Background Only a few medications have been approved for the prevention and treatment of digital ulcers in Japan. Ethnicity has been reported to affect the severity and occurrence rate of digital ulcers, which are potentially caused by more common autoantibody prevalence in the systemic sclerosis (SSc) patients of some ethnic groups; however, information on Japanese and Asian patients is limited. In the present study, the adverse events and development of digital ulcers were investigated when bosentan was administered to Japanese SSc patients. We focused on liver function test abnormalities, which are one of the characteristic adverse events of bosentan, baseline patient characteristics, and the onset/resolution time of the associated adverse events. The occurrence and healing of digital ulcers over time in each patient were also examined.
Methods Twenty-eight (28) patients were enrolled in 9 study sites in Japan. This was a multi-center, single arm, open-labeled study conducted in order to investigate the safety and efficacy of bosentan in Japanese patients who had or had a previous history of SSc-related digital ulcers. The safety of the drug was monitored and the clinical course of digital ulcers was assessed up to Week 52 of the treatment.
Results The adverse events observed in ≥5% of patients, i.e., at least two patients during the 52-week treatment period, were upper respiratory tract infections (14/28, 50.0%), liver function test abnormalities (12/28, 42.9%), the development of new digital ulcers (7/28, 25.0%), anemia (5/28, 17.9%), peripheral edema (4/28, 14.3%), diarrhea (3/28, 10.7%), urinary tract infections (2/28, 7.1%), arthralgia (2/28, 7.1%), constipation (2/28, 7.1%), and herpes zoster (2/28, 7.1%). Of the 12 patients (42.9%) with liver function test abnormalities, 4 (14.3%) showed AST and/or ALT elevations >3 × the upper limit of normal, occurring before Week 16 for two patients and after Week 16 for the other two. All elevated liver enzymes normalized upon withdrawal of the drug. During the 52-week observation period, 25% (7/28) of patients developed new digital ulcers, the mean (± SD) number of which was 0.6±1.3.
Conclusions The adverse events observed in the present study were similar to those previously reported with the use of bosentan, demonstrating the safety of the drug for Japanese patients; however, 4 out of 28 patients had adverse events associated with liver function disorders, which are one of the characteristic adverse effects of bosentan. These results indicate that liver function needs to be monitored regularly in patients treated with bosentan.
Disclosure of Interest None declared