An update on recent randomized clinical trials in systemic sclerosis.

Systemic sclerosis (SSc) is an autoimmune disorder characterized by a remarkable clinical heterogeneity and variable disease course. In this multifactorial condition, the interaction of several pathogenic pathways related to inflammation, vasculopathy and fibrosis promote organ damage. The understanding of the pathogenesis of SSc has improved in recent years leading to the identification of relevant therapeutic targets. Over the last few years, insightful clinical trials have been published and great progress has been made in developing effective therapeutic options. The positive results of the Safety and Efficacy of Nintedanib in Systemic SClerosIS (SENSCIS) trial have led to the approval by drug agencies of the first drug for SSc-related interstitial lung disease. However, the majority of clinical trials have focused on immunosuppressive therapy. Although benefit trends have been observed, outstanding results have not been achieved and to date no immunosuppressant has been approved in SSc. Clinical trial design has evolved regarding inclusion criteria with the aim to enrich for progressive patients. Endpoints have also been revised to better cover the fields of patients' feelings and functioning. Finally, background synthetic immunosuppressants have been allowed in some trials evaluating targeted therapies opening the door to combination therapies. Herewith, we provide an overview of the most significant clinical trials developed in recent years for the management of SSc.