS providers.
Researchers from Colorado presented data from a study that surveyed individuals who took part in community-based wellness programs.10 The study found that the participants experienced a significant decrease in stress as well as increased feelings of overall health, positive behavior change, empowerment, and self-efficacy. For anyone not familiar with this term, self-efficacy is the ability we believe we have to meet challenges and achieve goals. Future studies in wellness should serve to identify specific strategies, either community-based or directed by MS centers, which can be employed to enhance wellness in the lives of people with MS.
In recent years, the concept of resilience has become of interest to MS researchers. Although many definitions may be found for resilience, one definition that is often used is the ability for a person to continue to move toward wellbeing in the face of illness and adversity.
Researchers from Canada performed a survey that examined levels of resilience in 300 individuals with MS. They found high levels of resilience among the survey respondents, although these levels in people with MS were still lower than individuals who had other medical conditions (spinal cord injuries or diabetes). More work needs to be done to understand the factors that might determine whether an individual with MS has a high or low resilience level, and how levels of resilience can impact the course of MS. Furthermore, interventions that can be identified to support those individuals with low resilience are needed.
Mindfulness is a cognitive technique that focuses on teaching people to approach stress and life challenges in a different way. The goal of mindfulness is to teach individuals to stay fully in the present, without added judgment or assumptions about their present or future situations. It was originally developed for people with cancer and chronic pain and has been shown to significantly decrease anxiety, depression, and stress in these and many other conditions.
Mindfulness has enormous potential for people with MS, where uncertainty for the future can often lead to increased stress and anxiety. In a study presented at the CMSC meeting, researchers from Ohio conducted a randomized trial of people with MS who were assigned to mindfulness, versus adaptive cognitive therapy, versus a control group that was put on a waiting list. Although no effect was seen on cognitive functioning, investigators found that the mindfulness group had improved emotional regulation during the course of the study. Future studies with mindfulness and MS should explore the broad potential for the use of this technique in the treatment of individuals with MS.11
Nutrition is a topic of high interest to individuals with MS and researchers. It is unclear if and how a person’s diet might impact their MS course, either in a positive or negative way. Utilizing the NARCOMS registry, researchers from the United States and Canada examined diet quality and its potential link to a person’s MS severity as well as associated symptoms. They reported their findings at the CMSC meeting. NARCOMS is an international registry of 37,000 people with MS who are asked to respond to questionnaires about their MS at regular intervals.
In this study, 7,400 NARCOMS participants responded to a survey that looked at the quality of their diet. Whole grains and diets high in fruits, vegetables, legumes, and red/processed meats, are some of the categories that were focused upon. Study investigators found that people who scored in the top 20 percent of highest diet quality (low in added sugar and red/processed meats; high in fruit, vegetables, and legumes) had lower levels of overall disability and less depression. Overall, people with higher diet quality scores were more likely to be older, have a leaner body mass index, and were non-smokers.
Education Regarding Mobility Devices
A large percentage of individuals with MS report at least some challenge with gait. While many people with MS might use a cane or walker to alleviate some of their difficulties, the use of these mobility devices has unexpectedly been associated in previous studies with an increased risk of falls.12
Many people do not receive any formal instruction on how to use their mobility device. Researchers from Oregon suspected that this lack of education might be part of the reason for the link between using a device and falls. They conducted a study to evaluate the effect of training with a mobility device on a person’s mobility and satisfaction with the device.
The study randomized 40 individuals with MS to either six weekly training sessions versus a group on a waiting list. After three months, researchers found that people in the device-training group had fewer falls coupled with greater satisfaction with their device. Furthermore, people in the device-training group showed a trend towards less sitting and greater walking. This study suggests that formal instruction on the use of a mobility device may be of significant benefit.
My MS Manager Presentation
MSAA’s free mobile phone application, My MS Manager™, was highlighted during the segment on shared decision making at the CMSC conference. Available for Android and iOS devices, the My MS Manager app allows users to track and manage their MS medications and symptoms, journal information, share data with physicians, and more. My MS Manager was developed in conjunction with @Point of Care, an app developer of innovative digital tools that connect clinicians, patients, and caregivers.
During the presentation, MS expert neurologist Dr. James Bowen discussed the results of a survey that demonstrated the impact of the MSAA app. Data for the survey were collected and analyzed from 9,910 individuals with MS and 12,234 clinicians. Results of the survey showed the My MS Manager app helps improve patient-clinician communication regarding MS, facilitates discussions about fatigue (addressed through the app’s fatigue-assessment scale), and provides those using the app with the sense that their clinician is more invested in their MS management.
Building on this success, MSAA and @POC plan to add updated features and symptom-management scales to the app in the near future. To download MSAA’s free My MS Manager app, members of the MS community may visit mymsaa.org/mobile.
We hope that this information is of interest and may be helpful to MSAA’s readers. However, with countless abstracts and posters presented at these meetings, covering all of the notable study results is not possible. To scroll through abstracts, readers may go to the 2017 AAN Annual Meeting poster webpage or to the 2017 CMSC Annual Meeting webpage for more information.
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
1 Havrdova E, et al. “No Evidence of Disease Activity on Ocrelizumab Treatment in Patients With Early Relapsing Multiple Sclerosis: Pooled Analysis of the Phase III OPERA Studies.” April 26, 2017; P4.391 (AAN)
4 Traboulsee A, et al. “Alemtuzumab Durably Slows Brain Volume Loss Over 6 Years in the Absence of Continuous Treatment in Patients With Active RRMS Who Were Treatment-Naive (CARE-MS I) or Had an Inadequate Response to Prior Therapy (CARE-MS II).” April 24, 2017; P2.104 (AAN)