Treatment options - now there are three.

The landscape of MS used to be as bleak as the Siberian steppe. People were told: "You have MS. We can help you manage your symptoms, but we have nothing for your disease."

Four years ago the treatment landscape began to soften. Hills appeared, and green trees. Today, the prospect is no longer bleak but it is no longer simple either. And not all of it is charted.

A Betaseron (Interferon beta-1b) is taken every other day, using a shallow under-the-skin injection called a subcutaneous injection. After brief training, a person with MS (or a family member) can do this at home without medical supervision.

Common side effects include injection site pain and inflammation, skin reactions, and short-ten-n flu-like symptoms. For most people, the fluish aches and fevers can be reduced, even eliminated, by taking aspirin or acetaminophen. Typically, the aches and fevers cease completely after a few months. For some they persist, and may have a major impact on quality of life. Much rarer side effects include depression and injection site skin breakdown (necrosis) which requires medical treatment.

In a large clinical trial, Betaseron reduced relapses by 34%, lessened the severity of relapses, and limited new lesions in the brain (as seen on MRI). The data on changes in disability status that were gathered were not statistically significant.

B Avonex (Interferon beta-1a) is taken once a week, using a deeper injection into muscle tissue called an intramuscular injection. With training, most people can learn to do this at home -- either by themselves or with the help of a friend or family member. However, some health-care professionals prefer medical supervision for this type of injection.

The common side effects are short-term flu-like symptoms. Mild anemia occurs but is less common. In the clinical trial, injection-site reactions occurred rarely and were not associated with the drug. The flu-like symptoms can be reduced by taking aspirin or aceteminophin.

The large clinical trial of Avonex showed patients had a 37% lower risk of the progression of disability, a 32% lower rate in relapses in people who completed two years of treatment, and fewer new lesions in the brain (as seen on MRI).

C Copaxone (copolymer 1) is taken every day, using the shallow subcutaneous injection method, which can be done at home by the person with MS or by a family member following brief training.

Common side effects include mild injection-site reactions such as swelling or reddening and, less commonly, a short-term spell of flushing, chest tightness, and sometimes, shortness of breath immediately after an injection. This reaction lasts about 15 minutes, and has no known long-term effects. There are no flu-like symptoms.

The large clinical trial of Copaxone revealed a 29% lower rate in relapses. An advisory committee to the FDA did not consider data on the progression of disability to be strong enough to warrant allowing any claim regarding this outcome. The clinical trial was not designed to measure changes in disability over the entire time of the trial.

So which option is best?

None of the clinical trials directly compared these drugs to each other, so the comparative merits are not clear from scientific data.

"We can counsel people, in general, about what they should know to make a choice, but the decision is up to the individual and her or his physician," said Dr. Stephen Reingold, who heads Research and Medical Programs at the National MS Society.

How do the options look to specialists who treat people with MS every day?

Dr. John Whitaker is chairman of neurology at the University of Alabama School of Medicine and chairman of the Society's Medical Advisory Board. He has focused on the care of people with MS and clinical trials of treatments for MS for more than 30 years:

"More experience will be required before the choice is clear," he said. "For patients who have been intolerant of Betaseron or have not responded, a switch to Avonex would seem logical. For the newly diagnosed patient for whom a betainterferon is indicated, the relative merits must be discussed with the individual and her or his family.

"Avonex is associated with fewer side effects, but we have more experience with Betaseron. The demonstrated effect of Avonex on disability is desirable, but Betaseron might possibly have a similar effect. It's not clear. As to how Copaxone will fit in -- it will be a while before we can say. However, Copaxone's milder side effects are also an advantage.

"It is wonderful that we finally have questions like these to grapple with," Dr. Whitaker concluded. "For so long, there was nothing we could do for the basic course of MS."

