What Are JAK Inhibitors?
Janus kinase (JAK) inhibitors are medicines that block signals in your body that cause inflammation. They treat moderate to severe psoriasis by calming the immune system and reducing the inflammation that causes plaques to form on your skin.
How Do JAK Inhibitors Work?
Janus kinases are enzymes – proteins that speed up chemical reactions in the body. Four enzymes are in the Janus kinase group:
- Janus kinase 1 (JAK1)
- Janus kinase 2 (JAK2)
- Janus kinase 3 (JAK3)
- Tyrosine kinase 2 (TYK2)
These enzymes are involved in the signals that cause inflammation. In psoriasis, there is too much inflammation in the body. An overactive immune system leads to the production of too many skin cells. The extra cells build up on the surface of the skin and create lesions called plaques.
Each of the two JAK inhibitors targets a different enzyme:
- Sotyktu targets the TYK2 enzyme
- Xeljanz targets the JAK1 enzyme
What JAK Inhibitors Are Used to Treat Psoriasis?
There are two JAK inhibitors that may be used to treat plaque psoriasis.
Deucravacitinib (Sotyktu) is a tyrosine kinase 2 (TYK2) inhibitor approved to treat moderate to severe psoriasis. This protein is related to those in the JAK family, but this medication does not block the pathways of JAK1, JAK2, or JAK3.
Tofacitinib (Xeljanz) is not approved for plaque psoriasis, but rarely, doctors may prescribe it off-label.
When Are JAK Inhibitors Prescribed for Psoriasis?
Sotyktu is approved to treat adults with moderate to severe plaque psoriasis who are candidates for body-wide treatments (like biologic drugs) or phototherapy.
Xeljanz is approved for adults with active psoriatic arthritis who haven't improved enough on another type of DMARD called a tumor necrosis factor (TNF) blocker. It is not approved to treat plaque psoriasis. Studies have shown that at the dosage recommended for plaque psoriasis, the drug is linked to a greater risk of pulmonary embolism (a blood clot that blocks blood flow to the lungs) and death.
How Do You Take JAK Inhibitors?
JAK inhibitors come as tablets that you take by mouth. The recommended dose of Sotyktu is 6 milligrams (mg) once a day. You can take the tablet with or without food.
Xeljanz comes in 5 mg and 10 mg tablets. Doctors prescribe either 5 mg or 10 mg twice a day. Xeljanz also comes in an extended-release version called Xeljanz XR. You take it once a day, and the medicine releases more slowly into your body.
How Effective Are JAK Inhibitors?
Researchers use different measures to see how effective medicines like JAK inhibitors are at clearing psoriasis plaques in studies:
Most people continued to see clearer skin for 2 years. In other studies, Xeljanz improved pain and swelling from psoriatic arthritis.
What Are Common Side Effects of JAK Inhibitors?
Upper respiratory tract infections are the most common side effect of JAK inhibitors. Because these medicines suppress your immune system, they can make you more likely to get infections like colds, sinus infections, laryngitis, pneumonia, or tonsillitis. Tell your doctor if you have any new symptoms like a fever, chills, a sore throat, or night sweats.
Other common side effects of JAK inhibitors include:
- Diarrhea
- Headache
- Mouth sores
To manage diarrhea, drink extra fluids and eat bland foods. To relieve a headache, you might take an over-the-counter pain reliever such as ibuprofen or acetaminophen. If you have these or any other side effects from your medicine, ask your doctor the best way to manage them.
Are JAK Inhibitors Safe?
These medicines do have risks, some of which can be serious.
Xeljanz carries a Boxed Warning, which is the most serious warning a drug can have. The warning is for possible but rare risks such as serious infections, cancer, blood clots, and heart problems like a heart attack or stroke.
Infections. JAK inhibitors calm down your immune system, which could put you at slightly higher risk of infections like these:
- Pneumonia
- COVID-19
- Cellulitis, a skin infection
- Shingles
- Urinary tract infections
- Appendicitis
- Tuberculosis
Because JAK inhibitors lower your immune system response, they can increase your risk of getting sick from a live vaccine. Avoid these vaccines while you're on a JAK inhibitor:
- Chickenpox
- Measles, mumps, rubella (MMR)
- Rotavirus
- Smallpox
- Yellow fever
Your doctor will test you for tuberculosis, hepatitis, and HIV before you start taking a JAK inhibitor. If you test positive, you'll get medicine to treat the infection.
If you had shingles, herpes, or hepatitis B in the past, this medicine might "wake up" the virus and restart the infection. Ask your doctor if you should get the shingles or hepatitis B vaccine before you start taking a JAK inhibitor.
Cancer. Rarely, people who take JAK inhibitors have developed cancers such as lymphoma or non-melanoma skin cancer. Tell your doctor before you start this medicine if you have cancer or you're at a higher risk of it.
