Abstract
BACKGROUND: Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by intense itch and eczematous skin lesions. Upadacitinib, a selective oral Janus kinase inhibitor, and dupilumab, a monoclonal antibody, are both approved treatments for moderate-to-severe AD. In period 1 of the LEVEL UP phase 3b/4 head-to-head study, upadacitinib-treated patients demonstrated higher simultaneous achievement of near complete skin clearance and little to no itch compared with dupilumab after 16 weeks of treatment in adults and adolescents with moderate-to-severe AD. OBJECTIVE: The objective of period 2 of the LEVEL UP study was to assess the efficacy and safety of switching from dupilumab to upadacitinib in patients with inadequate response to dupilumab. METHODS: Following period 1 of the LEVEL UP study, patients not achieving ≥ 75% improvement in the Eczema Area and Severity Index (EASI 75) from baseline at week 16 entered an additional 16-week extension phase (period 2). In period 2, patients receiving dupilumab were switched to upadacitinib 15 mg, with the potential to escalate to 30 mg based on clinical response. End points in period 2 included EASI 90, Worst Pruritus Numerical Rating Scale (WP-NRS) 0/1, and simultaneous achievement of both EASI 90 and WP-NRS 0/1 at week 20 and week 32. RESULTS: A total of 208 patients were switched from dupilumab to upadacitinib, entering period 2 of the study. At week 32, response rates for patients who switched were: 79.6%, 58.7%, and 19.9% achieving EASI 75, EASI 90, and EASI 100, respectively; 60.2% achieving Worst Pruritus Numerical Rating Scale improvement ≥ 4 among those with baseline WP-NRS ≥ 4; 37.0% achieving WP-NRS 0/1 among those with baseline WP-NRS > 1; and 26.8% simultaneously achieving EASI 90 and WP-NRS 0/1. Clinically, meaningful outcomes were also observed at week 20. No new safety signals were identified compared with the established safety profile of upadacitinib. CONCLUSIONS: The current findings suggest that switching from dupilumab to upadacitinib may be an effective treatment strategy for patients who do not meet moderate-to-optimal treatment targets with dupilumab. CLINICAL TRIAL REGISTRATION: LEVEL UP (NCT05601882).