JAK Inhibitors

Reviewed by: HU Medical Review Board | Last reviewed: August 2022

Janus kinase (JAK) inhibitors are drugs that help to reduce inflammation in the body. JAK inhibitors are known as disease-modifying antirheumatic drugs, or DMARDs. JAK inhibitors are usually taken long-term and may be used with other drugs.1

Some JAK inhibitors have been approved to treat adults with certain cases of axial spondyloarthritis (axSpA), including:

How do JAK inhibitors work?

Cytokines are tiny proteins that serve as messengers within your body. When they bind to receptors, they tell the cells that make up your body what to do. Cytokines are important for the immune system, and they affect inflammation and other processes in nr-axSpA and AS.2

JAK inhibitors block the activity of Janus kinase, a type of protein that is involved in sending signals from cytokines. By blocking JAK, JAK inhibitors can prevent cytokines from sending their signals. This can help to treat a variety of diseases, including nr-axSpA and AS.1


As of 2022, 2 JAK inhibitors have been approved by the US Food and Drug Administration (FDA):3,4

  • Xeljanz® (tofacitinib) – Approved to treat adult with active AS who have not responded to or cannot take one or more tumor necrosis factor (TNF) inhibitors
  • Rinvoq® (upadacitinib) – Approved to treat adults with:
    • Active AS who have not responded to or cannot take one or more tumor necrosis factor inhibitors
    • Active nr-axSpA with objective signs of inflammation who who have not responded to or cannot take one or more TNF inhibitors

What are the possible side effects?

Side effects can vary depending on the specific drug you are taking. Common side effects of JAK inhibitors taken for AS and nr-axSpA include:3,4

  • Nasal congestion and runny nose
  • Upper respiratory tract infections
  • Increased cholesterol levels
  • Headache
  • Rash
  • Diarrhea
  • Shingles
  • Acne
  • Cold sores
  • Flu

Both Xeljanz and Rinvoq have boxed warnings, the strictest warning from the FDA. They have these warnings because they may cause severe and life-threatening side effects, including:3,4

  • Increased risk of serious infections, including tuberculosis (TB)
  • Increased risk of heart attack, stroke, or death in people over 50 who also have heart disease
  • Increased risk of certain cancers, including lymphomas and lung cancers
  • Allergic reactions
  • Blood clots
  • Tears in the stomach or intestines
  • Changes in certain lab test results, including low white and red blood cell counts, high cholesterol levels, and high liver enzymes

JAK inhibitors work on the immune system. This can make people more likely to get infections. Call your doctor right away if you have any signs of infection while taking these drugs, such as:3,4

  • Fever or chills
  • Shortness of breath
  • Unusual tiredness
  • Cough
  • Muscle aches

These are not all the possible side effects of JAK inhibitors. Talk to your doctor about what to expect when taking JAK inhibitors. You also should call your doctor if you have any changes that concern you when taking JAK inhibitors.3,4

Other things to know

Before starting a JAK inhibitor, your doctor will likely request blood work. This is to check for infections like hepatitis and TB. The results will also show if you have blood count problems, like low white or red blood cell counts. Your doctor will also monitor you for signs and symptoms of hepatitis B or C and TB during treatment with a JAK inhibitor.3,4

JAK inhibitors should not be used if you have an infection. You should take these medications only if your doctor tells you to. If you take them, you may be at higher risk of developing shingles (herpes zoster).3,4

JAK inhibitors may harm an unborn baby. If you can become pregnant, you should use birth control during treatment and for some time after the last dose of a JAK inhibitor. You should also not breastfeed during treatment with a JAK inhibitor and for some time after the last dose. Talk to your doctor about your options for birth control and breastfeeding while taking a JAK inhibitor.3,4

Before starting a JAK inhibitor, tell your doctor if you:3,4

  • Are being treated for an infection or have had an infection that does not go away or keeps coming back
  • Are a current or past smoker
  • Have diabetes, chronic lung disease, HIV, or a weak immune system
  • Have had a heart attack, other heart problems, or a stroke
  • Have liver or kidney problems
  • Have TB or have been in close contact with someone with TB
  • Have had shingles
  • Have or have had hepatitis B or C
  • Have unexplained stomach pain, have a history of diverticulitis or ulcers in your stomach or intestine, or are taking non-steroidal anti-inflammatories (NSAIDs)
  • Have low red or white blood cell counts
  • Have recently received or are scheduled to receive any vaccines
  • Live in, have lived in, or have traveled to certain parts of the country where there is an increased risk of getting certain kinds of fungal infections

Also tell your doctor about any other health conditions and any other drugs, vitamins, or supplements you take. This includes over-the-counter drugs.

Take JAK inhibitors as prescribed by your doctor. Do not stop the drug if your symptoms improve or you go into remission. The best way to control your symptoms is to follow the treatment plan in place from your doctor.3,4

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