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What are JAK inhibitors and how do they work?

Medically reviewed by Leigh Ann Anderson, PharmD. Last updated on July 15, 2025.

Official Answer by Drugs.com

Janus kinase (JAK) inhibitors are a group of medicines that help block immune system signals in the body that can lead to swelling (inflammation) and pain in conditions like rheumatoid arthritis, ulcerative colitis, and psoriatic arthritis. They work by blocking enzymes that lead to overactivity of the immune system. JAK inhibitors come in oral and topical (skin) formulations.

When used for the treatment of rheumatoid arthritis, Janus kinase (JAK) inhibitors are part of a wider group of drugs called DMARDs (Disease-Modifying Anti-Rheumatic Drugs). DMARDs help to slow down ongoing joint damage in rheumatoid arthritis.

Xeljanz was the first JAK inhibitor approved by the FDA in November 2012 for the treatment of rheumatoid arthritis.

List of JAK Inhibitors

JAK inhibitors approved in the United States include:

How do they work?

Janus kinase (JAK) inhibitors work by slowing down the overactivity of the immune system that can lead to inflammation and pain. They do this by inhibiting the activity of one or more JAK enzymes (JAK1, JAK2, JAK3, and TYK2) found in the cell.

The immune system is the body’s natural defense against infection and other diseases. But sometimes the immune system can become overactive and cause medical problems. By blocking JAK enzymes, JAK inhibitors help to decrease the immune system reaction that can lead to inflammation, pain and other symptoms.

Enzymes are proteins in the body that help to facilitate processes in the body, like chemical reactions. JAK enzymes promote inflammatory signals in the body which are associated with cytokine (interleukin, interferon) release. Cytokines are small proteins that affect the growth of cells that are involved in inflammation and the immune response. JAK-dependent cytokines have been shown to lead to a number of inflammatory and autoimmune diseases.

What are JAK inhibitors used for?

JAK inhibitors are approved by the FDA to treat a variety of medical conditions involving the skin, joints, gastrointestinal tract and other systems. Further descriptions of these conditions can be found in the approved uses section below.

FDA approved uses for JAK inhibitors

Cibinqo (abrocitinib) - In January 2022, the FDA approved Pfizer’s Cibinqo (abrocitinib), an oral Janus kinase 1 (JAK1) inhibitor.

Inrebic (fedratinib) - Inrebic, an oral JAK2 inhibitor, was approved in August 2019 for the treatment of adult patients with myelofibrosis. Inrebic is given by mouth once a day.

Jakafi (ruxolitinib) - Jakafi is a JAK1/JAK2 inhibitor used for the treatment of myelofibrosis and polycythemia vera in adults; and graft-versus-host disease in patients 12 years of age and older. Jakafi tablets are administered twice daily.

Leqselvi (deuruxolitinib) - In July 22024, the Sun Pharma announced approval of Leqselvi (deuruxolitinib) 8 mg tablets for the treatment of adults with severe alopecia areata. Leqselvi is a JAK1/JAK2 inhibitor.

Litfulo (ritlecitinib) - In June 2023 the FDA cleared Pfizer’s Litfulo for treatment of severe alopecia areata in adults and adolescents 12 years and older.

Ojjaara (momelotinib) - In September 2023, the FDA approved GSK’s Ojjaara, a JAK1/JAK2 and activin A receptor type 1 (ACVR1) inhibitor for the treatment of myelofibrosis in adult patients with anemia. Ojjaara tablets are administered orally once daily.

Olumiant (baricitinib) - In June 2018, the FDA first approved Eli Lilly’s Olumiant tablets to be used for the treatment of rheumatoid arthritis in adults. It is now also approved in adults to treat severe alopecia areata and COVID-19 in certain hospitalized patients with breathing trouble.

Related: COVID-19: Prevention, Treatment and Vaccines

Opzelura (ruxolitinib cream) - Opzelura from Incyte is a JAK inhibitor approved for the treatment of atopic dermatitis (eczema) and for repigmentation in nonsegmental vitiligo in adults and children 12 years of age and older. Over-activity of the JAK signaling pathway has been shown to drive inflammation in atopic dermatitis and vitiligo.

Rinvoq, Rinvoq LQ (upadacitinib) - AbbVie's Rinvoq was first approved in August 2019 for the treatment of adults with moderate-to-severe rheumatoid arthritis (RA) who have had an inadequate response or intolerance to methotrexate. Rivoq comes as an extended-release oral tablet (Rinvoq) and as an oral liquid solution (Rinvoq LQ). These two formulations are not interchangeable. Rinvoq is not a substitute for Rinvoq LQ.

Rinvoq has also been approved to treat several autoimmune-type inflammatory diseases, including:

Vonjo (pacritinib) - Vonjo, from CTI BioPharma, is a JAK2/FLT3 multikinase inhibitor for the treatment of adult patients with myelofibrosis with severe thrombocytopenia (low platelet counts). It was first approved by the FDA in February 2022. Vonjo capsules are administered orally twice daily with or without food.

Xeljanz, Xeljanz XR (tofacitinib) - Xeljanz, from Pfizer, is an oral JAK inhibitor used to treat rheumatoid arthritis, ulcerative colitis, psoriatic arthritis, and ankylosing spondylitis in adults; and polyarticular juvenile idiopathic arthritis in patients 2 years of age and older. It was first approved by the FDA in November 2012.

In studies, Xeljanz has been shown to inhibit JAK1/JAK2, JAK1/JAK3, and JAK2/JAK2, but how these combinations contribute to the therapeutic effect is not fully known.

Xeljanz XR, the extended-release form of Xeljanz, is approved to be used in adults for the treatment of rheumatoid arthritis, ulcerative colitis, psoriatic arthritis, and ankylosing spondylitis.

This list may not be all-inclusive of all approved products. This is not all the information you need to know about JAK inhibitors for safe and effective use and does not take the place of your doctor’s directions. Review the full product information and discuss this information and any questions you have with your doctor or other health care provider.

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How do Rinvoq and Dupixent compare?

Rinvoq (upadacitinib) and Dupixent (dupilumab) differ significantly in how they work, their approved uses, side effect profiles, and cost structures.

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Which JAK inhibitors are approved in the U.S?

List of JAK inhibitors approved in the United States include:

  • Cibinqo (abrocitinib)
  • Inrebic (fedratinib)
  • Jakafi (ruxolitinib)
  • Leqselvi (deuruxolitinib)
  • Litfulo (ritlecitinib)
  • Ojjaara (momelotinib)
  • Olumiant (baricitinib)
  • Opzelura (ruxolitinib)
  • Rinvoq (upadacitinib)
  • Vonjo (pacritinib)
  • Xeljanz (tofacitinib)
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What is the MOA and half-life for Rinvoq?

Rinvoq (upadacitinib) is an oral medicine that works by blocking intracellular Janus kinase (JAK) enzymes to help to reduce inflammation and pain in conditions such as rheumatoid arthritis. The half-life ranges from 8 to 14 hours and is the time it takes for half (50%) of the drug to be eliminated.

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