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Atopic dermatitis (AD) is a heterogeneous, chronic skin condition characterized by severe itching and eczematous lesions.1 Itch-dominant AD, marked by intense itch and mild-to-moderate skin lesions, can affect 21%–29% of patients with AD and substantially impacts quality of life (QoL).2 Despite its prevalence, data on systemic treatments for itch-dominant AD are limited. Abrocitinib, a Janus kinase 1–selective inhibitor, and dupilumab, an anti–interleukin 4 receptor antagonist, are approved systemic therapies for moderate-to-severe AD.3, 4 Abrocitinib has demonstrated sustained efficacy up to 48 weeks of treatment, supporting its role as an option for chronic AD management.5 In the JADE DARE (NCT04345367)6 and COMPARE (NCT03720470)7 clinical trials, abrocitinib showed a greater proportion of patients achieving a ≥4-point improvement in Peak Pruritus Numerical Rating Scale score (PP-NRS4) compared with dupilumab.6, 7 However, the relative efficacy of abrocitinib in itch-dominant AD was not assessed. This post hoc analysis evaluates abrocitinib and dupilumab's efficacy in improving itch and QoL in itch-dominant AD. The analysis included adult patients aged ≥18 years enrolled in JADE DARE6 and COMPARE7 receiving either oral abrocitinib 200 mg once daily or subcutaneous dupilumab 300 mg every 2 weeks in combination with topical therapy for 16 weeks. Itch-dominant AD was defined by baseline lesion severity (Investigator's Global Assessment [IGA] score of 3 or Eczema Area and Severity Index [EASI] score of 16 to 21) and a PP-NRS score of 7 to 10. Efficacy assessments included the proportion of patients achieving PP-NRS4, an itch-free state (PP-NRS 0/1) and a Dermatology Life Quality Index (DLQI) score of <2. Of 1194 patients with available baseline IGA and PP-NRS data, 498 (41.7%) had itch-dominant AD, including 255 and 243 patients in the abrocitinib 200 mg and dupilumab treatment arms, respectively (Table 1). Of 1190 patients with baseline EASI and PP-NRS data, 279 (23.4%) had itch-dominant AD, including 134 and 145 patients in the abrocitinib and dupilumab treatment arms, respectively. Demographics were comparable between treatment arms, regardless of whether baseline IGA + PP-NRS or EASI + PP-NRS scores were used to define itch-dominant AD. At Week 2, a greater proportion of patients with IGA + PP-NRS–defined, itch-dominant AD achieved PP-NRS4 with abrocitinib (55.7%) than with dupilumab (30.9%) (Figure 1a). By Week 16, response rates were comparable (68.1% vs. 66.5%, respectively). Similar patterns were observed in patients defined by baseline EASI + PP-NRS scores (Figure 1b). Of patients with IGA + PP-NRS–defined, itch-dominant AD, treatment with abrocitinib resulted in a greater proportion achieving an itch-free state: 17.3% of patients achieved PP-NRS 0/1 at Week 2 versus 2.9% of patients treated with dupilumab. This difference was maintained through Week 16 (35.3% vs. 20.9%, respectively; Figure 1c). Similar trends were observed in patients with itch-dominant AD defined by baseline EASI + PP-NRS scores (Figure 1d). For QoL, a greater proportion of patients with IGA + PP-NRS–defined, itch-dominant AD achieved a DLQI score <2 with abrocitinib as early as Week 2 vs. dupilumab (21.2% vs. 6.3%). Improvements continued through Week 16 (37.9% vs. 23.8%, respectively; Figure 1e). Similar results were observed in patients defined by baseline EASI + PP-NRS scores (Figure 1f). In patients with itch-dominant AD, abrocitinib was associated with earlier and higher threshold efficacy itch response8 and greater improvements in QoL compared with dupilumab in combination with topical therapy. Additionally, abrocitinib 200 mg with concomitant topical therapy demonstrated sustained itch relief up to Week 16. Taken separately, the results of JADE DARE and COMPARE were consistent between studies.6, 7 Estimates for differences in treatment effect of abrocitinib versus dupilumab were based on controlling, via Cochran–Mantel–Haenszel weighting, for the individual study effect. These findings suggest that abrocitinib may be a viable option for managing itch-dominant AD—a phenotype associated with significant disease burden. However, the post hoc nature of the analysis