DOI: 10.6084/m9.figshare.31026204
title: Dose-dependent effectiveness and patient-reported outcomes with JAK1 inhibitors in atopic dermatitis: a 36-week multicenter real-world cohort

description: Dose-stratified real-world data for JAK1 inhibitors in AD are limited. To compare effectiveness and safety of standard vs high doses of abrocitinib and upadacitinib in routine care. 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). A total of 124 patients were analyzed (abrocitinib 100 mg, <i>n</i> = 28; abrocitinib 200 mg, <i>n</i> = 32; upadacitinib 15 mg, <i>n</i> = 30; upadacitinib 30 mg, <i>n</i> = 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; <i>p</i> = 0.036) and in 22/34 (64.7%) versus 14/30 (46.7%) for upadacitinib (OR 2.92, 95% CI 1.16–7.38; <i>p</i> = 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 <i>p</i> &lt; 0.01). Safety was comparable across groups. High-dose JAK1 regimens achieve faster, numerically greater disease control without short-term safety tradeoffs, supporting escalation in suboptimal responders. <b>Higher Doses of JAK1 Inhibitors Improve Eczema Control Without Extra Safety Risks</b> Atopic dermatitis (AD), also called eczema, is a long-term skin disease that causes itching, redness, and discomfort. JAK1 inhibitors are tablets that calm the immune system and help control AD. Two commonly used JAK1 inhibitors are abrocitinib and upadacitinib, which can be given in lower or higher daily doses. It is important to know whether the higher doses work better in real-life care. We evaluated the medical records of 124 adults with atopic dermatitis who were treated in three centers in Turkey. Patients received abrocitinib at either 100 mg or 200 mg per day, or upadacitinib at either 15 mg or 30 mg per day. We measured how many people achieved major skin improvement by Week 12, using a score called the Eczema Area and Severity Index (EASI-75), which means at least a 75% reduction in skin symptoms compared to the start. We found that more patients improved on the higher doses: about 63% with abrocitinib 200 mg and 65% with upadacitinib 30 mg, compared with 36% and 47% on the lower doses. Higher doses also brought faster itch relief and quicker disease control, often within 12 weeks. Side effects were similar across groups. Our findings suggest that increasing to higher doses of JAK1 inhibitors may be a safe and effective option for patients whose eczema does not improve enough on standard doses. <b>What’s already known about this topic?</b>Real-world, dose-stratified evidence for JAK1 inhibitors in atopic dermatitis is scarce, with most data derived from randomized trials rather than routine practice.<b>What does this study add?</b>In a 36-week multicenter cohort, higher-dose abrocitinib and upadacitinib achieved faster, greater clinical and patient-reported improvements, numerically higher minimal disease activity rates, and maintained comparable safety versus standard doses.<b>How does this study impact current management guidelines?</b>This study supports dose-escalation of JAK1 inhibitors as an effective and safe strategy when standard regimens are insufficient, providing real-world evidence that may guide future treatment algorithms. <b>What’s already known about this topic?</b> Real-world, dose-stratified evidence for JAK1 inhibitors in atopic dermatitis is scarce, with most data derived from randomized trials rather than routine practice. <b>What does this study add?</b> In a 36-week multicenter cohort, higher-dose abrocitinib and upadacitinib achieved faster, greater clinical and patient-reported improvements, numerically higher minimal disease activity rates, and maintained comparable safety versus standard doses. <b>How does this study impact current management guidelines?</b> This study supports dose-escalation of JAK1 inhibitors as an effective and safe strategy when standard regimens are insufficient, providing real-world evidence that may guide future treatment algorithms.