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Review

Advances in biological and targeted therapies for systemic sclerosis

, , , & ORCID Icon
Pages 325-339 | Received 26 Jan 2023, Accepted 23 Mar 2023, Published online: 26 Apr 2023
 

ABSTRACT

Introduction

Systemic sclerosis (SSc) is a severe, and often life-threatening, autoimmune disease, which causes inflammation and fibrosis of the skin and internal organs. There are currently limited effective therapeutic options for patients with SSc. There are recently completed and ongoing phase 2 and 3 studies looking at biologic therapies for SSc that target the underlying pathogenesis of the disease.

Areas covered

The purpose of this review is to describe completed and ongoing trials of different biologic therapies for the treatment of SSc. This review discusses biologic therapy directed at multiple pathways that are believed to contribute to inflammation and fibrosis in SSc including T cell, B cell, direct cytokines, and JAK signaling. Data presented is based on authors’ expertise of completed and ongoing trials.

Expert opinion

Tocilizumab and rituximab have supporting data to advocate for use in early SSc. Data from tocilizumab showed preservation of forced vital capacity (FVC) and beneficial effects on global composite measure. Recent data from different trials with rituximab in SSc (with and without interstitial lung disease) show beneficial effects on skin and FVC with good tolerability. We highlight the molecular heterogeneity in early SSc phenotype and the need to account for this in future trials.

Article highlights

  • Systemic sclerosis (SSc) is a rare, multi-organ autoimmune disease with the highest mortality of any rheumatic disease.

  • There is an unmet need for effective therapeutic options for patients with SSc.

  • In the last decade there have been multiple phase 2 and 3 trials investigating use of biological and targeted therapies for SSc, which have demonstrated tolerability and have shown promising results for stabilization/improvement in skin and pulmonary function.

  • Tocilizumab is currently the only FDA approved biologic therapy for SSc, specifically for SSc-associated ILD.

  • Additional large, multi-center studies that incorporate the mode of action and precision medicine are needed of the biological and targeted therapies to confirm efficacy and safety.

Abbreviations

ATX=

Autotaxin

CTLA-4=

Cytotoxic T-lymphocyte associated antigen 4

dcSSc=

Diffuse cutaneous systemic sclerosis

DLCO=

Diffusing capacity for carbon monoxide

ECM=

Extracellular matrix

FVC=

Forced vital capacity

HSCT=

Hematopoietic stem cell transplant

IFN=

Interferon

ILD=

Interstitial lung disease

JAK(i)=

Janus kinase (inhibitor)

lcSSc=

Limited cutaneous systemic sclerosis

LPA=

Lysophosphatidic acid

LPAR1=

Lysophosphatidic acid receptor 1

mRSS=

Modified Rodnan Skin Score

RCT=

Randomized Controlled Trial

RNAP=

RNA polymerase

SSc=

Systemic Sclerosis

SSc-ILD=

Systemic sclerosis associated interstitial lung disease

STAT=

Signal transducer and activator of transcription

TGF=

Transforming growth factor

Th1=

T helper 1

Th2=

T helper 2

TL1A=

Tumor necrosis-like cytokine 1A

Declaration of interest

D Khanna declares grant support from Bayer, BMS, Horizon, Immune Tolerance Network, NIH and Pfizer; consultancy fees from AbbVie, Astra Zeneca, Amgen, Bayer, Chemomab, Boehringer Ingelheim, CSL Behring, Genentech/Roche, Horizon, Janssen, Merck, Mitsubishi Tanabe Pharma and Prometheus Pharma. R Domsic declares support from Aisa Pharma and AstraZeneca. ML Whitfield declares research support from BMS and Celdara Medical LLC; consulting fees from BMS and Celdara Medical; has served on advisory boards for Acceleron and Boehringer Ingelheim. ML Whitfield is a Scientific Founder of Celdara Medical, LLCz. AHL Low declares grant support from National Medical Research Council; consulting fees from Boehringer Ingelheim and Johnson & Johnson. 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.

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