may limit the generalizability of the results. Future research should focus on larger prospective studies to confirm these findings and explore the long-term efficacy and safety of abrocitinib in diverse patient populations. Understanding the mechanisms behind differential responses to abrocitinib and dupilumab could further optimize treatment strategies for itch-dominant AD. We thank Dr. Delphine Staumont-Salle (CHU Lille, Université de Lille, CEREO Centre de Référence des Syndromes Hyperéosinophiliques, U1286 Inserm INFINITE, Lille, France), who contributed to the early development of the article. Editorial/medical writing support under the guidance of the authors was provided by Kathleen Proudfoot, PhD, at Nucleus Global, and was funded by Pfizer Inc., New York, NY, USA, in accordance with Good Publication Practice (GPP 2022) guidelines (Ann Intern Med. 2022; https://doi.org/10.7326/M22-1460). Pfizer's generative artificial intelligence (AI)–assisted technology—MAIA (Medical Artificial Intelligence Assistant)—was used in the production of the first draft of this manuscript. After using this tool/service, the authors reviewed and edited content as needed and take full responsibility for the content of this publication. The studies included in this analysis were sponsored by Pfizer Inc.—including the development of protocols, implementation of the studies, data collection and analysis—and supported the manuscript preparation. JIS served as an investigator for Celgene, Eli Lilly and Company, F. Hoffmann-La Roche, Menlo Therapeutics, Realm Therapeutics, Regeneron Pharmaceuticals and Sanofi; as a consultant for Pfizer Inc., AbbVie, Anacor, AnaptysBio, Arena Pharmaceuticals, Dermavant, Dermira, Eli Lilly and Company, Galderma, GlaxoSmithKline, Glenmark, Incyte, Kiniksa Pharmaceuticals, LEO Pharma, Menlo Therapeutics, Novartis, Realm Therapeutics, Regeneron Pharmaceuticals and Sanofi; and as a speaker for Regeneron Pharmaceuticals and Sanofi. MdB-W is a consultant, advisory board member and/or speaker for Pfizer, AbbVie, Almirall, Arena, Aslan, Eli Lilly and Company, Galderma, Janssen, LEO Pharma, Regeneron and Sanofi. JOdF has served as an assessor for AbbVie, Almirall, Astellas, Eli Lilly and Company, Galderma, GlaxoSmithKline, Novartis, Pfizer Inc., Sanofi and Uriach; has served as a speaker for AbbVie, Astellas, Beiersdorf, LEO Pharma, MSD, Novartis and Sanofi; and has conducted clinical trials for AbbVie, Astellas, Bayer, Eli Lilly and Company, LEO Pharma, Novartis, Pfizer Inc. and Sanofi. JFS has served as a speaker, advisory board member and/or investigator for AbbVie, Almirall, Amgen, AstraZeneca, Bristol Myers Squibb, Eli Lilly and Company, Galderma, Incyte, LEO Pharma, Novartis, Pfizer Inc., Regeneron and Sanofi. BE, DEM, PB, IH-M, EG and MM are employees and shareholders of Pfizer Inc. RC has served as an advisor, consultant, speaker and/or investigator for AbbVie, Acelyrin, Alumis, Amgen, AnaptysBio, Apogee Therapeutics, Arcutis Biotherapeutics Inc., Argenx, Astria Therapeutics Inc., Avalere Health, Beiersdorf, Boehringer Ingelheim, Bristol Myers Squibb, Cara Therapeutics, Castle Biosciences, CLn Skin Care, Dermavant, Eli Lilly and Company, EMD Serono, Formation Bio, Galderma, Genentech, GlaxoSmithKline, Incyte, Johnson & Johnson, Kenvue, LEO Pharma, L'Oréal, Nektar Therapeutics, Novartis, Opsidio, Pfizer Inc., RAPT Therapeutics, Regeneron, Sanofi, Sitryx, Takeda, TRex Bio and UCB. All study documents and procedures were approved by the appropriate institutional review boards/ethics committees at each study site. The studies were conducted in accordance with the ethical principles of the Declaration of Helsinki and all International Council for Harmonisation good clinical practice guidelines. All local regulatory requirements were followed. Informed consent was obtained from all participants of the individual studies included in this analysis. Upon request, and subject to review, Pfizer will provide the data that support the findings of this study. Subject to certain criteria, conditions and exceptions, Pfizer may also provide access to the related individual de-identified participant data. See https://www.pfizer.com/science/clinical-trials/trial-data-and-results for more information.