10 JAK Inhibitor Side Effects to Know About
Key takeaways:
Janus kinase (JAK) inhibitors are medications that affect the immune system. They treat health conditions such as rheumatoid arthritis, ulcerative colitis, and COVID-19.
Common JAK inhibitor side effects include respiratory infections, nausea, and headache. People also commonly experience acne and raised cholesterol. These can generally be managed at home with lifestyle changes or medications.
Serious JAK inhibitor side effects like heart attack or stroke, blood clots, and risk of cancer are rare but possible. Your healthcare team should monitor you for signs and symptoms of these serious side effects.
Table of contents
Janus kinase (JAK) inhibitors are medications that treat a variety of health conditions, such as rheumatoid arthritis (RA), ulcerative colitis, and COVID-19. Common JAK inhibitors include Xeljanz (tofacitinib), Rinvoq (upadacitinib), and Olumiant (baricitinib). While these medications can be effective, they may also cause side effects.
Oral JAK inhibitors tend to have similar side effects. Most are relatively mild. But you’ll also find many carry boxed warnings (the FDA’s strictest medication warning) for potentially life-threatening side effects. These JAK inhibitor side effects are rare, but it’s still helpful to know about them.
Good to know: There’s a topical JAK inhibitor, Opzelura (ruxolitinib), that’s applied to the skin. It tends to be better tolerated overall than oral JAK inhibitors because less medication reaches your bloodstream. But the side effects we discuss below are still possible.
JAK inhibitor side effects at a glance
Many JAK inhibitor side effects are generally mild in nature. These can often be managed at home with lifestyle changes or medications. But for more serious side effects, you might need medical treatment. The risks for individual side effects vary between JAK inhibitors. Ask your healthcare team for more information on your specific medication.
Common JAK inhibitor side effects include:
Mild infections, such as upper respiratory tract infections
Headache
Nausea
Fatigue
Diarrhea
Acne
Raised cholesterol
Raised blood pressure
Elevated liver enzymes (a marker of liver function)
Rare but serious JAK inhibitor side effects include:
Serious infections, such as pneumonia or shingles
Damage to the stomach or intestines
Changes in blood cell counts, such as anemia (low red blood cells)
JAK inhibitors that are approved to treat autoimmune or inflammatory conditions also carry a boxed warning for:
Heart attacks
Strokes
Blood clots
Higher risk of certain cancers
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These boxed warnings are based on a study comparing the JAK inhibitor Xeljanz to the biologic medication Humira (adalimumab) for the treatment of RA. This study found that people taking Xeljanz had a higher risk for developing these serious side effects than Humira. But the risk is still very low overall.
Below, we’ll cover 10 notable JAK inhibitor side effects in more detail.
1. Upper respiratory infections
One way JAK inhibitors work is by lowering your immune response. So your immune system may have trouble fighting off infections while you’re taking it.
Upper respiratory tract infections (URTIs) are the most common infections people experience while taking JAK inhibitors. Top examples include the common cold and sinus infections.
Most URTIs are caused by viruses and go away on their own. So you usually won’t need to take an antibiotic. But you can treat your symptoms at home.
With your prescriber’s approval, consider taking over-the-counter (OTC) cold medication to help relieve your symptoms. Getting enough sleep and staying hydrated can also help your body fight off the infection. If it’s been a week or more and your symptoms aren’t going away, let your healthcare team know.
2. Other infections
Other infections are also possible while taking JAK inhibitors. These can include urinary tract infections, oral thrush, and ear infections. You may also be more likely to have a flare-up of herpes simplex virus, the virus that causes cold sores and genital herpes.
More common infections like these can be easily treated with antibiotic, antiviral, or antifungal medications. But you may need to see your prescriber so they can determine which treatment is best for you.
More serious infections, such as shingles and pneumonia, are also possible. But these are rare JAK inhibitor side effects. Your prescriber may ask you to temporarily stop taking your JAK inhibitor if you develop a serious infection.
While taking a JAK inhibitor, watch for symptoms of an infection. Cough, chills, and a fever are symptoms you should let your healthcare team know about right away.
3. Acne
Acne is a common JAK inhibitor side effect, especially if you’re taking it for atopic dermatitis (eczema). The reason for this isn’t clear. But experts believe acne could be caused by the effects JAK inhibitors have on the skin.
Some cases of acne from JAK inhibitors are mild and resolve without treatment. But if your acne isn’t going away or seems excessive, let your prescriber know. They might recommend using a prescription or OTC acne treatment.
4. Nausea
Nausea is another common JAK inhibitor side effect. But it’s often mild and gets better without treatment.
If you find yourself having nausea frequently, there are a few things you can try. Taking your JAK inhibitor with food can help reduce nausea. Also try staying hydrated, eating smaller but more frequent meals, and avoiding spicy or greasy foods. You can also check with your healthcare team about taking an OTC medication for nausea like bismuth subsalicylate (Pepto-Bismol).
