MS Research Update 2018

Written and compiled by Tom Garry with Stephen Krieger, MD and Michelle Fabian, MD

Reviewed by Jack Burks, MD
Edited by Susan Courtney


The 2018 edition of MSAA’s MS Research Update provides important new data on approved and experimental treatments for MS, serving as 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 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 be aware that due to the timing of the national and international MS conferences, study data from 2018 conferences generally could not be included in the Update. Information in this publication includes data presented at the 2017 conferences, as well as any important updates that occurred in early 2018. Please visit MSAA’s website at mymsaa.org for future summaries of 2018 conference highlights.

The 2018 MS Research Update is made possible through contributions in honor of: Randi and Carl Bushner, and an anonymous supporter.


Introduction

This 2018 MS Research Update has been designed to highlight experimental medications 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 emerging areas of MS research.

This 2018 edition of MSAA’s MS Research Update is again being printed as a stand-alone issue, reflecting the great diversity and wide scope of research progress in MS. With so much ongoing research, it all cannot be covered here. Therefore, not all study results and medications are included.

The information presented 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 2017 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).

Please note that this MS Research Update reports 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 medications 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.”

In addition to exploring this MS Research Update, readers are encouraged to review a paper titled, “The Use of Disease-Modifying Therapies in Multiple Sclerosis: Principles and Current Evidence; SUMMARY.” The paper, available at mymsaa.org/msc-dmt-summary, outlines in a reader-friendly fashion the evidence supporting the use of FDA-approved DMTs for the long-term treatment of MS.

The paper is the result of a 2016 conference in which experts from member organizations of the Multiple Sclerosis Coalition (MSC), including the Multiple Sclerosis Association of America (MSAA), collaborated to assess the current data on the effectiveness of these medications. One goal of this meeting was to demonstrate the strong evidence base for MS therapies in order to support broad access to these approved medications for people with MS. Ultimately, the goal is to enable individuals with MS and their medical professionals to select the most appropriate medication available.

A version of this paper is also available for medical professionals, which is written in a more-detailed and highly scientific style. The professional version may be accessed on MSAA’s website for anyone to review by going to mymsaa.org/msc-dmt-summary.

Providing these resources is central to MSAA’s mission of being a leading resource for the entire MS community, improving lives today through vital services and support. Feedback and thoughts on the 2018 MS Research Update, and other MSAA publications and services are welcomed, and can be directed to the organization at (800) 532-7667 or editor@mymsaa.org.

Overview of MS Research Progress

Developments over the past year or more provide yet another reminder that while research inevitably leads us forward, the path is not straight and smooth, with detours, dead-ends, and disappointments – as well as breakthroughs – encountered along the way.

As last year’s edition of the MS Research Update was prepared for publication, the “breaking news” included at the 11th hour was the FDA’s March 2017 approval of Ocrevus™ (ocrelizumab). This new DMT was not only approved for relapsing forms of MS (RMS), but was also the first DMT approved for primary-progressive MS (PPMS). During the 25 years since 1993, when the FDA approved Betaseron® (interferon beta-1b) as the first MS treatment, the MS community has seen numerous milestones, and this new ability to treat PPMS truly ranks among the most important of those achievements.

The “breaking news” this year is mixed. March 2018 saw Biogen and AbbVie announce the withdrawal of their monoclonal antibody Zinbryta® (daclizumab) from markets worldwide. That decision follows reports from Europe of inflammation of the brain or nearby tissues in a dozen people taking the immune-modulating medication. The withdrawal comes less than two years after Zinbryta was approved for use in the United States for treating relapsing forms of MS. Recent months also saw disappointing trial results for medications that had encouraging initial findings. To cite one example, the experimental medication laquinimod missed its primary endpoints in trials evaluating its efficacy in RMS and PPMS.

