Over 12,000 neurologists and other researchers gathered in San Diego in March to share the most up-to-date research on treating neurological diseases such as multiple sclerosis at the annual American Academy of Neurology’s (AAN) meeting.
Here are a few highlights from the more than 500 MS-related presentations that focused on stopping MS, restoring function, and ending MS forever.
A small study of an oral blood-pressure medicine, Amiloride, found a reduction of brain shrinkage associated with the disease in 14 people with primary-progressive MS. Further testing in a larger study is now underway.
Researchers in a large trial of Gilenya for primary-progressive MS reported good progress in setting up the trial. This is one of several ongoing large studies in progressive MS.
Results of a study on peginterferon beta-1a (a new form of Avonex) designed to stay in the body longer than the standard form suggest that peginterferon injected every two or four weeks was effective in reducing relapse rates and the risk of progression of disability. The study is continuing into a second year and the trial sponsor Biogen Idec has announced plans to apply for FDA approval later this year. Another one-year phase III trial found that injections of twice the standard dose of glatiramer acetate (Copaxone) taken three times per week were effective in reducing relapses and MRI-detected disease activity, with no unexpected safety issues.
A large study in France (ENIGM) found that among 200 people who switched from natalizumab (Tysabri) to fingolimod (Gilenya), 32% experienced a relapse during the “washout” interval of 3 to 6 months when no therapy was given. The researchers concluded that switching increases the likelihood of disease reactivation and that the washout period should not be longer than 3 months.
Results of two phase III trials of oral dimethyl fumarate (Tecfidera), approved by the FDA in March, suggest that the treatment begins to take full effect after three months of use. This effect was sustained over the two-year span of the trials.
Several presentations focused on results from extension phases of completed clinical trials in relapsing-remitting MS. To read more, visit www.nationalMSsociety.org/2013AAN.
Exploring Disease Activity
An Argentinian study on whether vaccinations can trigger MS attacks found that yellow fever vaccines may substantially increase the risk of MS relapse; therefore, people with MS planning a trip to a region with an increased risk of yellow fever should discuss the risks and benefits of vaccination with their doctor.
A small study in Louisiana found that people with higher levels of glucose were more likely to have higher levels of disability. This important lead needs more study to prove a role for blood sugar in MS progression.
A few studies focused on ways to track disease progression, including one that analyzed serum samples from people with MS who were taking glatiramer acetate (Copaxone). The researchers were able to find antibody profiles that could detect those who responded to therapy and those who did not. Dr. Nicholas LaRocca of the National MS Society described efforts of the newly formed MS Outcome Assessments Consortium to accelerate development of more effective treatments for MS. They will analyze data from completed MS clinical trials and other studies and work with regulatory agencies to qualify a new outcome measure that can more sensitively track the impact of therapies on disease disability and progression in future trials.
Several studies focused on the benefits of exercise for brain function and MS symptoms such as fatigue, while others looked at how the brain can adapt to MS damage. To read blog posts by MS researchers on these and other studies, visit blog.nationalMSsociety.org.
A study on CCSVI did not find a significant difference between 61 people with MS and 20 people without MS when technicians trained in CCSVI assessment used various ultrasound techniques to detect the condition. The first results of another study of controlled endovascular treatment at six months found no adverse events, but also no sustained improvement in venous outflow.
|Professor Ebers, center, receives the John Dystel Prize from Drs. Timothy Coetzee and Bruce Cohen|
Ending the Disease Forever
Several reports focused on risk factors for MS, including one indicating that dietary salt may stimulate activity of key immune cells involved in MS attacks. Read more at www.nationalMSsociety.org/dietarysalt.
For his extensive work on understanding MS, including the importance of genetic factors in who develops the disease and how genes interact with environmental factors, Professor George Ebers was this year’s recipient of the John Dystel Prize for MS Research, given jointly by the Society and the AAN.
Read scientific summaries on the AAN’s website at www.abstracts2view.com/aan.
An increasing number of medical centers across the United States are collaborating on research on how and why multiple sclerosis happens in young people. Their work is already yielding valuable information on early MS triggers.
A Collaborative Approach
The Network of Pediatric MS Centers was initiated in 2006 through a grant from the National MS Society. Thanks to its multidisciplinary approach, researchers at participating institutions are gathering important data on the disease.
“We have been able to unravel key features, such as distinct characteristics of the disease on the MRI and in the spinal fluid of patients younger than 11,” says Emmanuelle Waubant, PhD, professor of Neurology and Pediatrics at the University of California – San Francisco, which is currently running a large study aimed at unraveling the triggers of pediatric MS. See box below, “What triggers MS?
Thus far, the network has learned that MRIs of patients under 11 show larger and more poorly defined MS scars compared to adults, and that MS scars in young patients often go away within a few months, which is very rare in adults. They also observed that the spinal fluid of young patients can show more inflammation than in adults.
These findings have helped make the way forward clearer. “Now that these distinct features in younger patients have been identified, accurate diagnosis in children with MS is made easier, and early treatment can better prevent disability onset,” says Dr. Waubant.
