JAK inhibitors for ulcerative colitis: a patient overview

JAK inhibitors are a newer category of medication used for moderate to severe ulcerative colitis. Unlike biologic medications — which are injected or infused — JAK inhibitors are taken orally as pills. If your gastroenterologist has mentioned them, or if you are looking for a plain-English explanation of what they are, this guide covers the basics.

What is a JAK inhibitor?

JAK inhibitors are small-molecule drugs that work by blocking enzymes inside cells called Janus kinases (JAK enzymes). These enzymes help transmit signals that activate the immune response. By interrupting these signals, JAK inhibitors reduce the immune activity that drives inflammation in the colon.

Unlike biologics — which are large proteins that block targets outside cells — JAK inhibitors are small enough to enter cells and block signaling from the inside. This is why they can be taken as a pill. For a full comparison with biologics, see our guide on biologics for ulcerative colitis.

JAK inhibitors approved for UC

Tofacitinib (Xeljanz)

Tofacitinib was the first JAK inhibitor approved for UC in the United States. It is approved for adults with moderately to severely active UC who have had an inadequate response or are intolerant to tumor necrosis factor (TNF) blockers.

• Taken as an oral tablet twice daily
• A higher induction dose is used for 8 weeks, then reduced to a maintenance dose
• Extended-release formulation (Xeljanz XR) is also available for once-daily dosing

Upadacitinib (Rinvoq)

Upadacitinib is a selective JAK1 inhibitor approved for adults with moderately to severely active UC who have had an inadequate response or intolerance to prior therapy.

• Taken as an oral extended-release tablet once daily
• Has shown strong efficacy in clinical trials and is considered more selective than tofacitinib

Ozanimod (Zeposia) — note

Ozanimod is sometimes grouped with this class in patient discussions, but it is technically a sphingosine-1-phosphate (S1P) receptor modulator — a different class of oral medication. It is also FDA-approved for UC.

How JAK inhibitors compare to biologics

Both biologics and JAK inhibitors are used for moderate to severe UC, but there are key differences:

Some patients and doctors prefer JAK inhibitors because of the convenience of oral dosing; others prefer biologics based on efficacy data, insurance coverage, or risk profile. See the full ulcerative colitis treatment options overview for context on where both fit in the treatment landscape.

Who might be a candidate?

JAK inhibitors are generally considered for patients with:

• Moderate to severe UC not adequately controlled by mesalamine or steroids
• UC that has not responded to one or more biologics
• A preference for an oral treatment over injections or infusions
• Specific disease characteristics that make a JAK inhibitor preferable

If mesalamine is not working and your disease is moderate to severe, your gastroenterologist may discuss JAK inhibitors as a step-up option. Your gastroenterologist will assess your overall health, disease activity, and medical history before recommending one.

Safety considerations

JAK inhibitors carry some specific risks that your doctor will discuss with you:

Infection risk

Like biologics, JAK inhibitors reduce immune activity and increase susceptibility to infections. Common infections (upper respiratory, urinary tract) occur more frequently. Serious infections, including opportunistic ones, can occur rarely.

Herpes zoster (shingles): JAK inhibitors are associated with an increased risk of shingles. The CDC recommends vaccination against shingles (Shingrix) before starting a JAK inhibitor in eligible patients.

Cardiovascular considerations

Higher doses of tofacitinib (used in rheumatoid arthritis) have been associated with elevated cardiovascular risk in older patients with certain risk factors. This information informed the prescribing information for all JAK inhibitors. Your doctor will review your cardiovascular history before prescribing.

Cancer risk

There is a potential increased risk of certain cancers with JAK inhibitor use. This is reflected in prescribing guidance. Your doctor will weigh these risks against the benefits based on your age, history, and disease severity.

Lab monitoring

Regular blood tests are required while on JAK inhibitors, including monitoring of:

• White and red blood cell counts
• Liver enzymes
• Cholesterol levels (JAK inhibitors can raise LDL cholesterol)

Pregnancy

JAK inhibitors should generally be avoided during pregnancy. If you are pregnant or planning pregnancy, discuss this with your gastroenterologist before starting treatment.

What to expect when starting a JAK inhibitor

• Some patients begin to notice improvement within days to weeks
• Your doctor will typically assess response at 8–12 weeks
• If one JAK inhibitor does not work, switching or changing class may be discussed
• Regular follow-up appointments and lab monitoring are part of ongoing treatment

When to contact a doctor

Contact your healthcare provider if, while on a JAK inhibitor, you notice:

• Signs of infection: fever, chills, unusual fatigue, or skin sores
• Symptoms of shingles: localised burning pain or a blistering rash on one side of the body
• Chest pain, shortness of breath, or leg swelling
• Significant changes in your UC symptoms

Questions to ask your doctor

• Is a JAK inhibitor the right next step for my disease?
• Which JAK inhibitor do you recommend — and why?
• What monitoring will I need while taking it?
• Should I get the shingles vaccine before starting?
• How does the cardiovascular risk apply to my specific situation?
• What are the signs of serious side effects I should watch for?
• Can I take this if I am planning to have children?
• What are my options if it does not work?

This content is for educational purposes only and does not constitute medical advice. Speak with your gastroenterologist about whether JAK inhibitors are appropriate for your situation.