Rituximab in Diffuse Cutaneous Systemic Sclerosis

Should We Be Using It Today?

Fiona M. McQueen; Kamal Solanki


Rheumatology. 2015;54(5):757-767. 

In This Article

Abstract and Introduction


There is new evidence that B-cell depletion could be an effective intervention in patients with SSc. Observational case–control study data from the European League Against Rheumatism Scleroderma Trials and Research group has suggested that rituximab therapy may reduce progression of skin thickening and lung fibrosis, especially in a subgroup with early dcSSc. These positive data remain preliminary and need to be viewed with caution, recognizing the spontaneous regression of skin thickening that may occur during early disease. In this review, we summarize the clinical evidence for the therapeutic use of rituximab in SSc as well as the basic science evidence suggesting that B cells and autoantibodies are the primary drivers of fibrosis in skin and lung tissue. We have also reviewed the parallels between SSc and the other CTDs where B-cell depletion therapy is efficacious.


Rheumatologists have been quick to embrace the advantages of targeted biologic therapy in RA,[1] and the lives of many patients have been transformed by the benefits these agents often bring. However, SSc remains a disease that many still consider untreatable; in its severe and diffuse form (dcSSC) it is associated with significant morbidity and mortality[2] and is one of the most distressing and disabling conditions a physician is likely to encounter in a lifetime of clinical practice. Because of its rarity and often slow progression, randomized controlled trials (RCTs) for this condition are difficult to perform, and results are slow to appear when new and potentially effective forms of management become available. Nonetheless, recent evidence (albeit observational study data) describing efficacy of i.v. rituximab (RTX) in SSc[3] suggests that there could now be an effective and relatively non-toxic intervention with the potential to reduce the disfiguring and distressing impact of this disease, which may take years to evolve. If this intervention exists now, in 2014, is it ethically defensible to withhold RTX management until RCT data are available? The European League Against Rheumatism (EULAR) Scleroderma Trials and Research (EUSTAR) group has initiated the Rituximab in Systemic Sclerosis (RECOVER) trial, but the primary outcome cannot be evaluated until late 2014, and formal reporting may be another 12 months away. Delay is of particular concern in dcSSC, because the window for intervention usually occurs relatively early in the disease course, hence the recent thrust to diagnose SSc in its very early stages with initiation of the Very Early Diagnosis of Systemic Sclerosis (VEDOSS) project[4] and the development of the new ACR/EULAR classification criteria for SSc.[5] Once fibrosis of skin, tendons and internal organs has occurred, this may then progress inexorably and irreversibly, leading to morbidity and premature mortality. In this article, we will review the literature on the therapeutic efficacy of RTX in SSc and will discuss this in the context of the role B cells may play in the aetiopathogenesis of SSc.