3 FDA-Approved Eczema Therapies Seen as ‘Game-Changing’

in Features, Indoor Allergies, Skin Allergy
Published: January 27, 2022

Adult and teen eczema sufferers now have three newer medications to treat the condition that causes painfully itchy, red, inflamed skin. The medications – one medicated cream and two pills – are in a class of drugs known as Janus kinase (JAK) inhibitors. In early 2022, they won U.S. Food and Drug Administration approval for use in eczema for the first time.

Phase 3 clinical trials show that these medications significantly improved eczema, even in many patients with severe disease. Leading physicians in the field of atopic dermatitis call these drugs the most significant advances in eczema treatment in decades.  

“For the appropriate patient, these medications will be game-changing,” says Dr. Peter Lio, a clinical assistant professor of dermatology and pediatrics at Northwestern University’s Feinberg School of Medicine in Chicago. “I’ve been focused on atopic dermatitis for more than a decade, and we have never seen anything like this.” 

Although all three medications are JAK inhibitors, there are significant differences among them.

JAKs and Eczema Relief

The first to win FDA approval, ruxolitinib (the brand Opzelura), is a topical cream for mild to moderate eczema. The approval was based on the results of two Phase 3 trials in more than 1,200 teens and adults. After eight weeks of using the cream twice daily, from 51 to 54 percent in the treatment group had clear or almost clear skin, compared to fewer than 15 percent in the non-medicated (placebo) group.

Dr. Emma Guttman-Yassky

The two daily pills – abrocitinib (the brand Cibinqo) and upadacitinib (Rinvoq) – are for patients with moderate to severe eczema. Because of the potential for side effects, the FDA says the medications should be reserved for those who have tried other oral or injectable eczema medications, but are not getting enough relief.

In two large Phase 3 trials for upadacitinib, as many as 80 percent of patients with moderate to severe eczema saw their symptoms improve by at least 75 percent after four months.  

Dr. Emma Guttman-Yassky, a professor of dermatology at Mount Sinai’s Icahn School of Medicine in New York City, says the oral JAK inhibitors work quickly, with some of her patients on upadacitinib finding itch relief starting within hours. By four weeks, a majority saw significant improvement in itch and there were also strong results in skin clearing.    

“We have patients with wounds all over the body who are completely clearing,” says Guttman-Yassky, the primary investigator on the upadacitinib trials. “This is super meaningful to the patients.”

How do JAK Inhibitors Work?

Janus kinases belong to a family of enzymes, which includes JAK1, JAK2, JAK3 and TYK2, that are part of the immune messaging cascade involving cytokines. Cytokines, which bind to cell receptors, are signaling molecules that orchestrate inflammation and itch in atopic dermatitis. JAK inhibitors block the action of the enzymes, resulting in decreased inflammation and eczema symptoms.

Other JAK inhibitors have been used for years to treat autoimmune and inflammatory diseases such as rheumatoid arthritis and ulcerative colitis. But this is the first time the medications have been approved for use in eczema.

How Are JAK Inhibitors Used?

The first line of treatment for eczema, which affects over 30 million Americans, remains moisturizers and topical corticosteroids. For many people, these are enough to relieve symptoms, Lio says. “Steroids are really reliable. They are very effective and most people are going to get better using them.” Lio, who runs an eczema clinic in Chicago, says the problem with steroid creams is that they have too many side effects for consistent, long-term use.

While many children will outgrow eczema or have less severe symptoms over time, some teens and adults continue to struggle with eczema’s itch, rash and misery. It’s this group that the JAK inhibitors will be used for, the dermatologist explains.

Ruxolitinib, the JAK inhibitor skin cream, can be used in patients who need something other than a topical steroid, but whose eczema isn’t bad enough to require an oral medication. The approval for ruxolitinib, which blocks JAK 1 and JAK 2, is for short-term use in those with mild to moderate eczema ages 12 and up, who are not getting relief from other topical medications.

The trial data for ruxolitinib suggest “it is fairly powerful and could potentially be the next step after steroids,” says Lio. “Or, in certain patients or certain areas of the body, it could even supplant primary use of topical steroids.”  

Guttman-Yassky says she’s also trying the topical JAK inhibitor in patients with more severe eczema who are doing well on other oral medications or injectables such as dupilumab (Dupixent). But such patients may still have a few hot spots.

“I usually give it for sensitive areas like the face or the folds, or in people who have a few residual areas” that aren’t responding to another treatment, she says.

Stepping Up to JAK Inhibitor Pills

As more potent drugs, the oral JAK inhibitors abrocitinib and upadacitinib are for patients with more severe or extensive eczema, who have already tried a “systemic” eczema medication. These include pills such as the oral steroid prednisone, oral immunosupressants such as cyclosporin, the injectable biologic drug dupilumab, or phototherapy.

