A placebo-controlled trial of cyclosporine enemas for mildly to moderately active left-sided ulcerative colitis. Cyclosporin use in the precolectomy chronic ulcerative colitis patient: a community experience and its relationship to prospective and controlled clinical trials. Pacific Northwest Gastroenterology Society. Efficacy of cyclosporin with corticotropin for refractory ulcerative colitis. Intravenous cyclosporine for severe attacks of ulcerative colitis: a survey of Canadian gastroenterologists. Ulcerative colitis disease activity following treatment of associated primary sclerosing cholangitis with cyclosporin. Cyclosporine enemas for treatment-resistant, mildly to moderately active, left-sided ulcerative colitis. Intravenous cyclosporine in attacks of ulcerative colitis Cyclosporine in severe ulcerative colitis refractory to steroid therapy. Intravenous tobramycin and metronidazole as an adjunct to corticosteroids in acute, severe ulcerative colitis. Cyclosporin A retention enemas in refractory distal ulcerative colitis and 'pouchitis'. A comparison of the quality of life in patients with severe ulcerative colitis after total colectomy versus medical treatment with intravenous cyclosporin. Efficacy and Efficiency of Oral Microemulsion Cyclosporin Versus Intravenous and Soft Gelatin Capsule Cyclosporin in the Treatment of Severe Steroid‐Refractory Ulcerative Colitis: An Open‐Label Retrospective Trial Infliximab in moderately severe glucocorticoid resistant ulcerative colitis: a randomised controlled trial Short‐ and long‐term outcome of patients treated with cyclosporin for severe acute ulcerative colitis Combined use of cyclosporine and azathioprine or 6-mercaptopurine in pediatric inflammatory bowel disease. High-dose intravenous cyclosporine in steroid refractory attacks of inflammatory bowel disease. Predictive factors of outcome of intensive intravenous treatment for attacks of ulcerative colitis Cyclosporin for refractory ulcerative colitis The effect of treatment on lymphokine‐secreting cells in the intestinal mucosa of children with Crohn's disease Randomized, double-blind comparison of 4 mg/kg versus 2 mg/kg intravenous cyclosporine in severe ulcerative colitis. Infliximab for refractory ulcerative colitis or indeterminate colitis: an open‐label multicentre study Intravenous cyclosporine versus intravenous corticosteroids as single therapy for severe attacks of ulcerative colitis.
BACKGROUND / AIMS Uncontrolled studies suggest that cyclosporine administered as an enema may be of benefit for left-sided ulcerative colitis and safer than intravenous or oral administration . The efficacy and safety of cyclosporine enemas for left-sided ulcerative colitis in a placebo-controlled trial was assessed . METHODS Steroid and mesalamine enemas were withdrawn before the study . Forty patients were assigned to 1 of 4 strata : no concomitant therapy , oral steroids , oral salicylates , or oral steroids and salicylates . After stratification , patients were r and omized to nightly treatment with 350 mg cyclosporine ( n = 20 ) or placebo ( n = 20 ) enemas . Clinical response was determined at baseline and 4 weeks by endoscopy , physician assessment , and a patient diary of daily symptoms . Trough blood cyclosporine levels were measured by high-performance liquid chromatography . RESULTS At 4 weeks , 8 of 20 patients ( 40 % ) who received cyclosporine showed clinical improvement compared with 9 of 20 patients ( 45 % ) who received placebo . One patient receiving cyclosporine had reversible neutropenia attributable to sulfasalazine , and another patient receiving cyclosporine was unable to tolerate the enema vehicle . No other toxicity was noted during the trial . Blood cyclosporine levels were detectable in only two patients . CONCLUSIONS Cyclosporine enemas administered in a dosage of 350 mg/day for 4 weeks are not efficacious in mildly to moderately active left-sided ulcerative colitis OBJECTIVE To define what effect seminal and controlled clinical trials have on practice patterns within a gastroenterological community . To define whether these practice patterns reproduce reported treatment methods and whether results comparable with those reported in such trials are noted within a community practice setting . METHODS Mailed surveies , with telephone follow-up , were sent to all members of the Pacific Northwest Gastroenterology Society . Respondents were queried regarding cyclosporin use in the precolectomy chronic ulcerative colitis ( CUC ) patient . Data collected included patient demographics , disease duration and extent , pre-treatment use of steroids , method , dosage , and duration of cyclosporin therapy , side effects , and short-term and subsequent clinical results . RESULTS Twenty-one percent of 81 respondents had used cyclosporin for precolectomy CUC , approximately one-half using constant infusion and one-half using parenteral bolus therapy .  