What patients need to know about the new topical inhibitor JAK
A new topical Janus kinase (JAK) inhibitor approved by the FDA on Sept. 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 new drug, this first-class cream, ruxolitinib (Opzelura, Incyte Corporation), requires new thinking about diagnosis, treatment plans, and response to patient safety concerns.
Zirwas, director of the Clinical Trials and Dermatology Center in Bexley, Ohio, offered recommendations for optimizing the first and only topical JAK inhibitor approved in the US as part of his Incyte-sponsored AD presentation at Maui Derm NP + PA Fall 2021, live from September 30 to October 2, 2021 in Asheville, NC, and virtually.1
Know the basic rules
The FDA has been very specific on the parameters of its approval. It started with the warning that Opzelura cream is “for the short-term, non-continuous chronic treatment of mild to moderate atopic dermatitis (AD)…”.
Zirwas has analyzed these fundamental principles into a few key considerations. “Previously, 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 that you would never treat systemically. and that moderate illness could go either way – topical or systemic medication, ”he said.“ For severe cases, topicals won’t work. ”
Then there is the question of duration. According to Zirwas, “short term” would typically cover 8 weeks of continuous topical cream use. “Opzelura should not be used continuously,” he recommended. “The dosage should be twice a day, but when the patient starts to see improvement, he may be able to go down to once a day. Treatment should be stopped as soon as the patient is cured or almost cured. It can be resumed if the patient relapses.
In terms of patient eligibility, the FDA noted that the cream is approved for “non-immunocompromised patients 12 years of age and older whose disease is not adequately controlled by prescription topical therapies, or when these therapies are not adequately controlled. are not recommended “.
“It’s great that the approval goes down to 12,” Zirwas said. “Statistically, AD is twice as common in children as in adults. But this does not reflect the fact that there are 4 times more adults than children. So we should consider AD as an adult disease. Studies have shown that 2-3% of adults suffer from psoriasis while 7% have AD. That’s up to 3 times more people with AD than psoriasis, and the number is expected to continue to increase. Consider that 90% have mild to moderate AD.
In his opinion, the possible population of AD patients may be even larger than it appears. “Some doctors tell me they don’t see a lot of AD patients, but that can be a misconception,” he said. “If physicians used the validated American Academy of Dermatology (AAD) consensus criteria, they would find that much of what is called an ‘unspecified’ skin condition is actually AD. “
The diagnosis should be AD if the disease is spongiotic, gritty, itchy and / or spares the groin and axillary regions, Zirwas said. He also pointed out that AD can be difficult to diagnose on colored skin because there may not be any redness.
Explore the effectiveness of a new approach
AD has long been a challenge to deal with. As Zirwas noted, some patients do not respond well to existing treatments and have uncontrolled disease as a result. “Many patients suffer from steroid phobia. They don’t want steroids; will not use steroids. So it becomes a major compliance issue, ”he added.
Opzelura’s mechanism of action sets it apart because it binds and inhibits interleukins such as IL-17 and IL-23. Recent research has shown that blocking deregulation of the JAK-STAT pathway may solve some of the most persistent problems in AD: itching, inflammation, and skin barrier dysfunction.2
Results from 2 randomized, double-blind, vehicle-controlled phase 3 studies (TRuE-AD1 and TRuE-AD 2) involving over 1,200 adolescents and adults obtained 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 an improvement of at least 2 points 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
Opzelura also helped reduce itching, 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
Zirwas pointed out that this topical JAK inhibitor has other benefits. It is non-steroidal, non-oily, and can be used on sensitive skin, colored skin, and on the skin anywhere on the body. Based on the results of clinical trials, it does not cause skin atrophy, thinning of the skin, burning or stinging. Equally important, he added, the effectiveness of results on the face and hand relates to 2 of the areas that have proven to be the most difficult to treat successfully.
AD — the skin is not functioning well enough to protect itself from the environment; sweat, natural bacteria and yeast that live on your skin, the fact that the water you bathe in contains magnesium, chlorine and calcium, the water is hot, air pollution, pollen in the air, clothes that rub on the skin, residual laundry detergents that cause AD
Be proactive when discussing risks
The cream will have a black framed warning label listing the risks of serious infections, increased risk of heart attack, stroke, or heart death. It’s important to make sure patients are aware before filling the prescription that the warning will be on the package, Zirwas said.
“Whenever I prescribe it, I will explain the risks of this drug whenever drugs like this are taken orally as a pill,” Zirwas said. The review on which the black box warnings are based looked at tofacitinib (Xeljanz, Pfizer). A similar review has yet to be done on a topical JAK inhibitor. Zirwas does not rule out some absorption of a topical, but points out that it would be much less than the oral medication on which these safety warnings are based.
Zirwas, however, lists several contraindications. “Avoid use in patients with serious active infections, including local infections. Do not start patients with active impetigo on Opzelura and stop if there is a rash. I wouldn’t do a test for hepatitis B and C, but if it’s in the patient’s history, I wouldn’t prescribe. He also didn’t want to test for tuberculosis. If the patient had signs and symptoms of tuberculosis such as fever or cough, they would be tested. He would not prescribe Opzelura to a breastfeeding patient. Any physician considering prescribing Opzelura in a pregnant patient should consult the patient’s obstetrician. “I would not prescribe a glass of water for a pregnant patient without consulting an obstetrician.”
Some increases in squamous cells have been noted, Zirwas says, but no dramatic increases. But if a patient had basal cell carcinoma, they would watch it much more closely.
He also noted that cost can be a barrier.
Zirwas was paid by Inctye Corporation.
1. Zirwas M atopic dermatitis: The burden of disease and the JAK-STAT pathway. Featured at Maui Derm NP + PA Fall 2021; September 30 – October 2, 2021, live in Asheville, NC, and virtual.
2. Bao L, et al. JAK-STAT. 2013; 2 (3): e24137. doi: 10.4161 / jkst.24137.