Practical suggestions on intravenous iloprost in Raynaud's phenomenon and digital ulcer secondary to systemic sclerosis: Systematic literature review and expert consensus

Background: Systemic sclerosis (SSc) is an autoimmune chronic disease characterized by vascular impairment, immune dysfunction and collagen deposition. Raynaud's phenomenon (RP) and digital ulcers (DU) are prominent features of SSc. Intravenous (IV) iloprost (ILO), according to the recently updated EULAR recommendations, is indicated for RP after failure of oral therapy. Moreover, IV ILO could be useful in DU healing. IV ILO is currently available mainly on the European market approved for RP secondary to SSc with 3–5 days infusion cycle. Unfortunately, data published varies regarding regimen (dosage, duration and frequency). Up to now, ILO has been studied in small cohorts of patients and in few randomized controlled trials. Methods: A systematic review of studies on IV ILO in patients with SSc complicated by DU and RP was performed. Insufficient data were available to perform a meta-analysis according to the GRADE system. We performed a three-stage internet-based Delphi consensus exercise. Results: Three major indications were identified for IV ILO usage in SSc: RP non-responsive to oral therapy, DU healing, and DU prevention. IV ILO should be administered between 0.5 and 2.0 ng/kg/min according to patient tolerability with a frequency depending on the indication. Conclusions: Although these suggestions are supported by this expert group to be used in clinical setting, it will be necessary to formally validate the present suggestions in future clinical trials.