Upadacitinib, an oral, once-daily selective Janus kinase (JAK) inhibitor, has demonstrated sustained efficacy and a consistent safety profile in adolescents aged 12-17 years with moderate to severe atopic dermatitis (AD) over 76 weeks of treatment. The findings, derived from a comprehensive analysis of data from three Phase 3 randomized clinical trials—Measure Up 1, Measure Up 2, and AD Up—were published in JAMA Dermatology. The study provides crucial long-term data supporting the use of upadacitinib in this patient population.
The study included 542 adolescent patients who were randomized to receive either 15 mg or 30 mg of upadacitinib daily, with or without topical corticosteroids. The primary endpoints included the achievement of at least a 75% reduction in the Eczema Area and Severity Index (EASI-75), a Validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD) score of clear (0) or almost clear (1) with at least a 2-grade improvement, and a Worst Pruritus Numerical Rating Scale (WP-NRS) improvement of 4 points or greater.
Sustained Efficacy Over 76 Weeks
At week 76, EASI-75 was achieved by 89.1%, 84.4%, and 87.8% of adolescents in the Measure Up 1, Measure Up 2, and AD Up trials, respectively, who were taking upadacitinib 15 mg. For those taking upadacitinib 30 mg, the EASI-75 response rates were 96.1%, 93.6%, and 82.7% in the same trials. These results indicate that the efficacy of upadacitinib was maintained or improved over the 76-week treatment period.
"The proportion of patients achieving more stringent skin clearance measures of EASI-90 and EASI-100 increased and were generally maintained or improved beyond week 16 through week 76 for all 3 studies," the authors noted. These deeper responses were more frequently observed in adolescents taking the 30 mg dose of upadacitinib.
Itch Improvement
Clinically meaningful itch improvement, defined as a 4-point or greater reduction on the WP-NRS, was also sustained through week 76. Patients who switched from placebo to upadacitinib at week 16 experienced similar improvements in itch, mirroring the trajectory of those who started on upadacitinib from the beginning of the study.
Safety Profile
The long-term safety profile of upadacitinib in adolescents was consistent with previous findings. Common adverse events included herpetic infections and creatine kinase elevations, but no new safety signals were identified. Serious infections were infrequent, and most opportunistic infections were mild to moderate in severity.
"Long-term outcomes up to 76 weeks for upadacitinib, 15 mg, and upadacitinib, 30 mg, with or without topical corticosteroids in moderate to severe AD were consistent with the known AE profile of upadacitinib," the researchers stated.
Impact on Adolescent Quality of Life
Atopic dermatitis affects approximately 20% of children, with a significant number of cases persisting into adolescence. The condition can have a profound impact on quality of life, affecting psychosocial development, self-esteem, and school performance. Effective treatments are crucial to mitigate these effects.
Study Limitations
The authors acknowledged that the study had some limitations, including a relatively small sample size of adolescents compared to adult studies. Additionally, the study only included patients aged 12 years and older with a body weight of 40 kg or greater, which limits the generalizability of the findings to younger or smaller patients.
Conclusion
The study's findings support upadacitinib as an effective and well-tolerated long-term treatment option for adolescents with moderate to severe atopic dermatitis. The sustained efficacy and consistent safety profile observed over 76 weeks provide valuable insights for clinicians managing this challenging condition.
