口服治疗特应性皮炎：FDA批准两种口服JAK抑制剂治疗中重度AD

Introduction: On January 14, 2022, the U.S. Food and Drug Administration (FDA) approved upadacitinib (RINVOQ®, upadacitinib) and abrocitinib (CIBINQO®) for the treatment of moderate to severe atopic dermatitis (AD).

On January 14, 2022, the U.S. Food and Drug Administration (FDA) approved two oral JAK-1 inhibitors for the treatment of moderate to severe atopic dermatitis (AD) - upadacitinib (RINVOQ®, upadacitinib) and abrocitinib (CIBINQO®), making them the first oral JAK inhibitors for this indication in the United States.

Atopic dermatitis is a chronic, relapsing, inflammatory skin disease with recurring chronic eczematous rashes as the main clinical manifestation, accompanied by significant dry skin and itching. It is a systemic disease. Patients often suffer from allergic rhinitis, asthma and other atopic diseases. It is currently incurable and can seriously affect the quality of life.

Commenting on the approval of upadatinib, Dr. Emma Guttman-Yassky, MD, professor and chair of the Department of Dermatology at the Icahn School of Medicine at Mount Sinai in New York, said: "This is big news because a few years ago, we didn't have systemic therapies that were safer than classic immunosuppressants like cyclosporine and methotrexate."

"So far, the only oral drug approved for the treatment of AD is oral prednisone, but its safety profile is worrying. Therefore, upadatinib is the first oral drug that we can prescribe to AD patients for long-term use."

Upadacitinib

Upadacitinib (Rinvoq, upadacitinib), developed by AbbVie, was approved for use in patients aged 12 years and above with moderate to severe AD. The approval was based on the results of three phase 3 trials involving 2,500 adult and pediatric patients aged 12 years and above with moderate to severe AD. Among them, the Measure Up 1 and 2 trials, led by Dr. Guttman-Yassky, evaluated the efficacy of upactinib compared with placebo; the AD UP trial evaluated the efficacy of uppatinib combined with topical corticosteroids compared with placebo.

In three trials, upadatinib (15 mg and 30 mg once daily monotherapy) met all primary and secondary endpoints at 16 weeks, with some patients achieving higher levels of skin clearance (based on the EASI-90 and EASI-100 indices).

Dr. Guttman-Yassky said: "I have been emphasizing that patients with AD need more treatment options. We need biologic drugs, we need oral drugs, and not everyone likes needles. The approval of the oral JAK inhibitor is part of the beginning of this action. Many patients have been on upadatinib maintenance treatment for more than two years, and they are very happy. Many of them have not responded to cyclosporine and other immunosuppressants, such as methotrexate and prednisone."

She expects oral upadatinib to be available in March 2022, and predicts that insurance companies will be happy to pay for the drug because of its excellent efficacy and because other treatments have been ineffective for many AD patients.

In August 2019, the FDA approved upadatinib for the treatment of adult patients with moderately to severely active rheumatoid arthritis (RA) who have an inadequate response or intolerance to methotrexate (MTX-IR).

On August 24, 2021, the European Commission (EC) approved upadatinib for the treatment of moderate to severe atopic dermatitis in adults and adolescents aged 12 years and older who require systemic therapy.

Abrocitinib

Abrocitinib (Cibinqo), developed by Pfizer, is approved for adults with moderate to severe AD. Its approval is based on the results of 5 clinical trials in a large-scale clinical program involving more than 1,600 patients. Recommended doses of the drug are 100 mg and 200 mg, with the 200 mg dose recommended for patients who have not responded to the 100 mg dose.

The safety and efficacy of abrocitinib have been evaluated in three randomized, placebo-controlled, phase 3 trials, in addition to one randomized, placebo-controlled, dose-ranging trial and one ongoing long-term, open-label, extension trial. In these trials, abrocitinib demonstrated consistent safety and good efficacy, with dramatic improvements in skin clearance, disease extent, severity, and rapid improvement in itching after 2 weeks compared with placebo.

In September 2021, the UK Medicines and Healthcare products Regulatory Agency (MHRA) granted marketing authorization to CIBINQO (abrocitinib) for the treatment of moderate to severe atopic dermatitis (AD) in adults and adolescents aged 12 years and older who are suitable for systemic treatment.

On December 9, 2021, the European Medicines Agency (EMA) approved Pfizer’s abrocitinib for the treatment of adult patients with moderate to severe atopic dermatitis.

Summary

The labels for abrocitinib and upadacitinib include a boxed warning for JAK inhibitors regarding the risk of serious infection, mortality, malignancy, major adverse cardiovascular events, and thrombosis.

Atopic dermatitis is more than just a rash, and it does not simply affect the surface of the skin. It is a chronic disease that will not only seriously disrupt patients' daily lives, but also have a negative impact on their emotional health. The approval of these two oral drugs has brought good news to AD patients. I believe that with the advancement of medical science, this incurable disease will eventually be conquered, allowing AD patients to return to their normal lives.

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