Heart problems and blood clots. In studies of Xeljanz to treat rheumatoid arthritis, the drug slightly increased the risk of a heart attack, stroke, or of dying from heart disease. That increased risk was only in people ages 50 and older who were already at a higher risk of heart problems because of other factors. Rarely, people who took Xeljanz developed deep vein thrombosis (DVT) or other blood clots. Some clots were life-threatening.
Allergic reactions. JAK inhibitors can cause a reaction in people who are allergic to them. Stop taking the medicine right away and call your doctor if you have symptoms like swelling or hives.
Other risks from these medicines include:
- Muscle damage called rhabdomyolysis
- High levels of triglycerides or low-density lipoprotein (LDL) cholesterol in the blood
- Liver damage
- Lower than normal levels of red and white blood cells
- A hole in the digestive tract, called a gastrointestinal perforation
Before you start on a JAK inhibitor, you'll also have blood tests to check your:
- Red blood cell and white blood cell counts
- Liver and kidney function
- Cholesterol levels
Avoid these medicines if you:
- Are allergic to any of the ingredients in them
- Have severe liver damage
- Have an active infection
It may not be safe for you to take a JAK inhibitor if you:
- Have an infection that doesn't go away or that keeps coming back
- Have been exposed to tuberculosis
- Have a condition like chronic lung disease or diabetes that increases your risk of infections
- Have had a heart attack or stroke
- Have liver or kidney disease
There isn't enough research to show whether JAK inhibitors are safe to take during pregnancy or while breastfeeding. If you are pregnant or you want to become pregnant, talk to your doctor before starting one of these medicines.
How Much Do JAK Inhibitors Cost?
Costs for both of these drugs can vary, depending on which pharmacy you use, but are typically several thousand dollars for a 30-day supply.
If you're uninsured and you need help paying for your medication, organizations like NeedyMeds may be able to help. Or you might qualify for Medicaid.
The company that makes Sotyktu offers a copay assistance program. People who are insured may pay as little as $0 a month with the assistance card. If you don't have insurance, a support coordinator can talk you through your savings options.
Xeljanz also offers a copay assistance program where qualified people with insurance coverage can pay as little as $0 per month. The company also has a service called Xelsource to help you understand your insurance benefits and out-of-pocket costs.
Clinical Trials of JAK Inhibitors for Psoriasis
Studies are looking at the safety and effectiveness of already-approved JAK inhibitors and new drugs in this class.
Some clinical trials compare JAK inhibitors with each other. Other studies compare JAK inhibitors to drugs in other classes to see which work better for psoriasis.
You can visit ClinicalTrials.gov to search for studies in your area or in other parts of the country. When you click on a study, you can see:
- Information about the trial and what it's studying
- Whether the study is still enrolling
- Where it's located
- What criteria you must meet to qualify
Your psoriasis doctor is also a source of information on clinical trials of JAK inhibitors and other medications. Your doctor may know about studies happening near you, and whether you're a good candidate for them.
Is a JAK Inhibitor for Psoriasis Right for Me?
Choosing your treatment plan for plaque psoriasis can be a challenge at times. This recap of the key criteria will help as you talk to your doctor to decide on your next steps.
Prior Treatments: If you're an adult with moderate to severe plaque psoriasis who are candidates for body-wide treatments (like biologic drugs) or phototherapy, Sotyktu may be a good choice for you. If you have plaque psoriasis and active psoriatic arthritis, and haven't gotten better on a tumor necrosis factor (TNF) blocker, Xeljanz may be right for you. It does have a risk of serious side effects, so talk to your doctor before you make your decision.
How You'll Take Your Medicine: Both types of JAK inhibitor are available as pills you take by mouth. This may make them an option to think about if you need a medication that's convenient for you to take yourself.
Potential Side Effects: Most of the possible side effects of JAK inhibitors are mild. They include respiratory infections, headache, nausea, and diarrhea. Talk to your doctor if you need help to manage these until they go away. JAK inhibitors affect your immune system, which could put you at slightly higher risk of several types of infections. Xeljanz carries a Boxed Warning -- the most serious warning a drug can have -- for rare but possible risks such as serious infections, cancer, blood clots, and heart problems.
Costs: The price of your medication may be an important factor in your treatment decision. You'll want to understand all your possible out-of-pocket costs for this type of medication. Look into all the payment assistance programs that may be available to you.
Medical History and Related Conditions: JAK inhibitors aren't right for everyone, including people who have liver or kidney damage, have had a heart attack or stroke, or have other conditions that raise their chance of infections.
If you have psoriatic arthritis and Treatment with TNF inhibitors hasn't helped, tofacitinib (Xeljanz) may be an option for you.
Take time to review all your treatment options and talk them over with your doctor so you can make the right decision about whether to use JAK inhibitors as part of your plaque psoriasis treatment plan.