Predictive Factors for Primary and Secondary Nonresponders to Upadacitinib in Patients with Moderate-to-Severe Atopic Dermatitis: A Real-World Study

Abstract: Background: Some patients with atopic dermatitis (AD) do not sufficiently respond to upadacitinib, a Janus kinase 1 inhibitor. However, predictive factors for nonresponders remain unclear in real-world practice. Objective: To identify predictive factors for primary and secondary nonresponders to upadacitinib 15 mg; primary nonresponders are defined as patients with investigator’s global assessment (IGA) >2 at week 12, while secondary nonresponders are defined as patients with IGA ≤2 at week 12 and IGA >2 at week 24. Methods: A prospective study was conducted from August 2021 to March 2024, involving 204 Japanese AD patients treated with upadacitinib 15 mg. Baseline clinical and laboratory indexes were compared between nonresponders and responders. Results: Primary nonresponders showed higher baseline eczema area and severity index (EASI), immunoglobulin E (IgE), thymus and activation-regulated chemokine (TARC), lactate dehydrogenase (LDH), neutrophil-to-lymphocyte ratio (NLR), C-reactive protein (CRP), systemic immune-inflammation index (SII), and systemic inflammation response index (SIRI) compared with responders. Secondary nonresponders had a higher proportion of previous systemic therapies, dupilumab, and corticosteroids. Conclusions: Higher baseline EASI, IgE, TARC, LDH, NLR, CRP, SII, and SIRI may predict primary nonresponders to upadacitinib 15 mg, while previous systemic dupilumab or corticosteroids may predict secondary nonresponders.