What’s New in MS Research: September 2018
Research into the causes, diagnosis, impact, and management of multiple sclerosis (MS) continues to move forward on a broad front and at a rapid pace. While many advances are announced at medical meetings, such as the annual gatherings of the American Academy of Neurology (AAN), American Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS), Consortium of Multiple Sclerosis Centers (CMSC), and European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS), other findings are reported in medical journals throughout the year. Below, we highlight several noteworthy studies published in recent months.
People with progressive MS who took the investigational agent ibudilast for 96 weeks had roughly one-half the amount of brain atrophy (the shrinking or reduction in brain volume) than the amount experienced by their counterparts who were given a placebo. These results are according to a study published in August in The New England Journal of Medicine. [Fox 2018]
The study enrolled 255 individuals with progressive MS. A total of 129 study participants received an oral dose of up to 100 mg of ibudilast daily. The other 126 participants received placebo. A slight majority of individuals in both groups had primary-progressive MS (PPMS), while the remainder had secondary-progressive MS (SPMS).
The main adverse events seen in the ibudilast group were gastrointestinal symptoms, headache, and depression. These occurred more often in people receiving the drug than in those receiving placebo. This Phase II trial was conducted at 28 sites, and was sponsored by the National Institute of Neurological Disorders and Stroke, among others.
Ibudilast is an oral anti-inflammatory and potentially neuroprotective agent being developed by MediciNova. The company is also exploring the potential role of ibudilast in treating amyotrophic lateral sclerosis – also known as ALS, or Lou Gehrig’s disease – and other conditions.
With limited treatment options for progressive forms of MS, this Phase II study is extremely interesting and promising. Hopefully it sets the stage for a Phase III trial examining the impact of ibudilast on MS symptoms and outcomes.
Gilenya® (fingolimod) reduced the annualized relapse rate in children and adolescents with MS relative to these individuals’ earlier relapse rates. This reduced relapse rate is also relative to other pediatric patients treated with interferon beta-1a (Avonex®). [Chitnis 2018]
This reduction in the annualized relapse rate was the main finding from the PARADIGMS study, the first global, completed, controlled, randomized study specifically designed for children aged 10 to 17 years with relapsing forms of multiple sclerosis. While the study was published in The New England Journal of Medicine in August 2018, results from the trial prompted the FDA to approve Gilenya in May 2018 as the first MS treatment for pediatric patients. Gilenya was approved for use in adults with relapsing MS in 2010.
A total of 215 children and adolescents participated in the PARADIGMS trial, with 107 randomized to receive Gilenya and 108 to receive interferon beta-1a. Participants in the Gilenya group received 0.5 mg of the oral agent per day (or 0.25 mg per day for those weighing 40 kg – roughly 88 pounds – or less). Participants in the comparison group received an intramuscular injection of 30 ug of interferon beta-1a per week. Both treatments were given for up to two years. The mean average age of the participants was 15.3 years, and these individuals had experienced a mean average of 2.4 relapses in the preceding two years – or more than one relapse per year.
The adjusted annualized relapse rate in the Gilenya group was 0.12 versus a 0.67 rate in the interferon beta-1a group. This absolute difference of 0.55 relapses was statistically significant. Compared to their peers receiving interferon beta-1a, children and adolescents receiving Gilenya also had roughly one-half as many new or newly enlarged central nervous system (CNS) lesions identified on magnetic resonance imaging (MRI).
A total of 89 percent of participants receiving Gilenya and 95 percent of those receiving interferon beta-1a experienced adverse events, with 16.8 percent of those taking Gilenya and 6.5 percent of those taking interferon beta-1a having serious adverse events. In the Gilenya group, serious events included convulsions in six participants, infection in four, and a reduction in white blood cell count in two. In the interferon beta-1a group, two individuals had infection and one experienced an abnormal heart rate.
The availability of a treatment shown to reduce relapses in children and adolescents represents a major milestone in pediatric MS. As the PARADIGMS study’s lead author Tanuja Chitnis, MD, and her colleagues noted, the reduction in relapses, lessened accumulation of new or enlarging CNS lesions, and higher rate of serious adverse events seen with Gilenya (relative to interferon beta-1a), underscore the need for longer studies to determine the durability and safety of Gilenya in pediatric patients. Meanwhile, however, clinicians and their young patients finally have an FDA-approved treatment option.
A study was designed to determine the effectiveness of group, cognitive rehabilitation (CR) therapy in women with relapsing-remitting MS (RRMS). The study found that these women performed better on memory assessments than their counterparts who did not participate in such sessions. [Mani 2018]
Researchers assigned 17 women with RRMS and evidence of impaired cognitive function to participate in eight, two-hour sessions of cognitive rehabilitation (CR) over a four-week period. Those CR sessions focused on memory, attention, and executive function. A second control group of 17 women with RRMS and cognitive impairment attended a separate set of group sessions that did not involve cognitive rehabilitation. All participants underwent assessment of cognitive function before the start of the group sessions and three months after the sessions ended.
