A comparison of oral prednisolone given as single or multiple daily doses for active proctocolitis. A method for assessing the quality of a randomized control trial. Low colectomy rates in ulcerative colitis in an unselected European cohort followed for 10 years. Azathioprine versus sulfasalazine in maintenance of remission in severe ulcerative colitis. Controlled trial of azathioprine in chronic ulcerative colitis. Azathioprine in Ulcerative Colitis: Final Report on Controlled Therapeutic Trial 6‐Mercaptopurine or methotrexate added to prednisone induces and maintains remission in steroid‐dependent inflammatory bowel disease Randomised controlled trial of azathioprine withdrawal in ulcerative colitis. The beneficial effect of azathioprine on maintenance of remission in severe ulcerative colitis A controlled trial of azathioprine in the management of chronic ulcerative colitis. Role of azathioprine in severe ulcerative colitis: one-year, placebo-controlled, randomized trial.
Forty mg has been shown to be the optimal daily dosage of prednisone for out patients requiring oral steroids for active proctocolitis . Although daily doses of oral steroids are commonly divided , a single dose each morning causes less adrenal suppression and is more convenient to take . A r and omized controlled trial has been performed on patients with proctocolitis , in which 23 received 40 mg prednisolone each morning as one dose , and 22 received 10 mg four times a day  , over two weeks  . Physicians unaware of the dosage schedule scored the disease activity and assessed the steroid side-effects when the patient entered the trial , at day 7 and at day 14 . Of those taking the divided dose the disease improved in 17 and failed to improve in five . No side-effects were observed in ten patients . Of those receiving a once daily regimen , 17 improved and six did not . Nine patients had no side-effects . Further assessment showed no difference between the two groups either in response rate or side-effects produced . When oral steroids are indicated for active proctocolitis , 40 mg prednisolone , as a single dose each morning can be recommended A system has been constructed to evaluate the design , implementation , and analysis of  r and omized control trials ( RCT ) . The degree of quadruple blinding ( the r and omization process , the physicians and patients as to therapy , and the physicians as to ongoing results ) is considered to be the most important aspect of any trial . The analytic techniques are scored with the same emphasis as is placed on the control of bias in the planning and implementation of the studies . Description of the patient and treatment material s and the measurement of various controls of quality have less weight . An index of quality of a RCT is proposed with its pros and cons . If published papers were to approximate these principles , there would be a marked improvement in the quality of r and omized control trials . Finally , a reasonable st and ard design and conduct of trials will facilitate the interpretation of those with conflicting results and help in making valid combinations of undersized trials BACKGROUND & AIMS The colectomy rate in ulcerative colitis ( UC ) is related to morbidity and to treatment decisions made during disease course . The aims of this study were to determine the  colectomy  risk in UC in the first decade after diagnosis and to identify factors that may influence the choice of surgical treatment . METHODS In 1991 - 1993 , 781 UC patients from 9 centers located in 7 countries in northern and southern Europe and in Israel were included in a prospect i ve inception cohort study . After 10 years of follow-up , 617 patients had complete medical records , 73 had died , and 91 had been lost to follow-up . RESULTS There were no significant differences in age , sex , or disease extent at diagnosis between patients followed for 10 years and those lost to follow-up . The 10-year cumulative risk of colectomy  was 8.7 % : 10.4 % in the northern and 3.9 % in the southern European centers ( P < .001 ) .  Colectomy  was more likely in extensive colitis than in proctitis , with an adjusted hazard ratio ( HR ) of 4.1 ( 95 % CI : 2.0 - 8.4 ) . Compared with the southern centers , the adjusted HR was 2.7 ( 95 % CI : 1.3 - 5.6 ) for The Netherl and s and Norway together and 8.2 ( 95 % CI : 3.6 - 18.6 ) for Denmark . Age at diagnosis , sex , and smoking status at diagnosis had no statistically significant influence on  colectomy rates . CONCLUSIONS The  colectomy rate was found to be lower than that in previous publications , but there was a difference between northern and southern Europe .  Colectomy  was associated with extensive colitis , but the geographic variations could not be explained BACKGROUND Azathioprine is useful as a steroid-sparing drug in patients with ulcerative colitis . Its role as monotherapy in the maintenance of disease remission has not been evaluated . METHODS In this prospect i ve , r and omized , open-label study , 25 patients with severe ulcerative colitis received either azathioprine ( 2.5 mg/Kg/day ; Group A , n = 12 ) or sulfasalazine ( 6 g/day ; Group B , n = 13 ) . All patients received oral corticosteroids in a tapering dosage schedule initially . Treatment failure was defined as either disease relapse or drug withdrawal because of adverse effects . RESULTS Five of 12 patients in Group A and 8 of 13 patients in Group B had sustained remission during the stipulated study period of 18 months ( p = ns ) . Two patients in Group A had to stop azathioprine because of adverse effects ( bone marrow suppression and acute pancreatitis ) . In Group A , all patients who