Patients with mild to moderate AD have a new topical treatment option, but physicians will need to prepare for some focused conversations about safety.
A new topical Janus kinase (JAK) inhibitor approved by the FDA September 21, 2021 to treat atopic dermatitis (AD) may be “the most exciting topical I’ve seen in 20 years,” according to Matthew Zirwas, MD. But, like any novel drug, this first-in-class cream, ruxolitinib (Opzelura, Incyte Corporation), requires some fresh thinking about diagnosis, treatment plans, and addressing patients’ safety concerns.
Zirwas, who is the director at the Clinical Trials and Dermatology Center in Bexley, Ohio, offered recommendations for optimizing the first and only topical JAK inhibitor approved in the United States as part of his presentation on AD sponsored by Incyte at Maui Derm NP+PA Fall 2021, held live September 30 to October 2, 2021, in Asheville, North Carolina, and virtually.1
Know the Ground Rules
The FDA was very specific about the parameters of its approval. That started with the caveat that Opzelura cream is “for the short-term and non-continuous chronic treatment of mild to moderate atopic dermatitis (AD)….”
Zirwas parsed those fundamentals into some key considerations. “It used to be that mild to moderate AD was defined by an Eczema Area and Severity Index (EASI) score of 1 to 8, but I would say mild disease is one you would never treat systemically and moderate disease could go either way—topicals or systemic drugs,” he said. “For severe cases, topicals won’t work.”
Then there is the issue of duration. According to Zirwas, “short term” typically would cover 8 weeks of continuous use of the topical cream. “Opzelura should not be used continuously,” he recommended. “Dosing should be twice daily, but when the patient begins to see improvement, they may be able to go down to once each day. Treatment should be stopped as soon as the patient is clear or almost clear. It can be restarted if the patient relapses.”
In terms of patient eligibility, the FDA noted the cream is approved for “non-immunocompromised patients 12 years of age and older whose disease is not adequately controlled with topical prescription therapies, or when those therapies are not advisable.”
“It’s great that the approval goes down to 12 years,” said Zirwas. “Statistically, AD is twice as common in kids as adults. But that doesn’t reflect the fact that there are 4 times as many adults as kids. So, we should be thinking of AD as an adult disease. Studies have shown that 2 to 3% of adults have psoriasis while 7% have AD. That’s up to 3 times as many people with AD as with psoriasis, and that number is expected to continue to rise. Consider that 90% have mild to moderate AD.”
In his view, the possible patient population with AD maybe even broader than it appears. “Some physicians tell me they don’t see many patients with AD, but that can be a misconception,” he said. “If physicians would use the American Academy of Dermatology (AAD) validated consensus criteria, they would find a lot of what is termed an ‘unspecified’ skin condition is really AD.”
The diagnosis should be AD if the condition is spongiotic, gritty, itchy, and/or spares groin and axillary regions, said Zirwas. He also pointed out that AD can be difficult to diagnose in skin of color, as there may not be any redness.
Explore a New Approach
AD has long been a challenge to treat. As Zirwas noted, some patients do not respond well to existing treatments and have uncontrolled disease as a result. “Many patients have steroid phobia. They don’t want steroids; won’t use steroids. So, that becomes a major compliance issue,” he added.
Opzelura’s mechanism of action sets it apart since it binds with and inhibits interleukins such as IL-17 and IL-23. Recent research showed that blocking the dysregulation of the JAK-STAT pathway could address some of AD’s most persistent issues: itch, inflammation and skin barrier dysfunction.2
Results of 2 randomized, double-blind, vehicle-controlled phase 3 studies (TRuE-AD1 and TRuE-AD 2) of more than 1200 adolescents and adults achieved Investigator’s Global Assessment (IGA) Treatment Success (IGA-TS, primary endpoint) at Week 8 (defined as an IGA score of 0 [clear] or 1 [almost clear] with at least a 2-point improvement from baseline): 53.8% in TRuE-AD1 and 51.3% in TRuE-AD2, compared to vehicle (15.1% in TRuE-AD1, 7.6% in TRuE-AD2; P<0.0001), according to a company press release.
Opzelura also helped to reduce itch, Investigator’s Global Assessment (IGA) Treatment Success (IGA-TS, primary endpoint) at week 8 (defined as an IGA score of 0 [clear] or 1 [almost clear] with at least a 2-point improvement from baseline): 53.8% in TRuE-AD1 and 51.3% in TRuE-AD2, compared to vehicle (15.1% in TRuE-AD1, 7.6% in TRuE-AD2; P<0.0001), added the press statement.
Zirwas pointed out that this topical JAK inhibitor has other upsides. It is non-steroidal, non-greasy, and can be used on sensitive skin, skin of color, and on skin anywhere on the body. Based on clinical trial results, it does not cause skin atrophy, thinning of the skin, burning or stinging. Equally importantly, he added, the efficacy of outcomes on the face and hand addresses 2 of the areas that have proven the most challenging to treat successfully.
Be Proactive When Discussing Risks
The cream will carry a black box warning label listing risks of serious infections, increased risk of heart attack, stroke, or cardiac death. It’s important to make sure patients are aware before they fill the prescription that the warning will be on the packaging, said Zirwas.
“Whenever I prescribe this, I will explain the risks of this medication whenever drugs like this taken as orally as a pill,” said Zirwas. The review upon which the black box warnings are based examined tofacitinib (Xeljanz, Pfizer). A similar review has not yet been done on a topical JAK inhibitor. Zirwas doesn’t rule out some absorption of a topical, but points out it would be much less than the oral medication these safety warnings are based on.
Zirwas, however, does list several contraindications. “Avoid use in patients with active serious infections, including local infections. Don’t start patients with active impetigo on Opzelura and stop in case of eruption. I wouldn’t test for hepatitis B and C, but if it’s in the patient’s history, I wouldn’t prescribe.” He also wouldn’t test for tuberculosis. If the patient was exhibiting signs and symptoms of TB such as fever or coughing, he would test. He wouldn’t prescribe Opzelura to a patient who was breastfeeding. Any physician considering prescribing Opzelura to a pregnant patient should consult the patient’s obstetrician. “I wouldn’t prescribe a glass of water to a pregnant patient without consulting an obstetrician.”
Some increases in squamous cell were noted, says Zirwas, but no dramatic increases. But if a patient had basal cell carcinoma, he would monitor them much more closely.
He also noted that cost may be an obstacle.
Zirwas was compensated by Inctye Corporation.
1. Zirwas M. Atopic Dermatitis: The burden of disease and the JAK-STAT pathway. Presented at Maui Derm NP+PA Fall 2021; September 30 - October 2, 2021, live in Asheville, North Carolina, and virtual.
2. Bao L, et al. JAK-STAT. 2013;2(3):e24137. doi:10.4161/jkst.24137.