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AB0626 IMATINIB FOR THE TREATMENT OF SYSTEMIC SCLEROSIS: RATIONALE, CLINICAL EVIDENCE AND FUTURE DEVELOPMENT
  1. A. Waheed1,
  2. C. Buckingham2,
  3. G. Brar2
  1. 1Imperial College London, London, United Kingdom
  2. 1Imperial College London, London, United Kingdom

Abstract

Background: Systemic sclerosis (SSc) is a chronic disorder of connective tissue affecting the skin and internal organs. The molecular mechanisms behind SSc are not entirely understood, but recent advances highlight key signalling pathways1 (see Figure 1). Fibrosis disrupts tissue architecture resulting in organ dysfunction. This causes significant morbidity and mortality1, therefore there is a clear need for identifying efficacious antifibrotic treatment.

Imatinib is a tyrosine kinase inhibitor with established use in some malignancies, and existing evidence that it can treat SSc2.

Objectives: The aim of this literature review is to summarise the current evidence and future developments of imatinib as antifibrotic treatment in SSc.

Methods: PubMed headings “systemic sclerosis”, “scleroderma”, “imatinib” and synonyms were used. See Figure 2.

Results:9 studies showed imatinib had positive efficacy in the treatment of SSc. 5 showed no improvement or adverse effects.

Conclusion: Overall, current evidence suggests that imatinib can be a useful drug to improve manifestations of SSc, for some. Despite inconclusive evidence, a dose-dependent relationship seems to exist for imatinib toxicities, with more research needed to ascertain a safe dose.

Gene expression profiles may distinguish patients that can benefit from imatinib3. Also, Notch signalling could be exploited to increase imatinib uptake into fibroblasts, thereby increasing efficacy4.

References: [1]Pattanaik D et al. Pathogenesis of Systemic Sclerosis. Frontiers in Immunology. 2015;6: 272

[2]Distler JHW et al. Tyrosine kinase inhibitors for the treatment of fibrotic diseases such as systemic sclerosis: towards molecular targeted therapies. Annals of the Rheumatic Diseases. 2010;69: 48-51

[3]Chung L et al. Molecular framework for response to imatinib mesylate in systemic sclerosis. Arthritis and Rheumatology. 2009 Feb;60(2):584-91

[4]Harrach S et al. Notch Signaling Activity Determines Uptake and Biological Effect of Imatinib in Systemic Sclerosis Dermal Fibroblasts. Journal of Investigative Dermatology. 2019; 139(2):439-4475

Acknowledgments: Skin Research Institute of Singapore

Disclosure of Interests: None declared

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