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.