MS Research Update 2017
Written and compiled by Michelle Fabian, MD and Stephen Krieger, MD
Includes additional material by
Margaret M. McCormick, RN, BSN, MSCN
Reviewed by Jack Burks, MD
Edited by Susan Courtney
MSAA’s 2017 edition of the MS Research Update provides important new data on approved and experimental treatments for MS, and is a valuable resource to the entire MS community. Please note that this update gives an overview of the research behind the approved and experimental medications and therapies for the long-term treatment of multiple sclerosis. It does not include information on any symptom-management medications or therapies.
For additional information about MS, symptoms and symptom management, as well as MSAA’s programs and services, please visit mymsaa.org or call (800) 532-7667. Questions to MSAA’s Client Services department may also be emailed to MSquestions@mymsaa.org.
Additionally, please note that due to the timing of the national and international MS conferences, study data from the 2017 conferences could not be included in this writing. Information in this publication includes data presented at the 2016 conferences, as well as any important updates that occurred in early 2017. Please visit MSAA’s website at mymsaa.org for future summaries of 2017 conference highlights.
The 2017 MS Research Update is made possible through contributions in honor of: Dr. Jules Kernan and Ms. Hannah Dennehy Lee and an anonymous supporter.
This year’s MS Research Update has been designed to highlight numerous experimental drugs currently under investigation for the long-term treatment of multiple sclerosis (MS), to provide new clinical trial data on some of the already-approved disease-modifying therapies (DMTs), and to describe the most exciting new areas of MS research. Please note that in order to keep this annual MS Research Update current and up to date, historical background and completed trials of approved DMTs are no longer included.
This 2017 edition of MSAA’s MS Research Update is again being printed as a stand-alone issue, reflecting the incredible diversity and scope of research progress in MS. Of course, there is nonetheless far too much ongoing research in MS therapeutics for all of it to be covered here. This is therefore not a complete list, and not all study results could be included.
This information is based on a wide range of sources, including extensive journal literature on MS and its management, a review of ongoing clinical trials, and papers presented at major national and international conferences. These include the 2016 conferences hosted by the American Academy of Neurology (AAN), the Consortium of Multiple Sclerosis Centers (CMSC), and the Americas and European Committees for Treatment and Research in Multiple Sclerosis (ACTRIMS and ECTRIMS).
In 2016, experts from member organizations of the Multiple Sclerosis Coalition (MSC), including the Multiple Sclerosis Association of America (MSAA), collaborated to develop and update a 2014 paper that summarized the current evidence that supports the FDA-approved DMTs for the long-term treatment of multiple sclerosis. The objectives were to provide evidence for the effectiveness of these medications and to provide support for broad access to these approved therapies for people with MS in the United States. Ultimately, the goal is to enable individuals with MS and their medical professionals to select the most appropriate medication available.
This professional paper, titled “The Use of Disease-Modifying Therapies in Multiple Sclerosis: Principles and Current Evidence,” is available on MSAA’s website for anyone to review. It has been written expressly for medical professionals, in a highly detailed and scientific style. This paper for professionals may be accessed by going to mymsaa.org/msc-dmt-full.
Following the release of the professional paper, member organizations of the MSC have collaborated to develop a summary, written in a more reader-friendly style to better serve the broader MS community. This paper is available on MSAA’s website as well and is titled, “The Use of Disease-Modifying Therapies in Multiple Sclerosis: Principles and Current Evidence; SUMMARY.” This summary directly correlates to the different sections found within the professional version, but has simplified the information to highlight main points and incorporate more commonly used terminology. In addition, the summary is followed by an extensive glossary to assist with those terms specific to describing the MS process. This paper on the approved DMTs is a valuable counterpart to this MS Research Update, which is focused on summarizing new and emerging data covering available therapies as well as emerging treatments still in development. This paper for the MS community may be accessed by going to mymsaa.org/msc-dmt-summary.
Please note that the authors of this MS Research Update have reported on the most recent study results available at the time of publication. While every effort has been made to provide meaningful, timely, and balanced information on each medication, keeping the length of information equal for each medication is not possible. Please know that the different lengths of text should in no way be considered as favoritism toward any one product. Additionally, references have only been cited for the newer study results.
As symptom-management drugs do not fall under the scope of this report, for more information on the specific symptoms of MS and treatments for managing these symptoms, please visit mymsaa.org and select “Symptoms” under “MS Information.”
