New promising drugs for the treatment of systemic sclerosis: pathogenic considerations, enhanced classifications, and personalized medicine
Alain Lescoat, John Varga, Marco Matucci‐Cerinic, Dinesh Khanna
Abstract
Introduction: Systemic sclerosis (SSc), also known as scleroderma, is a complex orphan disease characterized by early inflammatory features, vascular hyper-reactivity, and fibrosis of the skin and internal organs. Although substantial progress has been made in the understanding of the pathogenesis of SSc, there is still no disease-modifying drug that could significantly impact the natural history of the disease.Areas covered: This review discusses the rationale, preclinical evidence, first clinical eevidence,and pending issues concerning new promising therapeutic options that are under investigation in SSc. The search strategy was based on PubMed database and clinical trial.gov, highlighting recent key pathogenic aspects and phase I or II trials of investigational drugs in SSc.Expert opinion: The identification of new molecular entities that potentially impact inflammation and fibrosis may constitute promising options for a disease modifying-agent in SSc. The early combinations of antifibrotic drugs (such as pirfenidone) with immunomodulatory agents (such as mycophenolate mofetil) may also participate to achieve such a goal. A more refined stratification of patients, based on clinical features, molecular signatures, and identification of subpopulations with distinct clinical trajectories, may also improve management strategies in the future.