had treatment failure developed it in the first half of the study while in Group B treatment failure occurred in both halves . CONCLUSIONS The relapse rate of ulcerative colitis on maintenance therapy with azathioprine or sulfasalazine is comparable ; there was a trend towards earlier treatment failure with azathioprine A double-blind controlled trial of azathioprine in a dose of 2 - 2.5 mg/kg body weight over six months was conducted among 44 patients with active chronic ulcerative colitis . Three patients treated with placebo did not complete the trial because their disease became so severe that colectomy was performed . Among patients who completed the trial the mean dose of prednisolone necessary to control the disease decreased in those treated with azathioprine and those treated with placebo ; the reduction was greater among those who took azathioprine ( p less than 0.001 ) . Activity of the disease apparently improved in both treatment groups but a significant ( p less than 0.001 ) trend was observed only in those patients treated with azathioprine .  No serious side effects from azathioprine occurred during the trial but seven of 24 patients had to stop the drug because of nausea .  Azathioprine may have a role in the treatment of a few patients wih troublesome chronic colitis for whom conventional drug treatment is ineffectual , or for whom continuous systemic corticosteroid treatment is needed to control symptoms , and for whom surgical treatment is inappropriate Eighty patients , all of whom were suffering from a frank clinical attack of ulcerative colitis , were admitted to the trial . The attack was treated with a st and ard course of corticosteroids and the patients were immediately placed on treatment with either azathioprine in a dose of 2·5 mg/kg body weight or dummy tablets . The trial tablets were continued for one year while the patients were maintained under regular clinical , sigmoidoscopic , histological , haematological , and biochemical surveillance . If a patient relapsed during such maintenance treatment he or she was treated with a further course of corticosteroids without interrupting maintenance treatment . In the treatment of an actual attack of ulcerative colitis the results in the attacks which brought the 80 patients into the trial show that no benefit came from the addition of azathioprine to a st and ard course of corticosteroid therapy . Patients admitted in their first attack of ulcerative colitis showed no benefit from the one-year maintenance treatment with azathioprine  , the benefits of which were confined to patients admitted in a relapse of established disease . Even in these the difference between the treated group and the control group failed to reach statistical significance , but the difference was big enough to suggest that there is a prima facie case for regarding azathioprine as of some benefit in this group of patients Background As treatment of steroid‐dependent patients with inflammatory bowel disease ( IBD ) is controversial , we analysed the efficacy and tolerance of 6‐mercaptopurine ( 6‐MP ) and methotrexate ( MTX ) added to prednisone in increasing and maintaining the disease remission rate . Methods Seventy‐two steroid‐dependent IBD patients , 34 with ulcerative colitis ( UC ) and 38 with Crohn 's disease ( CD ) , receiving treatment with prednisone  were r and omly assigned in a 2:2:1 ratio to additionally receive , orally , over a period of 30 weeks 1.5 mg/kg/day of 6‐MP ( group A ) or 15 mg/week of MTX ( group B ) , or 3 g/day of 5‐aminosalicylic acid ( 5‐ASA ) ( group C ) . All patients who achieved remission were included in a maintaining remission study for 76 weeks . Remission was defined after stopping prednisone as a CD activity index of < 150 and normal serum orosomucoid concentration for CD patients and a Mayo Clinic score < 7 for UC patients . Results With regard to achieved remission , a significantly higher ( P < 0.05 ) rate existed for UC patients in group A ( 78.6 % ) than in group C ( 25 % ) , with no statistical differences in group B ( 58.3 % ) versus C. For CD patients , the rates were significantly higher ( P < 0.001 and 0.01 , respectively ) in groups A ( 93.7 % ) and B ( 80 % ) versus C ( 14 % ) . With regard to maintaining remission , UC patients in group A ( 63.6 % ) presented significantly higher rates ( P < 0.0015 and P < 0.001 , respectively ) versus 14.3 % in group B and none in group C. For CD patients , statistical differences ( P < 0.001 ) existed when comparing rates in groups A ( 53.3 % ) and B ( 66.6 % ) versus none in group C. Noticeable side effects appeared in 13.3 % of patients from group A and 11.5 % from group B. Conclusions These results suggest that 6‐MP or MTX added to prednisone could be effective in steroid sparing , as well as in achieving and maintaining remission in steroid‐dependent IBD patients . MTX was less effective in maintaining remission in UC patients OBJECTIVE --To determine whether azathioprine can prevent relapse in ulcerative colitis . DESIGN --One year placebo controlled double blind trial of withdrawal or continuation of azathioprine . SETTING --Outpatient clinics of five hospitals . SUBJECTS--79 patients with ulcerative colitis who had been taking azathioprine for six months or more . Patients in full remission for two months or more ( 67 ) , and patients with chronic low grade or corticosteroid dependent disease ( 12 ) were r and omised separately . 