Upadacitinib: A Promising Long-Term Treatment for Teens with Moderate-to-Severe Eczema

Original Article: Upadacitinib in Adolescents With Moderate to Severe Atopic Dermatitis: Analysis of 3 Phase 3 Randomized Clinical Trials Through 76 Weeks

What are the key takeaways of this article?

A new study published in JAMA Dermatology indicates that upadacitinib is a well-tolerated therapeutic option for managing moderate-to-severe atopic dermatitis (AD) in adolescents, with a favorable long-term efficacy profile. The study aimed to evaluate the long-term safety and efficacy of upadacitinib, an oral Janus kinase (JAK) inhibitor, in adolescents aged 12-17 years with moderate to severe AD. JAK inhibitors function by modulating the inflammatory cytokines involved in AD pathogenesis and directly mediate pruritus. The data were derived from three global phase 3 trials: Measure Up 1, Measure Up 2, and AD Up. The trials involved a total of 542 adolescent patients, who were randomly assigned to receive either 15 mg upadacitinib, 30 mg upadacitinib, or placebo, with or without topical corticosteroids, for up to 76 weeks.

The results revealed that adolescents treated with upadacitinib experienced significant and sustained improvements in disease severity through week 76. The Eczema Area and Severity Index (EASI-75, a measure that indicates the percentage of individuals achieving ≥75% improvement in lesion extent and severity) response rate was consistently high, with the 30 mg dose showing superior outcomes in achieving EASI-75 (82.7-96.1%) compared to the 15 mg dose (84.4-89.1%). This trend was similar for more stringent skin clearance measures (EASI-90 and EASI-100). Adolescents who were initially randomized to placebo and switched to upadacitinib after week 16 showed a rapid improvement in skin clearance and pruritus, reaching similar efficacy levels as those who were on upadacitinib from the start. In terms of pruritus, a greater proportion of adolescents in the upadacitinib groups achieved a 4-point or greater improvement in Worst Pruritus Numeric Rating Scale (WP-NRS) compared to those in the placebo group, and these improvements were maintained through week 76. The results indicate that upadacitinib was not only acutely effective, but also demonstrated a favorable long-term efficacy profile.

Regarding safety, upadacitinib was generally well tolerated in adolescents, with a safety profile consistent with prior studies in adults. The most common adverse events (AEs) were acne and nausea, which occurred at low rates across the treatment groups. Serious adverse events, including infections, were rare and primarily involved mild or moderate eczema herpeticum (1.1-4.0 events per 100 patient-years), with no new or severe safety concerns noted. Notably, no new major adverse cardiovascular events, venous thromboembolic events, or malignancies were reported. Rhabdomyolysis, which occurred in two adolescent patients, was linked to increased physical activity, highlighting the need for proper hydration during exercise, especially in this age group. The study also reported no significant impact on adolescent growth during the 76-week treatment period.

In conclusion, the long-term data from this study confirm that upadacitinib is an effective and well-tolerated treatment option for adolescents with moderate to severe AD. Both the 15 mg and 30 mg doses led to sustained improvements in disease severity, pruritus, and skin clearance, with the 30 mg dose showing superior efficacy in some outcomes. The safety profile of upadacitinib in adolescents was consistent with adult studies, supporting its use as a viable long-term treatment for this population. This study underscores the potential of upadacitinib as a key therapeutic option for managing moderate-to-severe AD in adolescents.

Publication Date: January 14, 2025

Reference: Paller AS, Mendes-Bastos P, Siegfried E, 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

Summary By: Miranda Branyiczky