Severe exacerbation of Crohn’s disease during sunitinib treatment

Abstract

Sunitinib is a multiple tyrosine kinase inhibitor of the vascular endothelial growth factor and platelet-derived growth factor pathway and inhibits angiogenesis, cell proliferation, and tumor cell invasion, and stimulates apoptosis. Treatment with sunitinib in first-line metastatic renal cell carcinoma improves progression-free survival and overall survival compared with interferon-α. Crohn's disease is characterized by chronic immune-mediated intestinal inflammation. Although the exact pathogenesis of Crohn's disease remains unknown, the involvement of angiogenesis is acknowledged. It is unknown whether sunitinib interferes with the natural course of Crohn's disease. We describe a patient with metastatic renal cell carcinoma and a history of Crohn's disease who was treated with sunitinib and developed a severe exacerbation of Crohn's disease. After rechallenge with sunitinib, a second exacerbation occurred. We therefore conclude that angiogenesis inhibitors should be administered with care in patients with a history of Crohn's disease.

Angiogenesis in Inflammatory Bowel Disease

“…These drugs are used in the treatment of renal cell cancer and hepatocellular carcinoma, but they cause activation of the bowel disease in patients with IBD [ 89 ]. Boers-Sonderen et al [ 90 ] described a patient with metastatic renal cell carcinoma and a history of Crohn's disease who was treated with sunitinib and developed severe exacerbation of Crohn's disease. After rechallenge with sunitinib, second exacerbation occurred.…”

IL-23 and IL-2 activation of STAT5 is required for optimal IL-22 production in ILC3s during colitis

“…Whereas tofacinitib might be a good treatment strategy when used in addition to anti-tumor necrosis factor- (TNF-) therapy in patients with ulcerative colitis (45), it lacks therapeutic efficacy for Crohn's disease (46). Common side effects of JAK-STAT inhibitors are diarrhea and occasional exacerbation of Crohn's disease (47). Because of the differential roles of STAT3 and STAT5 that we have demonstrated, and the detrimental effects seen with inhibitors of multiple receptor tyrosine kinases, our work suggests that the development of more specific inhibitors for specific JAK or STAT proteins could help ameliorate unfavorable side effects in patients with IBD.…”

Gut inflammation induced by drugs: Can pathology help to differentiate from inflammatory bowel disease?

“…Case reports and observational studies describe IBD‐like histological changes, including FAC and chronic colitis, in a range of other medications, including tyrosine kinase inhibitors such as dasatinib, 93 , 94 sunitinib and sorafenib, 95 , 96 proteasome inhibitor bortezomib, 97 immune modulators such as tacrolimus, 68 azathioprine, 98 leflunomide, 69 hydroxycarbamide 53 treatments for hepatitis C including interferon and/or ribavirin, 99 , 100 , 101 , 102 sofosbuvir, simeprevir, 103 , 104 and gold. 105…”

“…88 There are isolated case reports of development of de novo IBD or flaring of IBD linked to administration of IL-1 antagonists, including anakinra and canakinumab, 70,89 anti-IL-6R antibody tocilizumab, 71,86 CTLA-4-Fc fusion protein abatacept, 90,91 and the anti-vascular endothelial growth factor monoclonal antibody bevacizumab. 92 Case reports and observational studies describe IBD-like histological changes, including FAC and chronic colitis, in a range of other medications, including tyrosine kinase inhibitors such as dasatinib, 93,94 sunitinib and sorafenib, 95,96 proteasome inhibitor bortezomib, 97 immune modulators such as tacrolimus, 68 azathioprine, 98 leflunomide, 69 hydroxycarbamide 53 treatments for hepatitis C including interferon and/or ribavirin, [99][100][101][102] sofosbuvir, simeprevir, 103,104 and gold. 105 Isotretinoin is a synthetic analogue of vitamin A, approved for treatment of severe recalcitrant nodular acne.…”