However, March 2018 also saw the publication of results from the Phase III EXPAND trial, which evaluated the selective sphingosine 1-phosphate (S1P) receptor modulator siponimod in secondary-progressive multiple sclerosis (SPMS), a disease state sorely in need of effective therapies. The multi-national trial involved more than 1,600 patients with SPMS. It showed that, compared to placebo, siponimod cut the annualized relapse rate in half, reduced confirmed disability progression, and slowed the rate of brain volume loss.1 On the basis of these and other findings, Novartis announced in late March that it will seek FDA approval for siponimod for SPMS in the first half of 2018.2

Other breaking news, as this edition of the MS Research Update was being prepared, is the FDA’s February 2018 approval of a second dose option for Glatopa® (glatiramer acetate injection), at 40 mg given three-times weekly for relapsing forms of MS.3 Additionally, in May 2018, the FDA approved Gilenya® (fingolimod) as the first treatment specifically indicated to treat pediatric MS.

The past year also saw several other significant advances in the development of experimental therapies. These include ibudilast, an experimental medication also known as MN-166, which showed a 26-percent reduction in confirmed disability progression in a Phase II trial of people with progressive MS. Based on those findings, the company developing ibudilast in MS is making plans for a 700-patient Phase III trial.4

Meanwhile, a December 2017 study published in The Lancet reported that the over-the-counter medication clemastine fumarate showed evidence of promoting remyelination, which is the restoring of the myelin sheath that covers central nervous system (CNS) cells and supports their function. This effect was seen in 50 patients with RMS who were experiencing chronic demyelinating optic neuropathy while on immuno-modulating therapy.5 While this was a small, single-center study whose findings need to be confirmed on a larger scale, it represents another step toward the goal of understanding and addressing demyelination, the central process in the development of MS.

In other cases, medications with promising data may face delays as they navigate the regulatory process. For example, on the basis of positive results from two large Phase III trials, Celgene submitted a New Drug Application (NDA) to the FDA for use of ozanimod in relapsing forms of MS. Ozanimod belongs to a class of drugs called S1P receptor modulators, which essentially trap immune cells in the lymph nodes so that they cannot enter the CNS and create lesions. In February 2018, however, the FDA declined to accept the NDA, saying that two sections of the NDA were insufficient to allow a complete review. In response, Celgene expressed its confidence in ozanimod and said it would work with the FDA to address outstanding items.

Exciting work is also being done in examining whether medications long used to treat other conditions – including antibiotics and the anti-epilepsy agent phenytoin – may have re-purposed roles in treating MS. Stem cell and genetic research is advancing as well, and there is an increasing and intriguing focus on how diet and the gut microbiome (bacteria) – or immunologic milieu of the gastrointestinal tract – affect MS and its treatment.

Finally, two growing areas of research are outgrowths of the progress made over the past two decades in offering people with MS a variety of therapies. The first area concerns “comparative effectiveness,” and typically draws on large databases and sophisticated statistical methods to assess which medication is likely to be most effective and safe in a given type of patient. This is key to helping physicians and patients make the best possible decision about treatments.

The second area examines the long-term safety of disease-modifying therapies. By analyzing data from “extension studies” of the clinical trials that led to the initial approval of medications, and from patient registries, long-term safety studies are created. These provide critical information on medications that tens of thousands of patients may now be taking for 10 or even 20 years or longer.

Keeping up with the vast array of medications, techniques, and new areas of inquiry in MS is challenging, and at times can be overwhelming to healthcare professionals, patients, and family members alike. Of all the challenges we face in MS, having too many advancements is perhaps the most-welcomed one! We hope this MS Research Update serves as a useful guide to many of the highlights as well as the hurdles 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.

In reporting on recent research, this publication describes clinical trials involving numerous participants. It is important to remember that those study populations are made up of individual men and women who each made the decision to participate in a trial. By making this decision, a person chooses to take an active role in furthering our understanding of MS and its treatment, to the potential benefit not only of herself or himself, but of all people with multiple sclerosis.

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 open this MS Research Update with this note of gratitude to all the individuals 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 medications under investigation should be considered as preliminary, because additional studies and/or evaluations may be needed to prove the safety and efficacy of these medications. 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

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.

Phase II

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.

Phase III

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

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.



FDA-Approved Medications

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.


Experimental Medications

Administered Orally

Monoclonal Antibody Medications

About Monoclonal Antibodies

Antibodies are proteins that are produced by the immune system in response to a foreign substance, to help protect the body from infection and disease. Monoclonal antibodies are derived from a single antibody cell and are identical to that single cell (cloned 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” (standing for Monoclonal AntiBodies) including alemtuzumab (Lemtrada), ocrelizumab (Ocrevus), and natalizumab (Tysabri), which are already approved for MS. Several other monoclonal antibodies have shown promise in MS, and three of these are reviewed in this section.

