What’s new in rheumatoid arthritis treatment?

woman's arthritic hands
Rheumatoid arthritis typically affects many different joints on both sides of the body, especially the finger joints.

Posted June 23, 2010

By Stanley M. Naguwa, M.D. 

Rheumatoid arthritis is one of the many autoimmune diseases that still baffles medical science. No one knows why the body turns against itself, attacking and destroying healthy tissue. But advances in the basic science of these disorders is leading to ever-deeper understanding. As a result, more treatment options are rapidly becoming available.

About 1 percent of Americans suffer from rheumatoid arthritis. Like most autoimmune diseases, it affects women in far greater numbers than men. Usually beginning in young- to middle-adult years, this chronic and potentially disabling disorder occurs worldwide.

A complex disease

Stanley Naguwa is a clinical professor of rheumatology, allergy and clinical immunology with UC Davis Health System.

The mechanism of rheumatoid arthritis is complex. White blood cells, which normally keep invading organisms at bay, mount an attack on the body’s joints. The besieged cells respond by releasing chemicals that induce inflammation. This process leads to stiffness, pain, redness, loss of function and joint deformities. Tendons, ligaments, cartilage and even bone may eventually be destroyed.

Typically, many different joints on both sides of the body are affected, especially the finger joints. In addition, generalized fatigue is often present. In rare cases, membranes surrounding the heart and lungs become inflamed, making the disease life-threatening.

Proactive treatment

Rheumatologists, or doctors who specialize in the treatment of arthritis, used to treat the problem in a crisis-management style. They first recommended general pain killers, then waited until signs of joint damage appeared before calling out the big guns. We have since learned that a proactive strategy is better. By treating aggressively early on, long-term damage can be slowed or prevented.

By treating aggressively early on, long-term damage can be slowed or prevented.

Currently, the first-line medication is methotrexate, sometimes in combination with hydroxychloroquine and sulfasalazine. It is still the standard against which all newer medications are measured and works by impairing the function of inflammatory cells.

While the newer non-biologic drugs have not proved substantially better than methotrexate, they can serve as an alternative if methotrexate can’t be tolerated or can be used in combination with methotrexate for increased improvement.

Since late 1998, leflunomide (Arava), taken as a daily tablet, has been available. It acts by stopping the proliferation of white blood cells that initiate joint destruction. The result is less inflammation and a slowing of the damaging process.


New, so-called “biologic response modifiers” include etanercept (Enbrel), which is injected under the skin twice a week, and infliximab (Remicade), which is given at periodic intervals by infusion in a vein. Both act by blocking tumor necrosis factor, one of the major substances responsible for inflammation and joint damage. Both are slow-acting, and months may pass before the benefits are apparent. These medications have been associated with a few deaths and are not to be used during an active infection. There are now eight biologic response modifiers — or BRMs.

Biologic response modifiers are very expensive and do not show a clear advantage over methotrexate when used alone, although improvements are noted when they are used in addition to methotrexate. There may be evidence that BRM monotherapy is equal to methotrexate clinically, but may be superior in preventing joint damage. The combination of BRMs and methotrexate may work faster than methotrexate alone.

Risks and benefits over the long term are also not yet clear. Whether it’s best to take advantage of these new options greatly depends on individual circumstances, and must be carefully considered between a doctor and patient.

No 'magic bullet'

One other update about new medications: All arthritis sufferers have plenty of experience with the non-steroidal anti-inflammatory drugs (NSAIDs), which relieve pain and reduce inflammation. A newer class of pain relievers, known as COX-2 inhibitors and include celecoxib (Celebrex) and rofecoxib (Vioxx), was initially greeted with enthusiasm and high sales.

But let the buyer beware: These drugs are not magic bullets! Their advantage is that gastrointestinal complications are reduced, but they are no more effective against rheumatoid arthritis than the older and considerably cheaper NSAIDs.

Vioxx and Bextra were withdrawn from the market in the mid-2000s for safety reasons. The Food and Drug Administration asked all sponsors of marketed prescription NSAIDs, including Celebrex, to include warnings highlighting the potential for increased risk of cardiovascular events and for serious and potentially life threatening gastrointestinal bleeding. For Celebrex or celecoxib, this included specific information on controlled clinical trial data that demonstrated an increased risk of adverse cardiovascular events. Drug makers were also asked to commit to conduct a long-term study of the safety of Celebrex compared to naproxen and other appropriate drugs.

Manufacturers of over-the-counter NSAIDs were also been asked to include more specific information about potential cardiovascular and gastrointestinal risks, and safe use of the drugs.

Do the benefits of COX-2 inhibitors justify the risks and the expense? I wouldn’t recommend COX-2 inhibitors for occasional aches and pains unless one is prone to GI bleeding and ulcers. Even for chronic use, if finances are of concern, I would only strongly recommend them for patients at significant risk for developing ulcers. 

Keep up with developments

Keep up with new developments in arthritis. They are occurring at a rapid rate. Check out the Arthritis Foundation website at www.arthritis.org and the American College of Rheumatology at www.rheumatology.org. Then talk to your doctor about new advances and find out what options you should be incorporating into your own treatment plan.