The right treatment for ulcerative colitis (UC) can make a big difference in your quality of life. If your treatments stop working or cause too many side effects, it’s important to know your options. UC medications have two major goals: stopping intestinal inflammation (reaching remission) and keeping the inflammation at bay.
If you continue to have flares and symptoms while taking treatments such as aminosalicylates and biologics, your doctor may recommend a newer option: Janus kinase (JAK) inhibitors.
What Are JAK Inhibitors?
JAK inhibitors belong to a group of medications called small-molecule compounds. Because of their small size, they can leave your bloodstream and reach areas of tissue that other drugs can’t. Once there, they can block signals that cause inflammation and calm down your immune system.
How JAK inhibitors treat ulcerative colitis
JAK inhibitors target an enzyme called Janus kinase (JAK), which works like an air traffic controller for inflammation messages within your cells. When you have ulcerative colitis, these enzymes let in messengers called cytokines, which cause inflammation in your large intestine.
Besides cytokines, JAK enzymes direct more than 50 other kinds of chemical messengers that affect inflammation, like specialized immune system proteins called interferons.
But JAK inhibitors put a stop to this.
These medications work by getting inside your immune cells to block these inflammation-causing signals at their source. Once JAK inhibitors stop the flow of inflammation messages to your intestines, they have a chance to heal, which improves UC symptoms.
Then, as you keep taking JAK inhibitors, they continue to block those signals and help prevent future inflammation.
When Are JAKs Prescribed?
When the FDA first approved JAK inhibitors, they recommended these medications for people who had already tried TNF inhibitors such as adalimumab (Humira) or infliximab (Remicade) but still had symptoms.
But because they’re so fast-acting and effective, guidelines may soon change to use JAK inhibitors earlier. The FDA has approved the use of upadacitinib for people with moderate-to-severe UC who can’t take TNFs and have tried one other systemic therapy. Other JAK inhibitors not yet approved by the FDA are already being considered for standard treatment in other countries, and researchers in the U.S. continue to study them.
JAK Inhibitor Benefits: How They Compare
Compared to other UC treatments, JAK inhibitors come with some advantages.
Here’s how they compare with other common treatments:
| How they lower inflammation | How you take them | How fast they can start working | |
|---|---|---|---|
| JAK inhibitors | Block many immune cell messages that cause inflammation | By mouth | 1-3 days |
| Aminosalicylates | Stop the body from making inflammation-causing chemicals | By mouth | 2 weeks |
| Corticosteroids | Calm down inflammation-triggering signals | By mouth, rectum, or injection | 2 weeks |
| Immunomodulators | Change how the immune system responds to threats | By mouth or injection | 3 months |
| Biologics | Target inflammation-causing proteins | By injection or IV | 2 weeks |
They work faster
Unlike some other treatments that can take months to start working, JAK inhibitors knock out intestinal inflammation fast — sometimes within days. The FDA has approved tofacitinib (Xeljanz) for UC and upadacitinib (Rinvoq) for both UC and Crohn’s disease.
They come as pills vs. injections
Unlike other advanced UC treatments like some immunomodulators and biologics, JAK inhibitors come in pill form. “This is a substantial advantage in an arena where most advanced therapies are given as injections or IV infusions,” says Stephen Bickston, MD, associate chief of the Division of Gastroenterology, Hepatology, and Nutrition at the Virginia Commonwealth University School of Medicine in Richmond.
You can adjust treatment quickly
JAK inhibitors also have a shorter half-life than other UC medications, says Jessica Philpott, MD, PhD, a gastroenterologist who specializes in inflammatory bowel disease at the Cleveland Clinic in Ohio. This means they leave your system faster.
“With a JAK, we can stop the medication, and it will quickly be out of the patient's system if we need to stop immunosuppression, but we can restart quickly,” Philpott says.
Their effectiveness doesn’t fade
Another advantage of JAK inhibitors is that your body won’t make antibodies to fight them off, which happens with some biologic therapies, says Raseen Tariq, MD, a gastroenterologist at VCU Health in Richmond, Virginia.
When antibodies form against a medication, it makes that medication less effective, but JAK inhibitors are safe from this risk. “This can make long-term treatment more predictable for some patients,” Tariq says.