Side effects attributed to the cyclosporin were noted in eight of 30 patients ( 27 % ) , and acute colectomy was avoided in 17 patients ( 57 % ) . Subsequent colectomy was required in an additional nine patients ( 73 % total ) within a 6-month follow-up period , a significantly higher colectomy rate than that reported in prospect i ve trials . CONCLUSIONS Potential reasons precluding cyclosporin use within the gastroenterological community may include lack of knowledge about cyclosporin therapy for CUC , lack of opportunity , skepticism , fear of medication side effects , survey sampling error , or treatment philosophy . Potential reasons for failure to duplicate the results reported in controlled trials are more complex but may include inadequate treatment duration the learning curve associated with the use of a new medication , or acceptance of colectomy as the treatment of choice in patients with acutely or chronically debilitating disease BACKGROUND / AIMS Cyclosporin was reported to be useful for steroid-resistant severe ulcerative colitis in the short term , but limited data are available on the long-term follow-up of such patients . Our aim was to assess the short- and long-term efficacy of combination therapy with cyclosporin and corticotropin for steroid-resistant ulcerative colitis . METHODOLOGY Twenty-one patients with ulcerative colitis who did not respond to corticosteroid therapy  , were treated with corticotropin , and 9 patients ( 43 % ) of them achieved complete remission . Twelve patients ( 57 % ) who did not achieve complete remission by corticotropin alone were given combination therapy with cyclosporin and corticotropin . RESULTS In 12 patients who received combined therapy with cyclosporin and corticotropin , clinical severity was distinctly improved in 11 patients ( 92 % ) by combination therapy within 2 weeks and 7 patients ( 58.3 % ) entered into complete remission with salicylazosulfapyridine or 5-aminosalicylic acid alone . Two patients ( 16.7 % ) demonstrated insufficient effect and continue to receive a lower dosage of cyclosporin or corticosteroid . Three patients ( 25 % ) failed to respond to the combination therapy and required colectomy . Three of 7 patients who entered into remission relapsed 0.5 , 5 and 5.5 months ( average : 3.7 months ) after cyclosporin withdrawal , but the clinical severity at the time of relapse was milder than that at the beginning of the treatment , namely , moderate in 2 patients , and mild in 1 patient . There were no significant adverse effects in our series . CONCLUSIONS We demonstrated that oral cyclosporin in combination with corticotropin was highly effective for ulcerative colitis refractory to corticosteroid or corticotropin therapy and severe relapse was uncommon during several years of follow-up UNLABELLED A single r and omized trial evaluated the use of intravenous cyclosporine treatment for severe attacks of ulcerative colitis .  The perceived efficacy and safety of this intervention were measured through a survey of the membership of the Canadian Association of Gastroenterology ( CAG ) . METHODS All CAG members were mailed a survey with questions regarding their familiarity with the data supporting the use of cyclosporine , their perception of the efficacy and toxicity of the drug , and whether patients who fail conventional treatment should receive this therapy . The proportion of respondents who had used cyclosporine to treat severe ulcerative colitis was determined . RESULTS One hundred and sixty-one responses were received ( 34 % response rate ) . Sixty-four per cent of respondents were academic faculty members and 82 % treated patients with severe colitis . Using multivariate analyses , positive associations were found between the respondents ' age ( P = 0.004 ) and subspecialty training in gastroenterology ( P = 0.001 ) , and whether respondents treat patients with severe ulcerative colitis . Twenty-six per cent of individuals had prescribed cyclosporine for this indication , of whom 88 % were in academic practice ( P = 0.007 ) . Over 90 % of respondents believe that further clinical trials are needed before cyclosporine becomes accepted as st and ard therapy . CONCLUSIONS Although the use of cyclosporine is measurable among Canadian gastroenterologists , the