CombiRX: the NIH makes a landmark study possible.

MS can be treated with "disease-modifying drugs, but even the most powerful of them only "modifies" MS. Many people have wondered if one of these drugs works part way why not add another?

Is A + B better than either alone?

MS researchers have also been asking this question. After preliminary pilot trials showed that taking Avonex plus Copaxone is safe, the National Institutes of Health (NIH) began a multi-million dollar trial last year to get solid answers about effectiveness.

Head to head and hand in hand

The CombiRX trial is taking place in more than 70 centers across North America. It's designed to involve 1,000 people with newly diagnosed relapsing MS. They will be followed for three years, to see if their responses hold up over time. The trial is "randomized" (meaning people are selected by chance to be in one of three groups) and "double-blind" (no one knows who is in which group), but it is not "placebo-controlled." Instead of giving some people an inactive placebo only, all volunteers receive at least one FDA-approved MS treatment. They all inject themselves every day (as is standard for Copaxone) and once a week (standard for Avonex). But for half of them, some of the shots are blanks.

For the first time since disease modifiers arrived on the scene, two major pharmaceutical companies have joined hands to assist in a trial that compares two rival drugs, head to head, as well as looking at whether the combination would improve outcomes. Teva Neuroscience, Inc., producer of Copaxone, and Biogen Idec, source of Avonex, are each providing $20 million worth of free medication. Their cooperation makes this trial possible.

What's it like to be in this study?

Amy H. is 33, with a job, a husband, and three kids. (The youngest is four.) A year ago, she made an appointment at Marshfield MS Clinic in Wisconsin to get a second opinion from Dr. Loren Rolak. Her chiropractor didn't think her recurring numb feet came from pinched nerves. She was surprised when he told her to get an MRI of her brain, not her spine--and flattened when his diagnosis was confirmed by Dr. Rolak. But she picked herself up and started learning about MS on the Internet. Dr. Rolak told her she'd be eligible for the trial.

"Taking eight shots a week does get old," she said recently, "and visits to the clinic every three months require a three-hour drive. But I haven't had any relapses since I started. Both drugs are proven to work, so it's a win-win for me whatever I'm getting. And it's important. How else can the scientists learn?"

Mary R. feels much the same way. The 44-year-old loan officer said that the clinic visits are draining. "I get there at 8 a.m. and I'm lucky if they're finished with me by 12:30." But visits give her the chance to ask "a ton of questions." She doesn't have to make phone calls about small nagging worries and she feels reassured about how she's doing. Her two children are 16 and 19. "This trial may help my grandkids someday," she said.

What do the researchers hope to learn?

"Because every volunteer is on a known active therapy, we have the ethical luxury of being able to follow people for a long time," said Dr. Fred Lublin of the Corinne Goldsmith Dickinson MS Center at New York's Mt. Sinai School of Medicine. He is the central clinical coordinator for the trial, which involves experts in MRI, genetics, neuroimmunology, and statistics at three other leading academic medical centers and the NIH.

"First, we'll learn if combining two drugs with two different mechanisms of action works better than either one alone; next, we'll get data on how an interferon stacks up against glatiramer acetate, and finally, through separate funding from NINDS (National Institute for Neurologic Disease and Stroke) we expect to identify 'biomarkers' for guiding treatment choice," Dr. Lublin said.

"We're talking about the possibility of a blood test that will tell who is most likely to respond to a specific drug--a predictive test to do before choosing a therapy," he explained.

The long, comprehensive trial will also provide good information about the impact of therapy on quality of life and when or if disabilities accumulate. "This is what NIH funding for MS research can do," Dr. Lublin concluded.

Still recruiting: who can volunteer?

There are still openings for volunteers at some centers. Participants must be over 18 and not yet taking any disease modifier. For more information, contact your chapter or go to www.combirx.org.

Martha King is the editor of InsideMS.