Investigational drugs for the treatment of scleroderma: what’s new?

ABSTRACT

Introduction

Systemic sclerosis (SSc) is an orphan, chronic, autoimmune, fibrotic disease with unknown etiology characterized by progressive fibrosis of the skin and internal organs. SSc has the highest mortality, the deadliest among the connective tissue diseases, despite the introduction of new treatment options in the past decades.

Areas covered

The aim of the current systematic review was to investigate new targeted therapy and their impact on disease progression, mainly focusing on phase I and II clinical trials within the past three years.

Expert opinion

Despite recent groundbreaking advancements in understanding SSc pathophysiology, early diagnosis and early introduction of effective targeted treatments within the optimal window of opportunity to prevent irreversible disease damage still represents a significant clinical challenge. Ongoing significant research for new molecular and epigenetics pathways is of fundamental importance to offer new perspectives on disease phenotype and for the development of personalized treatment strategies.

KEYWORDS:

• systemic sclerosis
• pathogenesis
• investigational drugs
• targeted therapy
• clinical trials

Article highlights

• So far, only biological therapies targeting IL-6 and CD20 have been approved for SSc management

• The most promising future therapies for SSc are those targeting key pathophysiological points such as inflammation, myofibroblast differentiation and ECM development.

• Targeting multiple receptors and mediating different signaling has been proven successful in SSc (e.g. for nintedanib), offering a strong background for modeling future studies.

• New experimental drugs with dual anti-inflammatory and antifibrotic effects (Zirixtra, Romilkimab, Belolumosudil, Dersimelagon, SAR100842, PRA 023, Brodamulad, and Divolizimab) might be promising for SSc management

• Despite an advanced shift in the understanding of SSc pathophysiology, the exploration of new molecular and epigenetics pathways are still required giving a new perspective on the disease phenotype, and contributing to the development of personalized treatment strategies.

Declaration of Interest

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.

Additional information

Funding

This paper was not funded.