Readers may also note that studies involving progressive forms of MS are highlighted with the mention of progressive MS appearing in bold type. This is because all but one of the 15 presently approved DMTs are for relapsing forms of MS, and the authors of this publication want to also bring studies for progressive MS to the readers’ attention.
Overview of MS Research Progress
A dramatic shift has taken place in the treatment of people with MS since the United States Food and Drug Administration (FDA) approved the first MS treatment, Betaseron® (interferon beta-1b), 24 years ago. The “watch and wait” approach to MS therapy has become a thing of the past, in favor of a proactive strategy to prevent MS-disease activity and disability. Treatment is now typically started after a person has experienced the first episode of MS, or a clinically isolated syndrome (CIS). CIS is defined as a single attack (or the first appearance of one or more symptoms characteristic of MS), with a very high risk of developing MS, when no other diseases or causes for symptoms are apparent. The use of magnetic resonance imaging (MRI) scans to identify lesions characteristic of MS has expedited diagnosis. Numerous studies with multiple types of DMTs have confirmed that early treatment at the time of CIS is beneficial in the long term.
Until recently, all of the approved DMTs were for relapsing forms of MS. In March 2017, Ocrevus™ (ocrelizumab) was the first treatment to be approved for two types of multiple sclerosis (MS): relapsing forms of MS (RMS) and primary-progressive MS (PPMS). Given via IV (intravenous) infusion twice per year, this was the first time that a medication was available to individuals with primary-progressive MS, representing a great advancement in the treatment of this form of the disease.
Ocrevus joins multiple new DMT options that have been approved in the last three years for relapsing forms of MS, including: Zinbryta® (daclizumab), a monoclonal antibody self-administered subcutaneously (under-the-skin) once per month; a new 40 mg formulation of Copaxone® (glatiramer acetate), dosed three times per week; Glatopa®, a generic equivalent of the daily 20 mg dose of glatiramer acetate; Plegridy® (peginterferon beta-1a), an interferon which is dosed once every two weeks; Lemtrada® (alemtuzumab), a new agent given by a series of infusions once yearly that was approved by the FDA at the end of 2014. With the success of research initiatives and the expanding number of approved medications, the choice of disease-modifying therapy has grown more complex.
In addition to the medications that have achieved FDA approval, there have been both major recent successes and setbacks in MS research. Although there was disappointment in the failure of Tysabri and Gilenya to succeed in progressive forms of the disease, the field saw two significant advances with the success of Ocrevus in primary-progressive MS in 2015 and siponimod in secondary-progressive MS in 2016. While Ocrevus was approved in 2017, siponimod is still moving through regulatory review, the final step before it too can be used to treat people with MS.
An attempt to develop a therapy to boost remyelination, anti-LINGO-1, disappointed in a recent clinical trial, but the use of a high-dose of the vitamin Biotin (in a small Phase IIb/III study) surprised many people with success in progressive MS, and is moving on into further study. The field of MS research has also moved forward with several types of stem-cell based research, which have generated positive, although complicated, results in 2016.
It can be challenging to keep up with the vast array of medications, techniques, and new areas of inquiry all seeking to make breakthroughs in this disease, and we view that as a “good problem to have.” We hope this MS Research Update serves as a useful guide to many of the highlights as well as the challenges facing our field, and provides insight into the many steps needed to investigate and prove that a new treatment strategy is both safe and effective for people with MS.
As always, no research successes can be achieved without the participation of people with MS in clinical trials, and we encourage interested readers to ask their providers about possible opportunities to contribute to MS research. The more diverse populations that enroll in clinical trials, the more meaningful are the results. We begin this MS Research Update with this note of gratitude to all the people with MS who made these trials possible. For more information about participating in clinical trials for the treatment of MS and its symptoms, readers may visit mymsaa.org/clinicaltrials
Editor’s note: Initial study results from therapeutic agents under investigation should be considered as preliminary, since additional studies and/or evaluations may be needed to prove the safety and efficacy of these agents. MSAA does not endorse or recommend any specific products or therapies. Readers are advised to consult their physician before making any changes to their medication, diet, exercise, or other treatment regimen.
Trial Phases for Investigating Treatments
Phase I studies are primarily concerned with assessing the drug’s safety. This initial phase of testing in humans is done in a small number of healthy volunteers, and is designed to determine what happens to the drug in the human body – how it is absorbed, metabolized, and excreted.
