title: Safety and tolerability of bosentan for digital ulcers in Japanese patients with systemic sclerosis: Prospective, multicenter, open-label study.
abstract: A multicenter, open-label study was performed to investigate the safety and tolerability of bosentan in Japanese patients with systemic sclerosis (SSc) and secondary digital ulcers. Twenty-eight patients were enrolled. The safety and tolerability of bosentan was monitored over 52 weeks of study treatment (primary end-point), 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-week 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-related serious adverse events in two patients, which were abnormal liver function tests and fluid retention (pericardial effusion) in one patient each. During the 16-week 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.
authors.affiliation: Department of Dermatology, Faculty of Medicine, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kanazawa, Japan.
authors.forename: Yasuhito
authors.initials: Y
authors.lastname: Hamaguchi
authors.affiliation: Department of Internal Medicine, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Sumida
authors.affiliation: Institute of Rheumatology, Tokyo Women's Medical University, Tokyo, Japan.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Kawaguchi
authors.affiliation: Department of Dermatology and Plastic Surgery, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan.
authors.forename: Hironobu
authors.initials: H
authors.lastname: Ihn
authors.affiliation: Department of Collagen Disease and Infection Medicine, Kitasato University Hospital, Sagamihara, Japan.
authors.forename: Sumiaki
authors.initials: S
authors.lastname: Tanaka
authors.affiliation: Department of Dermatology, University of Tokyo Graduate School of Medicine, Tokyo, Japan.
authors.forename: Yoshihide
authors.initials: Y
authors.lastname: Asano
authors.affiliation: Department of Dermatology, Gunma University Graduate School of Medicine, Maebashi, Japan.
authors.forename: Sei-Ichiro
authors.initials: SI
authors.lastname: Motegi
authors.affiliation: Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Masataka
authors.initials: M
authors.lastname: Kuwana
authors.affiliation: Department of Internal Medicine, Toho University School of Medicine, Tokyo, Japan.
authors.forename: Hirahito
authors.initials: H
authors.lastname: Endo
authors.affiliation: Department of Dermatology, Faculty of Medicine, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kanazawa, Japan.
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Takehara
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000740:Anemia / Q000139:chemically induced; D018771:Arthralgia / Q000139:chemically induced; D000077300:Bosentan; D003248:Constipation / Q000139:chemically induced; D003967:Diarrhea / Q000139:chemically induced; D065128:Endothelin Receptor Antagonists / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D005260:Female; D005385:Fingers; D006562:Herpes Zoster / Q000139:chemically induced; D006801:Humans; D007564:Japan; D008099:Liver / Q000187:drug effects; D008111:Liver Function Tests; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012595:Scleroderma, Systemic / Q000097:blood / Q000150:complications*; D012883:Skin Ulcer / Q000097:blood / Q000188:drug therapy* / Q000209:etiology; D013449:Sulfonamides / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D016896:Treatment Outcome; D014945:Wound Healing / Q000187:drug effects*
chemical_list: D065128:Endothelin Receptor Antagonists; D013449:Sulfonamides; D000077300:Bosentan
keywords: adverse event; bosentan; digital ulcer; dual endothelin receptor antagonist; systemic sclerosis