Low-Dose Cyclosporine for the Treatment of Crohn's Disease

Feagan, Brian G.; McDonald, John W.D.; Rochon, James; Laupacis, Andreas; Fedorak, Richard N.; Kinnear, Douglas G.; Saibil, Fred; Groll, A.; Archambault, A; Gillies, R. R.

doi:10.1056/nejm199406303302602

Cited by 236 publications

(66 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Cyclosporine has a beneficial therapeutic effect in patients with chronic active Crohn’s disease and resistance to or intolerance of corticosteroids [48,49,50] but none for maintenance therapy [51, 52]. The data on the safety of cyclosporine during pregnancy in humans is primarily derived from transplant recipients.…”

Section: Resultsmentioning

confidence: 99%

Pregnancy and Crohn’s Disease

et al. 2005

View full text Add to dashboard Cite

Crohn’s disease commonly affects women of childbearing age. Available data on Crohn’s disease and pregnancy show that women with Crohn’s disease can expect to conceive successfully, carry to term and deliver a healthy baby. Control of disease activity before conception and during pregnancy is critical, to optimize both maternal and fetal health. Generally speaking, pharmacological therapy for Crohn’s disease during pregnancy is similar to pharmacological therapy for non-pregnant patients. Patients maintained in remission by way of pharmacological therapy should continue it throughout their pregnancy. Most drugs, including sulfasalazine, mesalazine, corticosteroids, and immunosuppressors such as azathioprine and 6-mercaptopurine, are safe, whereas methotrexate is contraindicated.

show abstract

Section: Resultsmentioning

confidence: 99%

Pregnancy and Crohn’s Disease

et al. 2005

View full text Add to dashboard Cite

show abstract

“…This may be an explanation of why medications such as infliximab are effective in some patients with UC (18) as well as in patients with CD (19). In addition, this may also be an explanation for the finding that other drugs such as cyclosporine with benefit in the acute phases of disease (20) do not have maintenance benefits (21) and why medications such as mercaptopurine become less effective with continued usage (22). As therapy for subtypes of IBD becomes more cytokine specific, it will be interesting to determine whether new-onset disease will respond differently than long-standing disease and which combinations or sequences of therapies should be used.…”

Section: Discussionmentioning

confidence: 99%

Peripheral Blood Intracellular Cytokine Analysis in Children Newly Diagnosed with Inflammatory Bowel Disease

et al. 2002

View full text Add to dashboard Cite

“…Initial studies focused on short courses of high-dose intravenous CsA therapy, and have demonstrated impressive success for the treatment of fulminant colitis and the healing of refractory Crohn's disease fistulas. However, multiple attempts to convert high-dose CsA to an oral maintenance strategy, akin to the success in transplant immunosuppression, have paradoxically failed to demonstrate efficacy (5)(6)(7)(8)(9)(10)(11). The precise cellular and molecular mechanisms that underlie this lack of efficacy in the long term treatment of chronic intestinal inflammation have remained undefined, and may result from the emerging profile of adverse effects of CsA on nonimmune cell populations, including the vascular endothelium.…”

mentioning

confidence: 99%

Cyclosporine A Enhances Leukocyte Binding by Human Intestinal Microvascular Endothelial Cells through Inhibition of p38 MAPK and iNOS

Rafiee¹,

Johnson²,

Li³

et al. 2002

Journal of Biological Chemistry

View full text Add to dashboard Cite

The calcineurin inhibitor cyclosporine A (CsA) modulates leukocyte cytokine production but may also effect nonimmune cells, including microvascular endothelial cells, which regulate the inflammatory process through leukocyte recruitment. We hypothesized that CsA would promote a proinflammatory phenotype in human intestinal microvascular endothelial cells (HIMEC), by inhibiting inducible nitric-oxide synthase (iNOS, NOS2)-derived NO, normally an important mechanism in limiting endothelial activation and leukocyte adhesion. Primary cultures of HIMEC were used to assess CsA effects on endothelial activation, leukocyte interaction, and the expression of iNOS as well as cell adhesion molecules. CsA significantly increased leukocyte binding to activated HIMEC, but paradoxically decreased endothelial expression of cell adhesion molecules (E-selectin, intercellular adhesion molecule 1, and vascular cell adhesion molecule-1). In contrast, CsA completely inhibited the expression of iNOS in tumor necrosis factor-␣/lipopolysaccharide-activated HIMEC. CsA blocked p38 MAPK phosphorylation in activated HIMEC, a key pathway in iNOS expression, but failed to inhibit NFB activation. These studies demonstrate that CsA exerts a proinflammatory effect on HIMEC by blocking iNOS expression. CsA exerts a proinflammatory effect on the microvascular endothelium, and this drug-induced endothelial dysfunction may help explain its lack of efficacy in the long-term treatment of chronically active inflammatory bowel disease.

show abstract

Low-Dose Cyclosporine for the Treatment of Crohn's Disease

Abstract: In our patient population, the addition of low-dose cyclosporine to conventional treatment for Crohn's disease did not improve symptoms or reduce requirements for other forms of therapy.

Cited by 236 publications

References 23 publications

Pregnancy and Crohn’s Disease

Pregnancy and Crohn’s Disease

Peripheral Blood Intracellular Cytokine Analysis in Children Newly Diagnosed with Inflammatory Bowel Disease

Cyclosporine A Enhances Leukocyte Binding by Human Intestinal Microvascular Endothelial Cells through Inhibition of p38 MAPK and iNOS

Contact Info

Product

Resources

About