Rheumatoid Arthritis Drug May Top Old Drug

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Rheumatoid Arthritis Drug May Top Old Drug

News Review from Harvard Medical School

June 19, 2014

News Review From Harvard Medical School -- Rheumatoid Arthritis Drug May Top Old Drug

A newer drug improved symptoms for more people than the usual drug given first to people with rheumatoid arthritis, researchers report. Methotrexate, an old drug, is typically what people receive first when diagnosed with this disease. A newer drug, tofacitinib, helps to reduce inflammation in this disease. It works in a different way than methotrexate. The new study included 956 people with rheumatoid arthritis. They had not yet been treated with methotrexate. They were randomly divided into 3 groups. One group received methotrexate. The others took tofacitinib, in different doses. After 6 months, signs and symptoms of the disease had improved more in the groups receiving tofacitinib. About 26% of those taking the smaller dose and 38% of those taking the larger dose had at least a 70% improvement. About 12% of those taking methotrexate improved that much. About 4% of those taking tofacitinib and 1% of those taking methotrexate developed shingles. Five people taking the new drug and 1 person taking the old drug developed cancer. But the numbers were small, so this difference could have been the result of chance. The New England Journal of Medicine published the study. The HealthDay Physician's Briefing news service wrote about it June 18.


By Robert H. Shmerling, M.D.
Harvard Medical School


What Is the Doctor's Reaction?

What's new in the treatment of rheumatoid arthritis?

It's a question I hear often. And the answer has changed a lot in the last 20 years. Research through these years has increased our understanding of the disease. That has led to development of new and highly effective treatments. Since the late 1990s, the U.S. Food and Drug Administration (FDA) has approved 11 new drugs. Rheumatoid arthritis is still not considered a curable disease. Yet these new options have improved the lives of millions of people with the disease.

Tofacitinib (brand name Xeljanz) is among the newest drugs. The FDA approved it in November 2012. It works in a different way than other recently approved drugs. It blocks an enzyme called Janus kinase. This stops several chemical messengers from triggering inflammation. Tofacitinib is taken as a pill rather than by injection. That is another way it's different from most of the other recently approved drugs for rheumatoid arthritis.

A new study asks an important question that arises with the arrival of any new drug: is it as good as the old ones? Is it possibly even better?

New research attempts to answer these questions. The study appears this week in the New England Journal of Medicine. Researchers compared the effectiveness of tofacitinib to that of methotrexate. This drug has been around for decades. It is the most common first choice of treatment for rheumatoid arthritis. The study included nearly 1,000 people with rheumatoid arthritis.

After 6 months of treatment:

  • The symptoms and signs of joint inflammation improved more in the tofacitinib-treated group than among those receiving methotrexate.  Compared with methotrexate, twice as many people receiving the approved dose of tofacitinib had 70% improvement. With a higher dose of tofacitinib, 3 times as many people had 70% improvement.
  • The X-rays of people receiving tofacitinib showed less joint damage than those of people treated with methotrexate. The differences were small, however.
  • Herpes zoster (shingles) developed in 4% of the tofacitinib group and 1% of the methotrexate group.
  • Cancer developed in a small number of patients. The rate was slightly higher in those assigned to receive tofacitinib. The numbers were too small to draw definite conclusions about cancer risk.

This study provides important information for people with rheumatoid arthritis and their doctors. In fact, these results suggest that tofacitinib might be considered before methotrexate for a person with newly diagnosed rheumatoid arthritis. However, the side effects and the cost of tofacitinib (about $25,000 to $30,000 a year) will likely slow the acceptance of tofacitinib as a "first-line" drug.


What Changes Can I Make Now?

The cause of rheumatoid arthritis is not known. Therefore, there is no known way to reliably prevent it. 

However, we do know that risk is higher in some groups. These include people who smoke and those who have gum inflammation (gingivitis) caused by particular bacteria. You may be able to reduce your chances of developing rheumatoid arthritis by not smoking and by taking good care of your teeth and gums.

You may be able to avoid other common types of arthritis, such as osteoarthritis. Here's what you can do:

  • Avoid excess weight. Obesity increases the risk of osteoarthritis. It is thought that millions of cases could be avoided if more people maintained a healthy weight. And that would reduce the need for hip and knee joint replacements.
  • Avoid joint injury. Joint damage related to trauma can lead to osteoarthritis. Measures to avoid injury include:
    • Proper athletic training
    • Proper athletic technique
    • Not taking unnecessary risks at work or at play

There are more than 100 types of arthritis. Early diagnosis and treatment can make a big difference in how well you feel and how well you can function months or years after symptoms begin. So see your doctor for evaluation if you have major or persistent joint pain, stiffness or swelling.


What Can I Expect Looking to the Future?

It seems likely that tofacitinib and related drugs will be studied soon for a variety of diseases. Tofacitinib has shown promise for psoriasis and allergic diseases. A related drug, ruxolitinib, has already been approved for a serious blood disorder (called myelofibrosis). It has shown promise in the treatment of psoriasis. 

Future research should clarify the potential risks of taking tofacitinib. For example, larger and longer-term studies will be needed to determine whether tofacitinib affects cancer risk.

Most of the new medicines for rheumatoid arthritis have been quite expensive and require injections. I hope that more treatments will become available in pill form and that the price will eventually come down.

When one of my patients asks me what's new in the treatment of rheumatoid arthritis, it's likely I'll have even more to say in the years ahead.

Last updated June 19, 2014

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