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Efficacy and Safety of Upadacitinib vs Dupilumab in Adults and Adolescents With Moderate to Severe Atopic Dermatitis
TAKE-HOME MESSAGE
- This phase IIIb/IV study assessed the safety and efficacy of upadacitinib versus dupilumab in patients with moderate to severe atopic dermatitis. The patients were randomized to receive upadacitinib or dupilumab for 16 weeks. Treatment with upadacitinib was associated with superior efficacy in terms of achieving an Eczema Area and Severity Index–90 response and a Worst Pruritus Numerical Rating Scale 0/1 response at week 16 compared with treatment with dupilumab.
- Treatment with upadacitinib was superior to treatment with dupilumab in patients with moderate to severe atopic dermatitis when evaluated based on the achievement of near-complete skin clearance and little to no itch at week 16.
abstract
This abstract is available on the publisher's site.
Access this abstract nowBACKGROUND
Atopic dermatitis (AD) is a chronic skin disease characterized by intense itch and eczematous skin lesions. Some patients continue to experience flares and substantial clinical burden despite ongoing systemic treatment.
OBJECTIVES
This study assessed the efficacy and safety of once-daily upadacitinib (UPA), initiated at 15 mg and dose-escalated to 30 mg based on clinical response, compared with dupilumab (DUPI) per its label. Week 16 primary analysis results are presented.
METHODS
Level Up is a phase 3b/4 global, randomized, open-label, efficacy assessor blinded study evaluating UPA vs DUPI in adolescents and adults with moderate-to-severe AD who had inadequate response to systemic therapy or when use was inadvisable. Patients were randomized to UPA or DUPI for 16 weeks of treatment (Period 1). Patients on UPA started on 15 mg and were dose-escalated to 30 mg if they did not achieve an Eczema Area and Severity Index reduction of at least 50% (EASI 50) or a ≥4-point Worst Pruritus Numerical Rating Scale (WP-NRS) improvement on/after Week 4, or EASI 75 on/after Week 8. The primary endpoint was simultaneous achievement of EASI 90 and WP-NRS 0/1 at Week 16. Ranked secondary endpoints included skin and itch responses at varying response levels and timepoints. Safety measures were assessed throughout the study.
RESULTS
Superior efficacy in achieving simultaneous EASI 90 and WP-NRS 0/1 response at Week 16 was demonstrated with UPA vs DUPI (19.9% vs 8.9%, respectively; p<0.0001). UPA showed superiority vs DUPI for all ranked secondary endpoints, with post-hoc analyses exhibiting higher itch response rates as early as Day 2. No new safety signals were identified during this period.
CONCLUSION
Treatment of moderate-to-severe AD with UPA, initiated at 15 mg and dose escalated based on clinical response, demonstrated superiority vs DUPI per its label for the primary endpoint of simultaneous achievement of near complete skin clearance (EASI 90) and little to no itch (WP-NRS 0/1) at Week 16, with all ranked secondary endpoints demonstrating superiority at varying skin and itch response levels and timepoints. There were no new safety signals identified compared to the previously reported safety profiles of UPA and DUPI.
Additional Info
Disclosure statements are available on the authors' profiles:
Efficacy and Safety of Upadacitinib vs Dupilumab in Adults and Adolescents with Moderate-to-Severe Atopic Dermatitis: Week 16 results of an Open-label, Randomized, Efficacy Assessor-Blinded Head-to-Head Phase 3b/4 Study (Level Up)
Br J Dermatol 2024 Oct 23;[EPub Ahead of Print], JI Silverberg, CG Bunick, HC Hong, P Mendes-Bastos, L Stein Gold, A Costanzo, N Ibrahim, C Sancho, X Wu, Y Han, G Levy, K Altman, B Calimlim, K EyerichFrom MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
This study provides insights into treatment options for adults and adolescents with moderate to severe atopic dermatitis by comparing the efficacy of upadacitinib (a JAK1 inhibitor) with that of dupilumab (an IL-4 inhibitor). In this 16-week trial, patients who received upadacitinib showed superior outcomes, achieving significantly higher levels of skin clearance (Eczema Area and Severity Index 90 response) and itch reduction (Worst Pruritus Numerical Rating Scale 0/1), compared with those receiving dupilumab. Notably, the superior efficacy of upadacitinib was observed as early as day 2 for itch relief and week 2 for skin clearance, which is a significant consideration in providing quick relief from atopic dermatitis symptoms. This study employed a unique, open-label, flexible dosing methodology for upadacitinib, where the patients initially received a 15-mg dose, which was then increased to 30 mg from week 4 to 16 if they were found to have an inadequate clinical response. Almost 70% of the patients required a dose adjustment before the study was completed to attempt to achieve the primary endpoint. This illuminates the potential real-world dosing practices, with the current FDA label recommending starting a 15-mg dose and increasing it to 30 mg per clinician judgment. However, although upadacitinib shows remarkable efficacy, the potential side effects of each medication should be carefully considered when selecting therapy. Notably, the safety profiles of upadacitinib and dupilumab were comparable to those noted in previous clinical trials. Overall, the findings from this study support upadacitinib as an effective treatment option for patients requiring both rapid and comprehensive control of atopic dermatitis. Although IL-4 blockade has been revolutionary in the treatment of atopic dermatitis, the role of JAK inhibitors is encouraging for patients who continue to suffer from moderate to severe disease.