Anti-TNF Drugs

What Happens If Your Anti-TNF Drug Doesn’t Work?

Anti-TNF drugs have improved the lives of countless people with inflammatory forms of arthritis, like rheumatoid arthritis (RA). But when one of these medicines quits working, or you simply don’t respond to an anti-TNF drug, which drug might your doctor prescribe next? Physicians who have puzzled over these questions received some clues about how to treat the disease from the results of a new clinical trial presented at the 2015 American College of Rheumatology (ACR) Annual Meeting.

Anti-TNF drugs, which belong to a class of medicines known as biologics, block the action of tumor necrosis factor (TNF), a protein that promotes inflammation. Five anti-TNFs are currently on the market: adalimumab (Humira), certolizumab pegol (Cimzia), etanercept (Enbrel), golimumab (Simponi, Simponi Aria) and infliximab (Remicade). Since the first anti-TNF medicines became available in the late 1990s, newer biologics have been developed that don’t target TNF, but instead block the action of other inflammation-causing proteins.

ACR treatment guidelines for RA recommend physicians prescribe a biologic –traditionally an anti-TNF drug – if you continue to experience pain, swelling and inflammation while taking drugs such as methotrexate. Although anti-TNF medications have spared legions of people with RA a great deal of pain and disability, they do not work for everyone. It’s estimated that one-third or more of RA patients don’t gain any or long-lasting relief from the first anti-TNF drug they try.

If your disease fails to respond to an anti-TNF medication, your doctor has several options. She can prescribe a different anti-TNF drug or she can opt for one of the non-TNF biologics, such as abatacept (Orencia), anakinra (Kineret), rituximab (Rituxan) or tocilizumab (Actemra). However, doctors faced with this choice have had scant evidence from scientific studies to guide the decision.

To help fill that void, researchers at France’s Strasbourg University Hospital recruited 292 RA patients whose disease didn’t respond to initial treatment with an anti-TNF drug. Half were randomly assigned to receive a different anti-TNF medicine, while the other half were given a non-TNF biologic. (Physicians were allowed to choose which specific drug in each category a patient would take.) One year later, 60% of the patients given a non-TNF biologic had maintained a good or moderate response to the medication, compared with 43% of those treated with a second anti-TNF drug. Moreover, patients who got a non-TNF biologic were twice as likely to achieve remission as those given an alternative anti-TNF.

“The results show a clear superiority… of changing the mechanism of action: when you fail one anti-TNF, it is better to use a drug [that doesn’t] again target TNF,” says lead author Jacques-Eric Gottenberg, MD, PhD. He adds that this study confirms observational studies and registry data.

The study’s overall results may change how some doctors treat people who don’t find relief from their first anti-TNF. “Traditionally, you were encouraged to use a second anti-TNF, but this shows you do much better if you switch classes,” says Mara Becker, MD, division director of rheumatology and associate professor of pediatrics at University of Missouri-Kansas City School of Medicine.

Rheumatologist Theodore Fields, MD, of the Hospital for Special Surgery in New York City says, “This moderate-sized study…may influence the number of patients failing their first TNF blocker who move to a different category of biologic agent.”

But Dr. Gottenberg notes, although the study suggests that non-TNF biologics may be a better choice for patients whose disease doesn’t respond (or respond adequately) to an initial anti-TNF drug, 40% of the participants got no relief from either second-line therapy. This emphasizes the need to discover new therapies for RA.

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