JOURNAL ARTICLE
REVIEW
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Innovative therapies for systemic sclerosis.

PURPOSE OF REVIEW: The purpose of this study is to review the evidence and recent developments leading to novel therapeutics in scleroderma.

RECENT FINDINGS: Recent advances have been made in understanding the key pathogenetic aspects of scleroderma, and these have led to potential targeted therapeutic agents for the management of these patients. Preliminary data from early clinical trials suggest that tyrosine kinase molecules may be potential candidates for therapy, especially in the fibrotic phase of the disease. On the basis of the new insights into the key role of effector T cells, in particular Th-17 and T regulatory subsets, T-cell-directed therapies including halofuginone, basiliximab, alemtuzumab, abatacept and rapamycin have been proposed to be clinically beneficial. By analogy, recent clinical studies with rituximab in diffuse cutaneous systemic sclerosis lend support that B cells may be important in the pathogenesis of the disease. 3-Hydroxy-3-methyl-glutaryl-CoA reductase inhibitors, endothelin receptor antagonists and phosphodiesterase type V inhibitor have been shown to be useful to treat the vascular manifestations associated with systemic sclerosis. Haematopoietic stem cell transplantation following immune ablation holds considerable promise in resetting of the immune system, and trial results are awaited.

SUMMARY: Although there is still no treatment that is unequivocally effective for scleroderma, there have been some promising developments over the past number of years with identification of novel candidate targets and innovative strategies, including targeted immunomodulatory therapies, tyrosine kinase inhibitors and agents that may promote vascular repair. These recent findings will need to be confirmed by larger, multicentre, randomized controlled trials, but they provide hope that these novel therapeutic agents may broaden the currently restricted therapeutic armamentarium of the disease.

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