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Xeljanz Alternatives

Patients seek Xeljanz alternatives to treat arthritis and colitis because of concerns over serious side effects. Treatments like enzyme blockers and different classes of disease-modifying anti-rheumatic drugs, or DMARDs, are effective but vary in cost and have their own serious side effects.

Last Modified: September 7, 2023
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What Are Xeljanz Alternatives?

Several medications currently on the market can work as alternatives to Xeljanz, the brand name for tofacitinib, to treat rheumatoid arthritis, psoriatic arthritis and ulcerative colitis. Because Xeljanz is available in both pill and liquid form and doesn’t need to be injected, the medication became popular quickly. However, studies have indicated serious Xeljanz side effects such as blood clots, pulmonary embolism and death.

In February 2021, the U.S. Food and Drug Administration issued a safety alert after multiple patients filed Xeljanz lawsuits. The safety alert stated that the drug increased the risk of serious cardiovascular problems and cancer in certain patients.

Many people are now seeking Xeljanz alternatives that offer similar benefits without the same risks. There are three general classes of drugs commonly used to treat rheumatoid arthritis: nonsteroidal anti-inflammatory agents, or NSAIDs; corticosteroids; and disease-modifying anti-rheumatic drugs, such as Xeljanz, that slow down the progression of the disease and improve symptoms.

Janus Kinase Inhibitors

Janus kinase inhibitors, including Xeljanz, are a type of targeted synthetic DMARD that block enzymes involved in inflammation. This can slow down the progression of autoimmune diseases such as rheumatoid arthritis, psoriatic arthritis and ulcerative colitis.

JAK inhibitors may be used as a second-line treatment for rheumatoid arthritis if other medications are ineffective or intolerable. JAK inhibitors are typically taken by mouth, either in pill or liquid form, making them more convenient than medications requiring injection.

Other JAK inhibitors that act as Xeljanz alternatives include Rinvoq (upadacitinib) and Olumiant (baricitinib). These medications work similarly to Xeljanz but may have different side effects and safety profiles.


Rinvoq, the brand name for upadacitinib, is an FDA-approved JAK inhibitor used to treat rheumatoid arthritis. It is orally administered and can be effective in reducing symptoms of rheumatoid arthritis. However, Rinvoq may increase the risk of serious infections, blood clots, cancer and cardiovascular events.


Similar to Rinvoq, Olumiant (baricitinib) is also an FDA-approved JAK inhibitor used to treat rheumatoid arthritis. It’s taken by mouth and may improve rheumatoid arthritis symptoms. As with Rinvoq, the risk of serious infections, blood clots, cancer and cardiovascular events is still present when taking Olumiant.

Disease-Modifying Anti-Rheumatic Drugs

There are three classes of DMARDs: conventional synthetic, targeted synthetic and biologic. Because it is made with traditional drug manufacturing techniques and taken orally, Xeljanz is not considered a biologic DMARD, but does have side effects similar to biologics.

Conventional DMARDs suppress the immune system to reduce inflammation. They may be less expensive, may take longer to work and can be administered orally.
Biologic DMARDs target specific proteins in the immune system that contribute to inflammation. They’re typically administered through injection and may be more expensive than conventional DMARDs.

Each type of DMARD has different side effects: Biologics may increase the risk of serious infections and other side effects, while conventional DMARDs may cause gastrointestinal problems and liver damage.

Biologics: Humira and Enbrel

Humira (adalimumab) and Enbrel (etanercept) are biologic DMARDs that can be used as Xeljanz alternatives to treat rheumatoid arthritis. Both medications are administered through injection and block a protein called tumor necrosis factor-alpha that contributes to inflammation. However, like other biologics, they may increase the risk of serious infections and other side effects.

Conventional DMARDs: Trexall

Trexall (methotrexate) is a conventional DMARD that is used first line to treat rheumatoid arthritis. Side effects may include nausea and diarrhea. Trexall is administered by mouth once a week. The mechanism for treatment of rheumatoid arthritis is unknown, but may affect immune function.

How to Switch to a Xeljanz Alternative

Speak with your doctor if you’re currently taking Xeljanz for rheumatoid arthritis but are interested in switching to an alternative medication because of safety concerns.

Your doctor may have you step down your current prescription and begin taking a new medication. Nonpharmacological treatments may also be recommended, including physical therapy, exercise and dietary changes.

Please seek the advice of a medical professional before making health care decisions.