majority believe that further clinical trials are necessary before the drug is accepted as a st and ard therapy Thirty five adult patients with precirrhotic primary sclerosing cholangitis were r and omly allocated to treatment for at least one year with low dose ( 4.1 mg/kg/day ) cyclosporin or placebo in a double blind trial . Thirty patients had coexisting ulcerative colitis , including three who had previously undergone colectomy and one who discontinued treatment after three months . Of the remaining 26 patients , 16 received cyclosporin and 10 received placebo . Endoscopy was performed at entry to confirm the diagnosis of inflammatory bowel disease . The ulcerative colitis disease activity was prospect ively classified annually as remission/mild , moderate , or severe using the Truelove and Witt 's criteria . Before treatment there were no differences between the cyclosporin and placebo groups in the number of patients with remission/mild colitis , 14/16 ( 88 % ) v 9/10 ( 90 % ) , and moderate colitis , 2/16 ( 12 % ) v 1/10 ( 10 % ) . During treatment , a remission/mild disease course was present in 15/16 ( 94 % ) v 6/10 ( 60 % ) , p = 0.05 and a moderate disease course in 1/16 ( 6 % ) v 4/10 ( 40 % ) , p = 0.05 . It is concluded that patients treated with cyclosporin for primary sclerosing cholangitis who have coexisting ulcerative colitis have a more benign course of colitis result ing both from improvement of moderately active colitis and from fewer flares of remission/mildly active colitis . These findings suggest that cyclosporin may be of benefit to the colon in patients with ulcerative colitis who are being treated with cyclosporin for primary sclerosing cholangitis Ten patients with treatment-resistant left-sided ulcerative colitis were treated in an open protocol with 350 mg cyclosporine enemas nightly for 4 wk . A 12-point clinical disease activity index ( DAI ) score was calculated at baseline and after 4 wk . Whole blood and colonic tissue cyclosporine concentrations were determined by HPLC at the end of the study . Five of 10 patients responded to treatment , defined as a decrease in the clinical DAI score > or = 3 points . Responders retained the enemas longer than nonresponders ( 7.5 + /- 1.3 vs. 3.3 + /- 2.2 h , p = 0.01 ) , and there was a positive correlation between decrease in the clinical DAI score and enema retention time ( r = 0.64 , p = 0.05 ) . The mean colonic tissue cyclosporine concentration was not significantly higher in responders than in nonresponders ( 2884 + /- 1635 vs. 2359 + /- 576 ng/g , p = 0.52 ) , and the correlation between decrease in the clinical DAI score index and colonic tissue cyclosporine  was weak ( r = 0.39 , p = 0.26 ) . Cyclosporine was undetectable in whole blood sample s from all patients , and there were no apparent side effects with treatment . In conclusion , 50 % of patients with treatment-resistant left-sided ulcerative colitis significantly improved during therapy with cyclosporine enemas for 4 wk . Patients with longer enema retention times were more likely to respond . A controlled trial is underway to investigate these findings further The present study reports the results of intravenous cyclosporine in 32 patients with refractory and /or severe attacks of ulcerative colitis ( UC ) . Twenty of 32 patients responded to intravenous cyclosporine ; cyclosporine was clinical ly effective and improved colonic lesions . However , one colonic perforation and one postoperative death were observed in two patients with severe endoscopic colitis who had failed to reach clinical remission with high-dose corticosteroids and cyclosporine . Moreover , after a median follow-up of 190 days , only one-third of the patients avoided colectomy . No predictive factor of response to cyclosporine was identified . This study confirms that cyclosporine is effective in severe UC but suggests that its use could be associated with serious complications in patients with severe lesions who had failed to settle with corticosteroids and cyclosporine BACKGROUND There has been no new effective drug therapy for patients with severe ulcerative colitis since corticosteroids were introduced almost 40 years ago . In an uncontrolled study , 80 percent of 32 patients with active ulcerative colitis refractory to corticosteroid therapy had a response to cyclosporine therapy . METHODS We conducted a r and omized , double-blind , controlled trial in which cyclosporine ( 4 mg per kilogram of body weight per day ) or placebo was administered by continuous intravenous infusion to 20 patients with severe ulcerative colitis whose condition had not improved after at least 7 days of intravenous corticosteroid therapy .  