ORAL ILOPROST IN RAYNAUDS-PHENOMENON SECONDARY TO SYSTEMIC-SCLEROSIS - A MULTICENTER, PLACEBO-CONTROLLED, DOSE-COMPARISON STUDY

Objective. To identify the optimal dose of oral iloprost bn the basis of efficacy and tolerability in patients with Raynaud's phenomenon sec ondary to systemic sclerosis. Design. Multicentre, randomized, paralle l-group comparison of two different doses of oral iloprost and placebo . Setting. European university hospitals. Patients. A total of 103 pat ients with Raynaud's phenomenon secondary to systemic sclerosis. Inter vention. Patients received one of three treatments for 6 weeks: placeb o, oral iloprost 50 mu g or oral iloprost 100 mu g. Each treatment was taken twice daily, giving total daily doses of iloprost of 100 and 20 0 mu g. Measurements. The frequency, total daily duration and severity of Raynaud's attacks were recorded in a specially designed patient di ary; 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 compl eted the assessments throughout the treatment period and 82 completed an additional 6 weeks of follow-up after treatment. Thirty-five patien ts received placebo, 33 received iloprost 50 mu g and 35 received ilop rost 100 mu g. The mean percentage reductions in the frequency, total daily duration and severity of Raynaud's attacks were numerically grea ter in the iloprost groups at the end of treatment and at the end of f ollow-up. At the end of treatment (6 weeks), there were significant tr eatment: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 treat ment differences in the total daily duration of attacks (P = 0.001) an d 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 tre atment as assessed by the physician were 44% placebo, 57% iloprost 50 mu g and 64% iloprost 100 mu g (not significant). Side-effects were re ported by 80% of patients on placebo, 85% on oral iloprost 50 mu g and 97% on oral iloprost 100 mu g. Premature discontinuations of treatmen t in each group were 9, 30 and 51%, respectively, with 6, 27 and 51% b eing due to adverse events. Conclusion. The results on the daily durat ion of Raynaud's attacks suggest that both 50 and 100 mu g oral ilopro st twice daily may be effective in the treatment of Raynaud's phenomen on secondary to systemic sclerosis. The 50 mu g iloprost dose was bett er tolerated in this patient group.