What Are JAK Inhibitors?

Janus kinase (JAK) inhibitors are targeted medicines that block a specific signal in your body. This signal plays an important role in inflammation and other symptoms of atopic dermatitis and other skin conditions. Medicines in this drug class treat atopic dermatitis by interrupting key inflammatory signals that activate immune responses to cause the irritation and itch that comes with this disease.

Which JAK Inhibitors Are Used to Treat Atopic Dermatitis?

JAK inhibitors that are used to treat atopic dermatitis include: 

 

How Do JAK Inhibitors Work?

JAK inhibitors target or block protein enzymes known as Janus kinases or JAKs for short. JAK enzymes play many roles in the body. They are important for cell growth, survival, development, and cell identity. They’re especially important in the immune system. JAK inhibitors are drugs designed to control autoimmune conditions, including atopic dermatitis, through effects on this pathway. 

JAKs include a family of related enzymes. There are four of them:

  • Janus kinase 1 (JAK1)
  • Janus kinase 2 (JAK2)
  • Janus kinase 3 (JAK3)
  • Tyrosine kinase 2 (Tyk2)

These enzymes receive signals that drive inflammation. When you have atopic dermatitis, an excess of substances that drive this inflammatory pathway causes your immune system to overreact. As a result, you get the red, inflamed, and itchy patches that come with this skin condition.

JAK inhibitors work in slightly different ways based on which JAK enzymes they target:

  • Abrocitinib (Cibinqo) targets JAK1
  • Baricitinib (Olumiant) targets JAK1 and JAK2
  • Ruxolitinib  (Opzelura) targets JAK1 and JAK2
  • Upadacitinib (Rinvoq) targets JAK1

Another major difference among JAK inhibitors is where they work. Most of the JAK inhibitors are taken by mouth to work throughout your body. But ruxolitinib (Opzelura) is a topical JAK inhibitor cream that you spread on your skin. 

Words to Know When You Have Atopic Dermatitis infographic

When Are JAK Inhibitors Used to Treat Atopic Dermatitis?

An oral JAK inhibitor may be an option for treating atopic dermatitis that is moderate or severe in adults or kids 12 and up. Your doctor may suggest a JAK inhibitor if other topical or systemic treatments for atopic dermatitis didn’t work or have stopped working. Oral JAK inhibitors come with more risks than other treatment options.

The topical JAK inhibitor ruxolitinib (Opzelura) is approved for people aged 12 and up for mild to moderate atopic dermatitis.

How Do You Take JAK Inhibitors?

You’ll put ruxolitinib (Opzelura) on your affected skin twice each day. 

You’ll take any of the oral JAK inhibitors once a day. Baricitinib (Oluminat) comes in a 2-milligram or 4-milligram tablet. You’ll usually take 4 milligrams each day. You’ll start taking upadacitinib (Rinvoq) at a dose of 15 milligrams once each day. If this starting dose doesn’t work well enough, your doctor may suggest doubling the dose. The recommended dose of abrocitinib (Cibinqo) for moderate-to-severe atopic dermatitis is 100 milligrams. Your doctor may suggest increasing the dose to 200 milligrams if the lower dose doesn’t give you relief.

Ask your doctor what you should do if you miss a dose or don’t take it on time. In general, if you've missed a dose, you should wait until your next dose. You shouldn’t take more than the recommended dose.

You can take JAK inhibitors along with other standard treatments for atopic dermatitis such as topical steroids, moisturizers, and emollients.

 

How Long Do You Take JAK Inhibitors?

You can use ruxolitinib (Opzelura) regularly for up to eight weeks. You also may use it for longer if you’re using it less often.

Oral JAK inhibitors are medicines that you’d keep taking. You wouldn’t plan to stop taking them after a set period. If you’re taking a JAK inhibitor for the first time, your doctor may want to see you after eight weeks to see how well it’s working. If it isn’t working after a few months, they may consider adjusting the dose or switching to another treatment option.

How Effective Are JAK Inhibitors?

Evidence about how well medicines including JAK inhibitors work comes from studies of participants in clinical trials. They can give you an idea how well these medicines work. But everyone is different, and your experience may differ.

To measure how well a treatment for atopic dermatitis is working, researchers use different tools including the Investigator Global Assessment (IGA) and the Eczema Area and Severity Index (EASI)-75. These rate the severity at a set time and improvement with treatment.

