Predictability of the postoperative course of Crohn's disease. Controlled trial of metronidazole treatment for prevention of Crohn's recurrence after ileal resection. Azathioprine versus mesalazine for prevention of postoperative clinical recurrence in patients with Crohn's disease with endoscopic recurrence: efficacy and safety results of a randomised, double-blind, double-dummy, multicentre trial Postoperative recurrence of Crohn's disease in relation to radicality of operation and sulfasalazine prophylaxis: a multicenter trial. Postoperative maintenance of Crohn's disease remission with 6-mercaptopurine, mesalamine, or placebo: a 2-year trial. Management of Crohn's Disease in Adults Incidence of Crohn's disease in four counties in southeastern Norway, 1990-93. A prospective population-based study. The Inflammatory Bowel South-Eastern Norway (IBSEN) Study Group of Gastroenterologists. Postoperative treatment with corticosteroids and salazosulphapyridine (Salazopyrin) after radical resection for Crohn's disease. Clinical course during the 1st year after diagnosis in ulcerative colitis and Crohn's disease. Results of a large, prospective population-based study in southeastern Norway, 1990-93. Prophylaxis of postoperative relapse in Crohn's disease with mesalamine: European Cooperative Crohn's Disease Study VI. Ornidazole for prophylaxis of postoperative Crohn's disease recurrence: a randomized, double-blind, placebo-controlled trial. A controlled double blind study of azathioprine in the management of Crohn's disease. Prophylactic mesalamine treatment decreases postoperative recurrence of Crohn's disease. Sulphasalazine in asymptomatic Crohn's disease. A multicentre trial. Azathioprine and mesalamine for prevention of relapse after conservative surgery for Crohn's disease.
Eighty-nine patients who had been treated by ileal resection for Crohn 's disease between 1979 and 1984 were included in a prospect i ve cohort follow up to study the natural course of early postoperative lesions . Recurrent lesions were observed endoscopically in the neoterminal ileum within 1 year of surgery in 73 % of the patients , although only 20 % of the patients had symptoms . Three years after surgery , the endoscopic recurrence rate had increased to 85 % and symptomatic recurrence occurred in 34 % . The ultimate course of the disease was best predicted by the severity of the early postoperative lesions , as observed at ileoscopy . Clinical parameters that influenced outcome were preoperative disease activity , the indication for surgery , and the number of surgical resections . When patients were stratified for preoperative disease activity , the severity of lesions found at endoscopy remained a strong predictive factor for symptomatic recurrence . In 22 other patients su bmi tted to " curative " ileal resection and ileocolonic anastomosis , the segment to be used as neoterminal ileum was carefully examined during surgery , and two large biopsies were taken before making the anastomosis . An ileoscopy was performed 6 months after surgery . Although all patients had a macroscopically normal neoterminal ileum and 19 had entirely normal biopsies at the time of surgery , 21 patients were found at ileoscopy to have developed ileitis involving a 15-cm segment ( range , 4 - 30 cm ) , and 20 had unequivocal microscopic lesions on biopsies . These studies suggest that early lesions in the neoterminal ileum after Crohn 's resection do not originate from microscopic inflammation present in this bowel segment at the time of surgery . The early postoperative lesions in the neoterminal ileum seem to be a suitable model to study the pathogenesis of Crohn 's disease and also to evaluate new therapeutic modalities , either to prevent development of these early lesions or to treat progressive recurrence BACKGROUND / AIMS New lesions recur within weeks to months after ileal resection and ileocolonic anastomosis for Crohn 's ileitis . A double-blind controlled trial was performed using metronidazole to prevent recurrence after ileal resection . METHODS Sixty patients who underwent curative ileal resection and primary anastomosis were included within 1 week after surgery . Thirty patients received metronidazole ( 20 mg/kg body wt ) daily for 3 months , and 30 patients received placebo . Treatment was then discontinued . Nine patients dropped out during treatment , 7 in the metronidazole group and 2 in the placebo arm . RESULTS At 12 weeks , 21 of 28 patients ( 75 % ) in the placebo group had recurrent lesions in the neoterminal ileum as compared with 12 of 23 patients ( 52 % ) in the metronidazole group ( P = 0.09 ) . The incidence of severe endoscopic recurrence was significantly reduced by metronidazole ( 3 of 23 ; 13 % ) as compared with placebo ( 12 of 28 ; 43 % ; P = 0.02 ) . Patients in the metronidazole arm had more frequent side effects . Metronidazole therapy statistically reduced the clinical recurrence rates at 1 year ( 4 % vs. 25 % ) . Reductions at 2 years ( 26 % vs. 43 % ) and 3 years ( 30 % vs. 50 % ) were not significant . CONCLUSIONS Metronidazole therapy for 3 months decreases the severity of early recurrence of Crohn 's disease in the neoterminal ileum after resection and seems to delay symptomatic recurrence Objective The aim of the study was to compare azathioprine versus mesalazine tablets for the prevention of clinical recurrence in patients with postoperative Crohn 's disease ( CD ) with moderate or severe endoscopic recurrence . Methods This was a 1 year , double-blind , double-dummy , r and omised study which took place in 21 gastroenterology centres in Austria , the Czech Republic , Germany and Israel . The study participants were 78 adults with CD who had undergone resection with ileocolonic anastomosis in the preceding 6–24 months without subsequent clinical recurrence and with a Crohn 's disease activity index ( CDAI ) score < 200 , but with moderate or severe endoscopic recurrence . The study drugs were azathioprine 2.0–2.5 mg/kg/day or mesalazine 4 g/day over 1 year . The primary end point was therapeutic failure during 1 year , defined as a CDAI score ≥200 and an increase of ≥60 points from baseline , or study drug discontinuation due to lack of efficacy or intolerable adverse drug reaction . Results Treatment failure occurred in 22.0 % ( 9/41 ) of azathioprine-treated patients and 10.8 % ( 4/37 ) of mesalazine-treated patients , a difference of 11.1 % ( 95 % CI −5.0 % to 27.3 % , p=0.19 ) . Clinical recurrence was significantly less frequent with azathioprine versus mesalazine ( 0/41 ( 0 % ) vs 4/37 ( 10.8 % ) , p=0.031 ) , whereas study drug discontinuation due to adverse drug reactions only occurred in azathioprine-treated patients ( 9/41 ( 22.0 % ) vs 0 % , p=0.002 ) . The proportion of patients showing ≥1 point reduction in Rutgeerts score between baseline and month 12 was 63.3 % ( 19/30 ) and 34.4 % ( 11/32 ) in the azathioprine and mesalazine groups , respectively ( p=0.023 ) . Conclusions In this population of patients with postoperative CD at high risk of clinical recurrence , superiority for azathioprine versus mesalazine could not be demonstrated for therapeutic failure . Clinical trial registration number NCT00946946 Recurrence rate is high after operation for Crohn 's disease . A multicenter trial was performed to study the effect of radical or nonradical operation and of sulfasalazine prophylaxis versus placebo on postoperative recurrence rate in 232 patients with Crohn 's disease . Sixteen medical and surgical centers participated in the study , 7 operating radically and 9 nonradically . The follow-up period lasted 3 years , the allocation to drug treatment was r and omized and double blind . Recurrence was significantly less frequent and occurred later in patients who were operated nonradically . Patients on sulfasalazine prophylaxis had a better prognosis than on placebo . This effect was statistically significant in the first 2 years of treatment . Both strategies were additive : nonradical operation and sulfasalazine had the best prognosis , radical operation and placebo was worst . It is concluded that postoperative recurrence is best prevented by resecting nonradically and prescribing 3 g of sulfasalazine daily at least over 2 years BACKGROUND & AIMS No therapy has been shown to reliably prevent the evolution of postoperative recurrence of Crohn 's disease . The aim of the current trial was to compare 6-mercaptopurine ( 6-MP ) and mesalamine with placebo for the prevention of clinical , endoscopic , and radiographic recurrence of Crohn 's disease after resection and ileocolic anastomosis . METHODS Five centers r and omized 131 patients to receive 6-MP ( 50 mg ) , mesalamine  ( 3 g ) , or placebo daily in a double-blind , double-dummy trial . Patients had clinical assessment s at 7 weeks and then every 3 months ; colonoscopy at 6 , 12 , and 24 months ; and small bowel series at 12 and 24 months . End points were clinical , endoscopic , and radiographic recurrence rates at 24 months . RESULTS Clinical recurrence rates ( intent to treat ) by life-table analysis at 24 months were 50 % ( 95 % confidence interval [ CI ] , 34%-68 % ) , 58 % ( 95 % CI , 41%-75 % ) , and 77 % ( 95 % CI , 61%-91 % ) in patients receiving 6-MP , mesalamine , and placebo , respectively . Endoscopic recurrence rates were 43 % ( 95 % CI , 28%-63 % ) , 63 % ( 95 % CI , 47%-79 % ) , and 64 % ( 95 % CI , 46%-81 % ) , and radiographic recurrence rates were 33 % ( 95 % CI , 19%-54 % ) , 46 % ( 95 % CI , 29%-66 % ) , and 49 % ( 95 % CI , 30%-72 % ) , respectively . 6-MP was more effective than placebo ( P < 0.05 ) at preventing clinical and endoscopic recurrence over 2 years . Patient withdrawals result ed in 69 % of the study population evaluable for the clinical recurrence end point . CONCLUSIONS 6-MP , 50 mg daily , was more effective than placebo at preventing postoperative recurrence of Crohn 's disease and should be considered as a maintenance therapy after ileocolic resection Guidelines for clinical practice are intended to suggest preferable approaches to particular medical problems as established by interpretation and collation of scientifically valid research , derived from extensive review of published literature . When data that will withst and objective scrutiny are not available , a recommendation may be made based on a consensus of experts . Guidelines are intended to apply to the clinical situation for all physicians without regard to specialty . Guidelines are intended to be flexible , not necessarily indicating the only acceptable approach , and should be distinguished from st and ards of care that are inflexible and rarely violated . Given the wide range of choices in any health-care problem , the physician should select the course best suited to the individual patient and the clinical situation presented . These guidelines are developed under the auspices of the American College of Gastroenterology and its Practice Parameters Committee . Expert opinion is solicited from the outset for the document . The quality of evidence upon which a specific recommendation is based is as follows : Grade A : Homogeneous evidence from multiple well- design ed r and omized ( therapeutic ) or cohort ( descriptive ) controlled trials , each involving a number of participants to be of sufficient statistical power . Grade B : Evidence from at least one large well- design ed clinical trial with or without r and omization , from cohort or case – control analytic studies , or well- design ed meta- analysis . Grade C : Evidence based on clinical experience , descriptive studies , or reports of expert committees . The Committee review s guidelines in depth , with participation from experienced clinicians and others in related fields . The final recommendations are based on the data available at the time of the production of the document and may be up date d with pertinent scientific developments at a later time BACKGROUND St and ardized criteria for Crohn 's disease ( CD ) have only recently been developed , and prospect i ve community-based incidence studies have been performed only during the past 3 decades . Geographic variations in incidence may therefore be due to differences in study design . METHODS From 1 January 1990 to 31 December 1993 all new cases of CD in four counties in southeastern Norway were prospect ively registered . RESULTS A total of 225 new cases yielded an annual incidence of 5.8/10(5 ) , with the highest incidence in mixed rural-urban areas . A peak of 11.2/10(5 ) in the annual incidence was found for the age group 15 to 24 years , with no significant differences in the overall annual incidence by gender . An average duration of 6 months of disease before diagnosis was unchanged during the 4 years . About half of the