Data from three randomized clinical trials, Measure Up 1, Measure Up 2, and AD Up, indicate that upadacitinib (Rinvoq; AbbVie) maintains efficacy and a favorable safety profile in adolescents with moderate to severe atopic dermatitis (AD) over 76 weeks. The findings, published in JAMA Dermatology, suggest that upadacitinib could be a valuable long-term treatment option for this patient population.
The study, led by Amy S. Paller, MD, from Northwestern University, included 542 adolescents aged 12 to 17 years. Participants were randomly assigned to receive once-daily upadacitinib (15 mg or 30 mg) or placebo, with or without topical corticosteroids, depending on the trial. The co-primary endpoints included achievement of EASI-75, vIGA-AD score of 0 or 1, and WP-NRS improvement of 4 points or greater.
Consistent Improvement in EASI-75 Scores
At week 76, EASI-75 was achieved by 89.1%, 84.4%, and 87.8% of participants in the Measure Up 1, Measure Up 2, and AD Up trials, respectively, in the 15 mg upadacitinib group. In the 30 mg group, EASI-75 was achieved by 96.1%, 93.6%, and 82.7% of adolescents, respectively. These results indicated maintenance or improvement in EASI-75 scores over the 76-week period.
Maintenance of vIGA-AD and WP-NRS Scores
Improvements in vIGA-AD scores (0 or 1) and WP-NRS scores (improvement of 4 points or more) were also maintained or improved through 76 weeks of treatment with upadacitinib at both 15 mg and 30 mg doses. These findings suggest that upadacitinib effectively reduces both skin inflammation and itch, key symptoms of atopic dermatitis.
Safety Profile
Importantly, the study found no new safety signals with either dose of upadacitinib during the extended evaluation period. This is particularly relevant given previous concerns about the long-term safety of JAK inhibitors. According to Paller, "Adolescents with moderate to severe atopic dermatitis now have five FDA-approved treatment options and several studies have suggested that upadacitinib has the earliest and highest efficacy among these. In this study, we were looking very carefully at the safety of this group long term because adolescents who take upadacitinib will likely be on this drug for a very long time."
Implications for Treatment
Approximately 40% of adolescents with atopic dermatitis have moderate to severe disease that cannot be adequately managed with topical medications alone. Upadacitinib, a selective JAK1 inhibitor, offers an oral treatment option that can reduce both skin inflammation and itch. Paller notes, "JAK inhibitors not only reduce skin inflammation but can also quickly reduce itch... From a rationale standpoint, having a JAK inhibitor offers the opportunity to target both the inflammation and itch directly."
The study authors conclude that upadacitinib, with its favorable benefit-risk profile, represents an effective long-term treatment option for adolescents with moderate to severe AD. As more evidence of safety accumulates, upadacitinib may be considered earlier in the treatment course, particularly for adolescents who struggle with topical medication adherence.
