Dose-dependent effectiveness and patient-reported outcomes with JAK1 inhibitors in atopic dermatitis: a 36-week multicenter real-world cohort

Background Dose-stratified real-world data for JAK1 inhibitors in AD are limited.Objective To compare effectiveness and safety of standard vs high doses of abrocitinib and upadacitinib in routine care.Methods Multicenter, retrospective cohort study. The primary endpoint was Week-12 achievement of Eczema Area and Severity Index (EASI)-75. Secondary outcomes included patient-reported improvements at Minimal Clinically Important Difference (MCID) thresholds, Minimal Disease Activity (MDA) at Week 36, time-to-EASI-75, and treatment-emergent adverse events(TEAE).Results A total of 124 patients were analyzed (abrocitinib 100 mg, n = 28; abrocitinib 200 mg, n = 32; upadacitinib 15 mg, n = 30; upadacitinib 30 mg, n = 34). At Week 12, EASI-75 was achieved in 20/32 (62.5%) versus 10/28 (35.7%) for abrocitinib (OR 2.94, 95% CI 1.06–8.15; p = 0.036) and in 22/34 (64.7%) versus 14/30 (46.7%) for upadacitinib (OR 2.92, 95% CI 1.16–7.38; p = 0.021), favoring the higher-dose regimens. Itch improvement was more frequent with higher doses. By Week 36, full minimal disease activity was observed in 30.2% of patients receiving abrocitinib 200 mg and 26.7% receiving upadacitinib 30 mg, compared with 18.4% and 20.0% in the lower-dose groups. Kaplan–Meier analysis showed faster responses with high doses (median 12 vs 36 weeks; log-rank p < 0.01). Safety was comparable across groups.Conclusion High-dose JAK1 regimens achieve faster, numerically greater disease control without short-term safety tradeoffs, supporting escalation in suboptimal responders.