FDA OKs Two Oral JAK Inhibitors for Refractory Atopic Dermatitis

The FDA approved the once-daily oral Janus kinase (JAK) 1 inhibitor abrocitinib (Cibinqo) for adults with treatment-refractory moderate-to-severe atopic dermatitis (AD), Pfizer announced.

The approval covers three doses: the recommended 100-mg dose, 200 mg for patients who do not respond adequately to 100 mg, and a 50-mg dose for patients with renal impairment or who are being treated with a cytochrome P450 2C19 (CYP2C19) inhibitor or are known to have poor metabolism of CYP2C19. Patients who do not respond to 50 mg of abrocitinib may receive 100 mg.

"The reality for patients living with chronic inflammatory skin disease such as moderate-to-severe atopic dermatitis is that many experience debilitating symptoms that are not managed by current treatment options," said Jonathan Silverberg, MD, PhD, of George Washington University in Washington, D.C., in a statement in the Pfizer announcement. "In multiple large-scale clinical trials, Cibinqo demonstrated strong efficacy at clearing skin, improving itch, and managing the extent and severity of eczema, offering a benefit-risk profile that supports the use of this treatment in the FDA-approved population."

In a related matter, the FDA expanded indications for upadacitinib (Rinvoq), another oral JAK inhibitor, to include patients 12 and older with refractory, moderate-to-severe AD. The drug also has approved indications for rheumatoid arthritis and psoriatic arthritis.

The FDA actions followed last year's approval of the topical JAK inhibitor ruxolitinib (Opzelura) for refractory moderate-to-severe AD.

Support for the abrocitinib approval came from five clinical trials, including three randomized, placebo-controlled, phase III studies. Additionally, the drug's safety was evaluated in a placebo-controlled dose-finding trial and a long-term open-label extension study.

"Across the trials, Cibinqo demonstrated a consistent safety profile and profound improvements in skin clearance, extent of disease, and severity, as well as rapid improvement in itch after two weeks, for some people living with AD versus placebo," according to the Pfizer statement. "In addition, a higher proportion of subjects treated with Cibinqo in two monotherapy trials achieved improvement in itching at week 12 compared to placebo."

The most commonly reported adverse events with abrocitinib were nasopharyngitis, nausea, and headache. Patients treated with the drug may have an increased risk of infection.

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