Four-month Rinvoq study

Thirty-eight percent to 48% of people who took 15 milligrams of Rinvoq daily for 16 weeks had an IGA score of clear to almost clear skin. Those who took 30 milligrams showed an even better response with 53% to 62% having clear to almost clear skin. That’s compared to 4% to 8% for people treated with a placebo.

Sixty percent to 70% of those taking 15 milligrams also had 75% improvement after 16 weeks. Seventy-three percent to 80% of those taking 30 milligrams had a 75% improvement. For those taking a placebo, 13% to 16% showed that much improvement.

Forty percent to 60% of those taking Rinvoq also reported less itching as early as the second day. The medicine also led to lower skin pain ratings and better sleep quality along with improved quality of life and lower depression and anxiety.

Three-month Cibinqo study

Twenty-four percent to 28% of people taking 100 milligrams of Cinqo had an IGA score of clear to almost clear skin compared to 8% to 9% for those taking a placebo. Thirty-eight percent to 44% of those taking 200 milligrams had an IGA score of clear to almost clear.

Forty percent to 45% of those taking 100 milligrams and 61% to 63% of those taking 200 milligrams also showed an EASI-75 score indicating 75% improvement from the start of the trial. That’s compared to 10% to 12% for those taking a placebo.

Thirty-eight percent to 45% taking 100 milligrams and 55% to 57% of those taking 200 milligrams reached the goals in itch reduction. It also led to improvements in nighttime itch.

Four-month Olumiant study

Forty-six percent of people taking Olumiant for 16 weeks had an IGA score of clear to almost clear skin.

Seventy percent of people taking Oluminant reached EASI-75 indicating a 75% improvement in atopic dermatitis. 

Fifty-three percent reached the study goal in itch improvement.

Two-month Opzelura study

Fifty-one percent to 54% of those using Opzelura for eight weeks continuously had clear to almost clear skin compared to 8% of those using a placebo.

Sixty-two percent of those using Opzelura achieved EASI-75, indicating at least a 75% improvement.

About 50% had reduced itch severity as soon as 12 hours after the first use.

Twenty-two percent to 25% had improved sleep quality.

Are JAK Inhibitors Safe?

JAK inhibitors are safe enough to use, but they do come with risks. Because oral JAK inhibitors target the immune system, they can come with more risk for infections. Your ability to fight infections should come back if you stop taking them.

Topical JAK inhibitors are generally safe to use as prescribed. But they may come with more risk for skin cancer or infections.

What Are the Common Side Effects of JAK Inhibitors?

Some common side effects of JAK inhibitors include:

  • Colds
  • Bronchitis
  • Ear infection
  • Urinary tract infections
  • Headache
  • Nausea

More rarely, people have had more serious side effects, including:

  • Blood clots
  • Pneumonia
  • Tuberculosis

Oral JAK inhibitors come with a black box warning that they may cause:

  • Serious infections, leading to hospitalization
  • Mortality
  • Cancer, including lymphoma and lung cancer
  • Major heart events
  • Blood clots

It can be scary to start a new medicine. Ask your doctor about any questions you have and share your concerns. Ask your doctor about which side effects you should watch for, when to call, and whether you have any special concerns based on your general health.

Who Should Not Take JAK Inhibitors?

Ask your doctor if a JAK inhibitor could help you if other treatments for atopic dermatitis aren’t working. You shouldn’t take a new JAK inhibitor if you are:

  • Already taking a JAK inhibitor
  • Are taking a biologic
  • Are taking immunosuppressants such as oral steroids

You also shouldn’t take a JAK inhibitor if you are:

  • Allergic or hypersensitive to them
  • Have an active, serious infection
  • Have perforations in your digestive or gastrointestinal (GI) tract
  • Have abnormal blood test results, such as changes in blood counts, liver enzymes, or lipids
  • Are pregnant or want to get pregnant
  • Are breastfeeding
  • Have severe liver damage

How Much Do JAK Inhibitors Cost?

Oral JAK inhibitors are costly medications. Their list price can be tens of thousands of dollars. The amount that any particular medicine will cost you out-of-pocket will depend on your health insurance plan and prescription coverage. It’s always a good idea to check with your insurance plan first to see which treatments they’ll cover and if you need a preauthorization. 

If costs are a concern, ask your doctor about financial assistance programs that may be available through the drug companies. You may be eligible for a copay assistance program that offers qualified insured people a cost as little as $0.

The list price for a tube of Opzelura is about $2,000. However, your cost will depend on your insurance coverage and whether you are eligible for a copay savings program from the company.

