More MS news articles for December 1998

New Treatments Ease Arthritis Pain

Biotech Firms Boost Optimism

By Justin Gillis
Washington Post Staff Writer
Monday, December 28, 1998; Page A01

A new generation of arthritis treatments emerging from the nation's research laboratories holds out hope for millions of Americans who suffer from one of humankind's oldest and most exasperating afflictions.

The treatments, some of which already are on the market, are particularly important to 2.1 million Americans, including 71,000 children, who have a form of the disease called rheumatoid arthritis. The disease can destroy joints and cause lifelong pain, but treatments are having such striking effects that some people with this disease have stopped using wheelchairs or walkers and resumed active lives.

Alyce Kelso, 63, used to work 10 or 12 hours a day as a bus driver. But then her immune system went haywire and began attacking the joints in her body. As her rheumatoid arthritis worsened, she had to stop working, and eventually she needed a wheelchair or walker to get around her home in Rochester, N.Y. She feared that she'd waste away in a rocking chair.

"I was just in pain every day of my life," she said.

Desperate, she enrolled in a study testing one of the first drugs for rheumatoid arthritis produced by the nation's budding biotechnology industry. Last year she started injecting herself twice a week with the compound Enbrel.

The results were electrifying. In weeks her swollen joints shrank, most of her symptoms cleared up and the pain dissipated. She canceled two surgeries to alleviate problems in her elbow and toes. The wheelchair and the walker fell by the wayside.

"My husband and my son used to have to do just about everything for me," she said. "Now my son says I've got too much energy. He tells me, 'Ma, will you go sit down?' "

Rheumatologists, doctors who specialize in treating arthritis, are watching in amazement as children who once used wheelchairs are instead running and jumping like other children. These doctors are pinching themselves as adult patients show up to report that, for the first time in years, the pain of rheumatoid arthritis is gone.

"This is the beginning of an entirely new era in the treatment of arthritis," said Daniel J. Lovell, a pediatric rheumatologist at Children's Hospital Medical Center of Cincinnati and director of a national network testing arthritis treatments in children. "I'm very optimistic that within the near future we'll have the ability to design treatment approaches that will work very effectively for large numbers of our patients."

Many doctors remain somewhat cautious, unsure of the long-term effects of drugs such as Enbrel. But these days, a rising sense of hope pervades their professional discussions. "It's too soon to be saying things like, 'By golly, we're going to cure rheumatoid arthritis,' " said Richard D. Brasington, clinical director of rheumatology at the Washington University School of Medicine in St. Louis. "But there's tremendous excitement and optimism."

New treatments such as Enbrel are designed to take advantage of detailed knowledge of the immune system, gained in recent years. The goal is to selectively tone down components of the system that seem to be overactive. The same strategy is working against the debilitating bowel ailment Crohn's disease, and it may prove useful in diseases as diverse as congestive heart failure and the nerve ailment multiple sclerosis.

Arthritis is a broad name for a group of more than 100 diseases that cause pain, tenderness and limited movement in or permanent damage to the joints. Overall, 43 million Americans, or 16 percent of the population, have some form of arthritis.

The most important types are osteoarthritis, the "wear and tear" form of the disease that people tend to get in their older years, and rheumatoid arthritis, which can occur at any age. Both involve activation of the immune system, but rheumatoid arthritis is a classic
"autoimmune" disease -- an ailment in which the body aggressively attacks its own tissues.

Many more Americans, about 20.7 million, have osteoarthritis, compared with the 2.1 million with rheumatoid arthritis, according to the Arthritis Foundation, an information and advocacy group based in Atlanta. But the rheumatoid variety, while mild in some people, can be particularly severe in others, leading to irreversible joint destruction and permanent disability.

Rheumatoid arthritis can crop up at any age -- some children are born with it -- but often it shows up in early to middle adulthood, debilitating people in the prime of their working lives. The ailment, for example, can give younger people gnarled, permanently disfigured hands.

After years of minimal progress, the nation's research labs are making headway against both forms.

In the case of osteoarthritis, research is proceeding on how to interrupt the underlying disease, with some promising strategies just beginning to reach human trials. More immediately, to combat the symptoms, scientists have created anti-inflammatory drugs that seem to promise pain relief without the serious side effects, such as bleeding ulcers, sometimes caused by aspirin, Advil and similar compounds.

An expert advisory panel recently urged the Food and Drug Administration to approve the first of these new drugs, the "super aspirin." The compound, developed by a unit of the Monsanto Co., could be on the market in the first half of next year and will be sold under the brand name Celebrex. Similar compounds are being developed by the world's major drug companies.

Even more excitement attends new treatments for rheumatoid arthritis. For generations, rheumatologists have watched, nearly helpless, as this ailment slowly wrecked the lives of patients. They developed numerous drugs that could offer temporary relief. And for decades, they have tried to slow the ailment's advance by using drugs that could suppress the immune system.

But these drugs were sometimes too much of a good thing: They killed immune cells not involved in arthritis, which in some people caused side effects that were worse than the disease. For people who could take them, the drugs worked well for perhaps half, but failed to offer significant relief for the rest.

