Header

UZH-Logo

Maintenance Infos

Tyrosine kinase inhibitors in the treatment of systemic sclerosis: from animal models to clinical trials


Iwamoto, N; Distler, J H W; Distler, O (2011). Tyrosine kinase inhibitors in the treatment of systemic sclerosis: from animal models to clinical trials. Current Rheumatology Reports, 13(1):21-7.

Abstract

Efficient antifibrotic therapies are not available for patients with systemic sclerosis (SSc). This review summarizes the current preclinical and clinical evidence for imatinib and related tyrosine kinase inhibitors as potential antifibrotic therapies for SSc and other fibrotic diseases. In experimental models of SSc, imatinib, nilotinib, and dasatinib demonstrated strong antifibrotic effects. Imatinib not only prevented fibrosis in the bleomycin-induced model of dermal fibrosis and the tight skin mouse-1 model but also reduced established fibrosis in a modified bleomycin model. Open-label, proof-of-concept trials in SSc showed moderate effects on skin fibrosis, biological measures of skin fibrosis, and lung fibrosis compared with baseline measures. However, whether this reflects the natural course of the disease or is a result of treatment effects is unclear and needs to be analyzed in larger, multicenter, randomized, placebo-controlled trials. Toxicity is expected from cancer trials with frequent mild to moderate adverse events.

Abstract

Efficient antifibrotic therapies are not available for patients with systemic sclerosis (SSc). This review summarizes the current preclinical and clinical evidence for imatinib and related tyrosine kinase inhibitors as potential antifibrotic therapies for SSc and other fibrotic diseases. In experimental models of SSc, imatinib, nilotinib, and dasatinib demonstrated strong antifibrotic effects. Imatinib not only prevented fibrosis in the bleomycin-induced model of dermal fibrosis and the tight skin mouse-1 model but also reduced established fibrosis in a modified bleomycin model. Open-label, proof-of-concept trials in SSc showed moderate effects on skin fibrosis, biological measures of skin fibrosis, and lung fibrosis compared with baseline measures. However, whether this reflects the natural course of the disease or is a result of treatment effects is unclear and needs to be analyzed in larger, multicenter, randomized, placebo-controlled trials. Toxicity is expected from cancer trials with frequent mild to moderate adverse events.

Statistics

Citations

22 citations in Web of Science®
27 citations in Scopus®
Google Scholar™

Altmetrics

Downloads

476 downloads since deposited on 12 Mar 2011
22 downloads since 12 months
Detailed statistics

Additional indexing

Item Type:Journal Article, refereed, further contribution
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Rheumatology Clinic and Institute of Physical Medicine
Dewey Decimal Classification:610 Medicine & health
Date:2011
Deposited On:12 Mar 2011 15:19
Last Modified:07 Dec 2017 06:34
Publisher:Springer
ISSN:1523-3774
Additional Information:The original publication is available at www.springerlink.com
Publisher DOI:https://doi.org/10.1007/s11926-010-0142-x
PubMed ID:21042889

Download

Download PDF  'Tyrosine kinase inhibitors in the treatment of systemic sclerosis: from animal models to clinical trials'.
Preview
Content: Accepted Version
Filetype: PDF
Size: 1MB
View at publisher