Treating Psoriatic Arthritis With JAK Inhibitors

If you have psoriatic arthritis (PsA), your doctor may prescribe Janus kinase inhibitors (JAK inhibitors) to relieve joint pain and inflammation. JAK inhibitors are a type of drug that inhibits certain enzymes associated with inflammation. By blocking these signaling enzymes, the body no longer produces inflammatory proteins that cause PsA symptoms.

JAK inhibitors are used to treat many types of autoimmune disease. They help temper an overactive immune system and, by doing, alleviate acute symptoms, protect joints and other tissues, and slow the progression of the disease.

In people with PsA, the body makes too many proteins called cytokines, which play a role in causing inflammation. When cytokines attach to immune system cells, they send a message to the cells to produce more cytokines, which means more inflammation. JAK inhibitors block this process, calming down the immune system and easing PsA inflammation, pain, and other PsA symptoms.

Older biologics, such as Humira (adalimumab), may not help some people in managing PsA symptoms. Clinical research suggests that as many as 18.9% of newly treated people and 29.7% of those previously treated with biologics will not achieve an adequate response to Humira. For these people, a JAK inhibitor may help to manage symptoms and improve quality of life.

A major advantage of JAK inhibitors is that they are available in pill form, whereas biologics must be given by injection or intravenous (IV) infusion.

As of 2018, there have been five JAK inhibitor drugs approved for use in humans by the U.S. Food and Drug Administration (FDA). Of these, Xeljanz (tofacitinib) is the only one approved for the treatment of PsA.

The FDA approved Xeljanz for the treatment of rheumatoid arthritis in 2012 and psoriatic arthritis in 2017. It can be used on its own or combined with methotrexate (a widely prescribed immunosuppressive drug).

A 2017 study in the New England Journal of Medicine reported that a twice-daily, 5-milligram dose of Xeljanz was superior to placebo in achieving a 20% reduction in PsA symptoms in three months.

As of 2019, Olumiant (baricitinib) is not yet approved for use in people with PsA. It was previously approved for the treatment of rheumatoid arthritis, an autoimmune disease characterized by the widespread inflammation of the joints and organs.

Other JAK inhibitors under investigation for the treatment of PsA include the experimental drug filgotinib (GLPG0634) and the FDA-approved rheumatoid arthritis drug Rinvoq (upadacitinib).

Because JAK inhibitors suppress the actions of the immune system, taking them puts you at risk for different kinds of infections. In clinical trials, some participants developed tuberculosis after taking Xeljanz and Olumiant, although the risk was considered to be low (less than 1%). 

JAK inhibitors also increase the risk of certain viral diseases, most especially shingles.

Common side effects of JAK inhibitors include:

• Upper respiratory infection
• Diarrhea
• Headache
• Flu-like symptoms
• Dizziness
• Easy bruising
• Urinary tract infection
• Weight gain
• Fatigue
• Shortness of breath
• Anemia (low red blood cell count)
• Thrombocytopenia (low platelet count)

On rare occasions, JAK inhibitors have been known to cause liver toxicity, typically reversible and mainly associated with the drug Xeljanz.

JAK inhibitors may also interact with disease-modifying anti-rheumatic drugs (DMARDs) and other immunosuppressants used to treat psoriatic diseases. This can lead to severe anemia, high cholesterol, and impaired kidney function.

Side effects tend to reverse on JAK inhibitors are stopped. This means your immune system will be able to fight infection once the drug is fully out of your system, usually within a matter of days.

JAK inhibitors like Xeljanz can be extremely beneficial for people who are unable to control their psoriatic symptoms with more conservative therapies. With that said, they are not for everyone. Be sure to let your doctor know if you have other chronic conditions like diabetes, heart disease, or lung disease before starting a JAK inhibitor.

You should also provide your doctor with a complete list of medications you are taking, both over-the-counter and prescription.