Trail-Blazing Arthritis Treatments

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Trail-Blazing Arthritis Treatments

By Delia K. Cabe, Medical Writer

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The treatment of rheumatoid arthritis has recently undergone a

revolution. Now over 2 million Americans--about one in ten--who suffer

from this debilitating disease can count on better options in their

quest for relief from pain, stiffness, and swollen joints. Drugs

approved within the last 2 years actually may keep the disease in check

more quickly and with fewer side effects--and there are others coming

soon.

" Prior to this time, we had not known that we could consistently make

them feel better, " says Dr. Lee Simon of Harvard Medical School. " We can

for the first time use proven therapies to change the inevitable course

of this disease. "

Standard Treatments: The Price of Relief

Until 1998, there were two classes of medications to treat the pain and

swelling of rheumatoid arthritis. But they prevented joint damage with

limited success. To relieve pain and swelling, nonsteroidal

antiinflammatory drugs (NSAIDs) have been the workhorses--and initial

therapy--of rheumatoid arthritis care.

The oldest NSAID is aspirin, developed a century ago to treat rheumatoid

arthritis. Other NSAIDs include ibuprofen and naproxen. But all of these

carry as much as a three times higher risk of causing upset stomach, or

worse, life-threatening gastrointestinal bleeding in users than among

those not taking NSAIDs.

When NSAIDs prove inadequate, doctors enlist disease-modifying

antirheumatic drugs (DMARDs). These include the antimalarial drug

hydroxycholorine, sulfasalazine, and methotrexate. " Methotrexate is the

gold standard, but, even so, 50% of patients have incomplete or no

response, " says Dr. Stanley B. Cohen of Southwestern Medical School in

Dallas.

Most DMARDs suppress an overly active immune system, a culprit in

rheumatoid arthritis, and in turn slow the rate of joint damage.

However, DMARDs may take months to work, cause numerous side effects,

and lose their effectiveness over time. While waiting for DMARDs to kick

in or during severe flares, people with arthritis may rely on

corticosteroids to reduce inflammation and suppress the immune system.

But these, too, have serious side effects, so their use is limited. With

so many drawbacks, no wonder physicians and their patients have been

eager for something better.

New Treatments

Since 1998, the Food and Drug Administration (FDA) has approved four new

drugs that offer much promise, not to mention long-lasting relief of

symptoms and fewer side effects than the older treatments. The advent of

these medications came about as result of a much better understanding of

the role that key players in the immune system play in rheumatoid

arthritis. " I think these drugs are extremely exciting, " Cohen says. " To

have these drugs is really going to lead to improvement in quality of

life. "

A DMARD whose FDA approval in September 1998 marked the start of this

revolution yields results in as little as 4 weeks. Leflunomide (brand

name Arava) retards joint damage and erosion and lessens the degree of

narrowing of the space between joints. The drug's major disadvantage is

that it remains in the body for up to 2 years and may cause birth

defects. Women who want to get pregnant need to discontinue taking

leflunomide and take a drug that eliminates it from the body.

At a recent meeting of the American College of Rheumatology, Cohen

presented the results of the longest study to date that compared the old

standby methotrexate to a newer therapy. In the study, 250 patients

taking leflunomide for 2 years continued to show significant improvement

in performing daily activities. Fewer side effects were also seen.

" Arava is as good or better than methotrexate, " Cohen says.

Aiming at a Better Target

Even more revolutionary is the new category of drugs called biologic

response modifiers--biologics, for short--because they are based on

chemicals found naturally in the body. Biologics target some of the

compounds in the immune system that are implicated in rheumatoid

arthritis.

One drug, etanercept (brand name Enbrel), inhibits the action of tumor

necrosis factor (TNF), a protein found in the body. Increased levels of

TNF occur in the fluid surrounding rheumatoid joints and prompt cells of

the immune system to attack and destroy cartilage. Because serious

infections and fatalities have occurred since its approval a year ago,

the FDA has recommended that physicians not prescribe the drug to

patients prone to infections. The FDA approved another TNF inhibitor,

infliximab (brand name Remicade), this past November.

But physicians are not about to stop prescribing methotrexate and other

older treatments. Instead, the new drugs will be used in combination

with methotrexate. This drug cocktail may thwart this incurable

disease--on several fronts at once.

What's more, physicians are treating rheumatoid arthritis more

aggressively based on recent research that shows joint damage may occur

within the first 6-12 months. Doctors predict that the new drugs

combined with the old used early on may lessen the impact of rheumatoid

arthritis in the long run.

In addition, people with arthritis now can reduce the risk of the

stomach problems, including life-threatening gastrointestinal bleeding,

associated with NSAIDs by using so-called " super aspirins. " These

painkillers, called COX-2 inhibitors, foil an enzyme in the body that

causes pain and inflammation. Since they are NSAIDs, although a gentler

variety, physicians need to watch for bleeding, ulcers, or perforation

of the gastrointestinal lining. COX-2 inhibitors are as effective at

reducing inflammation, and they led to a decreased likelihood of

gastrointestinal complications. Two such drugs approved recently are

celecoxib (brand name Celebrex) and rofecoxib (brand name Vioxx).

Short of a Cure, More to Come

More biologics and other drugs are on the horizon, as is gene therapy.

And people like Ferney, a 57-year-old retired nurse in the Dallas

area, are already benefiting from experimental therapies. Ferney never

got any respite from the pain and other problems caused by rheumatoid

arthritis despite taking more methotrexate and painkillers. " On a scale

of 1 to 10, my pain was a 5 most of the time, " she says.

So, at her doctor's urging, Ferney joined a clinical trial about 2 years

ago for a drug called anakinra (brand name Kineret). Anakinra inhibits

interleukin-1, which, like TNF, causes pain, swelling, and damage in

joints. " I was ready to try anything that wasn't going to give me

terrible side effects, " she says. Now she rates her pain a 1 or 2.

Still other medications under study are minocycline, an antibiotic used

to treat acne, and omega-3 fatty acids, which are found in some plant

and fish oils.

Given the strides made in arthritis treatment in the last 10 years,

researchers say there is indeed more hope than hype surrounding newly

approved treatments and drugs under investigation.

Jan.2000 © 2000 by Medscape Inc. All rights reserved.

Delia K. Cabe has been a consumer health writer for nearly 15 years.