Sustained AD Control After Abrocitinib: Dose Effects and Biomarker Insights

Introduction: Atopic dermatitis (AD) is a relapsing inflammatory skin disease characterized by eczematous lesions and pruritus. Abrocitinib, an oral Janus kinase (JAK)1-selective inhibitor, has demonstrated clinical efficacy and safety in multiple clinical trials and is approved for the treatment of moderate to severe AD. However, less is known about the durability of disease control after abrocitinib discontinuation. Procedure: This post hoc analysis used data from a phase 2b (NCT02780167) trial to examine disease control during a 4-week, drug-free, follow-up period in patients who received abrocitinib (100 or 200 mg) or placebo over 12 weeks. The proportions of total patients and Week 12 responders (≥75% improvement in Eczema Area and Severity Index [EASI-75]) who had a flare during follow-up were determined. Flares were defined as ≥50% loss of Week 12 EASI response with a new Investigator’s Global Assessment (IGA) score of ≥2.1 Whole-blood mRNA sequencing data from Weeks 0, 4, and 12 were analyzed in responders who remained flare-free after treatment discontinuation to identify differentially expressed genes. Results: In total, 121 patients were included in the analysis (abrocitinib 200 mg, 47; abrocitinib 100 mg, 41; placebo, 33). At Week 12, EASI-75 was achieved by 36 patients (76.6%) who received abrocitinib 200 mg, 22 (53.7%) who received abrocitinib 100 mg, and 8 (24.2%) who received placebo. Among Week 12 responders who received abrocitinib, more than half remained flare-free following treatment discontinuation, maintaining EASI <7 (clear to mild) and IGA 0/1 (clear or almost clear) (abrocitinib 200 mg, 69.4%; abrocitinib 100 mg, 54.5%). Among patients who remained flare-free after treatment discontinuation, those who received either dose of abrocitinib showed differential early transcriptomic changes from baseline to Week 4 compared with patients who received placebo. Transcriptomic analyses suggested reduced IFN-α and IFN-γ signaling and attenuation of inflammatory response and complement pathways relative to placebo. Conclusion: Most responders receiving either 200 mg or 100 mg of abrocitinib remained flare-free after treatment discontinuation. Additionally, exploratory blood transcriptomic analysis restricted to responders who remained flare-free revealed early expression changes in abrocitinib-treated patients versus placebo, most notably reduced type I and II interferon (IFN‑α and IFN‑γ) signaling, consistent with the known pharmacodynamic effect of JAK1 inhibition. Further investigation is warranted to better understand these changes in responder transcriptomic profiles and to identify potential biomarkers associated with disease control following treatment discontinuation.