A new study suggests that stress does not appear to increase the risk of developing MS.
The study, published in Neurology, May 31, 2011, focused on two large groups, totaling almost a quarter million women, from the Nurses’ Health Study, which has followed a large number of female nurses for decades. The nurses were asked to report on general stress at home and at work, and also any physical or sexual abuse as children or teenagers.
The investigators compared the answers between those nurses who had developed MS and those who had not. They also took into account age, ethnicity, smoking habits and other variables that have been linked to an increased chance of developing MS.
The researchers found that those who later developed MS had not responded significantly differently from those who had not developed MS. Although this sounds persuasive, more research is needed to definitively exclude stress as an MS risk factor.
Research increasingly points to low levels of vitamin D in the blood as a risk for developing MS. A new study, www.neurology.org/content/76/21/1824, funded in part by the National MS Society, does show that African-Americans with MS have lower levels of vitamin D than African-Americans who don’t have MS.
Researchers Jeffrey Gelfand, MD, Ari J. Green, MD, and colleagues at University of California, San Francisco, found that of the group with MS, 77% were deficient in vitamin D, compared to 71% of those without MS. The study, based on examining 339 African-Americans with MS and 342 without the disease, found no link between vitamin D levels and how severe the disease was.
African-Americans in general have an increased risk for low vitamin D levels, possibly because their skin has large amounts of melanin, which acts as a filter of ultraviolet light. This in turn limits how much vitamin D the body can produce. Study participants with a higher proportion of European genetic ancestry were less likely to have low vitamin D levels than participants with a lower proportion of European ancestry.
The risk of MS in African-Americans is about half that of Caucasians. However, the same researchers previously reported that African-Americans tended to have a more aggressive course of MS than Caucasians, a higher risk for mobility impairments, were more likely to develop MS later in life and were at higher risk for symptoms in the optic nerve and spinal cord.
Viruses are well recognized as causes of nervous system damage and inflammation, so it is possible that a virus may set off MS. Various types of evidence point in particular to an association between MS and Epstein-Barr, a herpes virus that causes infectious mononucleosis and other disorders. Now, a new study hints at another possible link, this time between herpes zoster and MS.
Researchers in Taiwan have reported that people who experienced an attack of the virus-triggered herpes zoster—which usually shows up as the skin rash known as shingles—were more than three times as likely to develop MS over the next year than individuals who did not have an attack. The study, reported in The Journal of Infectious Diseases (6/7/2011), used a large data set of Taiwanese people. However, since people of Chinese genetic background are at lower risk for MS than Caucasians, the researchers do not know yet if this finding will translate to other populations.
Flu season brings not just coughs and sniffles, but the question: Get a flu shot, or not?
Because there is a much higher risk of an MS relapse due to flu than to the flu vaccine, the Society generally recommends that people with MS get the shot. The injectable flu vaccine—which is an “inactivated” vaccine—has been studied extensively in people with MS and is considered quite safe. It may be taken by people on an interferon medication, glatiramer acetate, or mitoxantrone. It is not yet clear if the vaccine is as effective for those talking natalizumab or fingolimod.
It’s best to delay vaccination for four to six weeks after the onset of any serious exacerbations. People with MS should avoid FluMist, a live-virus flu vaccine (sometimes called LAIV for “live attenuated influenza vaccine”) delivered via nasal spray. For more information, go to www.nationalMSsociety.org/vaccinations.
MS Treatments are Moving Through the Research Pipeline
Did you know there are now 130 ongoing, planned, or recently completed MS clinical trials? These studies are bringing new hope for oral drugs, better options for people with Progressive MS, and novel approaches to alleviating symptoms. Disease-modifying drugs and procedures represent possible interventions to modify the natural course of the disease (instead of targeting symptoms or recovery from relapses).
Over a dozen Phase III clinical trials testing potential therapies are underway, and new treatments are being devised and tested in animal models. About one-third of experimental medications for MS reach Phase III trials that take several years and involve large patient groups. They are the definitive evaluation of effectiveness and safety. Following a positive Phase III trial, a treatment is submitted to the U.S. Food & Drug Administration (FDA), which is responsible for approval. Many treatments currently in clinical trial involve drugs used in other diseases, or have not been designed specifically for MS. There are also trials that combine drugs already in use for MS.
Two Phase III clinical trials for MS (‘DEFINE’ and ‘CONFIRM’) reported positively in October. Biogen Idec announced the experimental oral therapy BG 12 significantly reduced the average number of annual MS relapses in the two-year DEFINE Phase III trial of more than 1,400 people with relapsing-remitting MS (RRMS). Full details and evaluation of this study should help further define safety and effectiveness. Biogen Idec says these results set the stage for upcoming filings for FDA approval.
An oral formulation of a BG 12-like drug has been approved for use in Germany for treatment of psoriasis (an auto-immune disease) for about two years, offering extensive experience with long term safety. Availability of long term safety data distinguishes this drug from Gilenya, teriflunomide, and laquinimod.
Another drug, oral teriflunomide (Sanofi-Aventis), related to a drug used in rheumatoid arthritis, reduced the average number of MS relapses in a year significantly more than inactive placebo in a study of 796 people with relapsing MS. The therapy also reduced the volume of tissue damage and active areas of damage in those taking teriflunomide, compared to placebo after a two-year trial. The complete TEMSO study results are in The New England Journal of Medicine (2011;365:1293-303). These are the first Phase III results of oral teriflunomide for treating relapsing MS. These and results from additional Phase III studies now underway should help define the short-term safety and promise of teriflunomide. The long-term impacts, benefits, and potential adverse events are still to be determined.
Laquinimod—related to Roquinimex (Linomide)—has significant efficacy, but has significant safety concerns. Preliminary results of the Phase III ALLEGRO study with 1,100 RRMS patients were presented at the American Academy of Neurology. Laquinimod is found to be safe and well tolerated (gastro-intestinal side effects, back pain, insignificant liver enzyme changes). Phase III BRAVO study involved 1,200 patients with RRMS. It also compared the drug to placebo; progression and brain atrophy were reported.
The need for comparative trials is critical. As a general safety strategy, while new drugs offer attractive treatment options, switching for convenience should not be considered in the absence of long-term safety data and FDA approval. The risk of switching from one drug to another, for example from Natalizumab to an oral agent, may carry certain high risk concerns. And, patients using new oral drugs, when approved, will need careful monitoring.
Looking forward, studies pertaining to apparent neuroprotective effects of new oral agents will be of great interest in regards to seeking strategies to achieve a true disease-free state.
• Lancet Neurology Vol. 10 November 2011
The Society’s annual list of clinical trials in MS is now available online at www.nationalMSsociety.org/clinicaltrials.
It features 130 studies that are in progress or recently completed. These cover neuro-protective agents; symptom medications; rehabilitation interventions such as cycling for improving MS-related depression, mobility and cognitive function; and more.
More than 52,000 volunteers have participated or are currently participating in these studies. Their participation—and yours—makes it possible to look forward to new therapies for MS.
To find out about trials in the Greater New England states, visit www.nationalmssociety.org/clinicaltrialsGNE.
Resources to Find Clinical Trials
- MS International Federation