Highlights from the AAN and CMSC Annual Meetings
Two vital conferences providing the latest information and research on multiple sclerosis (MS) take place in the spring of each year. These are the American Academy of Neurology (AAN) and The Consortium of Multiple Sclerosis Centers (CMSC) Annual Meetings.
The 68th Annual Meeting of the AAN took place April 15-21, 2016, in Vancouver, Canada. More than 2,700 abstracts were presented during the scientific sessions. According to the AAN, “[Our] Annual Meeting is the world’s largest gathering of neurologists, bringing together more than 10,000 neurology professionals across the globe to network, discuss cutting-edge research, and take part in top-rated education programming across a wide variety of topics.”
To view the abstracts from this year’s AAN Annual Meeting, individuals may go to https://www.aan.com/conferences/2016-annual-meeting, select “Browse Abstracts,” and then select the topic of “MS and CNS Inflammatory Disease.”
The 30th Annual Meeting of The Consortium of Multiple Sclerosis Centers (CMSC) took place June 1-4, 2016, in National Harbor, Maryland. According to the CMSC, “Our meeting is unique in bringing together all groups committed to improving the lives of people with MS: neurologists, radiologists, physiatrists, other medical specialists, clinical researchers, basic scientists, nursing professionals, rehabilitation specialists, mental health professionals, members of the non-profit community and the corporate supporters. The content of the meeting includes state-of-the-art information on the latest treatments, research, models of care, epidemiology, genetics, and much more. The CMSC is proud to partner with thousands of MS professionals who work in healthcare, community service, the pharmaceutical industry and professional education.”
To view the abstracts from this year’s CMSC Annual Meeting, individuals may go to https://cmsc.confex.com/cmsc/2016/webprogram/meeting.html. To view presentations, individuals may visit http://cmscscholar.org/2016-presentations/.
Since these conferences feature thousands of abstracts and hundreds of sessions, covering all of the information presented at these meetings is not possible. However, a sampling of topics has been selected from these meetings with the hopes that these will be of particular interest to MSAA’s readers. Trial findings have been summarized in the paragraphs to follow. Readers should note that the studies mentioned are an extremely small fraction of what was presented.
EXPERIMENTAL AND APPROVED TREATMENTS
Stem Cell Transplantation Study Results
The five-year outcomes of Halt-MS were presented. This study, which was conducted at several locations in the United States and London, used both high-dose immunosuppressive therapy and autologous hematopoietic cell transplantation for the treatment of severe relapsing-remitting MS (RRMS).
This type of transplantation uses the stem cells from an individual’s own body. It requires several steps, which include taking stem cells from the patient’s blood, wiping-out the immune system (“ablation”) with high-dose chemotherapy, and transplanting the stem cells back into the patient. This procedure works to “reset” the immune system.
The Halt-MS study had 25 participants, with 24 who received the immunosuppression therapy and stem-cell transplantation according to protocol. During the first three years after the procedure, 121 “grade 3” and 93 (more serious) “grade 4” adverse events were reported. These were primarily related to blood or gastrointestinal issues. Between three and five years after the procedure, these numbers dropped to 15 grade 3 and zero grade 4 adverse events. Three individuals died, but none of these deaths were related to the study treatment.
At five years after the treatment was performed, more than 90 percent of the participants were free of disease progression and 86 percent experienced no relapses. The probability that a participant was free of disease activity according to magnetic resonance imaging (MRI) of the brain was 82 percent. Although T1- lesion volume increased at five years, T2-weighted lesion volume on MRI was significantly reduced as of six months compared to baseline, and this reduction was sustained throughout the five years.
The authors conclude that this procedure induces a high rate of remission of MS disease activity for individuals with severe RRMS. Additionally, this remission was sustained throughout the five-year period following the procedure, without the need for any other treatment therapy.
As noted in our 2016 edition of the MS Research Update, readers are cautioned that despite the remarkable results of this study, a high number of severe and life-threatening adverse events occurred, particularly in the first three years after the procedure. While many participants were free of MS-disease progression, relapses, and/or disease activity as shown on MRI, the treatment was not successful for all of the individuals who participated in the study. [CMSC, DX05]
Laquinimod Shows Consistent Reductions in Confirmed Disability Progression
Laquinimod, also known as Nerventra®, is an experimental oral treatment being studied in both RRMS and PPMS. In the phase III ALLEGRO and BRAVO trials, which studied the effects of laquinimod in RRMS, this medication showed consistent reductions of confirmed disability progression (CDP) at three months. Investigators from the United States and other countries wanted to learn if this effect continued through longer time intervals.
