Imatinib mesylate in scleroderma-associated diffuse skin fibrosis: a phase II multicentre randomized double-blinded controlled trial

Prey, S.; Ezzedine, Khaled; Doussau, Amélie; Grandoulier, A-S; Barcat, D.; Chatelus, Emmanuel; Diot, Élisabeth; Durant, C.; Hachulla, É.; Korwin-Krokowski, J-D de; Kostrzewa, E.; Quéméneur, T.; Paul, C.; Schaeverbeke, Thierry; Sénéschal, Julien; Solanilla, A.; Sparsa, A.; Bouchet, Stéphane; Lepreux, Sébastien; Fx, Mahon; Chêne, Geneviève; Taı̈eb, Alain

doi:10.1111/j.1365-2133.2012.11186.x

Cited by 94 publications

(47 citation statements)

References 17 publications

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“…Epigenetic mechanisms provide one promising avenue of this type, with histone deacetylase and DNA methyltransferase inhibitors (Huber et al, 2007;Beyer et al, 2012). Likewise, kinase inhibitors such as imatinib have been considered, but recent clinical trials showed conflicting results (Khanna et al, 2011;Spiera et al, 2011;Prey et al, 2012). Rho kinase inhibitors have also been used to reduce fibrosis (Zhou et al, 2013).…”

Section: Discussionmentioning

confidence: 99%

Targeting the Myofibroblast Genetic Switch: Inhibitors of Myocardin-Related Transcription Factor/Serum Response Factor–Regulated Gene Transcription Prevent Fibrosis in a Murine Model of Skin Injury

Haak

Tsou

Amin

et al. 2014

J Pharmacol Exp Ther

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Section: Discussionmentioning

confidence: 99%

Targeting the Myofibroblast Genetic Switch: Inhibitors of Myocardin-Related Transcription Factor/Serum Response Factor–Regulated Gene Transcription Prevent Fibrosis in a Murine Model of Skin Injury

Haak

Tsou

Amin

et al. 2014

J Pharmacol Exp Ther

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“…138 Imatinib mesylate, an inhibitor of PDGF and TGF-b, was similarly ineffective in the treatment of scleroderma. 139 Human recombinant TGF-b3 failed to meet endpoints in a phase III trial on human scarring, and the results of this study were not published. 140 Similarly, a trial evaluating the use of dermal fibroblasts for burn scars was terminated early, and results have not been made available.…”

Section: Emerging and Novel Treatments For Scarmentioning

confidence: 68%

Cutaneous Scarring: Basic Science, Current Treatments, and Future Directions

Marshall

Leavitt

et al. 2018

Advances in Wound Care

226

176

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Significance: Scarring of the skin from burns, surgery, and injury constitutes a major burden on the healthcare system. Patients affected by major scars, particularly children, suffer from long-term functional and psychological problems. Recent Advances: Scarring in humans is the end result of the wound healing process, which has evolved to rapidly repair injuries. Wound healing and scar formation are well described on the cellular and molecular levels, but truly effective molecular or cell-based antiscarring treatments still do not exist. Recent discoveries have clarified the role of skin stem cells and fibroblasts in the regeneration of injuries and formation of scar. Critical Issues: It will be important to show that new advances in the stem cell and fibroblast biology of scarring can be translated into therapies that prevent and reduce scarring in humans without major side effects. Future Directions: Novel therapies involving the use of purified human cells as well as agents that target specific cells and modulate the immune response to injury are currently undergoing testing. In the basic science realm, researchers continue to refine our understanding of the role that particular cell types play in the development of scar. SCOPE AND SIGNIFICANCEThis review begins with an overview of how human skin wounds heal, with an emphasis on the formation of scar as the end result of wound healing. This is followed by a review of recent developments in the cellular biology of wound healing and scarring, particularly related to stem cells and fibroblasts. Finally, traditional and novel treatments intended to prevent and reduce scarring are described. This review will be of interest to clinicians and basic scientists who wish to better understand the processes of wound healing and scarring as well as the treatment options available. TRANSLATIONAL RELEVANCEA great deal has been learned about the cellular and molecular pathways that contribute to scar formation. At the same time, clinicians have understood for centuries that certain techniques allow wounds to heal faster with less scarring. Despite the enormity of the clinical problem presented by scarring, there has been a failure to translate the basic science of scarring into improved scarring treatments that take advantage of specific molecular and cellular targets. However, in the field, there is optimism that recent advances will bridge the gap between the basic science and the clinical treatment of scarring. CLINICAL RELEVANCE Scarring of the skin affects millions of patients and in some, particularly children and burn victims, causes a great deal of suffering. Scar prevention mainly consists of the principles of wound closure without tension and avoiding infection and wound breakdown. Various treatments for established scars exist, with varying levels of effectiveness. Burn scars are particularly challenging, and treatment is largely supportive with the option for revision surgery to remove scarred skin. A novel drug-based treatment that makes use of a specific mole...

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“…The first promising results from an open clinical trial with imatinib in SSc demonstrated significant improvement in skin scores and FVC after 12 months, however, with numerous side effects, particularly edema. Unfortunately, these findings were not confirmed in two other randomized placebo-controlled clinical trials, one of which was closed for numerous early side effects, and the other failed to show significant improvement in skin scores, and was accompanied by numerous side effects as well [104][105][106].…”

Section: Testing Of Biological Agents and Small Molecules In Preclinimentioning

confidence: 92%

Animal Models of Systemic Sclerosis

Štorkánová¹,

Tomčík²

2017

Systemic Sclerosis

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Systemic sclerosis (SSc) is a rare, chronic connective tissue disease affecting the skin, vessels, musculoskeletal system, and internal organs. Despite advances in pharmacotherapy of organ manifestations and new knowledge about the pathogenesis of SSc, there is still no effective universal treatment of this serious disease. The aim of this chapter is to introduce traditional, most commonly used experimental animal models of SSc, clarify their basic pathological mechanism, describe their advantages and limitations, and outline their use in preclinical tests of potential therapeutic agents with subsequent clinical trials in patients with SSc. The existing models have already contributed significantly to preclinical testing of several available biological agents and small molecules, some of which achieved promising results in early clinical studies, and could provide better prospects for patients with this incurable disease.

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Imatinib mesylate in scleroderma-associated diffuse skin fibrosis: a phase II multicentre randomized double-blinded controlled trial

Abstract: This study failed to demonstrate the efficacy of imatinib 400 mg daily to improve skin fibrosis of diffuse scleroderma after 6 months of treatment based on validated outcome measurements.

Cited by 94 publications

References 17 publications

Targeting the Myofibroblast Genetic Switch: Inhibitors of Myocardin-Related Transcription Factor/Serum Response Factor–Regulated Gene Transcription Prevent Fibrosis in a Murine Model of Skin Injury

Targeting the Myofibroblast Genetic Switch: Inhibitors of Myocardin-Related Transcription Factor/Serum Response Factor–Regulated Gene Transcription Prevent Fibrosis in a Murine Model of Skin Injury

Cutaneous Scarring: Basic Science, Current Treatments, and Future Directions

Animal Models of Systemic Sclerosis

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