To learn more about pediatric MS and research in the field, visit www.nationalMSsociety.org/pediatricMS.
What triggers MS?
The Network of Pediatric MS Centers is currently recruiting 640 children with relapsing-remitting MS or clinically isolated syndrome (a single episode of MSlike symptoms) and 1,280 children without MS for a multiyear study to determine risk factors for developing MS. “We expect the study will provide precious pieces of information on risk factors for MS in general, and maybe help develop new treatments or preventative strategies,” says lead investigator Emmanuelle Waubant, PhD. For more information about participating and the 13 participating locations, contact firstname.lastname@example.org or call (415) 514-2476.
By Megan Weigel, CNP, ARNP-C, MSCN
In 1993, Betaseron was released to market as the first disease-modifying therapy for multiple sclerosis. With the approval of oral dimethyl fumarate (brand name Tecfidera™) by the U.S. Food and Drug Administration (FDA) in March, 2013, we now have 10 disease-modifying therapies to treat relapsing forms of MS—and more on the horizon.
Tecfidera is the third oral therapy approved to treat MS. A related compound, called Fumaderm (dimethyl fumarate and fumeric acid esters), has been used for decades in Europe to treat psoriasis. Tecfidera is a new and different formulation of dimethyl fumarate developed by Biogen Idec specifically to treat MS. Although its exact mechanism of action is not known, it is thought to inhibit immune cells active in MS and may even protect against damage to the brain and spinal cord.
Two large phase III studies (the DEFINE and CONFIRM trials) found that Tecfidera significantly reduced relapses and disease activity as detected by MRI. The most common side effects were flushing of the skin and gastrointestinal upset. Before starting treatment, the FDA recommends a recent (within six months) blood cell count, repeated annually thereafter.
The MS Emerging Therapies Collaborative, which includes the Society, provides downloadable information sheets at www.ms-coalition.org/emergingtherapies to facilitate communication between doctors and people with MS about newly approved treatments such as Tecfidera.
Here are potential therapies to keep an eye on as we move forward into 2013 and beyond.
Alemtuzumab, a monoclonal antibody that depletes circulating immune (T and B) cells thought to be responsible for MS attacks, would be administered by IV infusion for five days and then for three days one year later.
Genzyme applied to the FDA for approval of alemtuzumab to treat relapsing MS, based on positive results from several clinical trials, including one that showed a 55% decrease in relapses compared to interferon beta-1a (Rebif); however, the FDA asked the company to resubmit its application, so a timeline has not yet been established. While this therapy is powerful against MS, there is concern regarding adverse events, such as immune thrombocytopenic purpura (ITP, a bleeding disorder), and autoimmune thyroid disorders.
Laquinimod is a once-daily oral immune modulator that showed in phase III studies to decrease relapse rates, though not as robustly as investigators had hoped. This drug is about to be tested in another phase III study in 1,800 people with relapsing-remitting MS.
Daclizumab and ocrelizumab are two other monoclonal antibodies currently under study, with favorable results thus far. A highly concentrated liquid formulation of daclizumab is under study in relapsing-remitting MS. Experimental ocrelizumab given intravenously significantly reduced disease activity on MRI scans in a study of 218 people with relapsing-remitting MS. One person died due to brain edema; however, the relation of this death to the medication is unclear. Additional research, now going on in primary-progressive MS and relapsing-remitting MS, is needed to further determine ocrelizumab’s safety and benefits.
Research is also underway on potential treatments for progressive forms of MS and the International Progressive MS Collaborative, of which the Society is a member, plans to do all it can to speed the development of those treatments. Current clinical trials include natalizumab (Tysabri), fingolimod (Gilenya), and ocrelizumab.
When we consider treatment now, in particular the possibility of switching therapies, we weigh the safety and efficacy of our older, injectable disease-modifying agents against the seeming convenience and perhaps superior efficacy of newer agents. The sequencing of therapies is a new consideration, as well, as the effects of medications like natalizumab and fingolimod on the immune system may be prolonged.
Questions about new therapies may mean longer or more frequent appointments with neurologists to discuss their risk-benefit ratios. Additionally, people with MS may choose to see an MS specialist, or be referred to one by a general neurologist, for treatment recommendations.
However, the most encouraging part, in addition to the fact that treatments for MS may be getting more effective, of course, is that the research pipeline is full. Thanks to those who are committed to research funding, science is able to continue searching for the cure, and on that search, discover medications that will keep this disease as quiet as possible.
Megan Weigel is a Doctor of Nursing Practice and MS Certified Nurse who has been caring for people with MS for 12 years.
- CenterWatch - www.centerwatch.com
- NARCOMS - www.narcoms.org
- MS International Federation - www.msif.org
- CISCRP - www.ciscrp.org
- Research Match - www.researchmatch.org
- MS Discovery Forum - www.msdiscovery.org
- National Institutes of Health - www.nih.gov/health/clinicaltrials
- Patients Like Me - www.patientslikeme.com/clinical_trials