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Upadacitinib: Fast and more pronounced skin improvement in AD patients

Presented by
Prof. Jonathan Silverberg, George Washington University School of Medicine, USA
AAD 2022
Phase 3, Heads Up
A novel analysis of the Heads Up trial revealed that a larger proportion of adult patients with moderate-to-severe atopic dermatitis (AD) achieved incrementally greater levels of skin improvement with the Janus kinase (JAK) inhibitor upadacitinib compared with patients treated with dupilumab. This effect might lead to a better quality of life in these patients.

Previously, the superior efficacy of the selective JAK inhibitor upadacitinib compared with dupilumab for the treatment of moderate-to-severe AD was demonstrated in the phase 3b, randomised Heads Up study (NCT03738397) [1]. The primary study endpoint was the proportion of patients that achieved an improvement in the Eczema Area and Severity Index (EASI) by 75% from baseline at week 16. Participants were randomised 1:1 to receive either oral upadacitinib 30 mg once daily (with a placebo prefilled syringe every other week) or subcutaneous dupilumab 300 mg every other week (with an oral placebo tablet once daily after a 600 mg loading dose at baseline). In the current analysis, presented by Prof. Jonathan Silverberg (George Washington University School of Medicine, Washington DC, USA), skin improvement was compared between upadacitinib and dupilumab using the proportions of patients who achieved improvement on the EASI score from baseline by ≥50%, ≥75%, ≥90%, and ≥100% [2].

A total of 692 participants could be included in this analysis. At week 16, a greater proportion of patients achieved skin improvements with upadacitinib than with dupilumab for each EASI category (see Figure). The difference in the proportion of patients that achieved complete skin clearance was particularly pronounced: 27.9% of patients treated with the JAK inhibitor achieved a ≥100% improvement in the EASI score compared with 7.6% treated with dupilumab (P<0.01). EASI improvements among dupilumab-treated patients were numerically greater at week 24. However, the total proportion of patients who achieved incrementally greater skin improvement levels with dupilumab was still 28.1% lower relative to upadacitinib.

Prof. Silverberg concluded that achieving substantial levels of skin improvement with upadacitinib is likely to translate into improvements in the overall quality of life for patients with AD.


Figure: Greater EASI50, EASI75 EASI90, and EASI100 responses at week 16 with upadacitinib vs dupilumab (NRI-C) [2]

*P<0.05; **P<0.01; ***P<0.001. EASI75/90/100 were multiplicity-controlled endpoints; EASI50 was a post-hoc analysis. DUPI, dupilumab; EASI, Eczema Area and Severity Index; NRI-C, non-responder imputation incorporating multiple imputations to handle missing data due to COVID-19; QD, once daily; Q2W, once every 2 weeks; UPA, upadacitinib.


    1. Blauvelt A, et al. JAMA Dermatol. 2021;157(9):1047–1055.
    2. Silverberg, J et al. Achieving incrementally greater skin improvement thresholds with upadacitinib vs dupilumab in moderate-to-severe atopic dermatitis: Heads Up study results. P34599, AAD 2022 Annual Meeting, 25–29 March, Boston, MA, USA.

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