JAK Inhibitors for Rheumatoid Arthritis

If you have rheumatoid arthritis (RA), your doctor may suggest Janus kinase (JAK) inhibitors to help ease your joint pain and swelling. These drugs tamp down your overactive immune system -- the body's defense against germs -- to help prevent damage to your joints.


JAK inhibitors belong to a family of medicine called DMARDs (disease-modifying antirheumatic drugs). Two JAK inhibitors, baricitinib (Olumiant) and tofacitinib (Xeljanz), are approved by the FDA to treat rheumatoid arthritis. More should appear in the next few years if they succeed in clinical trials.

How JAK Inhibitors Work

If you have RA, your body makes too many proteins called cytokines, which play a role in inflammation. Some cytokines attach to receptors on immune cells, like a key fitting into a lock. When that happens, messages are sent to the cell to make even more cytokines.

JAK inhibitors put a wrench in the process by blocking the messaging pathway. This calms down your immune system and helps ease your RA symptoms.

Who Benefits?

You may be among the many people with RA whose symptoms are well-controlled with an older drug, such as adalimumab or methotrexate (Trexall). In that case, you may not need a JAK inhibitor.

But the older drugs don't always work for everyone. About 65% of people who take DMARDs, for example, get relief from symptoms. If you're not in this group, a JAK inhibitor might make a difference. In one study, about half of people with RA who didn't improve with biologic drugs had symptoms that were less severe after they took the JAK inhibitor tofacitinib for 3 months.

Another advantage of JAK inhibitors is that you can take them by mouth. You must inject biologics, such as adalimumab, into your skin, while doctors infuse others into the bloodstream. But you can take JAK inhibitors as a pill.

Side Effects

Because JAK inhibitors put the brakes on some immune system actions, they can leave you open to different kinds of infections. In clinical trials, a handful of people who took tofacitinib came down with tuberculosis (TB), a serious bacterial lung disease. You may also be more likely to get common viral diseases, such as herpes zoster (shingles), when you take JAK inhibitors. But the drugs have a short "half-life," which means that if you stop taking them, your body will soon get back its full ability to fight infection.

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JAK inhibitors can sometimes give you anemia due to the way they affect a protein in your body that's needed to make red blood cells. They can lower white blood cells counts as well.

The drugs may bump up your cholesterol numbers, but you can get around this side effect by taking a statin drug, such as atorvastatin (Lipitor), at the same time.

Some doctors are also worried that you may have higher odds of cancer if you take JAK inhibitors, because the drugs block immune system processes that prevent tumors. You may also have a greater chance of getting blood clots when you use these drugs.
Because these medications are fairly new, doctors are keeping tabs on their long-term safety. Check with your doctor to make sure these drugs don't cause any harm when you take them along with other medicines.

WebMD Medical Reference Reviewed by David Zelman, MD on January 17, 2019

Sources

SOURCES:

European Medical Journal: "JAK Inhibitors in the Treatment Algorithm of Rheumatoid Arthritis: A Review."

Annals of the Rheumatic Diseases: "Janus Kinase Inhibitors in Autoimmune Diseases."

Expert Opinion on Pharmacotherapy: "Chemical JAK Inhibitors for the Treatment of Rheumatoid Arthritis."

European Respiratory Journal: "Cytokines and the Lung."

Journal of Inflammation: "Tyrosine Kinases in Rheumatoid Arthritis."

The New England Journal of Medicine: "Placebo-Controlled Trial of Tofacitinib Monotherapy in Rheumatoid Arthritis."

Rheumatic Disease Clinics of North America: "Biologics in Early Rheumatoid Arthritis."

Drug Safety: "Thromboembolism with Janus Kinase (JAK) Inhibitors for Rheumatoid Arthritis: How Real is the Risk?"

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