Once a drug has been shown to be safe, it must be tested for efficacy. This second phase of testing may last from several months to two years, and involve up to several hundred patients. Phase II studies are often “double-blinded,” meaning that the participants, medical staff, and investigators are not told who is receiving the drug and who is receiving the placebo.
In a Phase III study, a drug is usually tested in several hundred to several thousand patients, usually in multiple medical facilities around the world. Phase III studies typically last two or more years. Only after a Phase III study is successfully completed can a pharmaceutical company request FDA approval for marketing the drug.
Phase IV clinical trials are conducted after a drug has been approved. Participants are enrolled to further monitor safety and side effects, while evaluating long-term efficacy.
Please note that not all of the approved treatments for MS have been included in this section. For a full listing, please see this chart giving an overview of the approved DMTs.
Monoclonal Antibody Medications
About Monoclonal Antibodies
Monoclonal antibodies are derived from cells that are identical (cloned from a single cell and then replicated). They are produced from animal tissue, most commonly laboratory mice. Humanized monoclonal antibodies are antibodies from non-human species, again commonly a mouse, whose protein sequences have been modified to increase their similarity to antibodies produced naturally in humans. Monoclonal antibodies can be extremely powerful and effective, as they can be specifically directed toward a certain part of a system while leaving the other parts of the system untouched. This can be very desirable when trying to impact a structure as complex as the immune system. The name of all monoclonal antibodies ends with “mab,” including alemtuzumab (Lemtrada), daclizumab (Zinbryta), ocrelizumab (Ocrevus), and natalizumab (Tysabri) , which are already approved for MS. Several other monoclonal antibodies have shown promise in MS, and two of these are reviewed in this section.
New S1P Receptor Modulators
Several investigational oral agents are currently under study that work in a similar manner as Gilenya in that they also trap the immune cells in the lymph nodes so that they cannot get into the CNS to create lesions. It is hoped that these agents, siponimod (BAF312), ozanimod (RPC1063), and ponesimod, will maintain or potentially improve on the efficacy and safety of Gilenya. However, researchers continue to remain vigilant with regard to risks, including cardiovascular side effects such as bradycardia (slowed heart rate) and infections.
Other Therapeutic Strategies
- Masitinib (also known as Kinavet® and Masivet®)
- Tcelna™ (formerly Tovaxin®)
- Tetracycline Antibiotics
New Therapies under Investigation
About New Therapies under Investigation
The earlier listing of approved and experimental drugs is only a fraction of the many treatments currently being studied. Some of the following are among the most exciting potential therapies under investigation. These very brief snapshots of highly technical concepts will warrant more in-depth explanations in the future, if pilot clinical trials are encouraging.
Anti-LINGO (opicinumab): LINGO-1 is a protein in the central nervous system whose role is to halt myelination and prevent the survival of neurons. Although this may seem counterintuitive for the body to create a protein with this function, in a healthy individual it performs an important job. All of the cells that make up the organs in the body receive “instructions” regarding when to grow and when to cease growing. Without these sorts of cellular “checks and balances,” tissues could grow without restraint, as seen in some cancers. Anti-LINGO-1 (BIIB033) is an agent with potential remyelinative properties, after animal studies showed that it blocks LINGO-1 from stopping the growth of myelin. It has been shown to promote spinal cord remyelination and axonal integrity in the animal model of MS (EAE).
Initial Phase I trials of anti-LINGO,33 involving 64 healthy adult volunteers and 42 people with relapsing or SPMS reported that the drug was well-tolerated, with no serious adverse events; headache was the most frequent side effect reported.
The first Phase II trial of anti-LINGO reported successful results in 2015.34 The study recruited individuals with newly-diagnosed MS involving the visual pathways (optic neuritis) to evaluate the drug’s effect on remyelination. The primary outcome of RENEW was an assessment of recovery of optic-nerve function measured by the speed at which the nerve conducts visual signals. This was studied by evaluating a test called Full Field Visual Evoked Potential (FF-VEP) in participants treated with anti-LINGO-1, compared with placebo.
Individuals who were treated with at least five of the six doses of anti-LINGO-1 showed a 34-percent improvement in optic-nerve conduction latency (delay in the speed of the visual signal) at week 24, compared with placebo. Further recovery in optic-nerve conduction was observed at the last study visit (week 32), with a statistically significant 41 percent improvement. Together, the data demonstrate evidence of treatment effect with continuous improvement observed 12 weeks following the last study dose.
