Systemic sclerosis (scleroderma): remaining challenges

Abstract

Despite progress in treating internal organ involvement in systemic sclerosis (scleroderma) (SSc), such as pulmonary disease, effective treatments for the hallmark of the disease, cutaneous fibrosis, remain elusive. None of the disease-modifying antirheumatic drugs (DMARDS) have shown proven efficacy for SSc skin fibrosis, and there remain no FDA-approved medications, all of which are off-label, for cutaneous fibrosis in SSc. This review article will briefly summarize conventional therapies, biologics and hematopoietic stem cell transplants and select ongoing clinical trials in SSc. The gold standard for measuring skin fibrosis in SSc is the modified Rodnan skin score (MRSSS). This is a validated test that measures skin thickness (0 to 3) at 17 locations for a total score of 51. Improvements in skin score over time are used in clinical trials to quantitate skin fibrosis. Although recording the Rodnan skin score is technically straightforward, requiring no special equipment, and noninvasive, the fluctuating natural history of the disease includes improvement over time without interventions, rendering meaningful trials difficult to assess. Understanding of the basic molecular mechanisms driving pathologic fibrosis in SSc remains lacking, and underpins the often empiric nature and likely the lack of efficacy of many therapeutics that have been tried. Although repeated skin biopsies might be a more precise way to follow disease progression and regression, this is necessarily invasive and requires special tools. Here, this review will look at conventional therapies, biologics, autologous hematopoietic stem cell transplantation, and catalog some of the ongoing clinical trials in SSc with a focus on cutaneous fibrosis.

Keywords: Systemic sclerosis; biologicals; clinical trials; therapy.