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Therefore, there is a pressing need to develop a coherent strategy for effective initial and subsequent selection of biologic agents. We interrogated 40 PsA patients initiating either tumour necrosis factor inhibitors (TNFi) or interleukin-17A inhibitors (17Ai) for active PsA. Patients achieving low disease activity according to the Disease Activity Index for PsA (DAPSA) at 3\u00a0months were classified as responders. Baseline and 3-month CD4<jats:sup>+<\/jats:sup>transcript profiling were performed, and novel signaling pathways were identified using a multi-omics profiling and integrative computational analysis approach. Using transcriptomic data at initiation of therapy, we identified over 100 differentially expressed genes (DEGs) that differentiated IL-17Ai response from non-response and TNFi response from non-response. Integration of cell-type-specific DEGs with protein\u2013protein interactions and further comprehensive pathway enrichment analysis revealed several pathways. Rho GTPase signaling pathway exhibited a strong signal specific to IL-17Ai response and the genes,<jats:italic>RAC1<\/jats:italic>and<jats:italic>ROCK<\/jats:italic>s, are supported by results from prior research. Our detailed network and pathway analyses have identified the rewiring of Rho GTPase pathways as potential markers of response to IL17Ai but not TNFi. These results need further verification.<\/jats:p>","DOI":"10.1038\/s41598-020-78866-2","type":"journal-article","created":{"date-parts":[[2020,12,10]],"date-time":"2020-12-10T11:09:12Z","timestamp":1607598552000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Rho-GTPase pathways may differentiate treatment response to TNF-alpha and IL-17A inhibitors in psoriatic arthritis"],"prefix":"10.1038","volume":"10","author":[{"given":"Sara","family":"Rahmati","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Darren D.","family":"O\u2019Rielly","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Quan","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dianne","family":"Codner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda","family":"Dohey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kari","family":"Jenkins","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Igor","family":"Jurisica","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dafna D.","family":"Gladman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vinod","family":"Chandran","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Proton","family":"Rahman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,12,10]]},"reference":[{"key":"78866_CR1","doi-asserted-by":"publisher","first-page":"ii18","DOI":"10.1136\/ard.2004.033217","volume":"64","author":"RGB Langley","year":"2005","unstructured":"Langley, R. 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