5. Headache
You might experience headaches while taking a JAK inhibitor. Mild headaches can usually be handled at home with some simple, medication-free strategies. Exercising regularly, staying well hydrated, and getting enough sleep can all help.
If your headaches are sticking around, try an OTC pain reliever like acetaminophen (Tylenol). But if your symptoms feel severe, don’t hesitate to contact your prescriber. They can suggest next steps for relieving your headache.
6. Anemia
Certain changes to your blood cell counts are possible with JAK inhibitors. Anemia (low red blood cells) is one example. This could contribute to other JAK inhibitor side effects, since symptoms of anemia often include headaches and fatigue.
While you’re taking a JAK inhibitor, your prescriber should routinely check your blood counts. If your lab work starts to look abnormal or concerning, they’ll let you know and may recommend changing, pausing, or stopping your treatment.
7. Raised cholesterol
Some people experience higher cholesterol while taking JAK inhibitors. While your body needs some cholesterol, too much can lead to blood vessel blockages. But experts don’t know for sure whether this JAK inhibitor side effect raises the risk for heart problems.
While you’re taking a JAK inhibitor, your prescriber should check your cholesterol levels regularly. If they believe your JAK inhibitor is affecting your cholesterol, they might ask you to stop taking it. Or they may suggest making lifestyle changes or taking a cholesterol-lowering medication if your JAK inhibitor is working well otherwise.
8. Blood clots and stroke
Blood clots are a potentially serious JAK inhibitor side effect. Blood clots can happen in the legs or arms. But they can also occur in more life-threatening areas, such as the brain (causing a stroke) or lungs (causing a pulmonary embolism).
There are typical symptoms that blood clots cause. Clots in the arms and legs can cause sudden redness, warmth, and pain in the affected area. If you notice any of these symptoms, contact your prescriber right away.
A stroke can cause weakness on one side of the body and slurred speech. And a pulmonary embolism can cause sudden trouble breathing or chest pain. If you experience these symptoms, go to the nearest ER or call 911.
9. Heart attack
Another serious JAK inhibitor side effect is a higher risk of heart attack. This might be caused by blood clots, or it might have other causes. Regardless, it’s a medical emergency that requires immediate attention.
Call 911 or go to the nearest ER if you experience the following symptoms:
Chest pain that lasts more than a few minutes, or goes away and comes back
Pain or discomfort in the upper body, such as the jaw, neck, or arms
Shortness of breath
Your prescriber should consider your heart attack risk before prescribing you a JAK inhibitor. Depending on your risk, they might recommend a different type of medication.
10. Higher risk of cancer
A higher risk of cancer is another rare but serious JAK inhibitor side effect. This includes several cancers such as lung cancer, lymphoma, and skin cancer.
You can use sunscreen and wear protective clothing to help lower your risk of skin cancer. But preventing or identifying other cancers is less straightforward. Your prescriber should account for your personal risk for cancer when prescribing a JAK inhibitor. And they may ask you to change or stop treatment if your risk increases during treatment.
The bottom line
Common Janus kinase (JAK) inhibitor side effects include headache, nausea, and acne. Other common side effects include mild infections like upper respiratory tract infections, urinary tract infections, and ear infections.
Heart attack or stroke, blood clots, and a higher cancer risk are among the most serious JAK inhibitor side effects. But these are rare. Your healthcare team can help you prevent or manage potential JAK inhibitor side effects.
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References
American Heart Association. (n.d.). Warning signs of a heart attack.
Centers for Disease Control and Prevention. (2023). Know the signs and symptoms of infection.
Clarke, B., et al. (2021). The safety of JAK-1 inhibitors. Rheumatology.
Gladman, D. D., et al. (2019). Changes in lipid levels and incidence of cardiovascular events following tofacitinib treatment in patients with psoriatic arthritis: A pooled analysis across phase III and long-term extension studies. Arthritis Care & Research.
Hoisnard, L., et al. (2022). Adverse events associated with JAK inhibitors in 126,815 reports from the WHO pharmacovigilance database. Scientific Reports.
Lee, S. D., et al. (2022). A case series of acne following Janus kinase inhibitors in patients with atopic dermatitis. JAAD Case Reports.
Lin, C. M., et al. (2020). Basic mechanisms of JAK inhibition. Mediterranean Journal of Rheumatology.
Song, Y-K., et al. (2022). Potential adverse events reported with the Janus kinase inhibitors approved for the treatment of rheumatoid arthritis using spontaneous reports and online patient reviews. Frontiers in Pharmacology.
U.S. Food and Drug Administration. (2022). FDA requires warnings about increased risk of serious heart-related events, cancer, blood clots, and death for JAK inhibitors that treat certain chronic inflammatory conditions.
