Objective: To identify the optimal dose of oral iloprost on the basis of efficacy and tolerability in patients with Raynaud's phenomenon secondary to systemic sclerosis.
Design: Multicentre, randomized, parallel-group comparison of two different doses of oral iloprost and placebo.
Setting: European university hospitals.
Patients: A total of 103 patients with Raynaud's phenomenon secondary to systemic sclerosis.
Intervention: Patients received one of three treatments for 6 weeks: placebo, oral iloprost 50 µg or oral iloprost 100 µg. Each treatment was taken twice daily, giving total daily doses of iloprost of 100 and 200 µg.
Measurements: The frequency, total daily duration and severity of Raynaud's attacks were recorded in a specially designed patient diary; physician's global assessment and adverse events were recorded at visits to the clinic. Analysis was performed on an intention-to-treat population.
Results: A total of 103 patients were recruited, 89 completed the assessments throughout the treatment period and 82 completed an additional 6 weeks of follow-up after treatment. Thirty-five patients received placebo, 33 received iloprost 50 µg and 35 received iloprost 100 µg. The mean percentage reductions in the frequency, total daily duration and severity of Raynaud's attacks were numerically greater in the iloprost groups at the end of treatment and at the end of follow-up. At the end of treatment (6 weeks), there were significant treatment differences in the total daily duration of attacks (P = 0.03), but not in the severity (P = 0.07) or the frequency of attacks (P = 0.37). At the end of follow-up (12 weeks), there were significant treatment differences in the total daily duration of attacks (P = 0.001) and in the severity of attacks (P = 0.007), but not in the frequency of attacks (P = 0.07). Percentages of patients improved at the end of treatment as assessed by the physician were 44% placebo, 57% iloprost 50 µg and 64% iloprost 100 µg (not significant). Side-effects were reported by 80% of patients on placebo, 85% on oral iloprost 50 µg and 97% on oral iloprost 100 µg. Premature discontinuations of treatment in each group were 9, 30 and 51%, respectively, with 6, 27 and 51% being due to adverse events.
Conclusion: The results on the daily duration of Raynaud's attacks suggest that both 50 and 100 µg oral iloprost twice daily may be effective in the treatment of Raynaud's phenomenon secondary to systemic sclerosis. The 50 µg iloprost dose was better tolerated in this patient group.