Insight into the Contrasting Findings of Therapeutic Trials of Digital Ischaemic Manifestations of Systemic Sclerosis

Abstract

Digital vascular complications are a major cause of disease-related morbidity in systemic sclerosis (SSc). Demonstrating treatment efficacy in the management of cutaneous vascular manifestations of SSc has been challenging. The contrasting findings of clinical trials of Raynaud’s phenomenon (RP) and digital ulcers (DU) for within-class medications have led to doubt on likely efficacy; with geographic variation in reimbursement policies and variation in clinical practice. In this paper, we compare the contrasting trials of phosphodiesterase inhibitors in the management of SSc-RP and endothelin receptor antagonists in the management of SSc-DU to help identify potential barriers for future successful clinical trials in these fields. Scrutiny of the contrasting clinical trials in these fields has identified a number of important differences in trial design and patient characteristics that may account for differences in clinical trial outcomes. These factors include differences in patient selection, impact of seasonal variation in weather, and the definitions applied to SSc manifestations. The contrasting findings of clinical trials of within-class medications for the management of digital vascular manifestations of SSc have been disappointing but can provide investigators with valuable insight into treatment response in SSc and the pre-requisites for future effective clinical trial design.