Effect of bosentan on skin fibrosis in patients with systemic sclerosis: a prospective, open-label, non-comparative trial

Kuhn, Annegret; Haust, Merle; Ruland, Vincent; Weber, Ramona; Verde, Pablo Emilio; Felder, Gerd; Ohmann, Christian; Gensch, K.; Ruzicka, Thomas

doi:10.1093/rheumatology/keq077

Cited by 63 publications

(39 citation statements)

References 31 publications

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“…Indeed, Seibold et al's placebo-controlled study of bosentan in SSc-ILD (described above) failed to show any significant treatment effect on skin thickness scores. This contrasts the results of another, albeit much smaller, prospective study which did highlight a significant improvement in mRSS with bosentan therapy (p < 0.001) [114]. Again, the lack of control subjects in this study makes it difficult to separate bosentan's effects on skin scores from the improvements sometimes seen in the natural progression of SSc.…”

Section: Endothelin Receptor Antagonistscontrasting

confidence: 95%

Translating Autoimmune Pathogenesis into Targeted Therapies for Systemic Sclerosis

Russell¹,

Sofat²

2017

Immunopathogenesis and Immune-Based Therapy for Selected Autoimmune Disorders

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Targeted therapies including tumour necrosis factor α (TNFα) inhibitors have transformed the management of a number of autoimmune conditions over the past 20 years. One autoimmune rheumatological condition with significant potential for the development of targeted therapies is systemic sclerosis (SSc). In this chapter, we use SSc as an example of how research into the pathogenic processes underlying autoimmune conditions can be translated into novel targeted therapies. We review the evidence base for a range of targeted therapies for SSc identified from a systematic literature search, before highlighting a number of studies currently underway.

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Section: Endothelin Receptor Antagonistscontrasting

confidence: 95%

Translating Autoimmune Pathogenesis into Targeted Therapies for Systemic Sclerosis

Russell¹,

Sofat²

2017

Immunopathogenesis and Immune-Based Therapy for Selected Autoimmune Disorders

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“…Consistent with such clinical evidence for the reversibility of liver fibrosis, we have previously reported that bone marrow-derived cells migrating into fibrotic liver contribute to the regression of experimental liver fibrosis by expressing MMP-13 and MMP-9 [97]. The concept of reversibility of intestinal fibrosis is in concordance with various observations from other organs such as the skin, kidney, lung, or heart [98,99,100,101,102,103]. …”

Section: Future Perspectivessupporting

confidence: 78%

Intestinal Fibrosis and Liver Fibrosis: Consequences of Chronic Inflammation or Independent Pathophysiology?

Rieder¹,

Bettenworth²,

Imai³

et al. 2016

Inflamm Intest Dis

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Background: Intestinal fibrosis and liver fibrosis represent a significant burden for our patients and health-care systems. Despite the severe clinical problem and the observation that fibrosis is reversible, no specific antifibrotic therapies exist. Summary: In this review, using an ‘East-West' scientific collaboration, we summarize the current knowledge on principal mechanisms shared by intestinal fibrosis and liver fibrosis. We furthermore discuss inflammation as the cause of fibrogenesis in both entities, depict unique features of intestinal and hepatic fibrosis, and provide a future outlook on the development of antifibrotic therapies. Key Messages: A collaborative effort in the field of fibrosis, covering multiple organ systems, will have the highest chance of leading to the development of a successful antifibrotic intervention.

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“…Provided that the now known side effects of plasma volume expansion can be successfully controlled for, ERAs are promising drugs since they are clearly antiproteinuric and hold potential for slowing CKD progression (Barton, 2008), for improving the clinical course of patients with PAH as suggested by the recently announced results of the SERAPHIN trial (Reuters.com), and might have therapeutic potential in selected patients with CHF or cancer. In addition, ERAs have been found to reduce formation of new digital ulcers related to scleroderma, but had no effect on healing existing ulcers (Korn et al, 2004;Kuhn et al, 2010) (Fig. 1), effects that may be related to the anti-inflammatory effects of ERAs in patients in with scleroderma (Bellisai et al, 2011).…”

Section: Current Perspectives For Era Therapy In Clinical Medicinementioning

confidence: 99%

Clinical trials with endothelin receptor antagonists: What went wrong and where can we improve?

et al. 2012

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In the early 1990s, within three years of cloning of endothelin receptors, orally active endothelin receptor antagonists (ERAs) were tested in humans and the first clinical trial of ERA therapy in humans was published in 1995. ERAs were subsequently tested in clinical trials involving heart failure, pulmonary arterial hypertension, resistant arterial hypertension, stroke/subarachnoid hemorrhage and various forms of cancer. The results of most of these trials - except those for pulmonary arterial hypertension and scleroderma-related digital ulcers - were either negative or neutral. Problems with study design, patient selection, drug toxicity, and drug dosing have been used to explain or excuse failures. Currently, a number of pharmaceutical companies who had developed ERAs as drug candidates have discontinued clinical trials or further drug development. Given the problems with using ERAs in clinical medicine, at the Twelfth International Conference on Endothelin in Cambridge, UK, a panel discussion was held by clinicians actively involved in clinical development of ERA therapy in renal disease, systemic and pulmonary arterial hypertension, heart failure, and cancer. This article provides summaries from the panel discussion as well as personal perspectives of the panelists on how to proceed with further clinical testing of ERAs and guidance for researchers and decision makers in clinical drug development on where future research efforts might best be focused.

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Effect of bosentan on skin fibrosis in patients with systemic sclerosis: a prospective, open-label, non-comparative trial

Abstract: In addition to the well-known effect of bosentan in prevention of DUs, the results of this study demonstrate that bosentan may also be effective at reducing skin fibrosis in patients with SSc.

Cited by 63 publications

References 31 publications

Translating Autoimmune Pathogenesis into Targeted Therapies for Systemic Sclerosis

Translating Autoimmune Pathogenesis into Targeted Therapies for Systemic Sclerosis

Intestinal Fibrosis and Liver Fibrosis: Consequences of Chronic Inflammation or Independent Pathophysiology?

Clinical trials with endothelin receptor antagonists: What went wrong and where can we improve?

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