Upadacitinib Shows Long-Term Benefits in Teens With Atopic Dermatitis

Treatment with the Janus kinase (JAK) inhibitor upadacitinib (Rinvoq) showed a favorable long-term benefit-risk profile through 76 weeks in adolescents with moderate to severe atopic dermatitis, an analysis of three phase III randomized trials showed.

At week 76 in the Measure Up 1, Measure Up 2, and AD Up trials, 84-89% of adolescents taking upadacitinib 15 mg achieved a reduction of 75% or more in the Eczema Area and Severity Index score (EASI-75), as did 83-96% of adolescents taking the 30-mg dose, reported researchers led by Amy S. Paller, MD, of the Feinberg School of Medicine at Northwestern University in Chicago.

Both doses of upadacitinib also met the study’s other two coprimary endpoints at week 76 — a score of clear or almost clear with at least 2 grades of improvement on the Validated Investigator Global Assessment for Atopic Dermatitis and a minimum 4-point improvement from baseline on the Worst Pruritus Numerical Rating Scale for those with a score of 4 points or higher at baseline, they noted in JAMA Dermatology.

Given atopic dermatitis’ negative impacts on quality of life among adolescents, including increased suicidality, “there remains a need for treatments available to this population,” the authors pointed out.

Shoshana Marmon, MD, PhD, of New York Medical College in Valhalla, told MedPage Today that “when initiating JAK inhibitors or other disease-modifying anti-rheumatic drugs, especially in younger patients, it is important to emphasize medication adherence, regular monitoring, infection prevention, and awareness of potential side effects.”

Overall, acne and nausea were the most common adverse events (AEs) with upadacitinib. Acne presented primarily as inflammatory papules, pustules, and comedones involving the face. Nausea was reported by 2.4% to 4.5% of patients across the three trials, with exposure-adjusted rates of 2.9 per 100 patient-years with the 15-mg dose, and 1.1 per 100 patient-years with the 30-mg dose.

Long-term outcomes were consistent with the known AE profile of upadacitinib. In Measure Up 1, Measure Up 2, and AD Up, rates of herpetic infection were 4.0, 1.9, and 1.1 events per 100 patient-years and rates of creatine kinase elevations were 11.6, 11.0, and 7.1 events per 100 patient-years. No new signals were observed with either dose.

All opportunistic infections were mild or moderate events of eczema herpeticum (EH); the increased risk of EH among patients with atopic dermatitis is likely due to impaired epidermal barrier function, Paller and team noted.

“No consistent dose relationship of exposure-adjusted event rates was observed for any AEs, severe AEs, or AEs leading to treatment discontinuation” between the two upadacitinib doses across the three studies, they wrote.

Sonya Kenkare, MD, of Illinois Dermatology Institute in Hinsdale, told MedPage Today that “this JAK inhibitor is a promising addition to the treatment armamentarium that dermatologists will have at their fingertips for adolescent patients. As with any JAK inhibitor, patients will need to be appropriately screened for their candidacy for this drug and monitored for adverse events.”

“The adverse events like infections and herpes zoster are manageable, and patients should be warned about these and other potential risks of this drug,” she added.

This analysis involved 542 adolescents (52.4% girls) with moderate to severe atopic dermatitis. Data were gathered from August 2018 to April 2022. Across the three trials, patients were randomized 1:1:1 to receive once-daily oral upadacitinib 15 mg or 30 mg, or placebo, either alone (Measure Up 1 and Measure Up 2) or with topical corticosteroids (AD Up) for 16 weeks. At week 16, placebo patients in all studies were re-randomized to receive 15 mg or 30 mg of upadacitinib.

For patients previously treated with placebo (with or without topical corticosteroids) during weeks 1 to 16 in all three studies, response rates increased after the switch to upadacitinib, then plateaued, and were maintained through week 76, which was similar to patients who continued with upadacitinib, Paller and colleagues noted.

There was one unexpected finding in the AD Up study — at week 76, fewer patients achieved EASI-75 with the 30-mg dose versus the 15-mg dose, which may have been because “concomitant use of topical corticosteroids was no longer required starting at the week 52 visit,” the authors suggested.

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