There are many reasons that people who are taking medications to help treat their multiple sclerosis might start to have second thoughts. Sometimes the side effects can be unpleasant or unbearable. Other times, the drug may not be helping them feel better or they continue to experience relapses. For some, the insurance costs may just be too high.
Until now, there has been very little information available about what happens when treatment is stopped in people with MS who are on disease-modifying therapies (DMT). Last week I came across a poster at the AAN meeting that addresses this important, unanswered question. Lead investigator Dr. Ilya Kister from the New York University (NYU) Langone Medical Centre set out to determine what happens to individuals whose disease symptoms have been stable when they decide to discontinue their DMTs. This is an important question, since identifying situations in which it is and isn’t safe for people with MS to stop taking their medications will go a long way to ensuring that disease symptoms don’t come back.
Research into the inflammatory nature of MS has led to profound progress in the treatment of the relapsing-remitting form of the disease. But this leaves us with many unanswered questions, and no treatment options, for progressive MS. Progressive MS bears severe consequences, including pronounced disability, cognitive decline, and extreme fatigue. As the need for treatments grows, so too do research efforts to help understand the onset and nature of progressive MS.
Encouraging results from one clinical trial conducted by Paris-based biotechnology company MedDay could pave the way for a novel, promising treatment option for people with progressive MS. The phase III, placebo-controlled clinical trial – dubbed MS-SPI – included 154 participants who were randomly selected to receive either MD1003 (treatment being evaluated) or a mock treatment (control) over a period of one year.
As the AAN conferences continues, so too do the updates on current and new treatments for MS. Here are some more highlights:
Efficacy and safety of alemtuzumab maintained after 4 years despite most patients not requiring additional treatment
Alemtuzumab was recently approved as a treatment for relapsing-remitting MS in Canada. It is a monoclonal antibody administered via intravenous infusion and has a dosing profile that is quite unique to the MS treatment repertoire: for the first treatment course, individuals receive one infusion of 12 mg alemtuzumab per day for five days. One year later, individuals receive one infusion per day for three days. Two pivotal phase III clinical trials for alemtuzumab in people with relapsing-remitting MS showed encouraging efficacy and safety results. Researchers have been observing individuals from these trials over time to assess the long term durability of the drug. The extension study enrolled 349 alemtuzumab-treated patients. At four years post-treatment, researchers noted that 73% of individuals treated in the first clinical trial did not require another round of alemtuzumab treatment beyond the initial two courses. As well, approximately 70% of treated patients were free of new lesions and MRI activity in years three and four, and rates of brain volume loss were reduced.
First data from long term follow up of people taking peginterferon beta-1a
Beta interferons are an approved treatment for RRMS. They work by reducing the immune response and inflammation in the central nervous system. Peginterferon beta-1a is an adaptation of interferon beta-1a. The modification allows the drug to exist in the body longer. Currently, peginterferon beta-1a is an approved MS treatment in certain countries, but is still under review by Health Canada. In a phase III clinical trial called ADVANCE, peginterferon beta-1a dosed at 125 μg every two weeks showed improvements as early as 12 weeks, with a 34% reduction in relapse rate compared to placebo. There was also a 36% reduction in people who relapsed compared to placebo. The first results of the extension phase of the study – called ATTAIN – were reported at AAN. They showed that the frequency of adverse events decreased in year 3 of treatment, with most common events being injection-site reactions and flu-like symptoms (adverse events were similar among those who received the treatment every 2 weeks versus every 4 weeks).
Two year data for emerging treatment daclizumab HYP
Daclizumab high-yield process (HYP) is a newly patented version of a drug that is commonly used to prevent rejection in organ transplantation. Daclizumab HYP prevents activation and growth of immune cells, and is administered once a month via under-the-skin injections. Results of a phase III clinical trial for daclizumab HYP – called DECIDE – demonstrated that treatment with daclizumab HYP resulted in a 45% reduction in relapse rate versus treatment with interferon beta-1a, and a 41% reduction in the proportion of people who experienced relapses. There was also a 54% reduction in the number of active lesions on MRI, and risk of disability progression was reduced by 27%. Adverse events were minor and manageable, with Infections and skin and liver-related effects more commonly seen in people treated with daclizumab HYP versus interferon beta-1a.
A large proportion of the AAN scientific program is centered on therapeutic advances. Whether it’s an early safety study, a phase II or III efficacy trial, an extension phase determining long term effects, or an observational study assessing how a drug is doing in the real world, research on the safety and benefits of treatments is critical knowledge for any conference attendee. We all have one main priority, and that is to improve the health and quality of life for people who are affected by neurological diseases, and so one of the reasons we come together at conferences like AAN is to gain information on the full repertoire of treatments.
