FDA approval of ruxolitinib (Opzelura, Incyte) adds the first new topical anti-inflammatory to the atopic dermatitis (AD) armamentarium in 50 years, but boxed warnings raise questions.
Matthew Zirwas, MD, a board certified dermatology, director, Ohio Contact Dermatitis Center, and a member of the North American Contact Dermatitis Group, Columbus, Ohio walked through what dermatologists need to know about the newly FDA-approved topical JAK inhibitor ruxolitinib (Opzelura, Incyte)during a presentation at Fall Clinical Dermatology Conference 2021, held October 21-24 in Las Vegas, Nevada and virtually.1
The FDA’s September 21, 2021 approval of ruxolitinib gave the dermatology community the first and only topical Janus kinase [JAK] inhibitor in the United States for short-term, non-continuous treatment of mild to moderate atopic dermatitis (AD). It is approved for use by non-immunocompromised patients 12 years and older whose disease is not adequately controlled with topical prescription therapies or if those therapies are not advisable, wrote the FDA.2
“We have not had a real breakthrough in topical anti-inflammatories since hydrocortisone was introduced over 50 years ago--until now,” said Zirwas, noting that calcineurin inhibitors are immunosuppressive, not anti-inflammatory.
Opzelura's approval gives physicians an alternative to steroids. That's particularly noteworthy at a time when patient concern about steroids' possible adverse effects (AEs) are impacting acceptance and adherence. Various recent studies have shown that anywhere from 31 to more than 97% of patients have some degree of steroid phobia.3
This novel topical also addressed a long-standing challenge. "The complexity of prescribing high-, medium- and low-potency steroids for the hands, body, and face respectively is a stumbling block to adherence," Zirwas added.
Topical ruxolitinib can be used on the face, hands, and body. Zirwas pointed out that this one-stop-shop capability allows for a single treatment that works wherever AD is present, simplifying the directions dermatologists need to give patients.
However, these advances came with a caveat in the form of a black box warning outlining risks identified in an FDA review of the first-ever JAK inhibitor ever to receive FDA approval, tofacitinib (Xeljanz, Pfizer) which treats moderate to severe active rheumatoid arthritis.
The list of adverse effects (AEs) includes serious infection, increased risk of heart attack, or cardiac, thrombosis, cancer and pulmonary embolism.4
Zirwas pointed out that the reviews was based on an oral medication and that the warnings may be “overdone” for a topical. Zirwas noted that with a topical such as ruxolitinib, about 6 to 10% of the drug is absorbed into the bloodstream, an 80 to 90% reduction from the systemic absorption of ruxolitinib when given orally.
Because of that, he added, he doesn’t expect to see the risk of AEs such as thrombosis and infections seen with oral JAK inhibitors. He also said that ruxolitinib has been approved orally for a number of years for hematologic indications and for graft-versus-host disease.
“I could imagine it being the case that we'll find out 10 years from now, that people who were using Opzelura had a really tiny increase in the risk of thrombotic events or a really tiny increase in in the risk of major adverse cardiovascular events or a really tiny increase in the rates of infection,” he said.
“I could imagine that. I don't think it's going to be the case," he added. "I don't think there's enough systemic absorption that we're going to see any clinic clinically meaningful adverse AEs as a result, but it is possible.”
Zirwas was compensated by Incyte Corporation.