JAK inhibitors are oral medications that can help reduce the overactive immune response associated with ulcerative colitis (UC).

UC is a type of inflammatory bowel disease (IBD) that causes chronic inflammation and sores on the inner lining of the large intestine. Experts do not know exactly what causes it, but they believe an overactive immune reaction may play a role.

Multiple types of medication are available to treat UC, including Janus kinase (JAK) inhibitors. JAK inhibitors are a type of oral medication that helps block inflammation.

The Food and Drug Administration (FDA) has approved two JAK inhibitors to treat UC: tofacitinib (Xeljanz) and upadacitinib (Rinvoq).

Read on to learn more about JAK inhibitors, including the potential benefits and risks.

JAK inhibitors are oral small-molecule drugs that block the action of JAK, a family of enzymes that help drive inflammation in the immune system.

Scientists have identified four types of JAK:

  • JAK1
  • JAK2
  • JAK3
  • tyrosine kinase 2 (TYK2)

These enzymes activate proteins that carry signals from one part of the immune system to another. Blocking the action of these enzymes helps suppress certain immune responses that cause inflammation.

“Unlike some of our directed monoclonal antibodies that hit one target or two, this knocks out many targets. So even though this is a small molecule and it’s oral, which is convenient, it’s actually a potent immunosuppressant,” Dr. Anjali Mone, a gastroenterologist at Lenox Hill Hospital in New York City, told Medical News Today.

The FDA has approved Xeljanz and Rinvoq to treat moderate to severe UC.

However, a doctor will likely try another type of medication before prescribing a JAK inhibitor for this condition.

In its 2020 guidelines, the American Gastroenterological Association (AGA) recommended infliximab (Remicade) or vedolizumab (Entyvio) as the first-line treatment for moderate to severe UC. Both of these medications are biologics, which is a different class of medication than JAK inhibitors.

If a person does not have an adequate or lasting response to treatment with Remicade, Entyvio, or other biologics, the doctor may prescribe another medication, such as Xeljanz or Rinvoq.

A doctor may also prescribe Xeljanz or Rinvoq to someone who has rheumatoid arthritis or psoriatic arthritis in addition to UC. The FDA has approved these medications to treat all three conditions.

Who should not take JAK inhibitors?

JAK inhibitors may not be a suitable treatment option for all people with moderate to severe UC.

“I would not recommend it for patients who are pregnant or breastfeeding or chestfeeding,” said Dr. Mone. “I would use caution in patients with a history of blood clots or heart problems. I would also avoid [it] in patients with active malignancy.”

Before taking JAK inhibitors, people should ensure that the prescribing healthcare professional is aware of any other medical conditions they have, particularly:

  • active infection
  • liver disease
  • kidney disease

In people with UC, an overactive immune response can cause the immune system to attack healthy tissue in the large intestine.

Cytokines play a role in this process. These proteins attach to receptors on the JAK-signal transducer and activator of transcription (JAK-STAT) pathway. This triggers an immune response and can cause the inflammation associated with a number of autoimmune and inflammatory conditions.

JAK inhibitors block cytokines from attaching to receptors in the JAK-STAT pathway. This reduces the amount of inflammation the immune system produces. JAK inhibitors are a treatment option for conditions involving an overactive immune response.

JAK inhibitors can help reduce inflammation and relieve symptoms in UC. For some people, they may provide a more effective treatment than biologics.

In a 2012 phase 2 clinical trial, 194 people with moderate to severe UC received Xeljanz or a placebo twice a day for 8 weeks. Clinical remission occurred in:

  • 33% of people who received 3-milligram (mg) doses of Xeljanz
  • 48% of people who received 10-mg doses of Xeljanz
  • 41% of people who received 15-mg doses of Xeljanz
  • 10% of people who received a placebo

Clinical remission means that the symptoms have resolved completely or nearly completely.

A series of three phase 3 clinical trials also found that Xeljanz was effective in inducing and maintaining remission in UC.

In two of these trials, participants with moderately to severely active UC received 10-mg doses of Xeljanx or a placebo twice per day. After 8 weeks, remission occurred in:

  • 16.6–18.5% of people who received Xeljanz
  • 3.6–8.2% of people who received a placebo

In the third trial, researchers recruited people who were already in remission from UC. These participants received 5-mg or 10-mg doses of Xeljanz or a placebo twice per day. After 52 weeks:

  • 34.3% of people who received 5-mg doses of Xeljanz were still in remission
  • 40.6% of people who received 10-mg doses of Xeljanz were still in remission
  • 11.1% of people who received a placebo were still in remission

A follow-up 2018 study found that people who received 10-mg doses of Xeljanz twice daily had reduced symptoms within 3 days of starting treatment.

