Back in 1997, Elissa “E.J.” Levy noticed that her hands were shaking. Then in her late 20s and living in San Francisco, she saw a physician who diagnosed her with essential tremor syndrome and put her on medication, “which I never took,” she recalls. The tremor eventually went away on its own. That was a clue, she says now, that the shakiness wasn't from essential tremor at all, but something else.
Four years later, having relocated to New York to become deputy director of the Bronx Prep Charter School, the athletic Levy found herself falling out of poses in yoga class. In January 2002, a neurologist at Mount Sinai diagnosed her with multiple sclerosis (MS), and determined that the tremors she had experienced five years earlier had probably been the disease's initial onset. This meant her condition was “secondary progressive” MS.
Patients with secondary progressive MS experience a slow worsening of their symptoms, often—though not always—coupled with occasional flareups and minor recoveries. The National Multiple Sclerosis Society reports that more than half of the 85 percent who begin with relapsing-remitting MS—characterized by partial or total recovery after attacks—will develop secondary progressive MS within 10 years, as Levy did.
“These are the people who say ‘I'm not doing as well this year as I was a couple of years ago, and I think I'm losing ground.’ Most of them have a degree of apparently irreversible limitations in neurological function—they can't walk as far as they used to, or they have symptoms like vision loss, impaired coordination, or bladder changes that have been present for months and aren't getting better,” says John Noseworthy, M.D., professor and chair of the department of neurology at the Mayo Clinic in Rochester, Minn.
Secondary progressive MS has proven a much more challenging form of the disease to treat than the early, relapsing-remitting form of the disease. The Food and Drug Administration (FDA) has approved six “disease-modifying agents”—that is, drugs aimed at slowing the course of the disease itself rather than alleviating symptoms; most of them can be used to treat relapsing-remitting MS, but only two are approved for secondary progressive MS.
A New Treatment Option
Last year, the FDA approved interferon beta-lb (Betaseron), long a staple of treatment for relapsing-remitting MS, for use in cases of secondary progressive MS as well. It became only the second drug specifically approved for that form of the disease; mitoxantrone (Novantrone), a chemotherapy drug aimed at slowing the destructive autoimmune process that leads to the loss of nerve-insulating myelin, was the first.
Just how useful is interferon beta-lb for people with relapsing-remitting MS? Last November, an analysis in the journal Neurology tried to answer that question, reviewing the combined results of large trials in both Europe and North America.
The good news: Interferon beta-lb appears to both reduce the number of new lesions, or abnormal areas of the brain tissue, seen on an MRI, and to reduce the number and frequency of attacks in people with secondary progressive MS.
“There is a period of time during secondary progressive MS when patients continue to have relapses, superimposed on a slow overall worsening of the disease,” says Patricia Coyle, M.D., professor and acting chair of the department of neurology at the State University of New York at Stony Brook, where she directs the MS Comprehensive Care Center. “That group of patients appears most likely to benefit from interferon beta-lb—those who still have an inflammatory component to their disease.”
Another group of patients who may particularly benefit from interferon beta-lb, according to the analysis in Neurology, are those whose secondary progressive MS has been marked by relatively rapid deterioration, as opposed to longer, slower progression of the disease.
What is less encouraging, however, is the fact that these studies don't seem to indicate that the drug significantly slows down the advancement of secondary progressive MS.
“What we need are neuroprotective therapies—sort of a nerve ‘fertilizer’—to preserve damaged nerve fibers for decades, not just months and years,” says Dr. Noseworthy. “There are many candidate treatments along those lines that are being studied now, and there is great excitement about a lot of them, but they're still in early research and haven't been approved yet.”
Making Treatment Decisions
Levy has tried most of the “disease-modifying” drugs now approved for treating MS—whether relapsing-remitting or secondary progressive. She started with interferon beta-lb. Particularly sensitive to medications, she found the drug's side effects—fever and chills, which she experienced after every injection—to be too much. The drug can cause fever and chills, and she was still getting them after every injection, even after five months. So she switched to glatiramer acetate (Copaxone), which seems to block myelindamaging T cells by acting as a “myelin decoy.”
Although she had no side effects on glatiramer acetate, by last summer, Levy's condition continued to worsen, and, with her doctor's approval, she elected to move to the most aggressive treatment possible: mitoxantrone. She will receive one infusion of the drug every three months for three years. “I wanted to do whatever I could to stop the progression of my MS before I was in a wheelchair,” she says. But it was a difficult decision. “It's so hard to tell how the disease is progressing—maybe the glatiramer acetate was working and I would've been in a wheelchair already without it.”
Communication with Your Doctor is Key
That is a very common scenario, says Dr. Noseworthy. “Often with MS, it's difficult for both the patient and the doctor to tell how well a drug is working,” he says. Decision-making in MS treatment is complex, and your decisions may change with time. That makes an open, communicative doctor–patient relationship essential. “You may decide that you can't tolerate side effects, or you want to become pregnant, or you want to be more aggressive with your disease. That's where trust and shared decision-making between doctor and patient becomes essential.”
Fine-tune Your Treatment
To fine-tune your own treatment, Dr. Coyle says, you and your doctor should focus on three main areas:
* Health and wellness. Don't ignore things like regular exercise, good nutrition, enough sleep, and controlling your weight. “Sometimes you can focus so much on the disease that can miss these basics, which are just as important to an MS patient as anyone else, if not more so,” she says.
* Symptom management. Make sure you're working with your doctor to control the symptoms that bother you most. Keep an inventory of symptoms that are bothering you and things that may have changed since your last visit, so that you can tell your neurologist at your next appointment and look for treatments together.One woman with secondary progressive MS came to Dr. Coyle in a wheelchair with a bladder problem that kept her from leaving the house out of fear of embarrassing accidents in public. “A simple prescription medicine completely transformed her life, and she's no longer a prisoner in her own home,” she says.
* Disease-modifying therapies. In secondary progressive MS, says Dr. Coyle, if there's evidence that inflammation is still present—such as continuing relapses, rapid deterioration, or MRI indicators—disease-modifying therapies are particularly important. In most cases, she says, the evidence best supports starting out with the use of an interferon-beta. “Mitoxantrone is clearly an option, but because of the more significant side effects, I'd suggest considering the interferonbetas first,” she says.
“In theory, you could consider using any drug that's approved for relapsing-remitting in MS in the secondary progressive stage, but we believe that the status of the disease is very different,” Dr. Coyle says. MS varies so widely in its progression and symptoms that there may be some patients who do benefit. “More trials may help us identify subsets of patients with secondary progressive MS who will benefit from these treatments.”
There are many reasons for optimism, says Dr. Noseworthy. “There are a lot of good drugs in the pipeline, and we're trying our best to understand which ones have the most promise for which patients. It has never been more important for patients to be informed about their illness.”
For more information about MS, visit the Web sites from these organizations:
National Multiple Sclerosis Society www.nmss.org
American Academy of Neurology www.aan.com
The Brain Matters www.thebrainmatters.org