To determine if confirmed disability progression continued to be reduced, investigators analyzed pooled data from these two trials. The time periods used were six, nine, and 12 months. For participants starting the trials with an Expanded Disability Status Score (EDSS) of 5.0 or less, an increase greater than 1 point was considered to be confirmed disability progression. For participants starting the trials with an EDSS greater than 5.0, an increase greater than 0.5 points was considered to be confirmed disability progression.
After all of the data was analyzed, the investigators found that confirmed disability progression continued to be reduced throughout all of the time periods studied. The authors state, “Despite increasingly demanding criteria for confirmed disability progression, a profound effect of laquinimod for reducing disability progression was consistently demonstrated.” [AAN, P3.069]
Readers may note that given the positive results of studies with RRMS, laquinimod is also being studied in a PPMS trial. This study, called ARPEGGIO, began in 2015 and is anticipated to run through the end of 2017.
Editor’s note: In a study that is conducted for a short time, such as one year, evaluating changes in EDSS scores below 5 (those of ambulatory people) are difficult to objectively determine. Changes in relapse rate or MRI findings are much easier to quantify. While the results are encouraging, more study is needed into the effects of laquinimod on disability progression.
Occurrence of Thyroid-Related Adverse Events with Lemtrada
Investigators from the United States and other countries looked at the occurrence of thyroid-related adverse events in individuals with RRMS following treatment with Lemtrada® (alemtuzumab). Lemtrada is an FDA-approved treatment given via IV infusion. This five-year summary of the incidence and timing of thyroid-related adverse events was done as part of the ongoing CARE-MS extension study.
The study found that during the five years following treatment, 39 percent reported some type of thyroid event, most of which were mild or moderate in severity. Serious thyroid events were reported by 4.4 percent of the study participants; 3.2 percent of individuals in this study underwent thyroidectomy. Thyroid events peak in year three and monitoring for thyroid problems is recommended for four years after the last dose of Lemtrada.
The authors note that most events were managed with first-line, conventional therapy. They emphasize the need for ongoing patient education and laboratory monitoring, which allow for early detection and treatment of these types of thyroid events. [AAN, P2.086]
Long-Term Treatment Slows Disability Progression for Individuals with Advanced MS
Investigators in Australia used an observational MS database to evaluate how disability progressed in individuals with advanced MS when taking an immunomodulatory therapy. Data from 1,560 individuals initially diagnosed with a relapsing form of MS were analyzed.
Although disease progression during advanced MS can vary greatly and may not be consistent with prior disease activity, researchers found that those who used a higher-efficacy disease-modifying therapy (DMT) and experienced a lower annual relapse rate had a lower risk of accumulating significant disability. When staying on the DMT, these individuals experienced a slower progression of advancing from an EDSS score of 3 to an EDSS score of 6.
The investigators conclude that reaching higher EDSS levels (including levels between 3 and 6 in this study), does not prevent patients from experiencing benefits through “highly effective immunomodulation.” The authors specifically reference the following medications: natalizumab (Tysabri®), fingolimod (Gilenya®), alemtuzumab (Lemtrada®), dimethyl fumarate (Tecfidera®), cladribine, rituximab, and mitoxantrone (Novantrone®). Please note that not all of these medications are approved or recommended for use in the United States. [AAN, P1.385]
Editor’s note: In addition to these retrospective findings with the newer medications, prospective data on Rebif shows that it is also effective in this group, and potentially other approved disease-modifying therapies as well.
SYMPTOMS AND TREATMENTS
Fewer Side Effects and Doses with Arbaclofen Extended Release Tablets (AERT) in Treatment of Spasticity
Spasticity is a common symptom in MS. It is a tightness or stiffness of the muscles, which can interfere with activities and can become painful. The standard treatment is oral baclofen, and while effective, it requires frequent dosing and tends to cause a significant increase in sleepiness. Baclofen contains arbaclofen, an ingredient believed to cause the reduction in spasticity.