In a 2020 phase 2 clinical trial, 250 people with moderate to severe UC received Rinvoq or a placebo once per day. After 8 weeks, clinical remission occurred in:

  • 8.5% of people who received 7.5 mg of Rinvoq
  • 14.3% of people who received 15 mg of Rinvoq
  • 13.5% of people who received 30 mg of Rinvoq
  • 19.6% of people who received 45 mg of Rinvoq
  • 0% of people who received a placebo

Two phase 3 clinical trials found that 8 weeks of treatment with 45 mg daily doses of Rinvoq induced clinical remission in 26.1% and 33.5% of people. In both trials, less than 5% of people who received a placebo experienced remission.

Other types of JAK inhibitors have also shown promise for treating UC. Studies are ongoing to confirm the safety and effectiveness of these medications. More research is necessary to learn how different JAK inhibitors compare with each other and with other treatment approaches.

Research has shown that JAK inhibitors are generally safe for people with UC, but they do carry the risk of side effects.

If a person thinks that they might be experiencing side effects from a JAK inhibitor or another medication, they should speak with the prescribing healthcare professional.

Healthcare professionals can order regular lab tests to check for signs of side effects from JAK inhibitors.


JAK inhibitors suppress the immune system, which may increase the risk of infections, such as:

  • herpes zoster, also known as shingles
  • upper respiratory tract infections
  • certain fungal infections

The varicella-zoster virus causes chickenpox and shingles. In phase 3 clinical trials, 19 people who received Xeljanz developed a herpes zoster infection compared with one person who received a placebo.

In a phase 2 clinical trial involving 250 people with UC, one person receiving Rinvoq developed a herpes zoster infection.

Herpes zoster infection is more common among older adults. Due to this, healthcare professionals may advise people 50 years or older to get a vaccination against herpes zoster. Multiple vaccines are available. A healthcare professional can help someone decide which vaccine may be best for them.

In rare cases, people who are taking JAK inhibitors develop serious and potentially life threatening infections. The risk of serious infections may be higher in people who are also taking corticosteroids, methotrexate, or other medications that suppress the immune system.

Cardiovascular health

JAK inhibitors may increase blood levels of cholesterol, including low-density lipoprotein (LDL) and high-density lipoprotein (HDL). “Usually lipids go up the first month, then stabilize,” said Dr. Mone, “and most of our young patients don’t have an issue with this.”

Some research has also linked JAK inhibitors to an increased risk of blood clots and cardiovascular events. However, a 2020 review of safety found that the risk of cardiovascular events is not significantly higher among people with autoimmune diseases who take JAK inhibitors.

More research is necessary to study the effects of JAK inhibitors on cardiovascular health in people with UC.

The FDA advises people with a history of blood clots or heart problems to talk with a doctor about the risks of taking JAK inhibitors, including Xeljanz and Rinvoq. People taking JAK inhibitors should seek emergency medical attention if they experience symptoms of a blood clot. These may include:

  • sudden shortness of breath
  • chest pain that gets worse with breathing
  • swelling of an arm or leg, which may present with tenderness or pain

Other side effects and risks

Other potential side effects of JAK inhibitors include:

  • rash
  • diarrhea
  • headaches
  • joint stiffness
  • bloating and gas
  • fatigue
  • dizziness
  • weight gain

Researchers have reported certain types of cancer in people who are taking JAK inhibitors. However, the 2020 review of safety found that the risk of cancer was not significantly higher in people taking this medication. More research is necessary.

Limited data are available on the risks of JAK inhibitors for people who are pregnant or nursing.

JAK inhibitors are oral medications that people swallow.

The standard dosage of Xeljanz to induce remission in UC is 10 mg twice daily for at least 8 weeks. However, in some cases, a person’s healthcare professional may prescribe a lower dosage.

Once a person is in remission, the healthcare professional will reduce their prescribed dosage of Xeljanz to the smallest amount necessary to maintain remission.

The recommended dosage for adults taking Rinvoq is 45 mg once per day for 8 weeks to induce remission. The recommended dosage to maintain remission is 15 mg once a day. People with severe or extensive UC may need a different maintenance dosage.

A person should work with their healthcare professional to determine a suitable JAK inhibitor dosage for them.

Sometimes, a healthcare professional may prescribe a JAK inhibitor in combination with other medication to manage UC.

Multiple types of medication are available to treat moderate to severe UC.

A healthcare professional will likely prescribe a biologic as the first-line treatment for this condition. If a biologic is not effective, the healthcare professional may prescribe another type of medication, such as a JAK inhibitor.

JAK inhibitors can help reduce inflammation and symptoms in people with UC. They may also cause side effects, including an increased risk of infection. Although more research is necessary, experts have also raised concerns about the increased risk of blood clots and cardiovascular events in people taking this medication.

A person can speak with a healthcare professional to learn more about the potential benefits and risks of JAK inhibitors and other treatment approaches for UC.