Upadacitinib and Dupilumab Demonstrate Superior Efficacy in the Treatment of Adolescent Atopic Dermatitis: A Network Meta-Analysis.

Summary

This PROSPERO-registered network meta-analysis of RCTs in adolescents with moderate-to-severe atopic dermatitis found upadacitinib (30 mg and 15 mg) and dupilumab (300 mg q2w) ranked highest for EASI75 and IGA0/1 responses. Dupilumab and tralokinumab topped itch improvement (PP-NRS4). Safety estimates were unstable due to limited sample sizes, underscoring the need for longer-term data.

Key Findings

• Upadacitinib 30 mg/day and 15 mg/day and dupilumab 300 mg q2w ranked highest for EASI75 and IGA0/1 vs placebo and other active comparators.
• Dupilumab 300 mg q2w and tralokinumab 300 mg q2w showed the greatest improvements in PP-NRS4 itch outcomes.
• Safety estimates (TEAEs, SAEs) were unstable due to limited sample sizes; adverse event profiles varied among drugs (e.g., nasopharyngitis, acne).

Clinical Implications

Upadacitinib and dupilumab should be prioritized for adolescents with moderate-to-severe AD, with individualized risk–benefit assessments and vigilant safety monitoring. Clinicians should consider tralokinumab for itch improvement and recognize uncertainties in long-term safety.

Limitations

• Long-term safety remains uncertain; safety estimates unstable due to limited adolescent sample sizes.
• Heterogeneity in trial designs and endpoints; adolescent-specific dosing and durations vary.

Future Directions

Undertake head-to-head adolescent RCTs with longer follow-up to refine efficacy/safety rankings, include patient-reported outcomes, and evaluate step-up/step-down and combination strategies.