A study was conducted at multiple centers in the United States to determine if Arbaclofen Extended Release Tablets (AERT) might provide some benefits over baclofen. It shares this same ingredient with baclofen (arbaclofen), but requires fewer doses and may cause fewer side effects.
In this 12-week study, AERT was compared to placebo and to baclofen in 354 randomized RRMS or SPMS participants who experience spasticity. AERT was given in 20-mg tablets twice daily, while baclofen 20-mg tablets were given four-times daily. A matching placebo was administered to participants in the placebo group.
The study had two co-primary endpoints, which were the mean changes in two scales (Total Numeric-transformed Modified Ashworth Scale and Clinician Global Impression of Change) at the conclusion of the 12-week treatment period. The results showed a significant improvement with AERT versus the placebo; no significant differences were found between AERT and baclofen. According to the MS Spasticity Scale (MSSS-88), AERT showed a statistically significant improvement in spasticity compared with placebo.
With regard to side effects, as compared to placebo, the baclofen group showed a statistically significant increase in sleepiness according to Epworth Sleepiness Scale (ESS), while the AERT group did not experience a significant increase. Additionally, individuals taking baclofen experienced drowsiness and dizziness more frequently than those in the AERT group. According to these study results, the authors state that AERT administered twice daily was effective, safe, and better tolerated than baclofen administered four times daily in MS patients with spasticity. [AAN, P3.034]
Computer-Based Training Program Improves Cognitive Function
A 12-week double-blind, randomized, and placebo-controlled study was conducted to see if a computer-based cognitive training program could improve cognitive function in adults with MS. In this trial, 71 participants were randomly assigned to an adaptive training program (done on computer), while 64 participants were randomly assigned the active placebo, which used specific computer games.
This study instructed participants to play their assigned game for a targeted total of 60 hours. To reach this target, they were instructed to play five days per week for one hour daily during the 12-week study period. Participants were given weekly coaching sessions as well as technical support. A battery of neuropsychological tests was given prior to starting the training program and following the completion of the program. From these tests, a composite score of cognitive performance was determined.
Although the participants who were in the active-placebo group had higher playing times, those who participated in the adaptive training program experienced significantly greater improvement in their cognitive performance scores. The authors conclude that this type of computer-based cognitive remediation can improve cognitive functioning in individuals with MS. [AAN, P2.170]
Treating Fatigue and Pain with Massage Therapy
Investigators from the Shepherd Center in Atlanta conducted a nonrandomized pilot study to determine the effectiveness of massage therapy on certain MS symptoms. The authors report that approximately one-third of individuals with MS use massage therapy as part of their treatment plan to help with symptoms not fully managed through traditional treatments. The objective of this study was to see how massage therapy might impact the symptoms of fatigue, pain, and spasticity, as well as to assess whether or not massage therapy can improve the participant’s perception of health and quality of life.
The 24 participants who completed the study were each given a massage therapy session once weekly for six weeks. Symptoms were assessed before and after each of these sessions. Additionally, several scales were used to determine the effects on symptoms and overall health perceptions. This information was collected prior to and following the six-week intervention period.
Results showed that massage therapy decreased fatigue and pain, while improving the perception of health and quality of life. Although massage therapy did not improve spasticity in this small study with no control group, the authors note that massage therapy should be considered as an option in the management of fatigue and pain in individuals with MS. They suggest that further study is warranted. [CMSC, RH14]
The Effects of Tai Chi on Balance and Gait
Tai chi is a form of martial arts that uses slow movements and deep breathing to promote a type of “moving meditation.” It is a gentle, mind-body exercise designed to rebalance the body’s capacity for healing. Improved flexibility and balance control are among the many benefits of tai chi.
Up to three-quarters of the MS population experience problems with balance; this contributes to the 50-percent greater risk of falls for individuals with MS versus the general population. Given the potential benefits of tai chi, a study was conducted at the Texas Woman’s University in Dallas to determine the effects of tai chi on different factors involved with balance and gait in people with MS.
