Long-standing remission of Crohnʼs disease under imatinib therapy in a patient with Crohnʼs disease

Magro, Fernando; Costa, Clara Maria Bastos Eloy da

doi:10.1097/01.mib.0000232468.15950.34

Cited by 28 publications

(18 citation statements)

References 31 publications

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“…Imatinib efficiently prevented disease and induced remission in an autoimmune arthritis model (13,14) and ameliorated autoimmune nephritis in a mouse model of lupus (15). These data are consistent with case reports and phase I studies in humans demonstrating a positive effect of imatinib on rheumatoid arthritis (16,17), psoriasis (18), spondyloarthritis (19), and Crohn's disease (20).…”

supporting

confidence: 77%

Tyrosine kinase inhibitors reverse type 1 diabetes in nonobese diabetic mice

Louvet

Szot

Lang

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

200

191

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The recent development of small-molecule tyrosine kinase (TK) inhibitors offers increasing opportunities for the treatment of autoimmune diseases. In this study, we investigated the potential of this new class of drugs to treat and cure type 1 diabetes (T1D) in the NOD mouse. Treatment of prediabetic and new onset diabetic mice with imatinib (Gleevec) prevented and reversed T1D. Similar results were observed with sunitinib (Sutent), an additional approved multikinase inhibitor, suggesting that the primary target of imatinib, c-Abl, was not essential in blocking disease in this model. Additional studies with another TK inhibitor, PLX647 (targeting c-Kit and c-Fms) or an anti-c-Kit mAb showed only marginal efficacy whereas a soluble form of platelet-derived growth factor receptor (PDGFR), PDGFR␤Ig, rapidly reversed diabetes. These findings strongly suggest that inhibition of PDGFR is critical to reverse diabetes and highlight a crucial role of inflammation in the development of T1D. These conclusions were supported by the finding that the adaptive immune system was not significantly affected by imatinib treatment. Finally, and most significantly, imatinib treatment led to durable remission after discontinuation of therapy at 10 weeks in a majority of mice. Thus, long-term efficacy and tolerance is likely to depend on inhibiting a combination of tyrosine kinases supporting the use of selective kinase inhibitors as a new, potentially very attractive approach for the treatment of T1D.autoimmunity ͉ diabetes ͉ tyrosine kinase inhibitor ͉ imatinib ͉ PDGFR

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supporting

confidence: 77%

Tyrosine kinase inhibitors reverse type 1 diabetes in nonobese diabetic mice

Louvet

Szot

Lang

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

200

191

View full text Add to dashboard Cite

show abstract

“…In a study from 2009 [23], imatinib induced the remission of diabetes in these mice, possibly via increasing β-cell mass by preventing β-cell apoptosis and increasing β-cell proliferation. In addition to the results obtained in animal models, a number of case reports have shown that imatinib mitigates other autoimmune diseases such as rheumatoid arthritis and Crohn's disease in humans [24,25].…”

Section: Effects Of Imatinib and Other Tkis In Animal Models With Enhmentioning

confidence: 94%

Potential utility of small tyrosine kinase inhibitors in the treatment of diabetes

Mokhtari

Welsh

2009

Clinical Science

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Altered tyrosine kinase signalling has been implicated in several diseases, paving the way for the development of small-molecule TKIs (tyrosine kinase inhibitors). TKIs such as imatinib, sunitinib and dasatinib are clinically used for treating chronic myeloid leukaemia, gastrointestinal stromal tumours and other malignancies. In addition to their use as anti-cancer agents, increasing evidence points towards an anti-diabetic effect of these TKIs. Imatinib and other TKIs counteract diabetes not only in non-obese diabetic mice, but also in streptozotocin diabetic mice, db/db mice, high-fat-treated rats and humans with T2D (Type 2 diabetes). Although the mechanisms of protection need to be investigated further, the effects of imatinib and other TKIs in human T2D and the rapidly growing findings from animal models of T1D (Type 1 diabetes) and T2D are encouraging and give hope to improved treatment of human diabetes. In the present article, we review the anti-diabetic effects of TKIs which appear to involve both protection against beta-cell death and improved insulin sensitivity. Considering the relatively mild side effects of TKIs, we hypothesize that TKIs could be used to treat new-onset T1D, prevent T1D in individuals at high risk of developing the disease, treat the late stages of T2D and improve the outcome of islet transplantation.

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“…Anecdotally, there has been some clinical success. Case reports document that patients receiving imatinib for CML noted significant improvement in Crohn disease for one patient 62 and in severe rheumatoid arthritis for three patients. 63 Imatinib improved cutaneous involvement in three cases of systemic sclerosis and has subsequently been shown to improve skin thickness scores and pulmonary function test results in a larger trial of 30 patients with scleroderma.…”

Section: Human Autoimmune Diseases Treated With Imatinibmentioning

confidence: 99%

Imatinib

Wallace

Gewin

2013

Journal of the American Society of Nephrology

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The treatments for many autoimmune diseases are limited in efficacy, and long-term use is associated with severe adverse events. The tyrosine kinase inhibitors have proven to be well tolerated for long treatment periods, with minimal adverse events, in the oncology population. These agents have recently been used to treat autoimmune diseases. We review the potential mechanisms whereby tyrosine kinase inhibitors may modulate the immune response and inhibit fibrogenesis and discuss the current evidence for their use in the treatment of autoimmune diseases of the kidney.

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Long-standing remission of Crohnʼs disease under imatinib therapy in a patient with Crohnʼs disease

Cited by 28 publications

References 31 publications

Tyrosine kinase inhibitors reverse type 1 diabetes in nonobese diabetic mice

Tyrosine kinase inhibitors reverse type 1 diabetes in nonobese diabetic mice

Potential utility of small tyrosine kinase inhibitors in the treatment of diabetes

Imatinib

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