What's going on with the diseased-modifying drugs? We're well into the second decade of the era of disease-modifying MS medications. What do we know about them now? And what do we know about why people take or don't take them?

If a tropical storm is headed your way, you nail boards over the windows and lay in supplies. After all that, maybe the storm arrives, or maybe it blows, past. Multiple scleriosis can be as maddeningly unpredictable as a hurricane, and when it's not knocking on your door, you probably want to ignore it. But MS requires attention, because, unlike the hurricane, the odds are fairly strong that your MS will be worse one day if you don't take steps to protect yourself.

Early on the sky may be blue

"By the time people are diagnosed, their MS has already been going on awhile," said Barbara Giesser, MD, Medical Director of the Marilyn Hilton MS Achievement Center at the University of California, Los Angeles. "There may be some nerve damage we can't see with our current methods." What can be seen in MRI studies is that most people have many "silent" attacks early on, and that lesions and brain atrophy can develop in people who are not having any symptoms or attacks that they can feel.

This early damage is why most MS specialists recommend early treatment with disease-modifying agents for people with relapsing forms of MS. The National MS Society's Medical Advisory Board spelled this out in its Consensus Statement.

"Early" means as soon as possible after diagnosis and, in certain cases, even before MS is confirmed. The disease-modifiers approved for treatment of MS are Avonex (interferon beta-1a), Betaseron (interferon beta-1b), Copaxone (glatiramer acetate), and Rebif (interferon beta-1a). Since the first of these--Betaseron--was approved in 1993, these four have come to be widely accepted as standard treatment for MS. Novantrone (mitoxantrone) and Tysabri (natalizumab) are also FDA-approved and known to be effective but have specific limits to their use.

A storm can be modified

If a hurricane can't be stopped but can be calmed down, what would that mean to the house that may lie in its path? The same element of chance is still in play. The hurricane might not come.

Numerous studies have now demonstrated that, used as prescribed, most people benefit from disease-modifying therapies. They decrease the frequency and severity of attacks, reduce the number of new lesions in the brain or spinal cord, and delay or reduce future disability. Moreover, several randomized, double-blind, placebo-controlled trials found that the therapies were more effective when started earlier in the course of the disease.

"Besides being effective, research also indicates that Avonex, Copaxone, Betaseron, and Rebif are safe in the long run, or at least for 10 to 20 years," said Robert P. Lisak, MD, professor and chair of Neurology at Wayne State University School of Medicine and neurologist-in-chief at the Detroit Medical Center. He went on to explain that it is difficult to maintain blind placebo-controlled trials for more than a few years, and therefore all the claims for long-term effectiveness have to be considered, "indirect, inferential and/or supportive--but not unequivocal. There is no apparent reason not to stay on one of them until we have something better," he summed up. Nevertheless, people need to work closely with their physicians as some of these drags do have the potential to cause serious side effects in some people.

Many do, some don't

Even without universal benefit, shouldn't a prescription for an MS disease modifier be virtually automatic for doctors? Shouldn't people automatically expect to take one when their diagnosis is relapsing MS?

Not so fast. About 60% of people with a relapsing form of MS are currently taking a disease-modifying drag, according to a national registry of about 31,000 people with MS. It's clear many others never start. Some stop their therapy after a time.

Professional misdirection?

For years after her 1994 diagnosis, neurologists told Liza Burton* that she had a 90% chance that her MS would not be disabling. "So I had no treatment at all for several years," Burton said. "I waited for symptoms to start bothering me, until my mobility was really impaired." In fact, experts now believe this high an estimate for benign MS is incorrect. Most studies show that an even larger majority of people with MS who go untreated will ultimately face disability.

Four months after starting treatment, Burton, 54, an editor in New York, regretted her wait. "If I knew then what I know now, no question I'd go on medication before it became a quality-of-life issue," she said. "If I hadn't waited, I don't think I would be in the bad shape I'm in now."