Several scales were used to measure the effects of tai chi on balance, strength, endurance, and fatigue following a six-week, community-based tai chi program. While class attendance by the 25 participants was excellent at 80 percent, only 15 participants returned for post-testing. Of the 15, 12 had RRMS and three had either SPMS or primary-progressive MS (PPMS).
Following the post-program testing, participants in this study experienced improvements in balance, endurance, and strength. In addition to a decrease in perception of fatigue, significant improvement was also seen in fatigue severity. Another interesting observation in this study was that while many participants began the classes exercising from a sitting position in a chair, by the conclusion of the six-week program, they were participating in the tai chi program while standing. [CMSC, RH05]
Poor Sleep Increases Fatigue and Cognitive Fatigue in MS
A study conducted at the University of Kansas Medical Center looked at the relationship between sleep quality, fatigue, and inattentiveness in people with MS. The study notes that up to 90 percent of people with MS experience fatigue, and approximately 50 percent report problems with their sleep. Both of these issues have a negative effect on quality of life.
This study had 52 participants with either RRMS or secondary-progressive MS (SPMS). The investigators found a significant association between poor sleep quality and increased fatigue, including an increase in cognitive fatigue. This latter type of fatigue not only reduces the ability to sustain attention, but also slows down reaction time.
Performing activities effectively requires continued attention and appropriate reaction times. Given that poor-quality sleep has been found to reduce these abilities, and with high percentages of individuals with MS reporting issues with sleep and fatigue, the investigators emphasize the need for medical professionals to consider the assessment of sleep quality as a part of one’s treatment plan. [CMSC, CG05]
EMOTIONAL AND PSYCHOLOGICAL STUDIES
Educational Socialization Program Improves Self-Efficacy and Loneliness
Researchers conducted a study to see if an educational socialization program could help to improve self-efficacy in individuals with MS. They also wanted to learn if improving self-efficacy could reduce perceptions of loneliness and depression. For anyone not familiar with the term, self-efficacy is the ability one believes he or she has to meet challenges and achieve goals.
The educational socialization program used for this study was the Community Reintegration for Socially Isolated Patients (CRISP). For 12 weeks, participants in the experimental group attended a combination of 12 educational and socialization groups. Individuals in the control group did not participate in any of the CRISP programs and only received their usual medical care provided at an MS center.
Compared to those in the control group, members of the experimental group who took part in the CRISP programs experienced significantly greater improvements in self-efficacy. As a result, loneliness was significantly reduced for those in this latter group. Depression, however, did not appear to be affected in either group. The authors of this study explain that CRISP may be an effective tool for individuals with MS to improve self-efficacy and reduce perceptions of loneliness. They suggest that further research is warranted. [AAN, P2.195]
Editor’s note: This study does not have an “active” placebo group where something unrelated is done on a regular basis. Without a placebo group, it is possible that these results may be due to a placebo effect of simply doing an activity. While these study results are encouraging, more research is needed to confirm these findings.
Depression and Suicidal Ideation in MS
According to a study conducted at the Mount Sinai Hospital in New York, only half of the MS population is screened for depression and suicidal ideation. As a result, these serious issues may go undetected in many individuals with MS. Investigators sought to determine the prevalence of suicidal ideation in individuals with MS as well as to identify possible predictors. Another objective was to evaluate whether or not one’s level of disability played a role.
The 34 participants in this observational study were recruited from a neurological clinic in an urban setting. The majority of this group was female, Caucasian, and educated. Approximately half were married and about two-thirds lived with either a partner or their family.
The potential for suicide was determined through two depression inventories. The study found that almost 12 percent of the 34 participants were subject to suicidal ideation. These individuals were non-Caucasian, unmarried, and living alone. While the level of disability did not appear to be associated with suicide ideation, those experiencing more frequent or severe relapses did carry a greater risk. The predictors of suicide ideation in MS included major depression, changes in appetite, sadness, and loss of pleasure.
