Rituximab in Diffuse Cutaneous Systemic Sclerosis
Rituximab in Diffuse Cutaneous Systemic Sclerosis
In summary, an observational case–control cohort study from the EUSTAR group has produced new evidence suggesting that RTX infusions may be effective in reducing the progression of skin thickening and fibrosing lung disease in SSc patients. The gains were not large but the study only assessed the results of one infusion in the short-term, and longer open-label studies have revealed greater benefits from ongoing RTX therapy. We have discussed the rationale for B-cell–depleting therapy in SSc patients and the biological effects of disease-associated autoantibodies on the process of fibrosis occurring in skin and lung tissue in this disease. Animal models of scleroderma have yielded useful information about the role of B cells in driving fibrosis, and the human model of GVHD is of particular interest because therapeutic use of RTX in that setting is now part of recommended haematology practice. There are strong parallels with B-cell autoimmunity, as is recognized in the other CTDs for which RTX is already established as an effective therapeutic agent, and an over-arching B-cell hypothesis fits well as an explanation for the pathogenic basis of these autoimmune diseases. However, the history of scleroderma is littered with failed therapies. Thus, if RTX were to be used today, it should either be in the context of a clinical trial or in specialized centres to ensure that outcome data are carefully collected and available to the international rheumatology research community. Moreover, on current evidence, its use could only be supported in those patients with the rapidly progressive diffuse form of the disease, where trialling unproven therapies is ethically justifiable. The question for the clinician managing such a patient is whether to take the evidence-based medicine approach and wait for RCT data, or to opt for RTX infusions now, and potentially influence the disease process immediately.
Summary
In summary, an observational case–control cohort study from the EUSTAR group has produced new evidence suggesting that RTX infusions may be effective in reducing the progression of skin thickening and fibrosing lung disease in SSc patients. The gains were not large but the study only assessed the results of one infusion in the short-term, and longer open-label studies have revealed greater benefits from ongoing RTX therapy. We have discussed the rationale for B-cell–depleting therapy in SSc patients and the biological effects of disease-associated autoantibodies on the process of fibrosis occurring in skin and lung tissue in this disease. Animal models of scleroderma have yielded useful information about the role of B cells in driving fibrosis, and the human model of GVHD is of particular interest because therapeutic use of RTX in that setting is now part of recommended haematology practice. There are strong parallels with B-cell autoimmunity, as is recognized in the other CTDs for which RTX is already established as an effective therapeutic agent, and an over-arching B-cell hypothesis fits well as an explanation for the pathogenic basis of these autoimmune diseases. However, the history of scleroderma is littered with failed therapies. Thus, if RTX were to be used today, it should either be in the context of a clinical trial or in specialized centres to ensure that outcome data are carefully collected and available to the international rheumatology research community. Moreover, on current evidence, its use could only be supported in those patients with the rapidly progressive diffuse form of the disease, where trialling unproven therapies is ethically justifiable. The question for the clinician managing such a patient is whether to take the evidence-based medicine approach and wait for RCT data, or to opt for RTX infusions now, and potentially influence the disease process immediately.
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