Switching to Upadacitinib Monotherapy Was Associated With Minimal or No Flares Following Inadequate Response to Dupilumab in Patients With Moderate-to-Severe Atopic Dermatitis

Patients with moderate-to-severe atopic dermatitis (AD) who have an inadequate response to biologic therapy may benefit from switching to a different treatment class. In the LEVEL UP and HEADS UP studies, most patients with inadequate response to dupilumab (DUPI) who switched to upadacitinib (UPA) achieved clinically meaningful improvements in skin and itch outcomes. However, patients who experience a partial response to DUPI may be concerned about losing their partial response or experiencing worsening symptoms after discontinuation, which may make them reluctant to switch treatments. This analysis assessed the occurrence of clinically meaningful skin lesions and itch flares after switching to UPA following inadequate response to DUPI. This post-hoc analysis included patients with moderate-to-severe AD who switched from DUPI to UPA monotherapy in the LEVEL UP and HEADS UP studies. In LEVEL UP, patients with inadequate response (defined as failure to achieve ≥ 75% improvement from baseline severity in Eczema Area and Severity Index score [EASI75]) to DUPI 300 mg at Week 16 switched to UPA 15 mg, with dose escalation to UPA 30 mg based on clinical response. For HEADS UP, patients with an inadequate response (defined as failure to achieve EASI75) with DUPI at Week 24 and who then received UPA 30 mg thereafter were analyzed. Skin lesion and itch flares were defined using validated minimal clinically important difference (MCID) thresholds as a ≥ 6.6-point increase in EASI score and a ≥ 4-point increase in Worst Pruritus Numerical Rating Scale (WP-NRS) score, respectively, from the time of switching. The proportions of patients experiencing a flare at any assessment through 16 weeks after switching were evaluated using analyses of observed-case data. At switch baseline, mean EASI and WP-NRS scores were 13.5 (SD, 7.7) and 3.9 (SD, 2.3), respectively, in LEVEL UP and 11.8 (SD, 4.6) and 4.1 (SD, 2.7), respectively, in HEADS UP. Through 16 weeks after switching, no skin lesion flares were observed in LEVEL UP (0/201) or HEADS UP (0/27). Among patients with WP-NRS ≤ 6 at switch, itch flares occurred in 3.6% (5/139) of patients in LEVEL UP and 4.8% (1/21) in HEADS UP. Among patients with an inadequate response to DUPI, switching to UPA monotherapy was associated with no observed skin lesion flares and infrequent itch flares through 16 weeks in LEVEL UP and HEADS UP. These findings may help inform treatment-switch discussions with patients concerned about worsening skin lesions or itch flares during the transition from DUPI to UPA.