Debi Sample's neurologists also told her that her MS was nothing to worry about. Sample, 51, an executive in Teaneck, New Jersey, was finally diagnosed back in 1984 after having been told that her MS was an anxiety attack, a stroke, a brain tumor, or Lou Gehrig's disease. In the early 1990s, when the drugs came on the market, she recalls being told that they were a good thing but there was "no great urgency." If they had been available sooner, "maybe they would have prevented my left leg from being so weak. I can't help but wonder how things could have been," she said.

People whose physicians aren't enthusiastic about the disease-modifying meds probably won't be enthusiastic either. And some doctors still do not advocate early treatment, advising instead that their patients "wait and see" if their disease takes a benign course. Why burden people who might never get worse with the cost and side effects of these drugs, they reason. And the fact does remain that the course of MS, for better or worse, cannot be accurately predicted for any individual.

"Technically, we are over-treating a small percentage of people, but there is no way to tell who that is," Dr. Giesser said. "'Benign' is a retrospective diagnosis, meaning you only know who is benign after many years without problems. There's just no way to know, starting off, how any one individual's disease will proceed."

Why people say no

Along with this uncertainty--will the hurricane damage my house or not?--there is more to a no-treatment choice. Many people are deeply bothered by injections or they suffer from persistent side effects, most notably flu-like symptoms, but also reactions at the injection sites, or depression. There is no way to guarantee that an individual is taking the best medication for his or her system, since both the disease and the individuals are so variable. In other words, for some people, boarded-up windows may not do enough.

Finally, there are profound psychological barriers.

"Reality gets in the way--life gets in the way," said Patricia Kennedy, RN, a nurse-practitioner at the Rocky Mountain MS Center in Denver, Colorado. "The drugs are a reminder that a person has MS. It's easy to miss one shot, easier to miss two, then three. Then someone might say, 'I missed all last week and I don't feel worse.'"

Kennedy has talked to many people who were symptomatic at the time of diagnosis but were feeling OK several weeks later, when it was time to choose a therapy. "They say, 'Things are better now, I don't need the drugs'" she said.

Psychotherapist Tamara Greeley, LCSW, who facilitates support groups for the newly diagnosed for the Society's New York City Chapter hears that too. "Some people feel like, "'If I don't have a headache, why take an aspirin?'"

Why people start and then quit

"People stop their drag because they lose faith in its effectiveness," said June Halper, MSCN, ANP, FAAN, also a longtime nurse practitioner who is executive director of the MS Center at Holy Name Hospital in Teaneck, New Jersey.

Despite the scientific evidence, many people simply aren't convinced. The major effects are deep within the brain, where they can't be seen or felt. And while meds lessen the risk of having new attacks, people taking them faithfully may still have some attacks. Moreover the drugs don't affect symptoms. Some are enduring shots and side effects without seeing any clear benefits.

So what makes it easier?

Education and encouragement are important reasons why people choose to begin and stay committed to taking a disease-modifying drug over time, most experts agree.

One research study found the four main reasons for discontinuing treatment to be adverse effects, disease progression, the perception that the drug wasn't working, and (for a surprisingly small percentage) the high cost.

"Education takes a lot of time and effort, but it sets you off on the right foot," Halper said. "Once people are taking a drug, we health-care professionals need to cheerlead. We need to recognize depression or other problems that can affect staying with it. Since there is no visible marker to indicate it's working, we need to give reinforcement. This isn't strange. You see non-adherence to treatment in many other conditions, even in ones that are immediately life-threatening, like AIDS or diabetes."

It's always a choice

Bonnie Butkas, 32, who does fund-raising and marketing for a youth theater, took a year learning and thinking, with the help of her family, friends, and a support group, before she could choose to start treatment. "It was good to take the time to figure it out. By the time I decided to take the med, I was really ready," she said. "If I'm tempted to go off, all I need is one hot day, and I'm reminded that this MS is real."

Maria Mancini was convinced to start her med when her neurologist told her she could always go off it again. Mancini, 50, a hospital worker who was diagnosed in 2001, said: "That was a good thing to say to me. I felt I had to do so many things I didn't want to do, and that offered the reality that no one was going to force me." Her continuing motivation comes from thinking back to "how bad my flare-up was before they figured out what was wrong. I would do anything to keep that from happening and to prevent further damage," she said.

