Efficacy and Safety of Upadacitinib Treatment in Adolescents With Moderate-to-Severe Atopic Dermatitis

Abstract

ImportanceAtopic dermatitis onset usually occurs in childhood. Persistence of disease into adolescence and adulthood is common. It is important to evaluate new treatment options in adolescents because of the high unmet need in this population.ObjectiveTo assess the efficacy and safety of upadacitinib to treat moderate-to-severe atopic dermatitis in adolescents.Design, Setting, and ParticipantsPrespecified analysis of adolescents enrolled in 3 randomized, double-blind, placebo-controlled phase 3 clinical trials in more than 20 countries across Europe, North and South America, Oceania, the Middle East, and the Asia-Pacific region from July 2018 through December 2020. Participants were adolescents aged 12 to 17 years with moderate-to-severe atopic dermatitis. Data analysis was performed from April to August 2021.InterventionsPatients were randomized (1:1:1) to once-daily oral upadacitinib 15 mg, upadacitinib 30 mg, or placebo alone (Measure Up 1 and Measure Up 2) or with topical corticosteroids (AD Up).Main Outcomes and MeasuresSafety and efficacy, including at least a 75% improvement in the Eczema Area and Severity Index from baseline and validated Investigator Global Assessment for Atopic Dermatitis score of 0 (clear) or 1 (almost clear) at week 16 (coprimary end points).ResultsA total of 552 adolescents (290 female; 262 male) were randomized. Mean (SD) age was 15.4 (1.8), 15.5 (1.7), and 15.3 (1.8) years for adolescents in Measure Up 1, Measure Up 2, and AD Up, respectively. In Measure Up 1, Measure Up 2, and AD Up, respectively, a greater proportion of adolescents (% [95% CI]) achieved at least 75% improvement in the Eczema Area and Severity Index at week 16 with upadacitinib 15 mg (73% [63%-84%], 69% [57%-81%], 63% [51%-76%]), and upadacitinib 30 mg (78% [68%-88%], 73% [62%-85%], 84% [75%-94%]), than with placebo (12% [4%-20%], 13% [5%-22%], 30% [19%-42%]; nominal P < .001 for all comparisons vs placebo). Similarly, a greater proportion of adolescents treated with upadacitinib achieved a validated Investigator Global Assessment for Atopic Dermatitis score of 0 or 1 at week 16 and improvements in quality of life with upadacitinib than with placebo. Upadacitinib was generally well tolerated in adolescents. Acne was the most common adverse event, and all acne events were mild or moderate.Conclusions and RelevanceIn this analysis of 3 randomized clinical trials, upadacitinib was an effective treatment for adolescents with moderate-to-severe atopic dermatitis, with an acceptable safety profile.Trial RegistrationClinicalTrials.gov Identifiers: NCT03569293 (Measure Up 1), NCT03607422 (Measure Up 2), and NCT03568318 (AD Up)

Recent advances in immunomodulators for atopic dermatitis

“…A third similar 16-week phase 3 trial ‘AD Up’ that allowed the use of a mid-potency TCS showed similar trend of improvement in atopic dermatitis outcomes [40 ▪▪ ]. The proportion of subjects in the groups placebo/TCS, upadacitinib 15 mg daily/TCS, and upadacitinib 30 mg daily/TCS who achieved the primary and secondary outcomes were: IGA (11 vs. 38 vs. 67%); EASI-75 (30 vs. 63 vs. 84%); NRS-4 itch (21 vs. 46 vs. 52%) (Table 2).…”

“…Upadacitinib is an oral JAK inhibitor that is FDA-approved for patients 12 years and older with moderate-to-severe atopic dermatitis. It was studied as a monotherapy in two phase 3 identical 16-week double-blind, randomized, placebo-controlled trials, ‘Measure Up 1’ and ‘Measure Up 2’ [40 ▪▪ ]. Three hundred and sixty-eight adolescents, 12–17 years old (weighing ≥40 kg) with moderate-to-severe atopic dermatitis (IGA 3–4) were randomized to three groups: placebo, upadacitinib 15 mg daily, and upadacitinib 30 mg daily.…”

Reanalysis of Study After Removal of Participants in 1 Trial of Upadacitinib for Atopic Dermatitis

“…In this article, we reported an analysis of 552 adolescents enrolled in 3 multicenter randomized clinical trials in more than 20 countries to assess the efficacy and safety of upadacitinib to treat moderate-to-severe atopic dermatitis in adolescents. We concluded that “upadacitinib was an effective treatment for adolescents with moderate-to-severe atopic dermatitis, with an acceptable safety profile.” (p526)…”

“…To the Editor On behalf of my coauthors, I write regarding a previously published article, “Efficacy and Safety of Upadacitinib Treatment in Adolescents With Moderate-to-Severe Atopic Dermatitis: Analysis of the Measure Up 1, Measure Up 2, and AD Up Randomized Clinical Trials,” which was published online first on April 12, 2023, and in the May 2023 issue of JAMA Dermatology . In this article, we reported an analysis of 552 adolescents enrolled in 3 multicenter randomized clinical trials in more than 20 countries to assess the efficacy and safety of upadacitinib to treat moderate-to-severe atopic dermatitis in adolescents.…”

Successful treatment of childhood lichen planus with upadacitinib

“…Three randomized clinical trials involving 552 adolescents have demonstrated that upadacitinib administered once daily through 16 weeks make the grade 3 liver enzyme (AST) infrequent (the AST was observed in only 1 patient in the 15-mg treatment group and 1 patient in the 30-mg treatment group). Hence, upadacitinib can be considered to be generally well tolerated and safe in adolescents, similar to that observed in adults [ 11 ].…”