Fatigue: MS predictor?

 Fatigue is one of the most common symptoms of MS, and may be the most prominent symptom in a person who otherwise has minimal activity limitations. Joseph Berger, MD, and colleagues (University of Kentucky, Lexington) looked at the frequency with which fatigue “heralds” the onset of MS. Among 5305 people with MS, 29% reported fatigue in the three years before MS diagnosis. In 30% of these patients, fatigue was the only symptom preceding MS diagnosis. Fatigue preceded MS diagnosis by an average of 501 days. The authors advise that, in people experiencing unexplained fatigue, a detailed neurologic history and exam should be conducted to rule out MS.

MS and Bone Health

Researchers report that low bone mass was more prevalent among people newly diagnosed with MS, or those with clinically isolated syndrome (CIS, a first episode of MS-like symptoms), than among controls without MS. The risk of bone loss had been known for people with MS, but this study shows that it can occur very early, even before MS has been diagnosed. Stine Marit Moen, MD, and colleagues at Oslo University Hospital report their findings in Neurology (2011;77:151-157).


The team measured bone density in several areas and the total body in 99 people newly diagnosed with MS, or those with clinically isolated syndrome (CIS, a first episode of MS-like symptoms), compared to 159 controls without MS. They also administered a questionnaire concerning risk factors for osteoporosis (a disease that causes bones to thin). More than half of the people with MS or CIS had low bone mass, compared with 37.1% of controls, and low bone mass remained significantly lower in the spine and hip even after adjusting for other possible risk factors.

The authors conclude that this study “calls for an active approach to optimize bone health in early stages of MS.”

Company Decides Not to Seek Approval of Cladribine for MS

Merck Serono announced that it has decided not to pursue approval of its oral therapy Cladribine for the treatment of relapsing forms of multiple sclerosis. According to a company press release, discussions with the U.S. Food and Drug Administration made it apparent that the ongoing clinical trials of the therapy would not address the FDA’s requirements for approval. Details of these requirements have not been made public.


In March 2011, the company received a letter from the FDA indicating that its application for approval was not ready in its current form and outlining requirements for additional information. The company has stated that it plans to complete the current clinical trials and patient registry that are underway, and that results will be published.

“It’s disappointing that completion of the Cladribine trials will not lead to approval of a new therapy option for people living with MS,” says Dr. Timothy Coetzee, Chief Research Officer at the National MS Society. “However, thanks to the many people who participated in these clinical trials, results from these studies will add to the body of knowledge about MS and should help spur new leads toward stopping MS, reversing its damage and ending MS forever.”

Additional therapies, including oral therapies, are currently making their way through the development pipeline.

Living with MS

Planning for the Future


Although MS is a progressive disease, the rate of progression differs from one person to another. The hallmark of MS is its unpredictability—which means that the doctor can’t predict with any certainty how far or fast a person’s MS is going to progress or what the outcome is likely to be. However, there are some factors that seem to suggest a better or worse prognosis. Taking these factors into account can help you and your family plan more effectively for the future.

Identifying Options

The key message to anyone living with advanced MS is that there is always more that can be done to make the situation better. If your doctor has “nothing more to offer,” it’s time to find another doctor (.pdf) - who will partner with you and other members of the health care team to manage your symptoms and maintain your quality of life. The National MS Society (1-800-344-4867) can recommend MS specialists and other resources in your area.

Learning to Redefine Control and Independence

Sometimes MS symptoms can progress to the point that they significantly interfere with daily activities. Changes like this can threaten your self-confidence and feelings of self-worth. When this happens, remember that maintaining control and independence in everyday life doesn’t necessarily mean doing everything the same way you did it before.

By allowing yourself to do things differently, you gain access to the world of assistive technology (AT)—an array of energy- and labor-saving tools and devices that allow you to stay active and productive. Rehabilitation professionals can help you navigate the world of AT and suggest ways to modify your environment at home and at work to optimize control and independence.

Dealing with Emotional Ups and Downs

Depression and other mood changes are common in MS, and grief is a normal reaction to the changes and losses that can accompany advanced MS. Getting the support you need to deal with these emotional challenges is essential to maintaining your quality of life.


Avoiding Complications

People with more advanced MS are at greater risk for certain kinds of complications. Examples include:

Osteoporosis (loss of bone density related to reduced mobility and weight-bearing exercise, as well as treatment with corticosteroids);

Pressure sores (damage to the skin caused by lack of mobility or long hours in a bed or wheelchair);

Aspiration pneumonia (a problem caused by swallowing problems that allow food particles in to the lungs);

Severe bladder or kidney infections (resulting from chronic urinary dysfunction).

To reduce your risk of complications, schedule regular check-ups with your MS doctor and report any unusual fevers or changes in your symptoms.

In a midwestern city2.avi

New MS Treatments

A number of new multiple-sclerosis medications are beginning to hit the market that promise to make it easier for patients to control flare-ups of the disease and slow its progression.

