JAK Inhibitors for Rheumatoid Arthritis

Medically Reviewed by David Zelman, MD on September 13, 2023
3 min read

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). Three JAK inhibitors, baricitinib (Olumiant), tofacitinib (Xeljanz), and upadacitinib (Rinvoq), are approved by the FDA to treat rheumatoid arthritis. More should appear in the next few years if they succeed in clinical trials.

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.

You may be among the many people with RA whose symptoms are well-controlled with an older drug, such as adalimumab (Humira) 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.

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.

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 cell 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. Your doctor will consider the risks that come with JAK inhibitors when deciding whether these are right for you, particularly if you are a smoker or are at risk for heart disease or cancer.

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.