The study concludes that early screening with the Beck Depression Inventory Fast Screen (BDI-FS) is critical in identifying individuals who may be at risk for suicide. The author also notes that more studies are needed to determine other factors associated with suicidal ideation, including the degrees of disability and relapses in MS. [CMSC, CG07]
POSSIBLE FACTORS IN THE MS PROCESS
Evidence of Gut Immunity Involvement with MS Pathogenesis
A current theory is that gut immunity may play a role in the development of MS and other autoimmune diseases. With the goal of learning more about this possibility, researchers conducted a study looking at gut immunity and microbiota in 23 people with RRMS as compared to 16 age-and-sex-matched healthy controls. All participants in this study were given esophago-gastro-duodenal endoscopy (EGDS), providing an inside view the throat, stomach, and intestines.
Intestinal mucosal samples were taken from each participant in the study and then analyzed. According to the samples taken, the investigators found that activated Th17 cells are present in the intestinal mucosa but not in peripheral blood cells. Th17 is an immune-system cell (lymphocyte) involved with the inflammation that causes damage to the myelin and nerves with MS. Compared to the control group, the individuals with MS had an increased Th17/FoxP3+Treg cell ratio (important T-cell subsets involved with the immune system).
The authors state that the data suggest a selective activation of Th17 cells in the intestinal mucosa of individuals with MS. They note that these findings provide the first evidence that gut immunity may be involved with MS pathogenesis and their next goal is to learn more about how diet and other factors can affect the disease course through changes in gut microbiota and intestinal immunity. [AAN, P3.007]
Editor’s note: The gut is a very large immune organ (with skin being the largest), so it’s no surprise to find immune cells there. Given that these specific immune-system cells are not found in the gut of people without MS, the question of cause and effect must be raised. Are the immune cells there to cause problems in MS, or are they the result of the person having MS with activated immune cells? These are the types of questions that further research will help to answer.
Body Mass Index and Severity of MS
Researchers in New Jersey were looking for a possible connection between the Body Mass Index (BMI) of individuals with MS and the severity of their disease. In this study, 573 people with MS were evaluated in terms of BMI and given a score of their MS severity. Of these 573 participants, 176 were obese, with a BMI greater than 30. Researchers found that the obese individuals had significantly higher scores in terms of disease severity versus those who were not obese. However, the authors note that the correlation between BMI and MS severity was modest and more studies are needed to better understand this relationship. [AAN, P1.371]
Treatment Adherence in Pediatric MS
In pediatric multiple sclerosis (POMS), disease-modifying therapy (DMT) is frequently prescribed to slow disease activity. However, up to half of this population has difficulty adhering to the medication. Staying adherent to one’s DMT is particularly important for children, as their school attendance, grades, and social activities are affected when experiencing flare-ups in disease activity.
The reasons behind this poor adherence have yet to be identified, so researchers in the United States and Canada conducted a randomized-control trial to learn about the challenges to staying adherent at a young age. Participants were children with MS from nine MS centers in North America. Electronic monitoring was used in conjunction with motivational interviewing to help children adhere to their treatment schedule. This was compared to only using attention control.
Researchers found that recalling initial symptoms at diagnosis (such as numbness or visual problems) was a motivator for children to stay on their medication. Using alarms, making the medication a part of their daily routine, and being reminded by parents, were all strategies that children can use to help stay on their medication. The participants also found the electronic monitoring to be helpful in tracking their daily patterns of medication adherence.
Getting distracted, going out with friends, and poor ability to self-inject, were all potential obstacles that can cause children to miss their dose. The investigators note that to their surprise, pain and fear did not play a role in reduced adherence to one’s medication. [AAN, P2.106]
Obesity May Increase the Risk of Pediatric MS
The authors of this study state that obesity during childhood and adolescence doubles the risk of pediatric and adult-onset MS. Working with more than 15 sites from across the United States, data from 394 non-Hispanic, white individuals with pediatric MS were compared with data from 10,875 controls. Researchers found a significant association between body mass index (BMI) and pediatric MS susceptibility, using a weighted BMI genetic risk score (BMI GRS).
According to the results of the study, this is the first time that evidence has been provided to support the theory that increased BMI is causally associated with pediatric MS and that BMI interacts with the status of HLA-DRB1*15:01, which is the strongest genetic predictor of MS. The authors also explain that obesity as a risk factor for pediatric MS may involve genetic factors that predispose the individual to increased BMI. This suggests that specific inflammatory mechanisms associated with the obesity pathway may be involved with disease onset. [AAN, P1.375]
Longer Breastfeeding May Reduce the Risk of Pediatric MS
A study in Virginia sought to learn if infant breastfeeding might provide any protection against the future risk of developing pediatric-onset MS. The authors note that both environmental and genetic factors play a role in this risk, and since breastfeeding may help provide protection from some other childhood autoimmune disorders, they theorize that it may help provide protection from developing pediatric-onset MS.
