Abrocitinib Sustains Skin Clearance in Moderate and Severe Atopic Dermatitis Through 112 Weeks

People with atopic dermatitis who start treatment with moderate disease and those who start with severe disease both responded to the oral drug abrocitinib, according to a post-hoc analysis of two randomized trials published in Dermatology and Therapy. After 16 weeks of treatment, higher proportions of patients achieved clear or almost clear skin with abrocitinib than with placebo, regardless of whether their baseline disease was classified as moderate or severe. By week 112, sustained responses were still observed in both severity subgroups, with no new safety signals identified.

The analysis pooled data from the phase 3 JADE COMPARE trial (ClinicalTrials.gov ID: NCT03720470) and its long-term extension, JADE EXTEND (NCT03422822). Atopic dermatitis is a chronic, relapsing inflammatory skin disease characterized by eczematous lesions, intense itch, and impaired quality of life, and its severity fluctuates over time. The burden it places on patients increases proportionally with disease severity, and itch is frequently reported as the most burdensome symptom. Current guidelines for moderate-to-severe disease recommend systemic options including immunosuppressants, the biologics dupilumab, tralokinumab, lebrikizumab, and nemolizumab, and oral Janus kinase inhibitors such as abrocitinib, an oral, once-daily JAK1-selective inhibitor approved for adults and adolescents aged 12 years and older with moderate-to-severe atopic dermatitis.

The question the researchers set out to answer was whether baseline severity influences treatment response. Clinical trial data for new atopic dermatitis treatments are routinely reported for the full moderate-to-severe population rather than separately for moderate and severe subgroups, an approach that has attracted criticism. In this exploratory analysis, patients were classified post hoc by baseline severity using several tools: combined Investigator’s Global Assessment (IGA) and Eczema Area and Severity Index (EASI) scores, percentage of body surface area affected (%BSA), and, in the short-term analysis, the Patient’s Global Assessment (PtGA). Moderate disease was defined as IGA 3 with EASI 16–25, or BSA 10–30%, or PtGA score 3; severe disease as IGA 4 with EASI greater than 25, or BSA above 30%, or PtGA score 4.

In JADE COMPARE, 837 patients were randomly assigned to receive oral abrocitinib 100 mg or 200 mg once daily, placebo, or subcutaneous dupilumab 300 mg every two weeks, all combined with topical medicated therapy, for 16 weeks. At week 16, higher proportions of patients with moderate or severe baseline disease achieved an IGA response of 0 or 1—meaning clear or almost clear skin with at least a two-point improvement from baseline—with abrocitinib than with placebo. Among patients with moderate disease measured by IGA/EASI, 40.8% achieved IGA 0/1 with abrocitinib 100 mg and 50.0% with 200 mg, compared with 18.0% on placebo. Among patients with severe disease, the corresponding rates were 19.1% with 100 mg and 43.2% with 200 mg, versus 2.8% on placebo.

Response rates for other endpoints followed a similar pattern, including a 75% or greater improvement in EASI (EASI-75), a four-point or greater improvement in the Peak Pruritus Numerical Rating Scale (PP-NRS4), and co-achievement of EASI-90—a 90% improvement from baseline—along with a PP-NRS score of 0 or 1, indicating no itch or mild itch. Abrocitinib responses were similar to or better than dupilumab in patients with moderate or severe disease when severity was determined by IGA/EASI scores or %BSA. However, when severity was measured by PtGA, responses favored dupilumab in patients with moderate disease and abrocitinib 200 mg in those with severe disease. Patients in both severity subgroups showed early and maintained responses over weeks 0 to 16, and itch, measured by the PP-NRS, improved rapidly within the first two weeks in abrocitinib-treated patients compared with those on placebo or dupilumab.

