Upadacitinib for atopic dermatitis: Efficacy and safety through 52 weeks

Published: August 14, 2021

Atopic dermatitis (also known as eczema) is a common chronic skin disease characterized by intense itch and eczematous (eg, red, thickened, and sometimes oozing) skin lesions. Moderate-to-severe atopic dermatitis is disabling and harms patients’ quality of life, including sleep, mental health, and physical and social function. For patients with moderate-to-severe atopic dermatitis, there is an unmet need for effective and safe oral medications that provide prolonged itch relief, skin clearance, and improved overall quality of life without high levels of treatment discontinuation because of negative side effects. Upadacitinib is a Janus kinase (JAK) inhibitor. Upadacitinib is approved in the United States, European Union, and other countries to treat moderate or severe rheumatoid arthritis. Upadacitinib is being investigated as treatment of atopic dermatitis and other immune-mediated conditions.

In a 2-part randomized-controlled clinical trial recently published in The Journal of Allergy and Clinical Immunology (JACI), Silverberg and colleagues investigated the safety and effectiveness of upadacitinib in combination with topical corticosteroids in adolescents and adults with moderate-to-severe atopic dermatitis through 52 weeks of treatment. Patients were initially randomized to receive upadacitinib (15 mg or 30 mg) or placebo in a double-blind fashion in combination with topical corticosteroids for 16 weeks (part 1). At week 16, patients randomized to placebo were re-randomized to receive treatment with upadacitinib (15 mg or 30 mg) and topical corticosteroids during a blinded extension period (part 2). Patients who received upadacitinib during the 16-week, double-blind, placebo-control portion continued to receive their originally assigned treatment during the extension period.

The study found that at 16 weeks, both doses of upadacitinib plus topical corticosteroids significantly improved the signs and symptoms of atopic dermatitis compared with placebo plus topical corticosteroids. Most patients receiving upadacitinib plus topical corticosteroids who achieved clear or almost clear skin and itch relief at week 16 maintained their response through week 52 of the study. More patients treated with upadacitinib 30 mg plus topical corticosteroids achieved clinical benefit compared with upadacitinib 15 mg plus topical corticosteroids. Upadacitinib plus topical corticosteroids was well tolerated through 52 weeks; no new important safety risks were observed beyond those described in the current label for rheumatoid arthritis. Acne with upadacitinib was reported frequently in atopic dermatitis studies; these cases of acne were nonserious and rarely led to treatment discontinuation. Except for the known dose-dependent risk of generally nonserious creatine phosphokinase elevations, safety results were similar between upadacitinib dosages.

This study by Silverberg et al provides the first evidence of long-term efficacy and acceptable safety of upadacitinib in combination with topical corticosteroids through 52 weeks of treatment. Upadacitinib plus topical corticosteroids provided clinically meaningful skin improvement in adolescents and adults with moderate-to-severe atopic dermatitis. This research supports the use of upadacitinib in combination with topical corticosteroids as an effective and well-tolerated long-term treatment option with a positive benefit-risk profile in adolescents and adults with moderate-to-severe atopic dermatitis. Future analyses will investigate the long-term impact of upadacitinib plus topical corticosteroids on patient-reported outcomes and health-related quality of life.

The Journal of Allergy and Clinical Immunology (JACI) is an official scientific journal of the AAAAI and is the most-cited journal in the field of allergy and clinical immunology.

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