A response to therapy was defined as an improvement in a numerical symptom score ( 0 indicated no symptoms , and 21 severe symptoms ) leading to discharge from the hospital and treatment with oral medications . Failure to respond to therapy result ed in colectomy , but some patients in the placebo group who had no response and no urgent need for surgery were subsequently treated with cyclosporine . RESULTS Nine of 11 patients ( 82 percent ) treated with cyclosporine had a response within a mean of seven days , as compared with 0 of 9 patients who received placebo ( P < 0.001 ) . The mean clinical -activity score fell from 13 to 6 in the cyclosporine group , as compared with a decrease from 14 to 13 in the placebo group . All five patients in the placebo group who later received cyclosporine therapy had a response . CONCLUSIONS Intravenous cyclosporine therapy is rapidly effective for patients with severe corticosteroid-resistant ulcerative colitis OBJECTIVES The aim of this study was to evaluate the role of metronidazole and tobramycin as an adjunct to corticosteroids in acute , severe ulcerative colitis . METHODS Thirty-nine consecutive patients with severe ulcerative colitis were r and omized on admission to the hospital to receive intravenously either metronidazole ( 0.5 g tid ) and tobramycin ( 4 mg/kg tid ) ( n = 19 ) , or placebo ( n = 20 ) . In addition , they were given parenteral nutrition , intravenous hydrocortisone ( 100 mg qid ) and hydrocortisone enemas ( 100 mg bid ) . All patients were assessed after 10 days of continuous treatment , or at any time a severe complication occurred . RESULTS Twelve of 19 patients ( 63.15 % ) treated with antibiotics and 13/20 patients ( 65 % ) with placebo showed substantial improvement . Seven patients in each group did not improve ( n = 9 ) , or developed complications ( n = 5 ) and underwent emergency colectomy without perioperative deaths or late deaths . CONCLUSIONS These results do not support the routine use of intravenous tobramycin and metronidazole in the treatment of severe ulcerative colitis The aim of this study was to evaluate the use of cyclosporin enemas in patients with distal ulcerative colitis and ' pouchitis ' resistant to all conventional medical therapy . In an trial 12 patients with distal ulcerative colitis unresponsive to treatment with topical and oral corticosteroids , 5-aminosalicylic acid , and oral immunosuppressive therapy together with 1 patient with ' pouchitis ' unresponsive to repeated courses of antibiotics , topical corticosteroids , and oral mesalazine received 250 mg cyclosporin administered daily as a retention enema . Changes in symptoms and the sigmoidoscopic/histologic appearances of the rectal mucosa were assessed at monthly intervals . Seven of 12 patients with ulcerative colitis improved . There was a strong correlation between clinical and histologic improvement ( p < 0.005 ) . Four of 12 patients showed no response . Three of these required colectomy , two of whom had more extensive disease than had previously been documented . The patient with pouchitis showed improvement in symptoms and ' pouchoscopy ' appearance but not in histologic score . Cyclosporin blood concentrations were very low and side effects negligible . Cyclosporin A retention enemas are safe and may be useful in the treatment of severe refractory distal ulcerative colitis . A controlled trial would now seem warranted Cyclosporin ( CSA ) has emerged as a medical alternative to colectomy in severe , steroid-refractory ulcerative colitis ( UC ) patients . This is the first formal quality -of-life study comparing such patients treated with intravenously administered cyclosporin with those treated surgically with colectomy .  Quality -of-life analyses were conducted in all patients who underwent colectomy or received intravenous CSA for severe UC from 1991 to 1995 using the Inflammatory Bowel Disease Question naire , a visual-analog scale ( VAS ) , and the Oresl and scale , with additional questions regarding health care utilization and medication use . The 18 CSA-treated patients reported a better ability to sleep ( p = 0.002 ; VAS ) , better stool consistency ( p < 0.001 ; VAS ) , less abdominal or rectal pain ( p = 0.009 , VAS ) , and fewer daytime ( p < 0.001 ; Oresl and ) , nighttime ( p = 0.006 ; Oresl and ) , and daily trips to the toilet ( p < 0.001 ; VAS ) than the 46 surgical patients . The mean number and rate of hospitalizations within the first year was also lower in the CSA patients ( p < 0.001 for both ) . The surgical patients reported fewer initial visits to their specialist ( p < 0.001 ) and less medication use ( p < 0.001 ; Oresl and ) . Patients with severe steroid-refractory UC treated with intravenously administered CSA scored as well as or better than their surgical counterparts . The use of CSA in selected patients is substantiated both by clinical results and quality -of-life analysis Summary : We have used cyclosporin to treat patients with acute steroid‐resistant ulcerative colitis since the beginning of 1991 . Of the 55 patients so far elected for treatment , 40 received the drug intravenously at 2 mg/kg/day for 14 days , with the responders being maintained on traditional soft‐gelatincapsule cyclosporin at a dose of 6‐8 mg/kg/day for 6 months ; the remaining 15 received oral microemulsion cyclosporin , 5 mg/kg/day , for 3 months . The doses were titrated to ensure whole‐blood drug concentrations of 60‐240 ng/ml , with levels of ‐200 ng/ml being attained by both regimens . One‐hundred percent of the patients receiving oral microemulsion cyclosporin and 65 % of those receiving the intravenous regimen achieved a short‐term response ( p = 0.011 ) . Both the responder subsets received  additional azathioprine  and relapsed on treatmcnt with the same frequency of 40 % . However , 17 % of the patients who received intravenous cyclosporin  developed major toxicity ( including one fatality ) , whereas no major toxicity was observed in the oral microemulsion cyclosporin group . The microemulsion formulation was therefore more effective than intravenous cyclosporin in achieving the shortterm remission of steroid‐unresponsive ulcerative colitis . As the maintenance drug , it led to the same frequency of disease relapse as traditional oral cyclosporin . However , because it did not involve invasive in‐hospital procedures or cause major toxicity , it was more efficient than the combination of the intravenous and traditional oral drug Background : Tumour necrosis factor production is increased in the mucosa of patients with active ulcerative colitis . The benefits of infliximab in Crohn ’s disease are established . We investigated its efficacy in ulcerative colitis . Methods : We conducted a r and omised placebo controlled trial of infliximab ( 5 mg/kg ) in the treatment of glucocorticoid resistant ulcerative colitis . Infusions were given at weeks 0 and 2 . Disease activity and quality of life were recorded over eight weeks of follow up . Remission was defined as an ulcerative colitis symptom score ( UCSS ) of ⩽2 and /or Baron score of 0 at week 6 . Patients not in remission were offered open label infliximab 10 mg/kg and review ed two weeks later . Results : After two weeks , there was no statistically significant difference between the infliximab and placebo groups in the proportion of patients with a Baron score of 0 ( 13 % ( 3/23 ) v 5 % ( 1/19 ) ( 95 % confidence interval ( CI ) −9 % to 24 % ) ; p=0.74 ) . After six weeks , remission ( UCSS ⩽2 ) rates were 39 % ( 9/23 ) versus 30 % ( 6/20 ) ( 95 % CI −19 to 34 % ; p=0.76 ) . The median improvement in UCSS was 3 for the infliximab group and 2.5 for the placebo group ( p=0.82 , Mann-Whitney U test ) . A Baron score of 0 was likely in either group ( 26 % ( 6/23 ) v 30 % ( 6/20 ) ( 95 % CI −30 % to 23 % ) ; p=0.96 ) . Improvement in the IBDQ and EuroQol was not significantly different between the groups ( p=0.22 and 0.3 , respectively , Mann-Whitney U test ) . Twenty eligible patients were given open labelled infusions . Remission was achieved in 3/11 ( 27 % ) patients initially treated with infliximab and in 1/9 ( 11 % ) patients treated with placebo . Conclusion : These data do not support the use of infliximab in the management of moderately active glucocorticoid resistant ulcerative colitis Recent evidence suggests that the immunosuppressive drug cyclosporin may be of benefit in treating patients with severe colitis who are steroid resistant . Although cyclosporin appears to be effective in reducing colectomy rates in the short term , few data are available on the long‐term follow‐up of such patients The aim of this study was to assess whether in steroid-resistant patients with pediatric inflammatory bowel disease ( IBD ) a combination of cyclosporine and azathioprine ( or 6-mercaptopurine ) could induce remission and subsequently permit maintenance on azathioprine/6-mercaptopurine as the sole immunosuppressive agent . Two boys and six girls ( six with ulcerative colitis and two with Crohn 's disease ; ages 3 - 17 years ) received 100 - 200 micrograms/kg/day cyclosporine