JAK Inhibitors

Inflammatory bowel disease (IBD) can include several conditions that involve chronic inflammation of the digestive tract, including Crohn's disease and ulcerative colitis. This long-term inflammation can cause severe damage to the gastrointestinal (GI) tract and cause symptoms like cramping or diarrhea.^1,2

There is no cure for IBD, but there are ways to treat the condition and address symptoms. One of these treatments is a class of drugs called Janus kinase (JAK) inhibitors. Kinase inhibitors are a type of medicine that treat many different conditions. They work by targeting certain kinases, which are a type of protein that cells use for many different functions.^1,2

How do JAK inhibitors work?

With IBD, your body makes too many proteins called cytokines. Cytokines play a role in inflammation. JAKs are enzymes that are involved in sending signals to cells to increase inflammation. JAK inhibitors are drugs that are broken down in the GI tract and then carried through the bloodstream to block inflammation reactions and pathways. This helps to reduce intestinal inflammation involved in IBD.^1,2

Examples of JAK inhibitors

As of 2024, 2 JAK inhibitors have been approved by the US Food and Drug Administration (FDA) to treat adults with moderate to severe ulcerative colitis (UC):^3,4

• Xeljanz^® (tofacitinib)
• Rinvoq^® (upadacitinib)

Rinvoq is also approved to treat adults with moderate to severe Crohn's disease.⁴

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 IBD 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
• Blood clots

JAK inhibitors supress 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.

Other things to know

Your doctor will request blood work before starting you on a JAK inhibitor. These will check for infections like hepatitis and TB. The results will also show if you have blood count problems, like low white blood cell or red blood cell counts. You should also be monitored for signs and symptoms of hepatitis B or C and TB during treatment with a JAK inhibitor.^3,4

You should not take JAK inhibitors if you have any kind of infection, unless your doctor says it is okay. You may be at higher risk of developing shingles (herpes zoster).^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 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 or 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, have lived, or have traveled to certain parts of the country (such as the Ohio and Mississippi River valley and the Southwest) where there is an increased risk of getting certain kinds of fungal infections

Some JAK inhibitors can harm an unborn baby. Talk to your doctor if you are taking one and plan to become pregnant or breastfeed. You may need to use contraception or stop breastfeeding while taking a JAK inhibitor.^3,4

Take JAK inhibitors as prescribed by your doctor. Do not stop your 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.²

Before beginning treatment for IBD, tell your doctor about all your health conditions and any other drugs, vitamins, or supplements you are taking. This includes over-the-counter drugs.