{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T22:10:54Z","timestamp":1780956654440,"version":"3.54.1"},"reference-count":27,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2018,10,17]],"date-time":"2018-10-17T00:00:00Z","timestamp":1539734400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100008792","name":"Novartis Pharma","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008792","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["acrjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Arthritis &amp; Rheumatology"],"published-print":{"date-parts":[[2018,12]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>Secukinumab (anti\u2013interleukin\u201017A [anti\u2013IL\u201017A]) is an effective therapy for ankylosing spondylitis and psoriatic arthritis, the prototypical forms of spondyloarthritis (SpA). We undertook this study to determine whether secukinumab modulates the immunopathology of target lesions without blunting systemic immune responses, using peripheral SpA as a model.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Twenty patients with active peripheral SpA were included in a 12\u2010week open\u2010label trial with secukinumab (300 mg once weekly from baseline to week 4 and then every 4 weeks thereafter). Outcomes included clinical response, cytokine production by peripheral blood cells using TruCulture technology, and histologic and real\u2010time quantitative polymerase chain reaction analysis of synovial biopsy samples before and after treatment.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>All patients completed the 12\u2010week study without severe adverse events (AEs) or severe treatment\u2010related AEs. The efficacy end point, the number of patients meeting the American College of Rheumatology 20% improvement criteria (achieving an ACR20 response) at 12 weeks, was achieved by 13 of the 20 patients, of whom 8 achieved an ACR50 response and 5 achieved an ACR70 response, with rapid and significant improvements in all clinical disease activity measures. Clinical improvement in joint counts was associated with a histologic decrease in synovial sublining macrophages (<jats:italic>P<\/jats:italic> = 0.028) and neutrophils (<jats:italic>P<\/jats:italic> = 0.004), both of which are sensitive synovial biomarkers of inflammatory response in peripheral SpA, as well as with decreased synovial expression of IL\u201017A messenger RNA (mRNA) (<jats:italic>P<\/jats:italic> = 0.010) but not of tumor necrosis factor mRNA. Systemically, secukinumab treatment decreased the C\u2010reactive protein level and the erythrocyte sedimentation rate (both <jats:italic>P<\/jats:italic> &lt; 0.01), and also decreased matrix metalloproteinase 3 production in the TruCulture system (<jats:italic>P<\/jats:italic> &lt; 0.05). However, with the exception of IL\u201017A itself, the capacity of peripheral blood cells to produce a broad panel of cytokines and chemokines upon stimulation with microbial antigens was not affected.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This mechanism\u2010of\u2010action study in peripheral SpA indicates that clinical improvement with secukinumab treatment is paralleled by immunomodulation of inflamed target tissues without compromising systemic immune responses.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.40581","type":"journal-article","created":{"date-parts":[[2018,6,5]],"date-time":"2018-06-05T06:34:28Z","timestamp":1528180468000},"page":"1994-2002","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":46,"title":["Brief Report: Interleukin\u201017 Blockade With Secukinumab in Peripheral Spondyloarthritis Impacts Synovial Immunopathology Without Compromising Systemic Immune Responses"],"prefix":"10.1002","volume":"70","author":[{"given":"Leonieke J. J.","family":"van Mens","sequence":"first","affiliation":[{"name":"Academic Medical Center, University of Amsterdam Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marleen G. H.","family":"van de Sande","sequence":"additional","affiliation":[{"name":"Academic Medical Center, University of Amsterdam Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Menegatti","sequence":"additional","affiliation":[{"name":"Pasteur Institute Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sijia","family":"Chen","sequence":"additional","affiliation":[{"name":"Academic Medical Center, University of Amsterdam Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iris C. J.","family":"Blijdorp","sequence":"additional","affiliation":[{"name":"Academic Medical Center, University of Amsterdam Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henriette M.","family":"de Jong","sequence":"additional","affiliation":[{"name":"Academic Medical Center, University of Amsterdam Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Inka A.","family":"Fluri","sequence":"additional","affiliation":[{"name":"Academic Medical Center, University of Amsterdam Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Talia E.","family":"Latuhihin","sequence":"additional","affiliation":[{"name":"Academic Medical Center, University of Amsterdam Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arno W. R.","family":"van Kuijk","sequence":"additional","affiliation":[{"name":"Amsterdam Rheumatology and Immunology Center\/Reade Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lars","family":"Rogge","sequence":"additional","affiliation":[{"name":"Pasteur Institute Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nataliya G.","family":"Yeremenko","sequence":"additional","affiliation":[{"name":"Academic Medical Center, University of Amsterdam Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dominique L. P.","family":"Baeten","sequence":"additional","affiliation":[{"name":"Academic Medical Center, University of Amsterdam Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,10,17]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1412679"},{"key":"e_1_2_8_3_1","first-page":"50","article-title":"Long\u2010term effects of interleukin\u201017A inhibition with secukinumab in active ankylosing spondylitis: 3\u2010year efficacy and safety results from an extension of the Phase 3 MEASURE 1 trial","volume":"36","author":"Baraliakos X","year":"2018","journal-title":"Clin Exp Rheumatol"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1314258"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2012.11.005"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2012-202245"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/1529-0131(200101)44:1<186::AID-ANR25>3.0.CO;2-B"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2010.133645"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1186\/ar1501"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.33396"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.37704"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780380602"},{"key":"e_1_2_8_13_1","first-page":"2286","article-title":"A new approach to defining disease status in ankylosing spondylitis: the Bath Ankylosing Spondylitis Disease Activity Index","volume":"21","author":"Garrett S","year":"1994","journal-title":"J Rheumatol"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1136\/ard.62.2.127"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1159\/000250839"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2003.018549"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2014.03.002"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780380107"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.21914"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.20477"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1159\/000343290"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2008.091389"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1186\/ar3351"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1111\/exd.12487"},{"key":"e_1_2_8_25_1","article-title":"Development of effector and regulatory T cells","author":"Souwer Y","year":"2015","journal-title":"WIRM"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1186\/ar3370"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0024048"},{"issue":"10","key":"e_1_2_8_28_1","article-title":"Anti\u2010TNF therapy in axial spondyloarthritis;\u202fprediction of therapeutic responses using immunological signatures [abstract]","volume":"68","author":"Rogge L","year":"2016","journal-title":"Arthritis Rheumatol"}],"container-title":["Arthritis &amp; 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