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Systemic sclerosis and localized scleroderma--current concepts and novel targets for therapy.

Oliver Distler1, Antonio Cozzio2

  • 1Division of Rheumatology, University Hospital Zurich, Gloriastr. 25, 8091, Zurich, Switzerland. oliver.distler@usz.ch.

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Summary

Novel targeted therapies show promise for systemic sclerosis (SSc), a fibrotic autoimmune disease. This review details four promising treatments, including soluble guanylate cyclase stimulators and kinase inhibitors, for SSc and localized scleroderma.

Keywords:
Interleukin-6Localized sclerodermaNintedanibSerotoninSoluble guanylate cyclaseSystemic sclerosis

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Area of Science:

  • Rheumatology and Immunology
  • Fibrotic Diseases
  • Translational Medicine

Background:

  • Systemic sclerosis (SSc) is a chronic autoimmune disease characterized by high morbidity and mortality, with skin and organ fibrosis being key manifestations.
  • A significant unmet need exists for effective anti-fibrotic therapies in SSc, driving research into novel molecular targets.
  • Recent advancements have identified and characterized potential molecular targets for fibrotic diseases.

Purpose of the Study:

  • To review and discuss the preclinical characterization of four targeted therapies currently undergoing clinical trials for SSc.
  • To provide an overview of the current classification, clinical presentation, diagnostic approach, and treatment options for localized scleroderma.
  • To explore the potential applicability of novel SSc targeted therapies to localized scleroderma.

Main Methods:

  • Review of preclinical data for four selected targeted therapies in SSc clinical trials.
  • Discussion of soluble guanylate cyclase (sGC) stimulators (e.g., riociguat) for vascular remodeling and fibrosis.
  • Analysis of interleukin-6 blockade, serotonin receptor 2b inhibition, and multityrosine kinase inhibitors (e.g., nintedanib).

Main Results:

  • Soluble guanylate cyclase (sGC) stimulators may address both vascular remodeling and tissue fibrosis in SSc.
  • Interleukin-6 blockade shows promise for early inflammatory stages of SSc.
  • Inhibition of serotonin receptor 2b signaling and multityrosine kinase inhibitors offer potential strategies for complex fibrotic pathways in SSc.

Conclusions:

  • Targeted therapies, including sGC stimulators, IL-6 blockers, serotonin receptor inhibitors, and multikinase inhibitors, represent promising avenues for SSc treatment.
  • Further investigation is warranted to determine the efficacy of these novel therapies in localized scleroderma.
  • The review provides a comprehensive overview of SSc, its management, and emerging therapeutic strategies.