Biologics Can Stop Working And Trigger Relapse

Scientists are examining a more confounding question about patients with RA who are in remission and then relapse: Why does it occur in people who are still taking medications?  “That can happen within months or even many years after a patient has been started on a drug,” says Dr. Hardin, who is also a professor of medicine in the division of rheumatology at the Albert Einstein College of Medicine, in the Bronx, New York.

The problem, explains Dr. Hardin, appears to be that some people with RA eventually become resistant to the very biologic medications that allowed them to attain remission. This phenomenon occurs when the body develops antibodies that counteract the benefit of the drug. An antibody is a protein made by the immune system, which is your body’s defense network. Normally, antibodies protect you from germs and other harmful substances that enter the body. However, scientists now know that some patients with RA eventually start producing antibodies that block the work of biologic drugs. That includes the widely used class of medications known as tumor-necrosis factor (TNF) inhibitors such as adalimumab (Humira) and infliximab (Remicade). As a biologic drug becomes less effective, a patient in remission will discover that his or her joint symptoms have returned.

Switching RA Medications May Help

Fortunately, an antibody that dampens the benefits of one biologic drug typically doesn’t target others, notes Dr. Hardin. “Switching to an alternative TNF inhibitor often provides an effective therapy,” he says. Moreover, there’s a critical strategy that can help prevent biologic-blocking antibodies from causing problems in the first place. Combining a biologic medication with a disease-modifying anti-rheumatic drug (DMARD) such as methotrexate or azathioprine—which helps turn down activity in the immune system—significantly reduces the risk of developing blocking antibodies, according to a scientific review published in JAMA Internal Medicine in August 2013. In fact, the package insert for infliximab indicates that the drug should be combined with methotrexate, for this very reason.

Alternating Remission and Relapse

About one-third of patients with RA have alternating periods of remission and relapse no matter what therapy they receive, says Dr. Hardin, although no one knows why this happens. One intriguing, if surprising, theory holds that certain forms of bacteria and other microbes in the human digestive tract may influence the severity of RA. Studies have confirmed that diet and other factors can alter the composition of bacteria in the gut. “A change in that bacterial flora could potentially change activity of the disease in an individual,” says Dr. Hardin. However, this theory is in its infancy, he notes, adding that understanding which RA patients in remission are most at risk for relapse, and why, is a critical and active area of investigation.

See Your Doctor if You Relapse

If you are in remission and joint pain and stiffness start to flare, tell your doctor soon.  “Flares are important,” says Dr. Fields. “They may be telling you that a drug that was initially working is losing its effectiveness.” Seeing your doctor promptly allows him or her to adjust your treatment plan, which can prevent serious damage to your joints and help you feel better.