Is biological therapy in systemic sclerosis the answer?

Systemic sclerosis is a systemic fibrosing disorder associated with significant morbidity and mortality, with no universally accepted disease-modifying therapy. Significant advances in the understanding of systemic sclerosis in recent years have guided the exploration of biological drugs in systemic sclerosis. In this narrative review, we summarize the published literature on biologic therapies in systemic sclerosis. A double-blind randomized trial, and an open label trial of tocilizumab (which antagonizes the interleukin 6 receptor), identified potential benefits in skin and lung fibrosis in systemic sclerosis; however, these differences failed to attain statistical significance. Two open-label trials compared rituximab (which depletes B lymphocytes) to conventional treatment/ cyclophosphamide in systemic sclerosis-associated interstitial lung disease (ILD), and revealed significant improvements in lung functions and skin disease with rituximab. Significant observational data also support the use of rituximab in skin, lung, muscle and joint manifestations of systemic sclerosis. Abatacept (which blocks T lymphocyte activation) has demonstrated utility for skin and joint disease in systemic sclerosis; a recent clinical trial failed to demonstrate benefits in improving skin thickness compared to placebo. Agents targeting type I interferons, interleukin 17 pathway, CD19 and plasma cells hold promise in systemic sclerosis; however, high-quality evidence is lacking. The results of different ongoing clinical trials targeting B lymphocytes, T lymphocytes, various cytokines (interleukins 6, 17, 4, 13, IL-1α), platelet-derived growth factor receptor, proteasome, integrins or oncostatin M may help guide future therapeutic regimens with biological agents in systemic sclerosis.