David
Co-Founder
The article, "Cyclosporine and Tacrolimus in the Treatment of Crohn's Disease" by Jenny Sauk and Simon Lichtiger is found on pages 673-676 of the book, "Advanced Therapy in Inflammatory Bowel Disease" and is supported by 16 references. For any of you interested in the deeper medical side of Crohn's Disease, this book is fantastic. This thread will contain information I feel is useful in the article and I also open it up for discussion.
Cyclosporine
- Cyclosporine (CSA) was originally developed as an immunosuppressant for organ transplantation.
- It blockers IL2 and inhibits T-cell activation
- Microemulsion preparations of CSA were developed (Neoral and Gengraf) because normal oral CSA absorption is poor in Crohn's Disease patients.
- No studies have tested these microemulsions in Crohn's Disease patients but they have performed better than standard cyclosporine for Ulcerative Colitis patients.
- Four trials have found IV Cyclosporine to be effective in Ulcerative Colitis patients at dosages of 2 to 4 mg/kg/day.
- The trials of Cyclosporine used low doses compared to the UC trials and only oral forms.
- Pooled trial data showed a response rate of 64% at a mean oral dose of 10 mg/kg/day. Long term remission was only 29%.
- 12 uncontrolled trials have found short term fistula closure rate of 77%. Long term closure after discontinuation was 40%.
- In controlled trials, doses of less than 5 mg/kg/day are ineffective.
- In a controlled trial with 71 patients of 7.3 mg/kg/day or placebo, 59% versus 32% were in remission at 3 months. However, only 11% remained in remission once the drug was discontinued.
- A cochrane review of cyclosporine found it to be ineffective For CD.
- In a study of 192 autoimmune patients on Cyclosporine, 21% had evidence of cyclosporine induced nephrotoxicity. However, the mean dose was 9.3 mg/kg/day
Tacrolimus
- Tacrolimus is a compound that binds to the FK binding protein found in cells.
- It inhibits the IL2 gene to stop T-Cell activation. It also inhibits IL-2, IL-3, IL-4, and TNF.
- Tacrolimus is well absorbed by the GI tract unlike Cyclosporine.
- Patients can experience improvement in as little as 5 days.
- It is hard to determine efficacy of Tacrolimus due to trials that used different doses, goals, and other end points.
- In a study of patients that did poorly on steroids, biologics, and immunomodulators, Tacrolimus with a trough level of 10-15 ng/mL, ALL patients improved but 63% were in remission at 4 months but 37% of those patients needs additional treatment with steroids or Remicade.
- Tacrolimus can also cause nephrotoxicity. Close monitoring of creatinine, BUN, blood pressure, and potassium levels.
- There have been some reports of non hodgkins lymphoma on Tacrolimus but they are thought to be EBV associated and 90% regressed when Tacrolimus was stopped.
The author feels CSA and Tacrolimus are not as effective as when used in UC but can be used as a bridge therapy.
Cyclosporine
- Cyclosporine (CSA) was originally developed as an immunosuppressant for organ transplantation.
- It blockers IL2 and inhibits T-cell activation
- Microemulsion preparations of CSA were developed (Neoral and Gengraf) because normal oral CSA absorption is poor in Crohn's Disease patients.
- No studies have tested these microemulsions in Crohn's Disease patients but they have performed better than standard cyclosporine for Ulcerative Colitis patients.
- Four trials have found IV Cyclosporine to be effective in Ulcerative Colitis patients at dosages of 2 to 4 mg/kg/day.
- The trials of Cyclosporine used low doses compared to the UC trials and only oral forms.
- Pooled trial data showed a response rate of 64% at a mean oral dose of 10 mg/kg/day. Long term remission was only 29%.
- 12 uncontrolled trials have found short term fistula closure rate of 77%. Long term closure after discontinuation was 40%.
- In controlled trials, doses of less than 5 mg/kg/day are ineffective.
- In a controlled trial with 71 patients of 7.3 mg/kg/day or placebo, 59% versus 32% were in remission at 3 months. However, only 11% remained in remission once the drug was discontinued.
- A cochrane review of cyclosporine found it to be ineffective For CD.
- In a study of 192 autoimmune patients on Cyclosporine, 21% had evidence of cyclosporine induced nephrotoxicity. However, the mean dose was 9.3 mg/kg/day
Tacrolimus
- Tacrolimus is a compound that binds to the FK binding protein found in cells.
- It inhibits the IL2 gene to stop T-Cell activation. It also inhibits IL-2, IL-3, IL-4, and TNF.
- Tacrolimus is well absorbed by the GI tract unlike Cyclosporine.
- Patients can experience improvement in as little as 5 days.
- It is hard to determine efficacy of Tacrolimus due to trials that used different doses, goals, and other end points.
- In a study of patients that did poorly on steroids, biologics, and immunomodulators, Tacrolimus with a trough level of 10-15 ng/mL, ALL patients improved but 63% were in remission at 4 months but 37% of those patients needs additional treatment with steroids or Remicade.
- Tacrolimus can also cause nephrotoxicity. Close monitoring of creatinine, BUN, blood pressure, and potassium levels.
- There have been some reports of non hodgkins lymphoma on Tacrolimus but they are thought to be EBV associated and 90% regressed when Tacrolimus was stopped.
The author feels CSA and Tacrolimus are not as effective as when used in UC but can be used as a bridge therapy.