For MS, the list of options grows each year. There are currently 10 approved disease-modifying therapies for MS (all indicated for relapsing-remitting MS) in Canada, with a number of others being tested in phase III clinical trials or submitted for Health Canada approval. As measures for treatment safety and efficacy are being discovered and refined, trials for MS drugs ensue and continue to reveal new knowledge about their benefits and risks in humans. Here are some of the first highlights reported at AAN.
One of the more interesting poster sessions I attended today here at AAN focused on risk factors in MS. In particular, there was an increase in research presented this year on the links between vitamin D and MS, and diet and MS. Turns out, new study results are suggesting that the association between either of these factors and the risk for MS may be related to the trillions of bacteria found within the gut. Collectively referred to as the gut microbiome or gut flora, these microorganisms reside in the digestive tract and enable the body to function normally. The bacteria have co-evolved with humans, thus building a symbiotic relationship that, if disturbed, can have significant consequences, and may lead to the development of autoimmune diseases.
In a poster presentation from Dr. Howard Weiner’s laboratory in Boston, MA, Stephanie Tankou presented evidence showing that low vitamin D levels are associated with increased MS relapses. They believe that that this correlation may be attributed to vitamin D deficiency-induced gut dysregulation or imbalance, leading to exacerbation of MS. In the study, researchers looked at vitamin D levels in the blood of 43 subjects. They also collected stool samples to assess the state of the subjects’ gut flora. Analysis revealed that subjects who had higher levels of vitamin D (above 40 ng/ml) had an abundance of an anti-inflammatory bacteria called ruminococcaceae, compared to subjects whose vitamin D levels fell below 40 ng/ml. The researchers concluded that the lower abundance of ruminococcaceae caused by vitamin D deficiency might be linked to increased inflammation in MS. The outcome of the study warrants further studies to elucidate the mechanism by which vitamin D regulates the composition of the microbiome in MS.
In a second poster presentation from Dr. Ellen Mowry’s group in Baltimore, MD and colleagues, it was reported that people living with MS differ from healthy controls in the levels of antioxidant and anti-inflammatory nutrients they consume from their diets. In the study, presented by Sandra Cassard, researchers evaluated the recorded diets of female participants enrolled in a vitamin D supplementation study. Analysis of 27 MS patients and 30 healthy controls revealed that the MS group has lower intake of folate, alpha-tocopherol, magnesium, lutein-zeaxanthin, and quercetin. The researchers concluded that the observed decrease in levels of these antioxidant and anti-inflammatory nutrients may have important implications for neurological health. They added that it is unclear whether low levels of the nutrients is a causative factor in MS or a consequence of the disease.
To view these and other abstracts from the conference, visit the AAN website.
The 67th American Academy of Neurology Annual Meeting officially begins today here in beautiful Washington, D.C. Last year’s meeting in Philadelphia broke attendance records and served as an important platform for doctors, researchers, trainees and allied health professionals to discuss highlights in MS research, along with updates in other brain diseases. That made me hopeful that this year’s meeting would be even more exciting, and would reflect the fast-paced, progressive nature of neurology – both on the research and treatment fronts. The American Academy of Neurology Annual Meeting – AAN for short – is one of the largest meetings in the world devoted to exchanging new knowledge and findings in neurology, identifying gaps in research and care of neurological disease, and arming neurologists-in-training with the tools they need to effectively treat and engage patients. This year over 2,500 cutting-edge abstracts were submitted, many of which are focused on MS in areas such as risk factors, co-morbidities, inflammation, clinical trials, emerging treatments, diet, pediatric MS, and symptom management. Over the next few days I will tackle the depth and breadth of this research by attending scientific lectures and poster sessions, in order to provide you with research updates both big and small that are presented throughout the week.
While reading about multiple sclerosis, you may have come across the blood-brain barrier and wondered what it’s all about. Many people think of the blood brain barrier (BBB) as some sort of membrane or casing that surrounds the brain and keeps anything from moving in and out. In fact, the BBB is a feature of the walls making up the blood vessels that supply the central nervous system (CNS), including the brain. The BBB is selectively permeable; that is, it lets certain substances pass across it between the blood and the CNS (and vice versa) while blocking the movement of others. This way, the BBB wields precise control over anything that enters or leaves the brain, in turn helping the brain to maintain a constant environment.