33 patients in remission received azathioprine and 34 placebo ;  five patients with chronic stable disease received azathioprine and seven placebo . MAIN OUTCOME MEASURE -- Rate of relapse . Relapse was defined as worsening of symptoms or sigmoidoscopic appearance . RESULTS --For the remission group the one year rate of relapse was 36 % ( 12/33 ) for patients continuing azathioprine and 59 % ( 20/34 ) for those taking placebo ( hazard rate ratio 0.5 , 95 % confidence interval 0.25 to 1.0 ) . For the subgroup of 54 patients in long term remission ( greater than six months before entry to trial ) benefit was still evident , with a 31 % ( 8/26 ) rate of relapse with azathioprine and 61 % ( 17/28 ) with placebo ( p less than 0.01 ) . For the small group of patients with chronic stable colitis ( six were corticosteroid dependent and six had low grade symptoms ) no benefit was found from continued azathioprine therapy .  Adverse events were minimal . CONCLUSIONS --Azathioprine maintenance treatment in ulcerative colitis is beneficial for at least two years if patients have achieved remission while taking the drug . Demonstration of the relapse preventing properties of azathioprine has implication s for a large number of patients with troublesome ulcerative colitis , who may benefit from treatment with azathioprine Background . The search is on to find more effective drug regimens for patients with severe ulcerative colitis , as conventional drugs such as sulfasalazine and its congeners fail to prevent relapse in a significant number of patients . Azathioprine has also been reported to be useful as a steroid-sparing drug in patients who suffer from frequent relapses . As these drugs when used individually fail to sustain remission in a significant number of patients , we evaluated the combination of these two drugs . Methods . Thirty-five newly diagnosed patients with severe ulcerative colitis were r and omized into two groups ; group A ( combination therapy ) received sulfasalazine and azathioprine , while group B ( sulfasalazine monotherapy ) received sulfasalazine and placebo . In addition , all the patients received steroids initially to achieve clinical remission . The patients were followed-up for a period of 1 year . The therapeutic outcome was measured by the number of patients who suffered relapse in each group . Results . All the patients completed the 1-year study period . While 4 patients ( 23.5 % ) in group A suffered relapse of disease , 10 ( 55.6 % ) in group B suffered relapse , the difference being statistically significant . The relapse-free period was also significantly longer in group A. Conclusions . Combination therapy ( sulfasalazine and azathioprine ) is more effective than sulfasalazine and placebo in the maintenance of remission in patients with severe ulcerative colitis To determine the efficacy of azathioprine in the treatment of ulcerative colitis , a 6-month double blind trial was carried out . Thirty patients with chronic ulcerative colitis who required the equivalent of at least 10 mg of prednisone per day over the 3 months prior to entering the study were r and omized into placebo and azathioprine ( 1.5 mg per kg ) treatment groups . Reduction of steriods was a major objective of the trial . Age and sex distribution , number of bowel movements , sense of well being , steroid dosage , and findings on proctoscopy , rectal biopsy , and colon X-ray initially were similar in the two groups . No side effects were associated with azathioprine . Although steroid dose was lower ( p less than 0.05 ) in the azathioprine group at the termination of the study , no difference between the two groups could be detected in the number of bowel movements , sense of well being , and findings on proctoscopy during the first 3 weeks compared with the last 3 and during the first 3 months compared with the last 3 . Although azathioprine does not confer dramatic benefit upon patients with chronic ulcerative colitis who require steroids , it does permit reduction of steroid dosage without apparent worsening of the disease . Its major value in ulcerative colitis may be in facilitating significant decreases or complete discontinuance of steroids OBJECTIVE To investigate the efficacy of azathioprine in treating patients with severe ulcerative colitis . DESIGN One-year , r and omized , placebo-controlled trial . SUBJECTS 83 patients with severe ulcerative colitis were enrolled . Fifty patients who relapsed within two months on corticosteroid withdrawal were r and omized into two groups . The azathioprine group received oral sulfasalazine ( 6 - 8 g/day ) , oral prednisolone ( 1 mg/Kg/day ) and oral azathioprine ( 2 mg/Kg/day ) . The placebo group received oral sulfasalazine ( 6 - 8 g/day ) , oral prednisolone ( 1 mg/Kg/day ) and placebo . Corticosteroids were tapered over 12 - 16 weeks . RESULTS Five patients ( 2 in azathioprine group , 3 in placebo group ) dropped out of the study . Three patients in the azathioprine group had side effects . The number of patients going into complete remission and partial remission was not significantly different in the two groups . The proportion of relapses in the azathioprine group was lower than in the placebo group ( p < 0.05 ) . CONCLUSIONS In patients with ulcerative colitis , azathioprine had no effect in achieving remission , when given in combination with prednisolone ; however , it lowers the proportion of relapses . Side effects like pancreatitis and hepatitis are mild and respond promptly to drug withdrawal
Background Published trials evaluating the efficacy of 6-thioguanine anti-metabolites in the treatment of ulcerative colitis ( UC ) have yielded conflicting results .
We performed a systematic review and meta- analysis to evaluate the clinical efficacy of 6-thioguanine anti-metabolites for the maintenance of clinical remission after st and ard induction with corticosteroids .