patients had isolated colonic disease , and one-quarter had isolated small-bowel disease . CONCLUSIONS This study confirms the high incidence figures for Sc and inavia , with a particularly high incidence in mixed rural-urban areas . Ileocolonoscopy improves the accuracy of the diagnosis and of the determination of disease extent , which may have therapeutic implication s for the treatment and follow-up of patients In a prospect i ve multicentre study , 97 patients with Crohn 's disease and operated on by a radical excision of the Crohn-involved bowel were r and omly divided into two groups , one treated 33 weeks postoperatively by corticosteroids and Salazopyrin and the other without any medical treatment postoperatively . The patients in the two groups were followed up during three years after the operation and an X-ray of the bowel was yearly performed . Thirteen patients were excluded for different reasons , which means that 84 patients were left for the study . There was no statistically significant difference in the number of recurrences after one , two , or three years of observation time in the two groups of patients . There was a statistically significantly longer time between diagnosis and operation in the group of patients with recurrences than in patients with no recurrences . This might mean that patients with Crohn 's disease undergoing an early operation have a better chance of escaping recurrences BACKGROUND The clinical course and prognosis in ulcerative colitis ( UC ) and Crohn 's disease ( CD ) have been described in many studies , mostly retrospective . Such studies are hampered by problems such as inclusion over a long time period , proper definitions , incomplete case records , and out date d methods of diagnosis . In a prospect i ve study we identified 846 patients with inflammatory bowel disease ( IBD ) over a 4-year period from 1990 to 1993 . Uniform diagnostic and therapeutic strategies were used as a basis for later assessment of the short-term clinical course in different subgroups of UC and CD and analysis of potential risk factors for relapse or surgery . METHODS At the time of follow-up , a mean of 16.2 months after diagnosis , 496 UC patients and 232 CD patients , altogether 98 % , were available for evaluation . A colonoscopy was performed in 88 % ( 410 of 465 ) of the UC patients attending a clinical examination and in 76 % ( 164 of 216 ) of the CD patients . RESULTS Eleven patients with UC and five patients with CD died during follow-up , four of complications related to IBD . The cumulative 1-year relapse rate in the remaining patients was 50 % for UC and 47 % for CD . Of the patients with relapses 11 % of the UC patients and 10 % of the CD patients had a chronic relapsing course without any difference with regard to the various disease categories in UC or CD . An increased risk of relapse was found in patients less than 50 years old only in UC . In UC a higher risk for surgery was found in patients with extensive colitis compared with left-sided colitis ( P = 0.011 ) , and CD patients with small-bowel involvement had a higher risk of surgery than patients with disease confined to the colon ( P = 0.021 ) . There was no excess risk of relapse or surgery in smokers as compared with non-smokers or former smokers , nor did the risk of relapse vary with the level of cigarette consumption in either UC or CD patients . CONCLUSION The high relapse rate of around 50 % for both UC and CD calls for a review of the existing treatment . Further follow-up will be necessary to improve our ability to make clinical decisions relating to medical and surgical treatment options BACKGROUND & AIMS This study investigated if long-term treatment with high-dose mesalamine reduces the risk of clinical relapse of Crohn 's disease after surgical resection . METHODS In a prospect i ve , r and omized , double-blind , multicenter study , 4 g of mesalamine ( Pentasa ; Ferring A/S , Vanlose , Denmark ) daily was compared with placebo in 318 patients . Treatment was started within 10 days after resective surgery and continued for 18 months . Primary outcome parameter was clinical relapse as defined by an increase in Crohn 's Disease Activity Index , reoperation , septic complication , or newly developed