However, the study showed no effect on secondary endpoints, including change in thickness of the retinal layers (optic nerve neurons and axons), or on visual function. Anti-LINGO-1 was generally well-tolerated in this study, noting that two participants had hypersensitivity (allergic) reactions at the time of infusion, and one patient had liver-function test abnormalities, which resolved after drug discontinuation. Taken together, these results provided an encouraging indication that anti-LINGO-1 is safe and may facilitate remyelination.
To that end, a second, larger Phase II trial (SYNERGY)35 was conducted, although Biogen announced in mid-2016 that the SYNERGY trial was not successful. The study involved more than 400 people with either RRMS or SPMS. Participants were randomized to one of five groups; four groups were given Anti-LINGO in different doses (3 mg, 10 mg, 30 mg, and 100 mg) plus Avonex, and the fifth group was given Avonex plus placebo. SYNERGY aimed to see whether the addition of anti-LINGO to Avonex could lead to an improvement in disability scores when compared to Avonex alone. Unfortunately, at the end of the 72-week study, no statistical difference was seen between the people on Anti-LINGO and those on placebo. There did seem to be some indication of a response in those participants who were under 40, those with RRMS, and those with MS for less than eight years in the low to mid-dosing range. It remains to be seen how this medication will be carried forward into further MS research.
Other experimental treatments under investigation to potentially foster remyelination or myelin repair include agents in early stages of development – and still with experimental names – such as GSK23951236 and rHIgM22.37
Amiloride, Phenytoin, and Sodium Channel Blockade: The accumulation of salt and potassium within the cells of MS lesions may possibly contribute to cellular injury and neurodegeneration (the breakdown of nerves). This hypothesis would suggest that by blocking certain channels in these cells, the buildup of these molecules can be prevented and neurodegeneration can also be prevented. This strategy was tested and data presented in 2013,38 looking at the use of amiloride – a potassium-sparing diuretic approved for the treatment of high blood pressure and congestive heart failure. This medication may have the potential to provide this neuroprotective activity.
The effect of amiloride has been studied in 14 people with PPMS using MRI markers of neurodegeneration as outcome measures of neuroprotection. Individuals underwent MRI scans before and during amiloride treatment, at a standard dose used for high blood pressure, for a period of three years.
Researchers found a significant reduction in the development of brain atrophy, as well as a slowing of the development of disability during the treatment phase in this small group of patients. These findings suggest that amiloride may exert neuroprotective effects. Because amiloride does not readily cross the blood-brain barrier to gain access to the CNS, the precise mechanism for these results is not clear. This pilot study was the first effort in people with MS to focus on neuroprotection using amiloride, and supports further investigation of this drug as a potential neuroprotective agent in MS.
It is worth noting that this strategy was successful in a study of the anti-seizure medication phenytoin (brand name Dilantin®), which also works by modulating sodium channels. A Phase II clinical trial assessed whether phenytoin could be neuroprotective in acute optic neuritis39 (AON). The study was comprised of 86 people with AON randomized within two weeks of symptom onset to receive either phenytoin (4 mg per kg daily) or placebo for three months. The primary outcome of this AON study was an evaluation of the structure of the retinal nerve fiber layer (RNFL) and macular volume (MV) at six months. Visual function, optic-nerve imaging, and visual-evoked potentials were also measured.
Of the original 86 participants, 81 were followed to study end. In these people, the average adjusted affected eye RNFL thickness at six months was higher in the active group versus placebo, resulting in a 30 percent protective-treatment effect. Adjusted MV (macular volume) showed a 34 percent protective-treatment effect. Vision generally recovered well, with no significant difference in visual outcomes between the treatment groups.
This intriguing study may have broad implications, as it found that the administration of a well-known, relatively safe drug seemed to be neuro-protective in the period directly following optic neuritis. Both amiloride and phenytoin may also represent potential combination strategies in conjunction with immune-modulating, disease-modifying therapies.
