{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T00:43:33Z","timestamp":1781052213814,"version":"3.54.1"},"reference-count":17,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2020,7,28]],"date-time":"2020-07-28T00:00:00Z","timestamp":1595894400000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2020,7,28]],"date-time":"2020-07-28T00:00:00Z","timestamp":1595894400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000005","name":"U.S. Department of Defense","doi-asserted-by":"publisher","award":["W81XWH\u201016\u20101\u20100296"],"award-info":[{"award-number":["W81XWH\u201016\u20101\u20100296"]}],"id":[{"id":"10.13039\/100000005","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000069","name":"National Institute of Arthritis and Musculoskeletal and Skin Diseases","doi-asserted-by":"publisher","award":["R01AR073284"],"award-info":[{"award-number":["R01AR073284"]}],"id":[{"id":"10.13039\/100000069","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["acrjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["ACR Open Rheumatology"],"published-print":{"date-parts":[[2020,8]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>The modified Rodnan skin score (mRSS) is often used as a primary outcome measure in systemic sclerosis (SSc) randomized clinical trials (RCTs). Previous cohort studies with predominantly European Caucasian patients showed that setting an upper limit of mRSS as a selection criterion for RCTs leads effectively to enrichment with progressive patients. This study aimed to demonstrate this effect in an ethnically diverse cohort, rich in patients positive for anti\u2010RNA polymerase III antibodies (Pol3).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We selected from the Genetics versus Environment in Scleroderma Outcomes Study (GENISOS) cohort patients with diffuse cutaneous SSc (dcSSc), who had mRSS of 7 or more at inclusion and a documented mRSS after 12 \u00b1 2 months. Progression of skin fibrosis was defined as an increase in mRSS greater than 5 points and 25% or more from baseline. To identify the optimal cutoff for the baseline mRSS yielding the highest sensitivity for progressive skin fibrosis, we developed ROC curves and logistic regression models with \u201cprogression\u201d as the outcome variable and a binary variable of baseline mRSS cutoff point as predictor.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We included 152 patients (age and disease duration [mean \u00b1 SD, years]: 48.7 \u00b1 13.0 and 2.4 \u00b1 1.5 respectively, 22.4% males, 34.2% Pol3\u2010positive). Seventeen patients (11.2%) had skin fibrosis progression after 12 \u00b1 2 months. An mRSS cutoff of\u00a027 or less had the highest probability of progression (odds ratio, 9.12; 95% confidence interval: 1.173\u201070.851; <jats:italic>P<\/jats:italic> = 0.035; area under the curve, 0.652; sensitivity, 94%).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>We demonstrated in an ethnically diverse cohort of patients with early dcSSc and with a high proportion of patients who are Pol3\u2010positive that setting an upper limit of the mRSS as a selection criterion leads effectively to cohort enrichment with progressors.<\/jats:p><\/jats:sec>","DOI":"10.1002\/acr2.11165","type":"journal-article","created":{"date-parts":[[2020,7,28]],"date-time":"2020-07-28T08:56:40Z","timestamp":1595926600000},"page":"496-502","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Enrichment Strategy for Systemic Sclerosis Clinical Trials Targeting Skin Fibrosis: A Prospective, Multiethnic Cohort Study"],"prefix":"10.1002","volume":"2","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8627-8817","authenticated-orcid":false,"given":"Carina","family":"Mihai","sequence":"first","affiliation":[{"name":"University Hospital Zurich, Zurich, Switzerland, and Cantacuzino Hospital Carol Davila University of Medicine and Pharmacy Bucharest Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rucsandra","family":"Dobrota","sequence":"additional","affiliation":[{"name":"University Hospital Zurich Zurich Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shervin","family":"Assassi","sequence":"additional","affiliation":[{"name":"The University of Texas McGovern Medical School at Houston"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maureen D.","family":"Mayes","sequence":"additional","affiliation":[{"name":"The University of Texas McGovern Medical School at Houston"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2413-1959","authenticated-orcid":false,"given":"Oliver","family":"Distler","sequence":"additional","affiliation":[{"name":"University Hospital Zurich Zurich Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,7,28]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/keu288"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.rmed.2016.09.011"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.41055"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(16)00232-4"},{"issue":"10","key":"e_1_2_8_6_1","article-title":"Efficacy and safety of tocilizumab for the treatment of systemic sclerosis: results from a Phase 3 randomized controlled trial [abstract]. Arthritis","volume":"70","author":"Khanna D","year":"2018","journal-title":"Rheumatol"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.39501"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1903076"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.5301\/jsrd.5000231"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2014-205226"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2015-208024"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2011-200742"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.24734"},{"key":"e_1_2_8_14_1","unstructured":"Scleroderma Clinical Trials Consortium.Rodnan skin score training. URL:https:\/\/sclerodermaclinicaltrialsconsortium.org\/sctc\u2010clinical\u2010studies\/rodnan\u2010skin\u2010score\u2010training(accessed on May 21 2020)"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780230510"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.38098"},{"key":"e_1_2_8_17_1","first-page":"202","article-title":"Scleroderma (systemic sclerosis): classification, subsets and pathogenesis","volume":"15","author":"LeRoy EC","year":"1988","journal-title":"J Rheumatol"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2017-211912"}],"container-title":["ACR Open Rheumatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Facr2.11165","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/acr2.11165","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/acr2.11165","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/acrjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/acr2.11165","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/acrjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/acr2.11165","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,2]],"date-time":"2025-10-02T17:21:40Z","timestamp":1759425700000},"score":1,"resource":{"primary":{"URL":"https:\/\/acrjournals.onlinelibrary.wiley.com\/doi\/10.1002\/acr2.11165"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,7,28]]},"references-count":17,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2020,8]]}},"alternative-id":["10.1002\/acr2.11165"],"URL":"https:\/\/doi.org\/10.1002\/acr2.11165","archive":["Portico"],"relation":{},"ISSN":["2578-5745","2578-5745"],"issn-type":[{"value":"2578-5745","type":"print"},{"value":"2578-5745","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,7,28]]},"assertion":[{"value":"2020-05-24","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-06-03","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-07-28","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}