Questionnaires were completed by the biological mothers of 26 individuals with pediatric-onset MS (POMS) and by the control group, which consisted of 39 individuals without MS. The groups differed in terms of breastfeeding: about 35 percent of the POMS group was breastfed, while 72 percent of the control group was breastfed; the duration also differed between groups. According to the preliminary analysis, researchers found that infants who were breastfed for less than four months had twice the risk of being diagnosed with pediatric-onset MS at a later time. [AAN, P1.377]
Editor’s note: More studies are needed to confirm this possible connection.
OTHER TOPICS OF INTEREST
Denmark Study Finds Children of Parents with MS Have Higher Grades
Knowing that research has shown that children of parents with MS may experience some negative psychosocial effects, investigators in Denmark conducted a study to see if having a parent with MS might affect educational performance and level attained. Through a nationwide Danish MS Registry, 4,317 children of Danish citizens with MS (diagnosed between 1950 and 1986) were included in the study. Their educational performance was compared to 34,536 children whose parents did not have MS.
While an equal portion of children in both groups reached similar educational levels, the children of individuals with MS achieved significantly higher average grades than those of parents without MS. In addition, significantly more children who had parents with MS completed a health-related education compared to those in the control group. [AAN, P1.382]
Gaps in Public Awareness of MS
Investigators in New Hope, Pennsylvania, conducted a public disease-awareness survey to determine the public’s knowledge and perceptions of MS. This virtual survey was completed by 306 respondents, representing all educational levels and socioeconomic backgrounds.
The investigators found that in general, public perceptions of MS were fair. Nearly half (44 percent) know someone with MS and more than half (54 percent) claim to be familiar with the disease. Most believe that MS can worsen family relationships and make work difficult. They also believe that problems with walking and mobility are the most disabling of MS symptoms. The vast majority of respondents (86 percent), however, are unaware of any approved treatments for MS, and more than half think that MS is fatal.
The authors conclude that while the public has some knowledge regarding symptoms and the impact of MS, large gaps still exist. This is particularly true in a lack of awareness of all of the symptoms of MS, the full impact on family life, available FDA-approved treatments, and the costs associated with MS. [CMSC, PO07]
Additional Reading for Professionals
At this start of this article, we noted that the CMSC presentations could be accessed by going to http://cmscscholar.org/2016-presentations/. These presentations cover a full array of topics, including research, symptom management, rehabilitation, and virtually any topic relating to MS. Every presentation is worthwhile for the professional or the educated reader to learn more about the newest study results available. Please note that these presentations are written for professionals, so much of the information may be challenging for the layperson.
While all of the presentations are extremely informative, the following sessions have been particularly popular and may be a good starting point for anyone wishing to learn more about the topics listed. These may be found at the following locations after going to http://cmscscholar.org/2016-presentations/.
Under “BASIC SCIENCE / ENVIRONMENTAL”
- # 5: “Presidential Lecture: Biomarkers and Genetic Variations Related to Glutamate Concentration in the Brain,” by Daniel Pelletier, MD
- # 11: “Cell-based Therapies in MS,” by Michael Racke, MD
- # 15: “Research Symposium: How T Cells and B Cells Work Together,” by Anne H. Cross, MD and Francisco J. Quintana, PhD
- # 18: “Progressive MS: What We Now Know,” by Alan J. Thompson, MD, FMedSci, FRCP
Under “COMPREHENSIVE CARE”
- # 5: “Expanding the MS Toolkit: Integrating Lifestyle Factors and Unconventional Medicine into MS Clinical Care,” by Allen C. Bowling, MD, PhD
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 Susan Courtney, MSAA Senior Writer
AAN information reviewed by Randall T. Schapiro, MD, FAAN
CMSC information reviewed by Donald A. Barone, DO
Both Dr. Schapiro and Dr. Barone are members of MSAA’s Healthcare Advisory Council.