Head and Neck Atopic Dermatitis: Therapeutic Response After Switching to Upadacitinib in Moderate-to-Severe Atopic Dermatitis Patients Who Had Inadequate Response to Dupilumab

Abstract

Head and neck (HN) atopic dermatitis (AD) imposes substantial burden on patients, given its visible nature and vulnerability to environmental triggers. Symptoms in these areas can cause psychosocial distress. While both upadacitinib (UPA) and dupilumab (DUPI) are established treatments for moderate-to-severe AD, persistent HN disease remains a therapeutic gap. This study evaluated the efficacy of switching to UPA in patients with moderate-to-severe AD who demonstrated inadequate HN response while receiving DUPI. This analysis evaluated data from patients with moderate-to-severe AD treated in two studies evaluating UPA vs DUPI: Heads Up (HU) and Level Up (LU). In HU, patients were randomized to DUPI 300mg or UPA 30mg (UPA30) before entering the open-label extension (OLE), which started at week 24. All patients, including those previously randomized to UPA and DUPI, received UPA30. In LU, patients were randomized to DUPI 300mg or UPA 15mg (UPA15) with dose escalation to UPA30 based on clinical response. The OLE began at week 16, at which point patients with inadequate disease response, as defined by an Eczema Area and Severity Index (EASI) score of <75%, either remained on UPA (staying on or escalating to UPA30) or switched from DUPI to UPA15 with dose escalation to UPA30 based on clinical response at week 20. Inadequate HN response was defined as not achieving HN EASI ≥75% (EASI75). Achievement of HN EASI ≥75/90/100% (EASI75/90/100) was assessed at week 4 and week 16 post-switch in DUPI-treated patients who had inadequate HN response. Among DUPI HN AD inadequate responders at the switch point, mean baseline HN EASI scores were similar between HU (2.7; n=50) and LU (2.8; n=165). Mean HN EASI scores at switch point were similar between DUPI inadequate responders in HU (week 24: 1.4; n=50) and LU (week 16: 1.8; n=102). Most patients in HU who switched from DUPI to UPA at week 24 achieved HN EASI75 (week 28: 81.3%; week 40: 80.9%) and HN EASI90 (week 28: 64.6%; week 40: 63.8%), with many achieving HN EASI100 (week 28: 35.4%; week 40: 46.8%). Median HN EASI improved from baseline by 95% one month after switching. Patients in LU who switched from DUPI to UPA at week 16 achieved HN EASI75 (week 20: 58.9%; week 32: 68.8%), HN EASI90 (week 20: 36.2%; week 32: 48.1%), and HN EASI100 (week 20: 20.9%; week 32: 33.8%). Median HN EASI improved from baseline by 78.3% and 87.9% at months 1 and 4 after switching, respectively. Most patients reported clinically meaningful improvement in overall itch after switching to UPA. In moderate-to-severe AD, switching to UPA improved HN lesions in patients who had inadequate response to DUPI. Many patients achieved improvement as early as 1 month after switching, supporting UPA as an effective therapeutic strategy for this patient population.