“The oral JAK inhibitors’ efficacy is among the most impressive I’ve ever seen,” says Lio. “Although as one might expect, this power does not come without the potential for side effects.”

And while there are similarities between abrocitinib and upadacitinib in that they act on the JAK pathways, “these medications are not interchangeable,” says Dr. Jonathan Silverberg, an associate professor of dermatology at George Washington University School of Medicine and Health Sciences.  

“No two JAK inhibitors are exactly alike,” says Silverberg, a lead author on one of the main abrocitinib studies. “Part of the excitement is to start using them and to gain more insight into where those differentiations are.”

Upadacitinib (Rinvoq)

Upadacitinib, from the drug maker AbbVie, was already in use to treat arthritis. The FDA now approved the medicine for moderate to severe atopic dermatitis in patients whose disease isn’t well controlled by other pills or injections, or when other treatments aren’t advised. The approved age range is 12 and older.

The dosage is a once-a-day, 15-mg pill that can be increased to 30 mg if needed.

The approval is based on three, Phase 3 trials involving more than 2,500 patients. The two main trials, Measure Up 1 and 2, found that after 16 weeks of taking upadacitinib, up to 70 percent of patients on the 15-milligram (mg) dose and 80 percent of patients on the 30-mg dose saw a significant improvement in eczema symptoms.  

Abrocitinib (Cibinqo)

Abrocitinib (Cibinqo), made by Pfizer, is a brand new drug. It’s also a once-a-day pill that blocks JAK1 and is for patients with moderate to severe eczema whose condition isn’t controlled by other oral or injectable eczema medications.

Dr. Peter Lio and Dr. Jonathan Silverberg

The recommended doses are 100 mg, or 200 mg for those not getting enough relief from the 100-mg dose. However, the approval is only for adults ages 18 and up as of now. According to Pfizer, the medication will be available in the next few weeks.

“I hope Pfizer will get the approval for adolescents. Both of them are excellent drugs and it’s nice we have two of them,” Guttman-Yassky says.

The approval was based on results of several clinical trials of more than 1,600 patients. In the JADE MONO 2 trial, after 12 weeks on abrocitinib, 44 percent of patients on the 100-mg dose and 61 percent on the 200-mg dose showed at least a 75 percent reduction in eczema symptoms, compared to 12 percent on a placebo.

Note: The upadacitinib trial ended at 16 weeks, while the Pfizer trial ended at 12 weeks, so they are not directly comparable.  

Black Box Warning

In September 2021, the FDA called for additional warning labels to be placed on all JAK inhibitors. The label warns that the drugs are associated with an increased risk of serious infections, heart attack, stroke, cancer, blood clots and death.

This came after a safety review of tofacitinib (Xeljanz and Xeljanz XR), which are prescribed in treating serious forms of arthritis and ulcerative colitis. Although tofacitinib is not used to treat eczema, the FDA reasoned that since other JAK inhibitors “share mechanisms of action with Xeljanz, FDA considers that these medicines may have similar risks.”  

To monitor for safety, eczema patients on oral JAK inhibitors will need to have a blood test before they start taking the drugs to measure their baseline levels of white and red blood cells, platelets and liver enzymes. Patients are expected to need periodic follow-up tests.

Blood tests won’t be needed for ruxolitinib, since it’s a topical JAK inhibitor and far less of the drug gets absorbed into the bloodstream.

In the clinical trials for the oral JAK inhibitors, the most frequent side effects included acne, nasal congestion, sore throat, headache or nausea. (Side effects differed slightly between the pills.) Guttman-Yassky says longer-term safety studies are ongoing.

A Fourth New Eczema Drug

In addition to the three JAK inhibitors, the FDA also recently approved tralokinumab (the brand Adbry), an injectable biologic medication for adults with moderate to severe atopic dermatitis.

Tralokinumab is the second biologic medication approved for treating eczema, the first being dupilumab. The new biologic is available for adults.

Julie Block, executive director of the National Eczema Association, said having so many options is important, because people with eczema often have to try different approaches before they find something that brings them relief. 

“There is a need for multiple treatments as there is no one-size-fits-all approach when it comes to atopic dermatitis,” says Block. “It’s a chronic, heterogenous disease that affects everyone differently.”

Silverberg says: “This is the Golden Age of atopic dermatitis. We have all these new options, and more are coming. So many patents have gone their entire life without hope about this disease. They are suffering in silence and have given up hope on a good degree of control. It’s such an exciting time – knowing that finally there are new options available.”

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