At the three-month follow-up, the CR group had significantly greater improvement from baseline in visual and verbal memory than the control group. The CR group also outperformed the control group in an overall assessment of memory function. Further, women in the CR group did better on a card-sorting exercise that tests memory than did those in the control group. Attention was the only domain in which no significant difference was found between the groups.
Cognitive impairment eventually affects up to two-thirds of people with MS. While this study had a small number of subjects and did not include men, it may have identified a valuable strategy for helping preserve or enhance memory function in people with RRMS.
More than one-third of people receiving care at an Australian MS clinic reported swallowing problems when specifically asked about the issue on a questionnaire. [Alali 2018]
Difficulty swallowing – known as dysphagia in medical terminology – was reported by 38 percent of the 103 adults with MS participating in this study. The nature and severity of the problems ranged from coughing and throat clearing, to choking on food and liquid. Patients also reported a reduced desire to eat, longer time required to eat, and mealtime anxiety.
Researchers conducting the study noted that, if left untreated, swallowing problems eventually can lead to complications including malnutrition, dehydration, and pneumonia. They recommended that people with MS who have dysphagia see a speech pathologist as early as possible for evaluation and management to improve swallowing function.
This study highlights the importance of promptly recognizing and addressing a common symptom of MS rather than minimizing its impact or deferring care.
The symptoms that most affect health-related quality of life (HRQoL) in people with progressive MS differ significantly from those affecting people with relapsing forms of the condition. [Barin 2018]
This difference between symptoms was the main finding from a study of 855 people participating in the Swiss Multiple Sclerosis Registry. Researchers used two scales with ranges from 0 to 100 to measure the impact of various symptoms in 611 people with relapsing-remitting MS (RRMS) and 244 people with progressive MS (PMS).
They found that in individuals with RRMS, gait and balance problems were the symptoms that had the most impact. By contrast, people with progressive MS cited spasticity and paralysis as the issues that most detracted from their health-related quality of life. Fatigue, depression, dizziness, and spasticity also were frequently cited issues for people with RRMS, while the PMS group identified pain as another symptom adversely affecting their quality of life.
While the findings are not surprising, given the different courses of relapsing-remitting and progressive MS, they reinforce the importance of understanding how several factors – including MS type – contribute to the disease burden that patients experience. They also underscore the need for people to talk with their clinicians, not only about the presence of various symptoms, but also about the extent to which each symptom is affecting their quality of life.
Growing up in a sunny area reduces the risk of developing multiple sclerosis (MS), according to a recent study by investigators in the United States and Canada. [Tremlett 2018]
The researchers matched 151 people with MS with 235 similarly aged healthy controls from the Nurses’ Health Study. The investigators classified each person as having low, medium, or high exposure to ambient ultraviolet (UV-B) light at ages 5 to15 years, 16 to 20 years, and every 10 years thereafter. The classification was based on factors including the latitude, altitude, and cloud cover where a person lived. Researchers also documented hours per week of sun exposure in summer and winter. A total of 98 percent of the study subjects were Caucasian, and the mean average age of MS onset in the 151 people with MS was 39.5 years.
The study found that people living in a high UV-B area before the mean average age of MS onset had a 45-percent lower risk of developing MS than people living in a low UV-B area. Additional analysis showed that having medium or high exposure at ages 5 to 15 cut the risk of MS by more than one-half, relative to people living in low-exposure areas.
This study extends a line of inquiry into the association between Vitamin D levels and MS risk. Sunlight is a major source of Vitamin D, and research has shown that many people with MS have relatively low levels of the vitamin. Additionally, epidemiological research has shown MS to be more prevalent in northern countries, where individuals receive less year-round sun exposure than in lower latitudes. Given the very real dangers of sun-related skin cancer, this research is not a reason to engage in tanning for potential preventive purposes, but it does add to the knowledge base about risk factors for MS.
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 Tom Garry, Medical Writer
Reviewed by Dr. Jack Burks, MSAA Chief Medical Consultant
Edited by Susan Wells Courtney, MSAA Senior Writer
Alali D, Ballard K, Bogaardt H. The frequency of dysphagia and its impact on adults with multiple sclerosis based on patient-reported questionnaires. Mult Scler Relat Disord. 2018;25:227-231.
Barin L, Salmen A, Disanto G, et al. The disease burden of multiple sclerosis from the individual and population perspective: Which symptoms matter most? Mult Scler Relat Disord. 2018;25:112-121.
Chitnis T, Arnold DL, Banwell B, et al. Trial of fingolimod versus interferon beta-1a in pediatric multiple sclerosis. N Engl J Med. 2018;379:1017-1027.
Fox RJ, Coffey CS, Conwit R, et al. Phase 2 trial of ibudilast in progressive multiple sclerosis. N Engl J Med. 2018;379:846-855.
Mani A, Chohedri E, Ravanfar P, et al. Efficacy of group cognitive rehabilitation therapy in multiple sclerosis. Acta Neurol Scand. 2018;137:589-597.
Tremlett H, Zhu F, Ascherio A, Munger KL. Sun exposure over the life course and associations with multiple sclerosis. Neurology. 2018 Apr 3;90:e1191-e1199.