Yet, despite her commitment--she says she has never once missed a shot--she has had stretches where she almost couldn't bear the act of injecting herself. She needed more than belief in her choice.

Getting over the gap

Mancini's experience is not uncommon. There is a gap between believing that one needs the injection and the reality of doing it day after week after month. MS clinicians say a number of techniques make what they call "adherence" easier.

Support groups can sometimes help. People with MS teach each other how to use the medications, deal with side effects, and they prime each other's motivation. Tamara Greeley said, "They help people stay on meds when they're discouraged. People get a lot of ideas from groups, especially about symptom management."

When someone is flagging, Halper likes to offer clinical tests such as a timed walk, a neurological exam, chart review, or even an MRI--that show people how they're doing. "We also ask them to make a deal," she said. "We ask them to please stay on the drug for one year, unless they have lots of relapses or intolerable side effects." And should that happen, trying another type of drug may work.

Kennedy believes people can provide their own motivation. "When people are struggling with the decision, I ask what they hope to gain by taking it," she explained. "They might say I want to walk my daughter down the aisle at her wedding or they talk about a special trip they want to take. I ask them to remember this, maybe even write it down. Later, if they're wavering, I ask, 'Is that still a reason?' That can help bring back the hope."

Tools can also be effective supports, gadgets such as electronic calendars that provide automatic injection reminders or grids for a personal computer that track and vary injection sites. "Having nurses available by e-mail can help too," Halper noted. "People may stop their drug if they don't get their questions answered quickly," she said.

"It takes a village to help someone stay on therapy," added Kennedy. Family, friends, health-care professionals--everyone should be aware of how important they are, month after month.

On the horizon

"I've been working with people with MS for almost 25 years," said Dr. Giesser. "Before the disease modifiers, we did symptom management, but we had to tell people that this disease was pretty much going to do what it wanted. Now it's a whole new world--and it's not as good as it's going to be." Promising therapies are being studied, therapies that may not need to be injected or infused. Some MS drugs in pill form may be available within a few more years.

"When I was first diagnosed, it was horrifying to think I'd be taking these shots for the rest of my life," Mancini said. "But I realized that 20 years ago they didn't have these drugs, and 20 years from now, they'll have something much better."

The Money Matters

Studies that found cost was low on the list of reasons for not taking a disease-modifying drug were conducted in 2005, well before January 1, 2006. That's when changes in Medicare Part D changed the prescription drug landscape. While this reform made prescription drugs more affordable for many, Medicare beneficiaries on the disease-modifying therapies--which typically cost from $16,000 to more than $34,000 a year--found themselves in the so-called "doughnut hole," struggling to cover drug costs where Medicare left off.

Many states were unable to help, and some major patient assistance programs exhausted their resources even before reviewing all new applicants, thus affecting other people whose non-Medicare coverage is inadequate. Right now, Medicare beneficiaries are urged to reexamine 2006 drug costs, compare available 2007 plans, and secure the best possible coverage. Open enrollment for 2007 ends December 31, 2006.

Moving forward

The National MS Society believes that every person with a prescription for an MS drug should be able to afford it. Medicare Part D is expected to evolve in 2007 and the Society will be active in the changes. Be part of the efforts. Be informed. Join the MS Action Network by calling your chapter or by going to nationalmssociety.org/Action Network.

* Not her real name.

NEW ON DVD 

Long-term efficacy of Disease-Modifying Therapy.

The latest long-term data on the FDA-approved disease-modifying therapies was presented and discussed at the 20th Consortium of Multiple Sclerosis Centers Conference, Scottsdale, Arizona, May 31-June 3, 2006. To order a copy of this professional presentation on DVD, download the order form on the Consortium's Web site: www.mscare.org/cmsc/dvd-2.html. Cost, including shipping, is $20.00 within the continental United States. For more information, e-mail the Consortium at [e-mail].

For a list of research articles about the disease-modifying drugs, go to nationalmssociety.org/MSDrugs.

Elinor Nauen is Newsweek's special sections health editor and has written on health topics for Self, Health, Organic Style, AARP's My Generation, and other national magazines.