Nowadays, using the techniques of genetic analysis, scientists are trying to determine which types of immune cells are involved in rheumatoid arthritis and how they communicate with one another. This has allowed scientists to design highly specific drugs to dampen the excessive immune reaction without, apparently, causing much collateral damage.

A prime target for the new drugs is a compound known as tumor necrosis factor-alpha. This protein was first discovered in association with cancer, but by now it's clear the substance is misnamed. It turns out to be involved in all sorts of inflammation, and excessive levels seem to play a role in a host of diseases, including rheumatoid arthritis.

Working with this knowledge, the Immunex Corp. of Seattle created a substance that, in effect, mops up excess tumor necrosis factor in the body. Research studies, in which Alyce Kelso was a participant, produced striking evidence of the drug's effectiveness. Severely afflicted patients, mostly people for whom all other treatments had failed, reported substantial relief within weeks of starting the drug.

Trisha Seletyn of Oak Hill, W.V., began limping when she was 2 years old. She now is 9 and is one of 71,000 U.S. children with rheumatoid arthritis. The disease grew worse over the years. "She got to the point where medicine wasn't working," said her mother, Teresa Seletyn. "She would drag herself by her front arms and kind of crawl on the floor."

She eventually had to use a wheelchair and was so ill that she missed all of second grade. One immune-suppressing drug caused her to vomit and her hair to fall out. Last year, pleading for something new to try, her parents learned about the tests of Enbrel.

Within two months of starting the injections, Trisha was out of her wheelchair and using a walker. She now is back in school, able to walk unaided for long periods of time and to play with her classmates. "I used to be real stiff," Trisha said. "This helps me to walk and stuff."

Enbrel has been tested in large, stringent trials involving patients who had either no benefit or bad side effects from existing treatments. Peggy Phillips, senior vice president of pharmaceutical development at Immunex, recalled getting "goose bumps" when her scientists analyzed their data and discovered how well Enbrel worked. Patients taking the drug toured the company and recounted their improvement, leaving many of Immunex's scientists in tears.

As awareness of these new treatments has spread, Wall Street has shown more interest. The stocks of many companies involved in arthritis research are up substantially. Immunex shares have gained nearly 142 percent in the last year to close on at $114.75 a share Dec. 24.

Based on evidence of its effects in adults, the FDA approved Enbrel for sale in the United States on Nov. 2. Another new drug, Arava, developed by Hoechst Marion Roussel AG, won approval in September. Its immune-suppressing action is broader than that of Enbrel, making it similar to some of the older arthritis drugs.

Scientists still are determining how to use these new drugs. While 85 percent to 90 percent of those who take Enbrel, for example, seem to get at least some benefit, a few people don't. The new drugs must be tested in numerous combinations, with each other and with older treatments, to see what strategies work best for which patients. Sorting all this out is certain to take years.

Moreover, while it's clear that the new drugs offer relief, doctors don't yet know whether they will stop the joint destruction typical of severe rheumatoid arthritis. Patients who are on Enbrel claim it does exactly that, but doctors are waiting for more scientific proof.

Another drug that targets tumor necrosis factor -- Remicade, developed by Centocor Inc. of Malvern, Pa. -- won approval earlier this year as a treatment for Crohn's disease, a severe ailment in which the immune system attacks and damages the bowels. Centocor has begun advanced human tests of Remicade for the treatment of rheumatoid arthritis, and has reported positive results. Conversely, Immunex plans to test Enbrel to see if it relieves Crohn's disease. Enbrel will also be tested in congestive heart failure and several other conditions.

A theoretical concern with drugs of this type springs from their ability to suppress parts of the immune system. Over the long term, will patients taking the medication be more susceptible to infections and cancers? Preliminary evidence suggests not, but doctors want to analyze years of data before they make a final judgment.

Aside from tumor necrosis factor, scientists have identified other immune system components that seem to be over-active in rheumatoid arthritis, diabetes, multiple sclerosis, heart failure and other ailments. They are busy designing and testing highly specific drugs that they hope will be useful in these illnesses.

After long-term safety worries, the biggest issue with these new treatments is likely to be cost. Enbrel, created by the cutting-edge techniques of genetic engineering, requires injections twice a week at more than $100 a shot. But patients who are using the new drugs say that even at prices like that, they may save money in the long run.

Before she started Enbrel, Kelso, the Rochester woman, was set to have surgery on her elbow, where a knot the size of a tennis ball had grown under her skin. Since she started the drug, the knot has shrunk to the size of a pea, the pain has dissipated, and she has put off the surgery, which would have cost thousands of dollars.

That's not the only change in her life.

"Because I feel so good, I have to tell myself, that's enough, no more today," she said. "I feel like I could go back to work. My wheelchair's in the closet, along with the cane. The crutches are down in the basement, gathering dust."


People seeking more detailed information about the latest research on arthritis can call the Arthritis Foundation at 1-800-283-7800 weekdays from 8:30 a.m. to 5 p.m. Eastern time and request a copy of "On the Way to a Cure," a recent publication.

*Those with Internet access can visit the Arthritis Foundation site,, on the World
Wide Web. In addition, the National Institute of Arthritis and Musculoskeletal and Skin Diseases, part of the National Institutes of Health, offers detailed information at

© Copyright 1998 The Washington Post Company