fistula . Risk factors for recurrence were prospect ively defined to be analyzed in a stepwise proportional hazards model . RESULTS Cumulative relapse rates ( + /-SE ) after 18 months were 24.5 % + /- 3.6 % and 31.4 % + /- 3.7 % in the mesalamine ( n = 152 ) and placebo ( n = 166 ) groups , respectively ( P = 0.10 , log-rank test , 1-sided ) . Retrospective analysis showed a significantly reduced relapse rate with mesalamine only in a subgroup of patients with isolated small bowel disease ( n = 124 ; 21.8 % + /- 5.6 % vs. 39.7 % + /- 6.1 % ; P = 0.02 , log-rank test ) . Probability of relapse was predominantly influenced by the duration of disease ( P = 0.0006 ) and steroid intake before surgery ( additional risk , P = 0.0003 ) . CONCLUSIONS Eighteen months of mesalamine , 4 g daily , did not significantly affect the postoperative course of Crohn 's disease . Some relapse-preventing effect was found in patients with isolated small bowel disease BACKGROUND & AIMS Crohn 's disease almost inevitably recurs after ileocolonic resection , and effective prophylactic therapy has not been identified . We investigated the efficacy and safety of ornidazole , a nitroimidazole antibiotic , for the prevention of clinical recurrence of Crohn 's disease after curative ileocolonic resection in a placebo-controlled double-blind clinical trial . METHODS Eighty patients were r and omized to ornidazole 1 g/day or placebo started within 1 week of resection and continued for 1 year . The primary end point was the proportion of patients with clinical recurrence at 1 year . Secondary end points were endoscopic recurrence at 3 months and 12 months after resection . RESULTS Two patients in the ornidazole group withdrew consent and were not dosed . Ornidazole significantly reduced the clinical recurrence rate at 1 year from 15 of 40 ( 37.5 % ) patients in the placebo group to 3 of 38 ( 7.9 % ) patients in the ornidazole group ( Fisher exact test , 8.03 ; P = .0046 ; odds ratio , 0.14 ; 95 % confidence interval , 0.037 - 0.546 ) . Ornidazole reduced endoscopic recurrence at 12 months from 26 of 33 ( 79 % ) in the placebo group to 15 of 28 ( 53.6 % ) in the ornidazole group ( chi2 , 4.37 ; P = .037 ; odds ratio , 0.31 ; 95 % confidence interval , 0.10 - 0.94 ) . Endoscopic recurrence at 3 and 12 months predicted clinical recurrence . Significantly more patients in the ornidazole group dropped out from the study because of side effects ( P = .041 ) . CONCLUSIONS Ornidazole 1 g/day is effective for the prevention of recurrence of Crohn 's disease after ileocolonic resection While immunosuppressive agents are used widely in the management of Crohn 's disease , their efficacy has not been well established in r and omised controlled trials . This study was design ed to examine whether azathioprine increases remission rate when used in conjunction with a diminishing dose regimen of prednisolone over a period of 12 weeks . It further examined whether azathioprine offers any therapeutic advantage over placebo in the maintenance of remission in Crohn 's disease over a period of 15 months . Sixty three patients with active Crohn 's disease were treated with a 12 weeks diminishing dose of prednisolone and at the same time entered into a r and omised , double blind 15 month trial of either azathioprine ( 2.5 mg/kg ) or placebo .  Remission rates between the two groups were compared at 12 weeks and at 15 months . There was no significant difference in the proportion of patients who had achieved and maintained remission by week 12 but at 15 months there was a highly significant difference in the proportion of patients in remission ( 42 % receiving azathioprine v 7 % receiving placebo ) , p = 0.001 . Using life tables this beneficial effect was reflected as the difference in the median number of days on the trial ( p = 0.02 ) . There were significantly greater decreases over the trial period in the median erythrocyte sedimentation rate , C reactive protein , and leucocyte count in the azathioprine group . There were no cases of severe bone marrow suppression or clinical pancreatitis . In conclusion , azathioprine offers a therapeutic advantage over placebo in the maintenance of remission in Crohn 's disease BACKGROUND & AIMS Recurrence of Crohn 's