New S1P Receptor Modulators

About S1P Receptor Modulators

Several investigational oral medications that are currently under study, work in a manner similar to 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, which include 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

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 early 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 it 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 experimental medication 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, involving 64 healthy adult volunteers and 42 people with RMS 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 2015.59 The study recruited individuals with newly-diagnosed MS involving the visual pathways (optic neuritis) to evaluate the medication’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 the thickness of the retinal layers (optic nerve neurons and axons), or on visual function. Anti-LINGO-1 was generally well-tolerated in this study. 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) 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.

A post-hoc analysis of the SYNERGY data examined whether any factors could predict which individuals with RRMS would have a greater and more enduring response to anti-LINGO than that seen in the overall study population. Researchers looked at nine demographic/clinical characteristics and 13 MRI findings. They found that three characteristics – shorter disease duration (≤20 years), lower baseline magnetization transfer ratio in T2 lesions (an MRI finding that may indicate lower myelin content in the lesions), and lower baseline values for diffusion tensor imaging – radial diffusivity (DTI-RD, an MRI finding that may indicate greater structural integrity) were predictive of a greater and longer-lasting treatment effect.60

Those findings helped inform the design of the Phase II AFFINITY trial, which was initiated in 2017. The multi-center trial seeks to evaluate the efficacy and safety of anti-LINGO (opicinumab) as an add-on therapy to interferon beta-1a. Investigators are recruiting 240 people with RMS who are adequately controlled on their interferon beta-1a therapy. The study’s primary endpoint is Overall Response Score (ORS), a measure of improvement and worsening of disability over time. AFFINITY investigators note that analysis of the SYNERGY results enabled them to take a more precise biological approach in evaluating opicinumab in their trial. They also noted that the MRI findings, which were predictive of a response in SYNERGY, suggest the possibility for repairing MS lesions through remyelination.61

In addition to anti-LINGO, other experimental treatments are under investigation to potentially foster remyelination or myelin repair. These include medications that are in very early stages of development.

Amiloride, Phenytoin, and Sodium Channel Blockade: The accumulation of salt and potassium within the cells of MS lesions may contribute to cellular injury and neurodegeneration (the breakdown of nerves). This hypothesis would suggest that by blocking channels that facilitate salt and potassium entering these cells, the buildup of these molecules can be prevented, and with that idea in mind, neurodegeneration might also be prevented.

This strategy was tested in a study of 14 people with primary-progressive MS (PPMS) who received amiloride – a diuretic approved for the treatment of high blood pressure and congestive heart failure. The study used MRI scans of the brain to examine whether the potassium-sparing activity of amiloride might have a neuroprotective effect. Patients received the standard dose of amiloride given to treat high blood pressure for three years.

In 2013, the researchers reported 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 participants. These findings suggest that amiloride may exert neuroprotective effects. However, because amiloride does not readily cross the blood-brain barrier to gain access to the CNS, the precise mechanism underlying these results is not clear. This pilot study was the first evaluation of the potential neuroprotective effects of amiloride in MS, and its results show that the agent warrants further investigation.

Amiloride is also being studied in the MS-SMART trial, an ongoing study 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 in the rate of brain atrophy. This study, which is expected to be completed in 2018, is intriguing because 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.

While studies of amiloride in MS focus on potassium channels, research involving the anti-seizure medication phenytoin (brand name Dilantin®) focuses on sodium channels. A Phase II clinical trial assessed whether phenytoin, which modulates sodium channels, could be neuroprotective in acute optic neuritis (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 the 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.62

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.

A follow-on study involving a subgroup of participants employed MRI to evaluate how phenytoin affected the tissue microstructure of the optic nerve. The study looked at the measured optic nerve magnetization transfer ratio – a possible marker of neuroprotection. The study found that phenytoin appeared to have a beneficial impact on the tissue microstructure of the optic nerve following optic neuritis, but with varying impact in different sections of the nerve – based on their location relative to the lesion that caused the optic neuritis.63

This intriguing research into phenytoin 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.