Amiloride is also being studied in a larger study, MS-SMART. This ongoing study40 is comprised of 440 individuals with SPMS who have been randomized to four different arms: amiloride, Rilutek® (riluzole ), Prozac® (fluoxetine), and placebo. Participants will be followed for 96 weeks. The main study measure is a comparison between the treatment arms and the placebo group to see if any differences occur in the rate of brain atrophy. This study is expected to finish in 2018 and is intriguing as it is simultaneously looking at multiple safe, currently available medications that may lead to neuroprotection. Furthermore, MS-SMART has employed an interesting trial design in that it has a shared-placebo group. This efficient design avoids the need for three similar trials to be conducted separately.
Clemastine is an older anti-histamine that is available over the counter. It was discovered41 to hold potential for re-myelination through the innovative laboratory work of a researcher in San Francisco. This finding led to a small Phase II placebo-controlled crossover study (participants are initially assigned to one study group and then switched midway through) of high doses of clemastine in individuals with evidence of damage to the optic nerve. Researchers reported that while on treatment, participants experienced a significant improvement in the transmission of the signal in the optic nerve and showed a trend toward improvement in visual function. Overall, the treatment was safe, though participants’ fatigue scores worsened. This medication is an attractive option to researchers and clinicians given its availability and favorable safety profile. However, it remains to be seen if it can truly work to bring about functional improvement through re-myelination.
Idebenone (Catena® or Sovrima®): This experimental drug, similar to coenzyme Q10, was initially developed to treat Alzheimer’s disease and other cognitive defects. Coenzyme Q10 is produced within your own body and is necessary for cells to grow and remain healthy. This substance also works as an antioxidant, helping to prevent injury from the oxidation process. It is being explored in MS because oxidative stress has been postulated to play a role in the death of myelin-producing cells, which has been linked to MS progression.
Oxidation is the body’s natural metabolism of oxygen. When disturbances occur in this process, “oxidative stress” can result, causing damage to the body’s cells and tissues. Oxidative stress is believed to be a contributing factor in many diseases, including those affecting the nerves and the immune system.
A double-blind, placebo-controlled Phase I/II clinical trial of idebenone,42 sponsored by the National Institute of Neurological Disorders and Stroke, recruited 44 participants with PPMS who had little to moderate disability. The trial began in July 2009 and was scheduled for completion in September 2016, with an extension trial continuing through 2018.
MIS416: This “therapeutic vaccine” is a potent activator of the innate immune system, which provides immediate defense against infection but does not result in long-lasting or protective immunity. As a side note to help explain this type of immune-system defense, the “innate” or “natural” immune response is nonspecific. It does not have any type of memory, and reacts in the same way each time it encounters a foreign entity, such as a virus or bacteria. MIS416 has been primarily tested in cancer and acquired infections, with the goal of enhancing the inherent capability of a person’s immune system to fight disease.
A Phase I/II study to evaluate the safety and tolerability of IV-administered MIS416 in people with either PPMS or SPMS presented interim results in 2012. This open-label, dose-escalation/confirmation trial showed MIS416 to be well-tolerated and identified a clinical dose for further evaluation. Moreover, during the dose-confirmation portion of the study, eight of 10 participants with SPMS who were treated with MIS416 for 12 weeks showed some improvement. A further Phase II study43 in SPMS was planned to be completed in late 2016.
Transdermal Administration of Peptides: A small Polish study of 30 individuals44 with RRMS evaluated the efficacy and safety of transdermal (skin patch) administration of two dose levels of three myelin peptides: MBP 85-99, PLP 139-151, and MOG, versus placebo. In the lower-dose group, which received 1 mg each of the three peptides, the annual relapse rate at one year was reduced by 65 percent compared with placebo. Progression, as measured by the Expanded Disability Status Scale (EDSS), was slightly lower, indicating that disability did not worsen, and may have slightly improved. Additionally, 56 percent were relapse-free versus 10 percent in the placebo group. The treated group also showed a decrease in gadolinium-enhancing lesion volume and T2-lesion volume. The treatment was safe and well-tolerated. This approach of using a combination of peptides may be pursued in future studies.
IL-17 Modulators: Secukinumab (AIN457) and CJM112. IL-17 is one of several cytokines produced by the immune system. Cytokines are small proteins that may stimulate or inhibit the function of other cells. IL-17 appears to be a major inflammatory component in MS.