Leith Kelley is a nurse with a Ph.D. in immunology, who has specialized in

caring for people with MS. She is on the staff at Allegheny University

Hospital in Philadelphia:

"It may be a mistake for people to focus too much on the percentages from the trials. In practice, one drug doesn't stand out as notably more effective than the others.

"In my view, living with the routine is the biggest factor people should consider. All these drugs help. They can all do something tangible, like keeping a person at work. But none of them cure MS. We measure their success by what is not happening.

"Often what's not happening is very clear: if you were having an exacerbation every month or two and have now gone a full year without needing steroids, I'd say stay where you are. But suppose you are having persistent side effects, but the drug is holding down your exacerbations. Should you switch? Or give the drug a year for the side effects to abate? There are many gray areas.

"The issues are also different depending on how long you've had MS. If you are newly diagnosed, I think you'd want to look for the drug with the lowest possible side effects.

"And there are personal matters. Betaseron and Copaxone injection sites are often visible on the skin for a while as redness or dark spots. The sites must be rotated so you may not be able to put them all in invisible areas. A woman who is dating told me the spots on her legs take away her control over when to discuss her health with someone she's serious about. Another woman was concerned about questions from people at work where no one knows she has MS. Avonex might be a better answer for both of them. But, for some patients, Avonex could entail a visit to the doctor every week.

"These aren't frivolous concerns. The medication is a presence in one's life. The people who've been most successful in integrating an injection routine into their lives have supportive family, including partners who are willing to give the shots, or they seek support from a group, or both.

"You, the person with MS, should be part of the decision with your physician," Leith Kelley concluded. "It may help to keep in mind that this won't be the standard for the rest of your life. I'm expecting better treatments to come along.

"Try to learn all you can about these medicines. Ask your doctor why he or she favors one over another. Decide which routine will work better with your lifestyle. And if you do decide to change from one to another, don't worry that you'll trigger an exacerbation. It is safe to switch."

Three Patient Support Programs

Each of the three manufacturers is sponsoring support programs designed to help people who are considering taking or who have decided to take their product.

A Berlex, manufacturer of Betaseron, offers "Multiple Sclerosis Pathways": 1-800-788-1467. It provides insurance and reimbursement assistance; an Indigent Patient Program; medical information over the phone from counselors; access to nurse-run peer support groups; a quarterly newsletter; educational brochures; a website at http://www.betaseron.com, and on-line bulletin boards. Injection training, which must be requested by the prescribing physician, is provided free of charge by experienced nurses. Participants receive a videotape, starter kit, guidebook, and take a hands-on class.

Berlex also sponsors HealthTalk Interactive: 1-800-335-2500. This is an hour-long taped discussion between health professionals. It is undated regularly and allows callers to leave questions on voice-mail.

For people with inadequate insurance, some financial aid is available through a separate, nonprofit Betaseron Foundation. Call 1-800-948-5777.

B Biogen, manufacturer of Avonex, offers the "Avonex Support Line": 1-800-456-2255. Callers can access reimbursement counselors; information on direct billing and assignment options and the Avonex Access Program for qualified uninsured patients; and information from telephone counselor about the drug and training materials. Information is also available from a website at http://www.biogene.com.

Injection training, which must be requested by the prescribing physician, is provided free of charge by experienced nurses. Participants receive a starter kit and videotape which they are asked to review before the hands-on class.

C Teva Marion Partners, manufacturer of Copaxone, offers "Shared Solutions": 1-800-887-8100. This drug has just received FDA approval for general marketing, but the drug is not yet available; FDA approval of packaging and promotional materials is pending. Though not yet fully operational, the program will be significantly enhanced upon product launch. For now, callers will receive a mailing of self-help educational materials, a reimbursement booklet, a packet of publications from the National MS Society, and will be added to a list for regular informational mailings. This is offered to all people with MS, without respect to their disease type or medication choice.

Local chapters of the National MS Society and the Information Resource Center will have details about the expanded "Shared Solutions" program when the drug is launched.