Clemastine is an older anti-histamine that is available over the counter. It was discovered to hold potential for remyelination through the innovative laboratory work of a researcher in San Francisco. This finding led to a small Phase II placebo-controlled crossover study (participants were initially assigned to one study group and then switched midway through the study) 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 improved visual function. Overall, the treatment was safe, although 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 clinical improvement through remyelination.5

Idebenone: This medication, similar to coenzyme Q10, initially was developed to treat Alzheimer’s disease and other cognitive defects. Coenzyme Q10 is produced within one’s 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, sponsored by the National Institute of Neurological Disorders and Stroke (NINDS), recruited 77 individuals with PPMS who had little to moderate disability. Study participants were randomized in a 1:1 ratio, and after a one-year observational pre-treatment phase, received either 2,250 mg of idebenone daily or placebo for two years. The study’s primary endpoint was change in the CombiWISE, a rating scale developed by NINDS researchers.

In March 2018, the Swiss company developing idebenone announced that while the trial showed that the medication was well tolerated, topline results showed no difference between idebenone and placebo in terms of the CombiWISE scale, changes in the volume of the brain’s ventricles, or other clinical assessments or biomarkers.64 Those findings constitute another disappointment in the effort to develop additional disease-modifying therapies for PPMS.

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 tested primarily 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 reported positive results. As a result, the Australian company developing the agent, Innate Immunotherapies, initiated a Phase IIB trial in which 93 people with SPMS were randomized in a 2:1 ratio to receive either MIS416 or saline placebo intravenously once weekly for a year. In June 2017, Innate Immunotherapies announced that an initial analysis of trial data showed no clinically meaningful or statistically significant difference between MIS416 and placebo across several measures of neuromuscular function or patient-reported outcomes. The company said it would further analyze the results to see if a subgroup of patients derived significant benefit from MIS416.65

These results are disappointing given the recent progress in leveraging immunotherapies to enhance the body’s ability to fight a variety of blood-system and solid-tumor cancers. Hopefully, these advances in oncology will soon have parallels in the treatment of MS.

ATL1102 is an oral medication 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 2014, 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 October 2017, Antisense Therapeutics – the Australian company developing ATL1102 – announced that after consultations with the FDA, plans were under way for a Phase IIB study of the medication at a 25 mg/week dose for six months. The company added that it would talk further with the FDA regarding criteria for testing higher doses of the medication in people with MS and about the safety monitoring that would be employed in following individuals on higher doses.66


New Directions in MS Research

New Therapeutic Approaches


Closing Notes

The study results and ongoing trials reported in this 2018 MS Research Update show the breadth and depth of efforts to develop effective therapies across the spectrum of multiple sclerosis to better understand how currently approved therapies can be used to optimize patient care.

The array of hypotheses being pursued, compounds being evaluated, and investigative strategies being employed is almost overwhelming, and is cause for great hope and encouragement. While disappointments and dead ends are an inevitable part of the process, the pace of our collective efforts seems to accelerate year after year, as each new finding – positive or negative – helps us refine and better direct our efforts.

A tremendous amount of work, however, still needs to be done, both at the molecular level and in terms of translating laboratory findings into individualized care that reaches all people with MS. Secondary-progressive MS remains an area where effective therapies are vitally needed. Similarly, to echo comments made in the closing section of the 2017 Update, it is imperative that we achieve greater ethnic, racial, and other diversity in study populations. This MS Research Update has summarized key trials in relapsing forms of MS, secondary-progressive MS, and primary-progressive MS, as well as promising investigations into neuroprotection, remyelination, repair, the genetic basis of MS, and the role the microbiome and diet, among other topics.

The number of available MS treatments has grown considerably in recent years, and now includes a therapy for primary-progressive MS, with more on the way. These new therapies are accompanied by new challenges, and also new risks, as we seek to identify the right medicine for the right patient at the right time… and to thoughtfully balance the benefits and risks of treatment strategies.

People with MS, as much as clinicians, need to be highly informed so that they are empowered to participate fully in the shared decision-making process. We hope that this update will be a valuable resource for individuals with MS and their families as they pursue that goal. 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.