How Quickly Do JAK Inhibitors Work?
JAK inhibitors improve symptoms faster than other treatment options. “Some patients begin noticing improvement in symptoms such as stool frequency or rectal bleeding within days to a couple of weeks, although achieving full remission may still take several weeks to months,” Tariq says.
In one clinical trial, participants noticed fewer symptoms within one to three days after starting upadacitinib. In another study, people saw improvement at an average of two to three days after starting tofacitinib.
Some people take a bit longer to respond to these medications, says Philpott. But even if they don’t work fast, JAK inhibitors may still improve symptoms after a few weeks. In one study, about half of those who didn’t see improvement after taking tofacitinib for eight weeks (but kept taking it) saw results by 16 weeks.
Which UC Symptoms Get Better With JAK Inhibitors?
JAK inhibitors block your immune system’s overreaction, which lessens inflammation and improves several UC symptoms.
Ulcerative colitis symptoms that get better on JAK inhibitors include:
- Rectal bleeding
- Frequent bowel movements
- Excessive daily bowel movements
- Sudden urge to poop
- Abdominal pain
- Fatigue
Some studies have even found that JAK inhibitors may prevent a UC complication called ankylosing spondylitis, which causes pain and inflammation in your spine and joints.
JAK Inhibitor Side Effects
Like any medication, JAK inhibitors can cause some negative effects. “Most side effects are manageable and often mild,” Tariq says.
Common JAK inhibitor side effects include:
- Acne (sometimes referred to as “JAK-ne”)
- Headaches
- Respiratory infections
- Infections of the nose and throat
Although rare, JAK inhibitors can also cause more serious problems, such as:
Some of these side effects, such as blood clots and heart problems, were found in research on JAK inhibitors taken for rheumatoid arthritis, but studies on these medications for UC haven’t yet shown this increased risk, Philpott says.
Even so, your doctor will always review your individual risks and involve specialists if needed before prescribing, Philpott says.
If you have certain side effects, such as swelling, fever, or dark stools, let your doctor know. They may want to pause or stop your medication.
Sometimes side effects need urgent attention. Call 911 or go to your nearest emergency room if you notice:
- Chest pain or pressure
- Confusion
- Trouble speaking
- Double vision
- Excess sweating
- Difficulty breathing
- Pain in your arms, back, neck, or jaw
As your body adjusts to your medication, side effects may fade. But it’s always a good idea to tell your care team about any new symptoms you notice after starting a new treatment. They can examine these effects and help you manage your symptoms or adjust medications if needed.
How to manage JAK side effects
To prevent and manage side effects from JAK inhibitors, your provider may lower the amount you take, Bickston says. They may also make these recommendations:
- See a dermatologist, who can treat “JAK-ne” and other skin concerns.
- Ask about headache treatment, which may include over-the-counter medications.
- Get the shingles vaccine, which can protect you from infection with the herpes zoster virus.
To stay on top of infections or complications, your doctor might also suggest regular lab tests, Tariq says.
What to Know Before Taking a JAK Inhibitor
Before you start a JAK inhibitor, your doctor will discuss the risks and benefits, review your medical conditions, and tell you about any reasons not to take it, Philpott says.
Who Shouldn’t Take a JAK Inhibitor
You may not be able to take JAK inhibitors if you have:
- Any active serious infections
- Advanced liver disease
- Low blood counts
- Risk factors for or a history of blood clots and cardiac events
These medications can make those conditions worse.
Experts don’t know how JAK inhibitors affect a fetus. So, you shouldn’t take a JAK inhibitor if you’re pregnant or may become pregnant.
JAK Inhibitors: Drug Interactions and Warnings
Because JAK inhibitors slow the immune system, you shouldn’t take them with other immunosuppressants, such as steroids or biologics. Medications taken on the same day can interact and cause unexpected symptoms, so it’s important to tell your doctor about every medicine and supplement you take, including those you buy over the counter.
How to Store JAK Inhibitors
Both tofacitinib and upadacitinib tablets can be stored at room temperature (up to 77 F). Liquid JAK inhibitor solutions can handle temperatures up to 86 F.
Throw away any leftover liquid in your bottle after it’s been open for 60 days. No matter the type, be sure to store all JAK inhibitors in a place that’s out of the reach of children.
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