Upadacitinib Effective Long-Term for Adolescents with Atopic Dermatitis

Amy S. Paller, MD

Credit: Northwestern Medicine

Long-term upadactinib treatment of adolescents known to have moderate to severe atopic dermatitis shows a favorable benefit-risk profile for the drug, new findings suggest, with sustained efficacy responses observed through 76 weeks.¹

These data resulted from research looking into long-term use of upadacitinib, an oral, once-per-day selective small molecule Janus Kinase (JAK) inhibitor known to have greater inhibitory potency for JAK1 than JAK3, JAK2, or tyrosine kinase 2. One of the investigators leading this analysis was Amy S. Paller, MD, from the Feinberg School of Medicine Department of Dermatology at Northwestern University.

In three previous phase 3 large double-blind, placebo-controlled randomized clinical studies known as Measure Up 1, Measure Up 2, and AD Up, treatment of atopic dermatitis with upadacitinib 15 mg or 30 mg was shown to be superior to placebo and topical corticosteroids through to the 16-week mark in adults and adolescents. This had also been sustained through 52 weeks, given the results of the blinded extension phases of these trials.^2,3

“The objective of the current study was to assess the efficacy of upadacitinib, 15 mg and 30 mg, with or without topical corticosteroids in adolescents aged 12 to 17 years with moderate to severe (atopic dermatitis) through 76 weeks,” Paller and colleagues wrote.¹

Trial Design

The investigators highlighted elements of the methodologies used for the Measure Up 1, Measure Up 2, and AD Up studies. They noted that these 3 studies are ongoing parallel, placebo-controlled, double-blind, global phase 3 randomized controlled trials (RCTs). A 16-week double-blind period of treatment was used in the RCTs, followed later by a blinded extension lasting 244 weeks.

Those included as participants in the Measure Up RCTs had been given random assignment in a 1:1:1 ratio to be given either placebo or 15 mg or 30 mg of oral upadacitinib, with the drug being provided in an extended-release tablet form. During the AD Up trial, subjects were administered the same dosages of upadacitinib or the placebo, though they were also treated with topical corticosteroids.

Individuals in the placebo cohorts of all 3 studies were rerandomized by the 16-week mark to either the 15 mg or 30 mg upadacitinib dose, and individuals already being given upadacitinib at either dose remained on their assigned therapy for the duration of the research. During AD Up, this was permitted from the 52-week mark and onwards, whereas in Measure Up 1 and Measure Up 2, the utilization of other topical options for atopic dermatitis was allowed at the investigator's discretion beginning at the 16-week mark.

The investigators’ coprimary endpoints determined to evaluate upadacitinib’s long-term efficacy included a reported Validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD) score in which patients were ranked clear (0) or almost clear (1) with at least a 2-grade improvement, a reduction of 75% or more in the Eczema Area and Severity Index (EASI-75), and a 4 or more point improvement on the Worst Pruritus Numerical Rating Scale (WP-NRS) for those who showed a baseline score of 4 or higher. These outcomes were looked at through to week 76.

Notable Findings

Overall, the research team noted the participation of 542 adolescents in these studies, adding that 52.4% had been reported as female. The team found that 89.1%, 84.4%, and 87.8% of adolescents being treated with 15 mg of upadacitinib in the Measure Up 1, Measure Up 2, and AD Up studies, respectively, succeeded in EASI-75 by the 76-week mark.

In a similar finding, the investigators reported that 96.1%, 93.6%, and 82.7% of the participating adolescents given 30 mg succeeded in reaching the same endpoint. Such results were determined to suggest the efficacy of upadacitinib had been either maintained or improved over the course of the RCTs’ 76 weeks.

Consistency in these improvements was also highlighted, given what the research team had measured using vIGA-AD scores of 0 or 1 and a 4-point or greater WP-NRS reduction from the point of baseline. Their long-term findings across each of the trials aligned with the established upadacitinib safety profile, as adverse event reports included herpetic infections (4.0, 1.9, and 1.1 events per 100 patient-years) and creatine kinase elevation (11.6, 11.0, and 7.1 events per 100 patient-years). There were not any new safety concerns observed for either of the studies’ dosages.

“In summary, these results through 76 weeks demonstrated that upadacitinib, with a favorable benefit-risk profile, was an effective long-term treatment option for adolescents with moderate to severe atopic dermatitis,” they concluded.¹

References

1. ^{Paller A, Mendes-Bastos P, Irvine A, et al. Upadacitinib in Adolescents With Moderate to Severe Atopic Dermatitis Analysis of 3 Phase 3 Randomized Clinical Trials Through 76 Weeks. JAMA Dermatol. Published online October 23, 2024. doi:10.1001/jamadermatol.2024.3696.}
2. ^{Simpson EL, Papp KA, Blauvelt A, et al. Efficacy and safety of upadacitinib in patients with
   moderate to severe atopic dermatitis: analysis of follow-up data from the Measure Up 1 and Measure Up 2 randomized clinical trials. JAMA Dermatol. 2022;158(4):404-413. doi:10.1001/jamadermatol.2022.0029}
3. ^{Silverberg JI, de Bruin-Weller M, Bieber T, et al. Upadacitinib plus topical corticosteroids in atopic dermatitis: week 52 AD Up study results. J Allergy Clin Immunol. 2022;149(3):977-87.e14. doi:10.1016/j.jaci.2021.07.036.}