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Imatinib for the treatment of rheumatic diseases

Nature Clinical Practice Rheumatology volume 3, pages 190–191 (2007)Cite this article

There has been much speculation on the potential use of kinase inhibitors for the treatment of autoimmune rheumatic diseases. Investigations of small-molecule inhibitors of p38 mitogen-activated protein kinases (MAPK) and other kinase pathways have been limited by toxicities, however, data suggest that the small-molecule tyrosine kinase inhibitor imatinib mesylate could provide therapeutic benefit for a range of autoimmune rheumatic diseases including scleroderma, pulmonary arterial hypertension (PAH), spondyloarthropathies, and rheumatoid arthritis (RA). Imatinib is approved by the FDA for the treatment of chronic myeloid leukemia (CML) and gastrointestinal stromal tumors (GIST). Imatinib potently inhibits a select set of tyrosine kinases at submicromolar concentrations, including the platelet-derived growth factor receptor (PDGFR), c-kit, and ABL-related kinases; imatinib also potently inhibits c-fms and LCK at micromolar concentrations. Selective inhibition of one or more tyrosine kinases could provide a potent therapeutic option for a variety of autoimmune and inflammatory diseases, for which current therapies are insufficient.

Scleroderma is a fibrotic disease that affects the skin, and can also affect visceral organs. Data published in 2006 suggest that anti-PDGFR autoantibodies might have a critical role in driving fibrosis in scleroderma.1 TGF-beta-stimulated signalling through Abl has also been identified as an important profibrotic pathway. Studies have demonstrated that imatinib inhibits fibrosis in rodent models of scleroderma2 and thus, might provide benefit in patients with scleroderma.

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Authors and Affiliations

  1. RT Paniagua is a MD and PhD candidate in the Immunology Program and WH Robinson is an Assistant Professor of Medicine in the Division of Immunology and Rheumatology at Stanford University School of Medicine, Stanford, USA.,

    Ricardo T Paniagua & William H Robinson

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  1. Ricardo T Paniagua
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  2. William H Robinson
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Correspondence to William H Robinson.

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Paniagua, R., Robinson, W. Imatinib for the treatment of rheumatic diseases. Nat Rev Rheumatol 3, 190–191 (2007). https://doi.org/10.1038/ncprheum0465

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