{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T16:44:34Z","timestamp":1790873074560,"version":"4.1.0"},"reference-count":31,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2010,3,26]],"date-time":"2010-03-26T00:00:00Z","timestamp":1269561600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatism"],"published-print":{"date-parts":[[2010,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Endothelin is implicated as a participatory pathway in systemic sclerosis (SSc). We tested this hypothesis in a 12\u2010month trial of bosentan, a nonselective endothelin receptor antagonist, as a therapy for SSc\u2010related interstitial lung disease (ILD).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Method<\/jats:title>\n                    <jats:p>Patients with SSc and significant ILD were recruited to this prospective, double\u2010blind, randomized, placebo\u2010controlled, parallel group study. The inclusion criteria were designed to select a cohort enriched for patients with active and progressive disease. Exclusion factors included significant pulmonary hypertension. Patients with a diffusing capacity for carbon monoxide of &lt;80% predicted and a 6\u2010minute walk distance of 150\u2013500 meters or a 6\u2010minute walk distance of \u2265500 meters with a decrease in oxygen saturation received bosentan or placebo. The primary efficacy end point was a change in the 6\u2010minute walk distance from baseline up to month 12. Secondary end points included time to death or worsening results of pulmonary function tests (PFTs). The safety and tolerability of bosentan were also assessed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Among the 163 patients, 77 were randomized to receive bosentan, and 86 were randomized to receive placebo. No significant difference between treatment groups was observed for change in the 6\u2010minute walk distance up to month 12. No deaths occurred in this study group. Forced vital capacity and diffusing capacity for carbon monoxide remained stable in the majority of patients in both groups. Significant worsening of PFT results occurred in 25.6% of patients receiving placebo and 22.5% of those receiving bosentan (\n                      <jats:italic>P<\/jats:italic>\n                      not significant).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>No improvement in exercise capacity was observed in the bosentan\u2010treated group compared with the placebo group, and no significant treatment effect was observed for the other end points. Although many outcome variables were stable, bosentan did not reduce the frequency of clinically important worsening. These data do not support the use of endothelin receptor antagonists as therapy for ILD secondary to SSc.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/art.27466","type":"journal-article","created":{"date-parts":[[2010,3,26]],"date-time":"2010-03-26T15:01:46Z","timestamp":1269615706000},"page":"2101-2108","source":"Crossref","is-referenced-by-count":102,"title":["Randomized, prospective, placebo\u2010controlled trial of bosentan in interstitial lung disease secondary to systemic sclerosis"],"prefix":"10.1002","volume":"62","author":[{"given":"J. R.","family":"Seibold","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C. P.","family":"Denton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D. 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J.","family":"Rubin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Wells","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Matucci Cerinic","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G.","family":"Riemekasten","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P.","family":"Emery","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H.","family":"Chadha\u2010Boreham","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P.","family":"Charef","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Roux","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C. M.","family":"Black","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2010,6,29]]},"reference":[{"key":"e_1_2_8_2_2","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2006.066068"},{"key":"e_1_2_8_3_2","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm.149.6.8004317"},{"key":"e_1_2_8_4_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa055120"},{"key":"e_1_2_8_5_2","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200702-326OC"},{"key":"e_1_2_8_6_2","doi-asserted-by":"publisher","DOI":"10.1165\/ajrcmb\/7.5.492"},{"key":"e_1_2_8_7_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1747.2001.01256.x"},{"key":"e_1_2_8_8_2","doi-asserted-by":"publisher","DOI":"10.1007\/s004080000058"},{"key":"e_1_2_8_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(01)06250-X"},{"key":"e_1_2_8_10_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa012212"},{"key":"e_1_2_8_11_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.20676"},{"key":"e_1_2_8_12_2","first-page":"S90","article-title":"for the RAPIDS\u20102 Investigators. 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