Secukinumab is a humanized monoclonal antibody to IL-17 that is FDA-approved to treat psoriasis. A proof-of-concept trial in RRMS45 enrolled 73 participants and showed a reduction in gadolinium-enhancing MRI lesions compared with placebo.46
A larger, Phase II trial was planned to enroll approximately 380 individuals with relapsing MS; the design of the study was presented at ECTRIMS in fall 2013, but was cancelled in favor of the clinical development of CJM112, which also targets IL-17 and is administered by subcutaneous injection. The design of the Phase II trial was presented at ECTRIMS in the fall of 2015. To date, no individuals with MS have received this experimental treatment.
ATL1102 is an oral agent that affects the VLA-4 system, the same molecular mechanism utilized by Tysabri. It does so via a novel mechanism of action, and falls into a class of “antisense oligonucleotides” not previously used in MS. The results of a Phase II trial were published in 201447, noting that ATL1102 decreased the emergence of new active brain lesions as compared with placebo, after only two months of treatment in approximately 70 individuals with RRMS. In 2016, the company announced its intent to run a Phase IIb trial of ATL1102, although it is unclear when it will begin.
Pixantrone (PIX) is under investigation as an alternative for the effective but cardio-toxic drug Novantrone® (mitoxantrone or MIX) in the treatment of aggressive RRMS or SPMS. In a Phase I/II study of 18 people with aggressive disease, results published in 201548 suggested that pixantrone was as effective as Novantrone, but with less cardiotoxicity. Although via a different mechanism of action than Rituxan and Ocrevus, pixantrone was shown in this study to reduce B cells by 95 percent. According to the authors,49 pixantrone is structurally similar to Novantrone and both medications have similar immuno-suppressive properties in animal studies. However, the authors state that pixantrone is less toxic to the heart.
SR-CRH-01 is a stabilized, neuropeptide, also known as Aimspro®. In a Phase II double-blind, placebo-controlled study of 20 people with SPMS presented in 2014,50 SR-CRH-01 was well-tolerated when given by subcutaneous injection twice weekly for four weeks, resulting in significant improvements in several secondary endpoints. These endpoints included the MS Functional Composite (MSFC), the Timed 25-Foot Walk (T25-FW), and the mean 9-Hole Peg Test (9-HPT). Larger, longer-term studies are warranted given these promising results. However, no new trials are presently being conducted.
New Therapeutic Approaches
- Vitamins and Electrolytes
- Stem Cells
- Genetic Studies
- The Microbiome and MS
- Diet and MS
In summary, the future of MS disease-modifying therapies (DMTs) for MS continues to be promising, both in terms of new information about currently approved DMTs and exciting results for emerging therapies. Advances in genetic and biomarker studies hold the promise that, in the future, it will be possible to personalize the decisions about MS therapy in a precise, biologically-driven manner.
More than ever, the field of MS research relies upon the willing participation of patients in clinical trials. We now recognize how ethnically, racially, genetically, and culturally diverse the MS community is, but diversity in our clinical trial populations is lacking. In 2015, data from six randomized, placebo-controlled trials were used to examine the baseline characteristics and clinical outcomes in white, black, Asian, and Hispanic populations. The results were challenging to interpret due to the incredibly low number of non-white participants in clinical trials, which in turn makes our clinical trial results hard to interpret in the real world. The field of MS research needs a diverse population recruited into clinical trials to truly know that these medications are globally effective in MS.
This MS Research Update has summarized the breakthrough trials that have occurred in PPMS and SPMS, as well as investigations into neuroprotection, remyelination, and repair. For the first time in the history of MS therapeutics, clinicians are realizing the possibility of offering treatments not only for relapsing MS, but also for the progressive forms of the disease. Furthermore, the goal of reversing the damage caused by this disease is within reach.
In recent years, our arsenal of MS therapies has grown considerably, with more on the way. Along with these new therapies come a host of new challenges and risks, which will require vigilance and a thoughtful approach to medication selection and management. Finally, well-designed studies looking at the impact of dietary supplements and other diet modifications will bring the sort of scientific rigor needed to truly answer these questions for individuals with MS.
As clinicians have more numerous and more complex treatment options to offer individuals with MS, the need for patient education and awareness has become more crucial. Now more than ever is the age of empowered, highly-informed patients, who can be true participants in their MS care in collaboration with their treatment team. We hope this update is a valuable part of that process. For more information about clinical trials, please visit www.clinicaltrials.gov; for participation opportunities, please visit mymsaa.org/clinicaltrials. For more information about MS and its treatments, please contact MSAA at (800) 532-7667, or visit mymsaa.org.