Current immunosuppressive and antifibrotic therapies of systemic sclerosis and emerging therapeutic strategies

ABSTRACT

Introduction

Systemic sclerosis (SSc) is a rare, difficult to treat disease with profound effects on quality of life and high mortality. Complex and incompletely understood pathophysiologic processes and greatly heterogeneous clinical presentations and outcomes have hampered drug development.

Areas covered

This review summarizes the currently available immunosuppressive and antifibrotic therapies and discusses novel approaches for the treatment of SSc. We reviewed the literature using the MEDLINE and ClinicalTrial.gov databases between May and September 2020.

Expert opinion

Available immunosuppressive and antifibrotic drugs only modestly impact the course of the disease. Most drugs are currently only investigated in the subset of patients with early diffuse cutaneous SSc. In this patient population, hematopoietic stem-cell transplantation is currently the only treatment that has demonstrated reversal of lung involvement, enhanced quality of life and reduced long-term mortality, but carries the risk of short-term treatment-related mortality. A great need to provide better therapeutic options to patients exists also for those patients who have limited cutaneous skin involvement. A better understanding of SSc pathophysiology has enabled the identification of numerous new therapeutic targets. The progress made in the design of clinical trials and outcome parameters will likely result in the improvement of effective management options.

KEYWORDS:

• Scleroderma
• interstitial lung disease
• fibrosis
• stem-cell transplantation
• treatment
• disease-modifying antirheumatic drugs

Article highlights

• Low SSc prevalence, great variability of clinical manifestations, and complex pathophysiology represent major challenges for clinical trial design.

• Currently, HSCT is the only treatment modality that has shown a benefit on long-term survival, but it is associated with a risk of treatment-related mortality.

• Nintedanib slows, but not fully abrogates, FVC decline in SSc-ILD.

• Significant advances in the understanding of SSc biology have led to the identification of a variety of new therapeutic targets.

• SSc remains a difficult to treat disease with high morbidity and mortality.

Declaration of interest

UA Walker has received speakers or advisor honoraria from Boehringer Ingelheim, BMS, GSK, and Roche. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.