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To characterize circulating inflammatory profiles and underlying systemic disease heterogeneity within AD patients, blood samples from adult patients (<jats:italic>N<\/jats:italic>\u00a0=\u00a0123) with moderate\u2010to\u2010severe AD in a phase 2\u00a0study of baricitinib (JAHG) were analysed. Baseline levels of 131\u00a0markers were evaluated using high\u2010throughput and ultrasensitive proteomic platforms, patient clusters were generated based on these peripheral markers. We implemented a novel cluster reproducibility method to validate cluster outcomes within our study and used publicly available AD biomarker data set (73\u00a0markers,<jats:italic>N<\/jats:italic>\u00a0=\u00a058 patients) to validate our findings. Cluster reproducibility analysis demonstrated best consistency for 2\u00a0clusters by<jats:italic>k<\/jats:italic>\u2010means, reproducibility of this clustering outcome was validated in an independent patient cohort. These unique JAHG patient subgroups either possessed elevated pro\u2010inflammatory mediators, notably TNF\u03b2, MCP\u20103 and IL\u201013, among a variety of immune responses (high inflammatory) or lower levels of inflammatory biomarkers (low inflammatory). The high inflammatory subgroup was associated with greater baseline disease severity, demonstrated by greater EASI, SCORAD Index, Itch NRS and DLQI scores, compared with low inflammatory subgroup. African\u2010American patients were predominantly associated with the high inflammatory subgroup and increased baseline disease severity. In patients with moderate\u2010to\u2010severe AD, heterogeneity was identified by the detection of 2 disease subgroups, differential clustering amongst ethnic groups and elevated pro\u2010inflammatory mediators extending beyond traditional polarized immune responses. Therapeutic strategies targeting multiple pro\u2010inflammatory cytokines may be needed to address this heterogeneity.<\/jats:p>","DOI":"10.1111\/exd.14389","type":"journal-article","created":{"date-parts":[[2021,5,18]],"date-time":"2021-05-18T12:54:06Z","timestamp":1621342446000},"page":"1650-1661","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["Insights into adult atopic dermatitis heterogeneity derived from circulating biomarker profiling in patients with moderate\u2010to\u2010severe disease"],"prefix":"10.1111","volume":"30","author":[{"given":"Jonathan T.","family":"Sims","sequence":"first","affiliation":[{"name":"Eli Lilly and Company Indianapolis IN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ching\u2010Yun","family":"Chang","sequence":"additional","affiliation":[{"name":"Eli Lilly and Company Indianapolis IN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard E.","family":"Higgs","sequence":"additional","affiliation":[{"name":"Eli Lilly and Company Indianapolis IN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah M.","family":"Engle","sequence":"additional","affiliation":[{"name":"Eli Lilly and Company Indianapolis IN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yushi","family":"Liu","sequence":"additional","affiliation":[{"name":"Eli Lilly and Company Indianapolis IN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sean E.","family":"Sissons","sequence":"additional","affiliation":[{"name":"Eli Lilly and Company Indianapolis IN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George H.","family":"Rodgers","sequence":"additional","affiliation":[{"name":"Eli Lilly and Company Indianapolis IN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric L.","family":"Simpson","sequence":"additional","affiliation":[{"name":"Department of Dermatology Oregon Health &amp; 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