The drugs, designed to be taken orally, represent a new generation of treatment for MS. Currently, people with the disease can choose from a range of drugs that are administered by injection.

Physicians say many people are reluctant to stick themselves with a needle and would be more comfortable taking a pill once or twice a day. This could encourage a greater number of MS patients to take medication as needed and could spur earlier treatment, which is important since disability from MS is cumulative.

Cost of the new drugs is expected to be high. Novartis AG's Gilenya, so far the only oral MS drug on the market, is priced at about $48,000 a year; the drugs still being developed are expected to cost about the same. That's higher than injectable drugs currently in use, which cost roughly $40,000 a year. Health insurers often pick up most of the expense of MS drugs.

There is a "tremendous desire" among MS patients to begin using oral treatments because of their ease of use, says Joseph Herbert, director of the MS Care Center at NYU Langone Medical Center. Still, he says, many physicians are being cautious about prescribing the oral drugs because their side effects can't be fully assessed until they are used widely for an extended period of time.

Among its side effects, Gilenya can increase a person's risk of infection and potentially lead to toxicity of the liver and an eye disease called macular edema, clinical trials have shown. Some of the oral drugs still in development are expected to have somewhat milder side effects.

The current injectable drugs have generally less severe side effects, including injection-site irritation and flu-like symptoms, although some patients incur more serious problems such as liver damage.

Elizabeth Fuchs, an MS patient on Staten Island, N.Y., began taking Gilenya about two months ago. The 49-year-old was diagnosed with MS about 12 years ago and had tried several injectable medications. Avonex, made by Biogen Idec Inc., required weekly intramuscular injections. She later switched to Copaxone, from Teva Pharmaceutical Industries, which is administered with a daily subcutaneous injection.

"It is just much easier to put a pill in your mouth and take a glass of water," Ms. Fuchs says. Not having to inject herself has made her feel more positive about having MS and even allows her to forget she has the disease, she says.

There is no cure for MS, a chronic, inflammatory condition that occurs when the body's immune system attacks its own central nervous system.

MS, which affects about 400,000 people in the U.S., is marked by symptoms such as vision problems, limb numbness and paralysis. Women are more likely to get the disease than men, and genetic factors may make certain individuals more susceptible, according to the National Multiple Sclerosis Society.

Gilenya, which received Food and Drug Administration approval last fall, is thought to work by reducing the quantity of circulating immune cells that can cause damage in an MS attack. More than 6,500 patients are taking the drug, according to the most recent Novartis data.

Recent data from large clinical trials of other drugs being developed, including Biogen Idec's BG-12, Teva Pharmaceutical's laquinimod, and teriflunomide, from Sanofi-Aventis SA, show they are also effective at controlling MS flare-ups and slowing the progression of disability from the disease. More data on the drugs are expected later this year and, assuming FDA approval, they could all be on the market in late 2012.

The success of any of these drugs isn't guaranteed. Another oral MS drug, Merck KGaA's cladribine, was rejected by U.S. and European regulators earlier this year amid long-term safety-related questions, including an increased cancer rate in patients taking the drug. The company says it remains committed to gaining approval.

Another drug, Biogen's Tysabri, was approved in 2004 but was later temporarily pulled from the market after it was linked to a rare brain infection. Tysabri, administered by intravenous infusion, became available again in 2006 but is limited mainly to patients who don't respond to other treatments.

A recent analysis by Novartis showed that Gilenya reduced relapses among MS patients by 54%. Disability progression was reduced by 30%, using a standard measurement of this process.

Biogen's BG-12 drug reduced MS flare-ups by a similar amount as Gilenya, but with fewer side effects. Smaller reductions in flare-ups were seen in trials with patients using laquinimod (23%) and teriflunomide (31%).

By comparison, Avonex, one of the leading injectable drugs, has been shown to reduce MS flare-ups by 32% and disability progression by 37% over two years.

Physicians say MS cases vary greatly and some drugs won't work for certain patients. Also, it is difficult to directly compare two different clinical trials.

NYU's Dr. Herbert says it is a challenge to get patients to use prescribed injectable therapies. Oral medications' ease of use should increase the number of patients who use the drug as required, he says. This also is expected to encourage some patients, especially those in the initial stages of MS, to begin therapy before the disease advances significantly.

"The data certainly suggest that starting therapy earlier does slow down the progression of the disease," says Timothy Coetzee, chief research officer for the National Multiple Sclerosis Society.

Doctors say they aren't likely to recommend a patient switch to one of the new oral drugs if an injectable drug currently in use is working. Although the ease of taking a pill, rather than an injection, is important, effectiveness of a given drug takes precedence. Patients who switch treatments run the risk of the new drug not being the right fit for them, says Mayo Clinic neurologist Mark Keegan.

Write to Thomas Gryta at thomas.gryta@dowjones.com

Book Trailer

I just completed a Savvy Authors' Workshop. View my new book trailer on YouTube: http://www.youtube.com/watch?v=ggw6dnVgYro