Clinical Trials of JAK Inhibitors for Atopic Dermatitis

Studies to understand the long-term effects of approved and new JAK inhibitors are underway. Some studies are looking at JAK inhibitors in combination or to see how they work in people of different age groups. For example, another topical JAK inhibitor, called delgocitinib, is used in other countries. It’s also under review for treating chronic hand eczema in the U.S. Other JAK inhibitors are in development, so you should expect the list of JAK inhibitors for atopic dermatitis to grow.

If you’re interested in participating in a clinical trial or exploring those that may be ongoing near you, visit ClinicalTrials.gov. Search for trials of JAK inhibitors for atopic dermatitis. You can focus your search based on:

  • Where you live
  • Whether it’s enrolling
  • Sex
  • Age
  • Study phase
  • Study type

How Long Have Oral JAK Inhibitors Been Used to Treat Atopic Dermatitis? 

The FDA approved the first two oral JAK inhibitors, abrocitinib and upadacitinib, for moderate-to-severe atopic dermatitis in 2022.

Can Children Take JAK Inhibitors for Atopic Dermatitis? 

JAK inhibitors aren’t approved for very young children. But kids aged 12 and up may be able to take them if their atopic dermatitis is more severe and other treatments aren’t working.

Is a JAK Inhibitor Right for Me? 

You’ll have lots of options to treat atopic dermatitis today. While that’s a good thing, it can make it harder to make treatment decisions. This recap of key factors to consider may help you in talking with your doctor and deciding together on a treatment plan and what to do next.

Your current treatment. An oral JAK inhibitor won’t be the first treatment you’ll try for atopic dermatitis that’s moderate to severe. If you’re taking other medicines or using topicals and aren’t getting relief, ask your doctor if it’s time to think about a JAK inhibitor.

Your disease severity. Oral JAK inhibitors are reserved for atopic dermatitis that’s moderate or severe and resistant to other treatment options. If your atopic dermatitis is more mild and not responding to other topicals, you may be a good candidate for Opzelura, which is a topical JAK inhibitor.

How you’ll take your medicine. Most JAK inhibitors are pills you’ll take once a day. Other treatment options for more severe atopic dermatitis are biologics that you’d have injected or infused. These differences may be something to consider when you’re making treatment decisions since it’s important to select a treatment plan that you can stick with. One reason atopic dermatitis treatments sometimes don’t work as well as they should is that people find them hard to continue long term.

Treatment side effects. JAK inhibitors are generally considered to be safe for treating moderate-to-severe atopic dermatitis. But they do come with a risk for potentially serious infections and other side effects. Oral JAK inhibitors come with a black box warning about potentially serious risks for infections, cancer, blood clots, or heart problems. Talk to your doctor about these risks to help you think through any concerns you have.

Cost. JAK inhibitors are costly medications. But your out-of-pocket costs will depend on your health insurance plan and what it will cover. Make sure you understand what your costs will be and whether you may be eligible for financial assistance before you begin a new treatment for your atopic dermatitis.

Show Sources

SOURCES:

The Journal of Allergy and Clinical Immunology: “JAK inhibitors in the treatment of atopic dermatitis.”

Immunological Reviews: “Janus kinases in immune cell signaling.”

National Eczema Society: “Abrocitinib,” “Baricitinib,” “Upadacitinib,” “Ruxolitinib,” “FDA Accepts LEO Pharma’s Filing of Delgocitinib Cream New Drug Application for the Treatment of Chronic Hand Eczema.”

American Academy of Dermatology Association: “Eczema types: Atopic dermatitis diagnosis and treatment,” “JAK inhibitors: What your dermatologist wants you to know.”

accessdata.fda.gov: “Rinvoq.”

JAMA Dermatology: “Long-term Efficacy of Baricitinib in Adults With Moderate to Severe Atopic Dermatitis Who Were Treatment Responders or Partial Responders: An Extension Study of 2 Randomized Clinical Trials.”

Journal of the American Academy of Dermatology: “Long-term safety and disease control with ruxolitinib cream in atopic dermatitis: Results from two phase 3 studies.”

Journal of Managed Care & Specialty Pharmacy: “JAK inhibitors and monoclonal antibodies for the treatment of atopic dermatitis: effectiveness and value.”

Pharmaceutics: “A Comprehensive Overview of Globally Approved JAK Inhibitors.”

Mayo Clinic: “Baricitinib (oral route).”

British Journal of Dermatology: “A practical guide to using oral Janus kinase inhibitors for atopic dermatitis from the International Eczema Council.”