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.

Treatment modalities and drug survival in a systemic sclerosis real-life patient cohort

“…For vasoactive agents, the results were quite different, revealing high and comparable retention rates for CCB, ERAs, and PDE5 inhibitors and limited numbers of cases who had to stop treatment mainly due to adverse events. These results are confirmed in other observational studies [35][36][37] and indicate that contrary to the unmet need of adequate immunomodulation in SSc, vasculopathy seems to be managed in a more efficient way after the introduction of advanced vasoactive regimens during the last 15 years. Our study has certain limitations.…”

Efficacy of Botulinum Toxin B Injection for Raynaud’s Phenomenon and Digital Ulcers in Patients with Systemic Sclerosis

“…In addition, a 1,000 and 2,000 U BTX-B injection accelerated the healing of RP-related intractable DUs, and prevented new formation of DUs, indicating that BTX-B might have therapeutic potential for severe RP symptoms. The oral endothelin receptor antagonist, bosentan, is clinically used for the prevention and treatment of DU in patients with SSc (39). In the present study, only one patient in the group treated with 2,000 U received bosentan before BTX-B treatment for several years, but severe RP and 3 DUs in the left hand were present at baseline.…”

<p>Management of digital ulcers in systemic sclerosis</p>

“…Multiple studies have finally proven that the efficacy and safety of bosentan is maintained in the long term. [44][45][46][47] On the basis of all these results, EULAR guidelines state that bosentan should be considered for reduction in the number of new DUs in SSc, especially in patients with multiple DUs despite the use of calciumchannel blockers (CCBs), PDE5 inhibitors, or iloprost therapy (strength of recommendation: A). 26 The aforementioned data refer only to bosentan, but recently data about other endothelin-receptor antagonists (ERAs) were published.…”

“…26 Another adverse effect, commonly reported, is fluid retention like peripheral edema or pericardial effusion. 47…”