The long-term findings came from a planned, interim analysis of the ongoing JADE EXTEND trial, which enrolled adults and adolescents aged 12 and older who had completed earlier qualifying JADE trials. All patients received oral abrocitinib 100 mg or 200 mg once daily, with or without topical corticosteroids, and were evaluated through week 112. At that point, the proportion of patients achieving IGA 0/1, EASI-75, PP-NRS4, or EASI-90 plus PP-NRS 0/1 responses remained high in both dose groups, whether baseline disease had been moderate or severe. IGA 0/1 was achieved at week 112 by 60.2% of patients with moderate disease on 100 mg and 64.3% on 200 mg, and by 38.6% with severe disease on 100 mg and 54.5% on 200 mg. The 254 adolescents in the analysis showed findings comparable to the overall population, although some adolescent subgroups were small.

Patient-reported outcomes reinforced these results. Among adults with a baseline Dermatology Life Quality Index score of at least 4, high proportions achieved the minimum clinically important improvement of four points or more from weeks 2 through 112, whether severity was assessed by IGA/EASI or %BSA. Adolescents with a baseline children’s DLQI score of at least 6 similarly sustained improvements of six points or more through week 112, regardless of baseline severity or the measure used. Across these measures, both doses showed greater responses than placebo in patients with moderate or severe disease, and patients with severe disease experienced the greatest itch improvement with the 200 mg dose.

Safety results were consistent with the previously published record of the JADE program. At week 16 in JADE COMPARE, there were no unexpected safety signals with either abrocitinib or dupilumab across severity classifications. Overall treatment-emergent adverse event occurrence was generally similar between moderate and severe disease by IGA/EASI, though the proportion of patients with at least one such event was numerically higher in severe disease when measured by %BSA or PtGA, and with the 200 mg dose. In JADE EXTEND, by the data cutoff of 5 September 2022, the most common treatment-emergent adverse events were atopic dermatitis and nasopharyngitis. Rates of serious adverse events, severe adverse events, and discontinuations due to adverse events were similar between dose groups, and the authors note that higher rates of events such as atopic dermatitis in severe subgroups may partly reflect underlying disease activity.

The authors caution that this was a post-hoc, exploratory analysis and was not powered to evaluate the interaction between baseline severity and treatment response or to compare abrocitinib with dupilumab within severity subgroups. Because JADE EXTEND is a long-term extension study, week 112 response rates were based on observed data without imputation for missing values, so long-term results may be subject to attrition bias, potentially inflating later response rates. Patients with prior biologic exposure were not eligible for enrollment, which may limit how broadly the findings apply, although published studies have reported generally comparable abrocitinib efficacy in biologic-experienced and biologic-naïve patients. Despite these limitations, the authors conclude that abrocitinib provided early and sustained improvement in skin clearance and itch through week 112 across moderate and severe baseline subgroups, that responses were consistent across several severity measures, and that more patients with severe baseline disease may achieve response with 200 mg than with 100 mg—observations that, they suggest, could inform starting dose and dose-titration decisions in routine practice.

Subject of Research: Long-term efficacy and safety of abrocitinib in moderate versus severe atopic dermatitis

Article Title: Does Baseline Severity of Atopic Dermatitis Impact the Long-Term Efficacy of Abrocitinib? Post-hoc Analysis of Two Randomized Trials

Article References: Pink, A. E., Rice, Z. P., Gooderham, M. J., Wang, F., Wollenberg, A., Biswas, P., Chan, G., Alderfer, J., & Watkins, M. (2026). Does Baseline Severity of Atopic Dermatitis Impact the Long-Term Efficacy of Abrocitinib? Post-hoc Analysis of Two Randomized Trials. Dermatology and Therapy, 16(11), 5777-5791. https://doi.org/10.1007/s13555-026-01937-1

Image Credits: AI Generated

DOI: 10.1007/s13555-026-01937-1

Keywords: atopic dermatitis, abrocitinib, JAK inhibitor, JADE COMPARE, JADE EXTEND, skin clearance, itch, post-hoc analysis, baseline severity, eczema, clinical trial, dermatology