November 25, 2019/Rheumatology & Immunology

Could a JAK Inhibitor Be Right for Your Rheumatoid Arthritis?

New class of medications for RA has a unique effect on the immune system

Rheumatoid arthritis and JAK medication

If methotrexate — the first drug doctors usually prescribe for rheumatoid arthritis — stops working for you, or you can’t tolerate it, there are a growing number of options. Thankfully, a wide range of medications can slow down the process that leads to joint damage. And as a result, most people with rheumatoid arthritis can be spared the worst effects of the disease.


Cleveland Clinic is a non-profit academic medical center. Advertising on our site helps support our mission. We do not endorse non-Cleveland Clinic products or services. Policy

These drugs fall into categories based on how they affect the immune system. “The newest drugs, called janus kinase (JAK) inhibitors, represent a new drug category because of the unique way they work,” says rheumatologist Matthew Bunyard, MD.

How drugs for RA work

Autoimmune diseases, including rheumatoid arthritis, occur because of a malfunctioning immune system. The immune system, which protects us from disease and helps heal injuries, goes awry and attacks healthy tissue. In the case of rheumatoid arthritis, the attack primarily targets the lining of joints (called the synovium).

Drugs for rheumatoid arthritis work by blocking parts of the immune system from wreaking havoc. Most people with rheumatoid arthritis start with the disease-modifying anti-rheumatic drug (DMARD) methotrexate, usually taken as a pill (but is also available as an injection). It has a proven track record as an effective medication. There are other DMARDs as well. But methotrexate doesn’t work well enough for everyone, and some people have side effects.

What happens when your first RA drug doesn’t work well enough?

The next step is to add or switch to another drug. The decision will be based on a discussion with your rheumatologist. Traditionally, the second drug has been a biologic DMARD. Most of these engineered drugs block chemicals (called cytokines) that are outside cells and promote inflammation.

Commonly used biologics block a cytokine called tumor necrosis factor, or TNF. Others target different cytokines (Il-6, IL-7) and cells (B-cells or T-cells) of the immune system.


There’s also another option: The newest drugs, the JAK inhibitors (AKA jakinibs), inhibit inflammation from inside cells. They block enzymes (JAK1, JAK2 and JAK3) that play a role in sending signals along a pathway that initiates an inflammatory process.

The first JAK inhibitor, tofacitinib (Xeljanz ®), became available in 2012. It can be used for both psoriatic arthritis and rheumatoid arthritis. A second one, baricitinib (Olumiant®) was FDA-approved in 2018 for rheumatoid arthritis only. Several others are being tested in clinical trials.

JAK inhibitors have the advantage of being taken as pills, whereas biologic drugs are given as either an injection or infusion.

Who is a JAK inhibitor right for?

“If you have an adverse reaction to methotrexate, you could be taken off that and given a JAK inhibitor,” Dr. Bunyard says. For people who tolerate methotrexate but have only a partial response (it doesn’t fully work for them), a JAK inhibitor might be added.

“A JAK inhibitor can be taken along with methotrexate, but it cannot be taken with a biologic drug,” Dr. Bunyard says.


Studies have shown that adding a JAK inhibitor to methotrexate is equally effective as adding a biologic to methotrexate.

Do JAK inhibitors have side effects?

All of the drugs used for rheumatoid arthritis have potential side effects, including the JAK inhibitors. Because the drugs suppress parts of the immune system, there’s an increased risk for infections and some cancers. The risk is low. Nonetheless, precautions should be taken.

Before starting these medications, you’ll be tested for tuberculosis. Vaccinations against pneumonia, influenza, shingles and hepatitis are recommended.

This article originally appeared in Cleveland Clinic Arthritis Advisor.

Learn more about our editorial process.

Related Articles

Person washing vegetables in kitchen sink during food preperation.
November 29, 2022/Diet, Food & Fitness
What’s the Best Diet for Rheumatoid Arthritis?

Say yes to whole foods, lots of fruits and vegetables, and anti-inflammatory antioxidants

Pregnant woman with rheumatoid arthritis sitting up on bed.
September 20, 2022/Rheumatology & Immunology
Having a Healthy Pregnancy When You Have Rheumatoid Arthritis

Having well-controlled RA at the time of conception is the key to keeping it under control while you’re pregnant

Woman in workout clothes does a lunge stretch in her living room as her cat looks on
Natural Remedies for Rheumatoid Arthritis

Diet and exercise are your best first steps

blood test for anemia
Are Rheumatoid Arthritis and Anemia Connected?

It’s not uncommon for individuals with RA to also have the blood disorder

A man holding a pilil and glass of water
How To Cope With Rheumatoid Arthritis Pain

The autoimmune disease can be managed with lifestyle changes and medication

close-up of hand with Psoriatic Arthritis
December 12, 2021/Rheumatology & Immunology
Psoriatic Arthritis vs. Rheumatoid Arthritis

What’s the difference between these types of inflammatory arthritis?

bunion surgery on foot
January 7, 2021/Orthopaedics
When Should I Have Surgery for My Bunions?

The short answer from an orthopaedic surgeon

Trending Topics

Person in yellow tshirt and blue jeans relaxing on green couch in living room reading texts on their phone.
Here’s How Many Calories You Naturally Burn in a Day

Your metabolism may torch 1,300 to 2,000 calories daily with no activity

woman snacking on raisins and nuts
52 Foods High In Iron

Pump up your iron intake with foods like tuna, tofu and turkey