Intravenous Iloprost Infusion in Patients with Raynaud Phenomenon Secondary to Systemic Sclerosis: A Multicenter, Placebo-controlled, Double-Blind Study

Intravenous Iloprost Infusion in Patients with Raynaud Phenomenon Secondary to Systemic Sclerosis: A Multicenter, Placebo-controlled, Double-Blind Study

From The Johns Hopkins University School of Medicine, Baltimore, Maryland; Robert Wood Johnson Medical School, New Brunswick, New Jersey; West Virginia University, Morgantown, West Virginia; University of Pittsburgh, Pittsburgh, Pennsylvania; Thomas Jefferson University, Philadelphia, Pennsylvania; Wayne State University, Detroit, Michigan; UCLA School of Medicine, Los Angeles, California; UCLA San Fernando Valley Program, Granada Hills, California; University of Oregon, Portland, Oregon; University of Chicago, Chicago, Illinois; Bowman Gray School of Medicine, Winston-Salem, North Carolina; State University at New York at Stony Brook, Stony Brook, New York; Berlex Laboratories, Wayne, New Jersey. Requests for Reprints: Fredrick M. Wigley, MD, The Johns Hopkins University, Division of Molecular and Clinical Rheumatology, 1830 East Monument Street, Suite 7500, Baltimore, MD 21205 Acknowledgments: The authors thank Gwenn Leatherman, RN, Mary J.F. Rykiel, RN, MAS, Linda Ehrlich, RN, MSN, Sue Connaughton, RN, MSN, and Carol Blair, RN, for technical assistance; Robert Lehr, MS, for the statistical analyses; Naomi Marcus, PhD, for assistance in preparing the report; and Shawnice M. Foster for secretarial support. Grant Support: Funded and coordinated by Berlex Laboratories, whose representatives (WD and JW) participated with the principal investigators in the study design, analysis, and manuscript preparation.

Abstract

Objective: To evaluate the efficacy and safety of iloprost, a prostacyclin analog, administered intravenously in patients with Raynaud phenomenon secondary to systemic sclerosis.

Design: Multicenter, randomized, parallel placebo-controlled, double-blind study.

Setting: University medical centers.

Patients: 131 patients with systemic sclerosis (101 women, 30 men) ages 20 to 79 years.

Intervention: Patients were randomly assigned to receive one of two parallel treatments of five daily sequential, 6-hour intravenous infusions of iloprost (0.5 to 2.0 ng/kg per min) or to receive a similar volume of placebo.

Measurements: Frequency of Raynaud attacks, Raynaud severity score, physician's overall rating of treatment effect, and digital cutaneous lesion healing.

Results: Of the 131 patients enrolled, 126 completed the 5-day infusion and 114 (87%) completed at least 6 weeks of follow-up. Sixty-four patients were randomly assigned to receive iloprost and 67 patients, to receive placebo. The mean weekly number of Raynaud attacks decreased 39.1% with iloprost and 22.2% with placebo (P = 0.005). In addition, the mean percentage of improvement in a global Raynaud severity score during the entire 9-week follow-up was greater in patients given iloprost (34.8%) than in those receiving placebo (19.7%) (P = 0.011). The physician's overall rating of treatment effect showed greater improvement with iloprost than with placebo at week 6 (52.4% compared with 27.4%; P = 0.008) and week 9 (60.9% compared with 26.9%; P < 0.001). At week 3, 14.6% more patients receiving iloprost had 50% or more lesions heal compared with those given placebo (95% CI, 0.9% to 30%). During the infusion, 59 (92%) of the patients receiving iloprost had one or more side effects compared with 38 (57%) of the patients receiving placebo.

Conclusion: Iloprost is effective for the short-term palliation of severe Raynaud phenomenon in patients with systemic sclerosis.