disease frequently occurs after surgery . A r and omized controlled trial was performed to determine if mesalamine is effective in decreasing the risk of recurrent Crohn 's disease after surgical resection is performed . METHODS One hundred sixty-three patients who underwent a surgical resection and had no evidence of residual disease were r and omized to a treatment group ( 1.5 g mesalamine twice a day ) or a placebo control group within 8 weeks of surgery . The follow-up period was a maximum of 72 months . RESULTS The symptomatic recurrence rate ( symptoms plus endoscopic and /or radiological confirmation of disease ) in the treatment group was 31 % ( 27 of 87 ) compared with 41 % ( 31 of 76 ) in the control group ( P = 0.031 ) . The relative risk of developing recurrent disease was 0.628 ( 90 % confidence interval , 0.40 - 0.97 ) for those in the treatment group ( P = 0.039 ; one-tail test ) using an intention-to-treat analysis and 0.532 ( 90 % confidence interval , 0.32 - 0.87 ) using an efficacy analysis . The endoscopic and radiological rate of recurrence was also significantly decreased with relative risks of 0.654 ( 90 % confidence interval , 0.47 - 0.91 ) in the effectiveness analysis and 0.635 ( 90 % confidence interval , 0.44 - 0.91 ) in the efficacy analysis . There was only one serious side effect ( pancreatitis ) in subjects in the treatment group . CONCLUSIONS Mesalamine ( 3.0 g/day ) is effective in decreasing the risk of recurrence of Crohn 's disease after surgical resection is performed During a six year period 43 patients with Crohns disease were included in a double-blind controlled trial of sulphasalazine given for one year as a possible treatment for reducing the relapse rate after resection or in asymptomatic patients with established disease . No trend in favour of sulphasalazine over the control group was observed . The difficulties of such a trial due to the small number of patients entered from nine hospitals , the varied nature of the disease , and the high incidence of complications , such as intraperitoneal abscess formation , are discussed BACKGROUND & AIMS Because the reoperation rate for Crohn 's disease is high after resective surgery , use of conservative surgery has increased . Mesalamine was investigated for the prevention of postoperative relapse , with disappointing results . The role of azathioprine in the postoperative setting is unknown . We aim ed to compare the efficacy and safety of azathioprine and mesalamine in the prevention of clinical and surgical relapse in patients who have undergone conservative surgery for Crohn 's disease . METHODS In a prospect i ve , open-label , r and omized study , 142 patients received azathioprine  ( 2 mg . kg -1 . day -1 ) or mesalamine ( 3 g/day ) for 24 months . Clinical relapse was defined as the presence of symptoms with a Crohn 's Disease Activity Index score > 200 and surgical relapse as the presence of symptoms refractory to medical treatment or complications requiring surgery . RESULTS After 24 months , the risk of clinical relapse was comparable in the azathioprine and mesalamine groups , both on intention-to-treat ( odds ratio [ OR ] , 2.04 ; 95 % confidence interval [ CI ] , 0.89 - 4.67 ) and per- protocol analyses ( OR , 1.79 ; 95 % CI , 0.80 - 3.97 ) . No difference was observed with respect to surgical relapse at 24 months between the 2 groups . In a subgroup analysis , azathioprine was more effective than mesalamine in preventing clinical relapse in patients with previous intestinal resections ( OR , 4.83 ; 95 % CI , 1.47 - 15.8 ) . More patients receiving azathioprine withdrew from treatment due to adverse events than those receiving mesalamine ( 22 % vs. 8 % ; P = 0.04 ) . CONCLUSIONS While no difference was observed in the efficacy of azathioprine and mesalamine in preventing clinical and surgical relapses after conservative surgery , azathioprine is more effective in those patients who have undergone previous intestinal resection
OBJECTIVES : Evidence from r and omized controlled trials ( RCTs ) for the use of 5-aminosalicylic acid ( 5-ASA ) drugs in Crohn 's disease ( CD ) in remission after a surgical resection is conflicting .
We conducted a systematic review and meta- analysis of RCTs to examine this issue .