An update on the pharmacotherapeutic options and treatment strategies for systemic sclerosis

ABSTRACT

Introduction

Systemic sclerosis (SSc) is a multi-dimensional connective tissue disease of unknown etiology. Given the immense clinical complexity of SSc, the treatment of this condition is not standardized and considerable heterogeneity exists in SSc management approaches. The purpose of this article is to highlight novel therapeutic strategies and new medications under development for the treatment of systemic sclerosis (SSc).

Areas covered

Herein, the authors focus primarily on recently completed clinical trials and phase 3 and 4 clinical trials of therapeutic agents that show promise in SSc. This review is organized by the clinical complications that occur in SSc, for which novel treatment strategies are under study.

Expert opinion

Combining therapies to address the individual manifestations of SSc is a cornerstone to the comprehensive management of this condition. Therapeutic strategies must take into account the organs involved, the level of disease activity in each area, and the disease stage. Controlling the complex biological network, progressive vasculopathy and fibrosis, as well as manifestations of end-organ dysfunction are all critical considerations when determining the best treatment approach for SSc.

KEYWORDS:

• Scleroderma
• systemic sclerosis
• treatment
• therapy
• update

Article highlights

• A variety of novel therapeutic strategies for the management of SSc now exist and are grounded in solid scientific research.

• These therapeutic strategies primarily target individual organ manifestations of SSc.

• Immunosuppressants with potential disease-modifying effects continue to be important components of the therapeutic armamentarium for SSc.

• Patients with refractory disease may require combination therapy with anti-fibrotics and/or other agents.

• Defining mechanistically based SSc subgroups based on biological and clinical profiles will reduce heterogeneity in clinical trial cohorts and may enhance our ability to detect treatment effects.

• Preventing both the onset and progression of individual organ manifestation remains an important unmet clinical need in SSc.

This box summarizes key points contained in the article.

Declaration of interest

ER Volkmann has received grant support from Corbus Pharmaceuticals and Forbius, and consulting fees from Forbius and Boehringer Ingelheim. ZH McMahan has received salary support from Corbus Pharmaceuticals for her work as a subinvestigator on the Lenabasum study. 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

One referee has received speaker’s fees, travel grants, research funding, or compensation for consultancies or board memberships from Abbvie, Actelion, Baxalta/Shire, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Chugai, Genzyme, Gilead Biosciences, Hexal/Sandoz, Janssen-Cilag, Merck Sharp and Dohme, Novartis, Pfizer, Roche, Sanofi Pasteur and UCB Pharma. Peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose.

Correction Statement

This article has been republished with minor changes. These changes do not impact the academic content of the article.

Additional information

Funding

Z McMahan is supported by the National Institutes of Health/National Institute of Arthritis and Musculoskeletal and Skin Diseases via grant K23 AR071473, the Scleroderma Research Foundation and the Jerome L Greene Foundation. ER Volkmann is supported by National Institutes of Health/The National Heart, Lung, and Blood Institute via grant K23 HL150237-01 and the Rheumatology Research Foundation.