Janus kinase (JAK) inhibitors can quickly and effectively manage ulcerative colitis (UC), especially when more conventional treatments haven’t worked.
UC is a type of inflammatory bowel disease (IBD) that causes inflammation in the large intestine and rectum. Symptoms include bowel urgency, rectal bleeding, diarrhea, and abdominal pain.
The goals of UC treatment are to manage symptoms, reduce levels of inflammation in the body, and induce or maintain remission.
Several medications are available to treat UC, including Janus kinase (JAK) inhibitors. So far, two JAK inhibitors have approval for treating UC in adults. The Food and Drug Administration (FDA)
Here’s more about how they work and whether they might be a good option for you.
Your immune system is a complicated network designed to protect you from things like viruses and bacteria, which can enter the body and cause illness. When triggered, your immune system mounts a powerful inflammatory attack to fight off potentially harmful organisms or substances.
UC develops when this attack targets otherwise healthy tissue in the large intestine and does not shut off. Researchers don’t yet fully understand the reasons for this response, but a family of enzymes called Janus kinase (JAK) enzymes are involved in the process.
JAK enzymes send signals to the immune system to release more inflammatory proteins called cytokines. Many different cytokines are involved in UC. Several of them are regulated by JAK enzymes.
JAK inhibitors block JAK enzymes from sending signals to the immune system. This prevents the release of inflammatory proteins that contribute to UC. When inflammation decreases, symptoms reduce, and UC goes into remission.
If your symptoms are mild to moderate, medications such as aminosalicylates (5-ASA) or corticosteroids might be enough to manage your UC.
If you’re dealing with moderate to severe symptoms, the 2024 American Gastroenterological Association (AGA) Clinical Practice Guidelines still recommend treatment with a biologic first. JAK inhibitors also have approval for moderate to severe UC, but at this point, biologics are generally the first choice.
Biologics block specific cytokines (inflammatory proteins). This can help with getting UC into remission and maintaining remission.
A cytokine called tumor necrosis factor (TNF) is involved in the inflammation of UC. Several biologics known as anti-TNF agents have approval for moderate to severe UC. They include infliximab (Remicade) and adalimumab (Humira).
Biologics don’t work for everyone. They don’t produce a response in about 30% of people who try them for the first time. Sometimes, a biologic medication works for a time but then stops being effective. This happens in up to 20% of people who take a biologic medication every year.
The AGA guidelines recommend JAK inhibitors for treating UC that doesn’t respond to a biologic or stops responding.
Some research suggests that JAK inhibitors could be a first-line treatment in the future, but there are some safety concerns, which means they won’t be the best option for everyone.
Clinical trials show that JAK inhibitors can be a quick and effective way to induce UC remission. Trials found that 37% to 43% of people with active UC reached clinical remission after 8 weeks of tofacitinib. At the 52-week mark, the rate of remission ranged from 34% to 61.7%.
Trials of the second FDA-approved JAK inhibitor, upadacitinib, found a remission rate of up to 80% after 8 weeks. After 52 weeks, the rate of clinical remission was 38%.
Some trials found that people experienced reductions in their symptoms after just a few days on a JAK inhibitor.
Another advantage of JAK inhibitors is that they are oral medications. People inject biologic medications at home or receive them through an infusion at a medical clinic. It’s easier to adjust the dose of a daily oral medication if needed.
Like all medications, there are possible risks and side effects associated with taking JAK inhibitors. It’s important to discuss the best way to manage your UC with your doctor.
Since JAK inhibitors modify immune signals, they lower your overall immune function, which can increase your risk of infection. It’s important to take steps to prevent illness, such as:
- washing your hands
- avoiding contact with people who are sick
- wearing a mask in crowded places
- staying up to date with recommended vaccinations
Anyone with an active infection should avoid taking a JAK inhibitor.
JAK inhibitors may be associated with an increased risk of cardiovascular disease, blood clots, and cancer. If you have a history of heart disease, are over the age of 65, currently smoke, or have a history of smoking, a JAK inhibitor might not be a good fit for you.
Side effects of JAK inhibitors include:
- headaches
- increases in blood pressure and cholesterol
- diarrhea
- respiratory infections
JAK inhibitors are oral medications. There are currently two FDA-approved JAK inhibitors for UC: tofacitinib (Xeljanz) and upadacitinib (RINVOQ).
If you are taking a JAK inhibitor for moderate to severe UC symptoms, your healthcare professional will likely recommend one of the following:
- tofacitinib 10 milligram (mg) tablet or liquid solution twice per day
- tofacitinib extended-release 22 mg tablet once per day
- upadacitinib 45 mg tablet once per day
Once your UC is in remission, you will likely switch to one of the following maintenance doses:
- tofacitinib 5 mg tablet or liquid solution twice per day
- tofacitinib extended-release 11 mg tablet once per day
- upadacitinib 15 to 30 mg tablet once per day
There are several treatments for ulcerative colitis (UC), including JAK inhibitors.
JAK inhibitors are a type of medication to manage moderate to severe UC. Doctors typically prescribe them if anti-TNF agents, a type of biologic medication, aren’t effective in getting the condition into remission or keeping it in remission.
Some safety concerns mean that JAK inhibitors aren’t right for everyone. Make sure to discuss all your options with a healthcare professional.