intravenously and then 4 - 10 mg/kg/day orally . Doses were adjusted to achieve trough serum cyclosporine levels of 100 - 200 mu/L ( Abbott 's TDX assay ) . Seven of the eight patients received azathioprine/6-mercaptopurine , and all were given a 5-aminosalicylate preparation and corticosteroids . The latter drugs were continued and then tapered off as clinical status allowed . Cyclosporine was continued for 3 - 10 months in those who responded . In seven of eight patients , there was a rapid clinical response ; one patient showed a transient response , but recurrent bleeding led to total colectomy 9 days after starting cyclosporine . Of the seven responders , three were able to discontinue prednisone and cyclosporine and are doing well on azathioprine at long-term follow-up ( 2 - 5 years ) . One who did not receive azathioprine/6-mercaptopurine maintained remission for 2 years after cyclosporine was stopped , one experienced a disease flare-up 5 months after start of cyclosporine treatment and required colectomy , one who did not tolerate 6-mercaptopurine had a flare-up during cyclosporine tapering and underwent surgery at 6 months , and one started to flare up with cyclosporine tapering at 6 months and was scheduled for surgery . No significant complications of treatment were observed . Seven patients had an initial response and four of them have so far not required surgery . These preliminary findings suggest that azathioprine/6-mercaptopurine can be used safely to maintain  cyclosporine-induced remission in children with IBD BACKGROUND / AIMS To determin whether cyclosporine is effective in inducing remission in patients with severe active inflammatory bowel disease , refractory to steroids . METHODOLOGY Twenty-three patients with severe and steroid-refractory inflammatory bowel disease ( 15 ulcerative colitis and 8 Crohn 's disease ) were included . The Mayo Clinic Score and the CDAI were used to evaluate activity . Cyclosporine ( 4 mg/kg/day ) was administered for a maximum of ten and a minimum of 7 days . RESULTS Ten of the 15 ulcerative colitis patients achieved remission with a mean response lag time to onset improvement of 8 days . Seven of these patients remained stable with mesalazine 4 months after cyclosporine treatment . Two patients relapsed and underwent colectomy on the 50th and 200th day after treatment . Five patients presented no response and required urgent colectomy . Six of the 8 Crohn 's disease patients achieved remission with a mean response lag time to onset improvement of 7 days . The 6 patients remained stable with mesalazine four months after cyclosporine treatment . The other 2 developed reversible renal failure and had to be released from the study . CONCLUSIONS Intravenous high dose cyclosporine is effective and can be used as a rapid onset treatment for acute steroid refractory IBD Intensive intravenous treatment remains the first line therapy of severe , uncomplicated attacks of ulcerative colitis Approximately 15 % of patients with ulcerative colitis will have a severe attack requiring hospitalisation for intravenous steroids at some stage in their illness.1 Sixty per cent of patients treated with corticosteroids will be symptom free by the end of five days , 15 % will have significant improvement , and 25 % will not improve . Those who fail to improve may be treated with intravenous cyclosporin or undergo colectomy . There have been four controlled studies of intravenous cyclosporin in patients with severe ulcerative colitis . Of 20 patients reported by Lichtiger et al , nine were r and omised to receive placebo and 11 to receive cyclosporin 4 mg/kg/day as a continuous infusion for 14 days.2 Nine of 11 cyclosporin treated patients ( 82 % ) responded compared with none of the placebo treated patients . Those who responded were continued on oral cyclosporin 8 mg/kg/day . At six months , 5/11 cyclosporin treated patients ( 45 % ) maintained a Background : Recent studies have shown both interleukin 2 ( IL‐2 ) and interferon gamma ( IFN ) to be elevated in patients with active Crohn 's disease compared to ulcerative colitis or non‐inflammatory bowel disease controls . However the effect of treatment on these lymphokines has not been studied BACKGROUND AND AIMS Cyclosporine A is highly effective in severe attacks of ulcerative colitis ( UC ) but is associated with important adverse effects that are mainly dose dependent . Our single center , r and omized , double-blind , controlled trial aim ed to evaluate the additional clinical benefit of 4 mg/kg over 2 mg/kg IV cyclosporine in the acute treatment of severe UC . METHODS Primary end point was the proportion of patients with a clinical response . Secondary end points included time to response , colectomy rate , and adverse effects . RESULTS Seventy-three patients were included . Day-8 response rates were 84.2 % ( 32 of 38 , 4 mg/kg ) and 85.7 % ( 32 of 35 , 2 mg/kg ) after a median of 4 days in both groups . Short-term colectomy rates were 13.1 % ( 4 mg/kg ) and 8.6 % ( 2 mg/kg ) . Mean cyclosporine blood levels were 237 + /- 33 in the 2-mg/kg group and 332 + /- 43 ng/mL in the 4-mg/kg group . Active smoking was inversely correlated with clinical response ( odds ratio , 0.06 ) , but concomitant azathioprine or steroids were not predictive . A trend toward a higher incidence of hypertension was observed in the 4-mg/kg group ( 23.7 % vs. 8.6 % , 2 mg/kg , P < 0.08 ) . CONCLUSIONS High-dose IV cyclosporine has no additional clinical benefit over low dose in the treatment of severe UC . Although we did not observe differences in adverse effects on the short term , the use of 2 mg/kg IV cyclosporine should provide an improved toxicity profile for medical treatment of severe UC Background : The efficacy of infliximab in ulcerative colitis ( UC ) and indeterminate colitis has been poorly assessed and preliminary results are conflicting BACKGROUND & AIMS Cyclosporine has been effective in patients with steroid-refractory attacks of ulcerative colitis ( UC ) . We investigated the effects of intravenous ( IV ) cyclosporine as single IV therapy ( without glucocorticosteroids ) for severe UC and compared these with the response to glucocorticosteroids . METHODS Patients with a severe attack of UC were r and omized to treatment with IV cyclosporine , 4 mg x kg(-1 ) x day(-1 ) , or with methylprednisolone , 40 mg/day , in a r and omized , double-blind , controlled trial . After 8 days , patients who had a response received the same medication orally in combination with azathioprine . Patients were followed up clinical ly , endoscopically , and by scintigraphy . Renal function was assessed using urinary inulin clearances . Endpoints were clinical improvement , discharge from the hospital , and remission up to 12 months after intravenous therapy . RESULTS Thirty patients were included . After 8 days , 8 of 15 patients ( 53 % ) who received methylprednisolone had a response to therapy vs. 9 of 14 ( 64 % ) receiving cyclosporine . In nonresponders , 3 of 7 methylprednisolone patients and 1 of 3 cyclosporine patients improved when both treatments were combined . No serious drug-related toxicity was observed with either treatment . At 12 months , 7 of 9 patients ( 78 % ) initially controlled with cyclosporine maintained their remission vs. 3 of 8 ( 37 % ) initially treated with methylprednisolone . No clinical ly significant decrease of renal function was observed . CONCLUSIONS Cyclosporine monotherapy is an effective and safe alternative to glucocorticosteroids in patients with severe attacks of UC
BACKGROUND Ulcerative colitis ( UC ) is characterized by a life-long chronic course with remissions and exacerbations .
Approximately 15 % of patients have a severe attack requiring hospitalization at some time during their illness .
These patients are traditionally treated with intravenous corticosteroids , with a response rate of approximately 60 % .
The patients who do not respond to steroid treatment  usually require surgical removal of the large bowel ( proctocolectomy or colectomy with an anal pouch  ) .
This surgical procedure essentially cures the patient from the disease but is associated with complications such as pouchitis .
Few alternative treatments exist for severe ulcerative colitis : immunosuppressive medications ( such as azathioprine ) have a slow onset of action and are therefore usually ineffective .
Antibiotics are not proven to be effective and biological treatments such as infliximab are still under investigation .
The introduction of cyclosporine-A ( CsA ) for use in patients with severe ulcerative colitis ( UC ) has provided an alternative to patients previously facing only surgical options .
Cyclosporine acts mainly by inhibiting T lymphocyte function , which is essential for the propagation of inflammation .
Unlike most other immunosuppressive agents , CsA does not suppress the activity of other hematopoietic cells , does not cause bone marrow suppression and has a rapid onset of action .
This review s aims to systematic ally assess the effectiveness and safety of CsA for severe UC .
OBJECTIVES This review aim ed to evaluate the effectiveness of  cyclosporine A for patients with severe ulcerative colitis .