Cyclosporin ulcerative colitis

Immunosuppressive agents such as azathioprine and mercaptopurine (a metabohte of azathioprine) are sometimes used for the treatment of IBD. These agents are generally reserved for cases that are refractory to steroids and may be associated with serious adverse effects such as lymphomas, pancreatitis, or nephrotoxicity. Cyclosporine has been of short-term benefit in acute, severe ulcerative colitis when used in a continuous infusion. 

Continuous IV infusion of cyclosporine (4 mg/kg/day) is recommended for patients with acute severe ulcerative colitis refractory to steroids. 

C. The information provided suggests the patient has mild to moderate disease. Initial therapy should be a 5-ASA containing product, which includes sulfasalazine and mesalamine. However, the patient has a sulfa allergy, precluding the use of sulfasalazine. Metronidazole is useful in the treatment of some patients with Crohn s disease. Cyclosporine has been used in patients with fulminant ulcerative colitis. Prednisone may have to be added to this patient s therapy, but only if he fails to respond to the mesalamine. It should not be used initially. 

Therapeutic pyramid approach to inflammatory bowel diseases. Treatment choice is predicated on both the severity of the illness and the responsiveness to therapy. Agents at the bottom of the pyramid are less efficacious but carry a lower risk of serious adverse effects. Drugs may be used alone or in various combinations. Patients with mild disease may be treated with 5-aminosalicylates (with ulcerative colitis or Crohn s colitis), topical corticosteroids (ulcerative colitis), antibiotics (Crohn s colitis or Crohn s perianal disease), or budesonide (Crohn s ileitis). Patients with moderate disease or patients who fail initial therapy for mild disease may be treated with oral corticosteroids to promote disease remission immunomodulators (azathioprine, mercaptopurine, methotrexate) to promote or maintain disease remission or anti-TNF antibodies. Patients with moderate disease who fail other therapies or patients with severe disease may require intravenous corticosteroids, anti-TNF antibodies, or surgery. Natalizumab is reserved for patients with severe Crohn s disease who have failed immunomodulators and TNF antagonists. Cyclosporine is used primarily for patients with severe ulcerative colitis who have failed a course of intravenous corticosteroids. TNF, tumor necrosis factor. 

Quan VA, Saunders BP, Hicks BH, Sladen GE. Cyclosporin treatment for ulcerative colitis complicated by fatal Pneumocystis carinii pneumonia. BMJ 1997 314(7077) 363 1. 

Pham CQ Efros Cb Beradi RR (2006) Cyclosporine for severe ulcerative colitis. Annals of Pharmacotherapy 40 96-101. 

Patients who are unresponsive to parenteral corticosteroids after 7 to 10 days should receive cyclosporine by intravenous infusion. Most hospitalized patients who are unresponsive to corticosteroids will respond to cyclosporine. Continuous intravenous infusion of cyclosporine (4 mg/kg per day) was rapidly effective in steroid-resistant acute severe ulcerative colitis and reduced the need for emergent colectomy. Intravenous cyclosporine has been recommended as an alternative to steroids in patients with severe attacks of ulcerative colitis (fulminant colitis). Patients who are controlled on intravenous cyclosporine can then be switched to an oral cyclosporine taper regimen. 

Steroids do not have a role in the maintenance of remission with ulcerative colitis because they are ineffective." Steroids should be gradually withdrawn after remission is induced (over 3 to 4 weeks). If they are continued, the patient will be exposed to steroid side effects without likelihood of benefits. For patients who require chronic steroid use (>20 mg/day), there is a strong justification for alternative therapies or colectomy. Azathioprine is effective in preventing relapse of ulcerative colitis for periods of up to 2 years. However, 3 to 6 months may be required before beneficial effects are noted. Oral azathioprine also maintains long-term remission after IV cyclosporine induction. ... 

Carbonnel F, Boruchowicz A, Duclos B, et al. Intravenous cyclosporine in attacks of ulcerative colitis Short-term and long-term responses. Dig Dis Sci 1996 41 2471-2476. 

Lichtiger S, Present DH, Kornbluth A, et al. Cyclosporine in severe ulcerative colitis refractory to steroid therapy. N Engl J Med 1994 330 1841-1845. 

D Haens G, Lemmens L, Geboes K, et al. Intravenous cyclosporine versus corticosteroids as single therapy for severe attacks of ulcerative colitis. Gastroenterology 2001 120 1323-1329. 

Sanborn WJ, Tremaine WJ, Schroeder KW, et al. Cyclosporine enemas for treatment-resistant, mildly to moderately active, left sided ulcerative colitis. Am J Gastroenterol 1993 88 640-645. 

Cyclosporine is effective in severe ulcerative colitis that has failed to respond adequately to glucocorticoid therapy. Between 50% and 80% of these severely ill patients improve significantly (generally within 7 days) in response to intravenous cyclosporine (2-4 mg/kg/day), sometimes avoiding emergent colectomy. Careful monitoring of cyclosporine levels is necessary to maintain a therapeutic level in whole blood of 300-400 ng/mL. 

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