{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T03:46:49Z","timestamp":1778644009307,"version":"3.51.4"},"reference-count":21,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2016,7,4]],"date-time":"2016-07-04T00:00:00Z","timestamp":1467590400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100005646","name":"Actelion Pharmaceuticals","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100005646","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Journal of Dermatology"],"published-print":{"date-parts":[[2017,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>A multicenter, open\u2010label study was performed to investigate the safety and tolerability of bosentan in Japanese patients with systemic sclerosis (<jats:styled-content style=\"fixed-case\">SS<\/jats:styled-content>c) and secondary digital ulcers. Twenty\u2010eight patients were enrolled. The safety and tolerability of bosentan was monitored over 52 weeks of study treatment (primary end\u2010point), while incidence and healing of digital ulcers were also assessed up to week 16. The following adverse events occurred in 5% or more of patients during the 52\u2010week treatment period: upper respiratory tract infection (50.0%), abnormal liver function tests (42.9%), digital ulcers (25.0%), anemia (17.9%), peripheral edema (14.3%), diarrhea (10.7%), urinary tract infection (7.1%), arthralgia (7.1%), constipation (7.1%) and herpes zoster (7.1%). Eight patients experienced at least one serious adverse event, including drug\u2010related serious adverse events in two patients, which were abnormal liver function tests and fluid retention (pericardial effusion) in one patient each. During the 16\u2010week observation period, seven out of 28 patients (25%) developed new digital ulcers. In this study, adverse events were comparable with those previously reported with bosentan. Approximately half of the patients had adverse events associated with abnormal liver function tests, thus we conclude that liver function should be monitored regularly during treatment with bosentan.<\/jats:p>","DOI":"10.1111\/1346-8138.13497","type":"journal-article","created":{"date-parts":[[2016,7,4]],"date-time":"2016-07-04T08:12:58Z","timestamp":1467619978000},"page":"13-17","source":"Crossref","is-referenced-by-count":17,"title":["Safety and tolerability of bosentan for digital ulcers in Japanese patients with systemic sclerosis: Prospective, multicenter, open\u2010label study"],"prefix":"10.1111","volume":"44","author":[{"given":"Yasuhito","family":"Hamaguchi","sequence":"first","affiliation":[{"name":"Department of Dermatology Faculty of Medicine Institute of Medical Pharmaceutical and Health Sciences Kanazawa University Kanazawa 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