{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T14:26:54Z","timestamp":1790519214451,"version":"4.1.0"},"reference-count":27,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2017,11,6]],"date-time":"2017-11-06T00:00:00Z","timestamp":1509926400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100004339","name":"Sanofi","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004339","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis & Rheumatology"],"published-print":{"date-parts":[[2018,10]]},"abstract":"Objective<\/jats:title>Preclinical studies suggest a role for lysophosphatidic acid (LPA<\/jats:styled-content>) in the pathogenesis of systemic sclerosis (SS<\/jats:styled-content>c). We undertook this study to assess SAR<\/jats:styled-content>100842, a potent selective oral antagonist of the LPA<\/jats:styled-content>1<\/jats:sub> receptor, for safety, biomarkers, and clinical efficacy in patients with diffuse cutaneous SS<\/jats:styled-content>c (dcSS<\/jats:styled-content>c).<\/jats:p><\/jats:sec>Methods<\/jats:title>An 8\u2010week double\u2010blind, randomized, placebo\u2010controlled study followed by a 16\u2010week open\u2010label extension with SAR<\/jats:styled-content>100842 was performed in patients with early dcSS<\/jats:styled-content>c who had a baseline modified Rodnan skin thickness score (MRSS<\/jats:styled-content>) of at least 15. The primary end point was safety during the double\u2010blind phase of the trial. Exploratory end points included the identification of an LPA<\/jats:styled-content>\u2010induced gene signature in patients\u2019 skin.<\/jats:p><\/jats:sec>Results<\/jats:title>Seventeen of 32 patients were randomly assigned to receive placebo and 15 to receive SAR<\/jats:styled-content>100842; 30 patients participated in the open\u2010label extension study. The most frequent adverse events reported for SAR<\/jats:styled-content>100842 during the blinded phase were headache, diarrhea, nausea, and falling, and the safety profile was acceptable during the open\u2010label extension. At week 8, the reduction in MRSS<\/jats:styled-content> was numerically greater in the SAR<\/jats:styled-content>100842 group than in the placebo group (mean \u00b1 SD<\/jats:styled-content> change \u22123.57 \u00b1 4.18 versus \u22122.76 \u00b1 4.85; treatment effect \u22121.2 [95% confidence interval \u22124.37, 2.02]; P<\/jats:italic> = 0.46). A greater reduction of LPA<\/jats:styled-content>\u2010related genes was observed in skin samples from the SAR<\/jats:styled-content>100842 group at week 8, indicating LPA<\/jats:styled-content>1<\/jats:sub> target engagement.<\/jats:p><\/jats:sec>Conclusion<\/jats:title>SAR<\/jats:styled-content>100842, a selective orally available LPA<\/jats:styled-content>1<\/jats:sub> receptor antagonist, was well tolerated in patients with dcSS<\/jats:styled-content>c. The MRSS<\/jats:styled-content> improved during the study although the difference was not significant, and additional gene signature analysis suggested target engagement. These results need to be confirmed in a larger controlled trial.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.40547","type":"journal-article","created":{"date-parts":[[2018,5,7]],"date-time":"2018-05-07T01:04:28Z","timestamp":1525655068000},"page":"1634-1643","source":"Crossref","is-referenced-by-count":108,"title":["Lysophosphatidic Acid Receptor 1 Antagonist SAR100842 for Patients With Diffuse Cutaneous Systemic Sclerosis"],"prefix":"10.1002","volume":"70","author":[{"given":"Yannick","family":"Allanore","sequence":"first","affiliation":[{"name":"Rheumatology A department Cochin Hospital Paris Descartes University Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oliver","family":"Distler","sequence":"additional","affiliation":[{"name":"University Hospital Zurich Zurich Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandre","family":"Jagerschmidt","sequence":"additional","affiliation":[{"name":"Sanofi R&D Chilly\u2010Mazarin 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