{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T19:33:35Z","timestamp":1789500815788,"version":"build-2803163510"},"reference-count":17,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,1,23]],"date-time":"2025-01-23T00:00:00Z","timestamp":1737590400000},"content-version":"vor","delay-in-days":22,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["acrjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["ACR Open Rheumatology"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>Scleroderma\u2010associated autoantibodies (SSc\u2010Abs) are specific in participants (pts) with systemic sclerosis and are associated with organ involvement. Our objective was to assess the influence of baseline SSc\u2010Abs on the trajectories of the clinical outcome assessments (COAs) in a phase III randomized controlled trial.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We used data on both the groups who received placebo (Pbo) and tocilizumab from the focuSSced trial. The SSc\u2010Ab panel was assessed centrally. We analyzed four groups with SSc\u2010Abs: anti\u2013topoisomerase 1 antibody (ATA), anti\u2013RNA polymerase 3 antibody (RNAP3), anti\u2010centromere antibody, and negative for all three (triple negative). We assessed the impact of baseline SSc\u2010Abs on six COAs: modified Rodnan skin score (mRSS), forced vital capacity (FVC%), Health Assessment Questionnaire Disability Index, patient and clinical global assessments, and American College of Rheumatology (ACR) Composite Response Index in Systemic Sclerosis (CRISS).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We observed that all COAs, except for FVC%, improved for the group who received Pbo during the 48\u2010week period. For mRSS, pts with RNAP3 showed the largest Pbo effect (7.20 per year, n = 14) and smallest for ATA (3.28 per year, n = 49). This trend was also seen for the ACR CRISS (0.00\u20131.00 scale), with median improvement at week 48 of 0.94 for RNAP3 versus 0.01 for ATA. ATA enriched for FVC% decline of 7.34% per year versus 2.54% per year for RNAP3. In the group who received tocilizumab, similar changes were seen in the mRSS and ACR CRISS with preservation of lung function, irrespective of SSc\u2010Ab type.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our result shows a differential effect of SSc\u2010Abs on the trajectories of COAs over 48 weeks in group who received Pbo. These findings highlight the importance of incorporating SSc\u2010Abs in trial design, either as a stratification factor or limiting the SSc\u2010Abs that are included in the trials.<\/jats:p><jats:p><jats:boxed-text content-type=\"graphic\" position=\"anchor\"><jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/acr211782-gra-0001-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text><\/jats:p><\/jats:sec>","DOI":"10.1002\/acr2.11782","type":"journal-article","created":{"date-parts":[[2025,1,23]],"date-time":"2025-01-23T05:43:23Z","timestamp":1737611003000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Impact of Scleroderma\u2010Associated Autoantibodies on Clinical Outcome Assessments: Post Hoc Analysis From a Randomised, Double\u2010blind, Placebo\u2010controlled, Phase 3 Trial of Tocilizumab in Scleroderma"],"prefix":"10.1002","volume":"7","author":[{"given":"Basmah","family":"Al Dulaijan","sequence":"first","affiliation":[{"name":"University of Michigan  Ann Arbor"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suiyuan","family":"Huang","sequence":"additional","affiliation":[{"name":"University of Michigan  Ann Arbor"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Celia J. F.","family":"Lin","sequence":"additional","affiliation":[{"name":"Genentech  San Francisco California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3975-8938","authenticated-orcid":false,"given":"Christopher P.","family":"Denton","sequence":"additional","affiliation":[{"name":"Royal Free Hospital and University College London  London United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1412-4453","authenticated-orcid":false,"given":"Dinesh","family":"Khanna","sequence":"additional","affiliation":[{"name":"University of Michigan  Ann Arbor"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,1,23]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(17)30933-9"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2665-9913(22)00217-X"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.41153"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-2600(20)30318-0"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm.159.1.9712108"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.39501"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2017-211912"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/keac363"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/rap\/rky002"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.3899\/jrheum.160867"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1177\/23971983231215470"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/keac639"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.30467"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.41965"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/1529-0131(200103)44:3<653::AID-ANR114>3.0.CO;2-Q"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1177\/23971983241278079"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.42510"}],"container-title":["ACR Open Rheumatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/acrjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/acr2.11782","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,2]],"date-time":"2025-10-02T15:25:42Z","timestamp":1759418742000},"score":1,"resource":{"primary":{"URL":"https:\/\/acrjournals.onlinelibrary.wiley.com\/doi\/10.1002\/acr2.11782"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1]]},"references-count":17,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2025,1]]}},"alternative-id":["10.1002\/acr2.11782"],"URL":"https:\/\/doi.org\/10.1002\/acr2.11782","archive":["Portico"],"relation":{},"ISSN":["2578-5745","2578-5745"],"issn-type":[{"value":"2578-5745","type":"print"},{"value":"2578-5745","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,1]]},"assertion":[{"value":"2024-06-08","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-11-19","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-01-23","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e11782"}}