Failure of Synbiotic 2000 to Prevent Postoperative Recurrence of Crohn’s Disease Predictability of the postoperative course of Crohn's disease. Postoperative Infliximab Is Not Associated with An Increase in Adverse Events in Crohn’s Disease Oral budesonide for prevention of postsurgical recurrence in Crohn's disease. The IOIBD Budesonide Study Group. 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. Mercaptopurine versus placebo to prevent recurrence of Crohn's disease after surgical resection (TOPPIC): a multicentre, double-blind, randomised controlled trial Adalimumab vs Azathioprine in the Prevention of Postoperative Crohn’s Disease Recurrence. A GETECCU Randomised Trial Crohn's disease management after intestinal resection: a randomised trial Effects of probiotic on intestinal mucosa of patients with ulcerative colitis. Postoperative maintenance of Crohn's disease remission with 6-mercaptopurine, mesalamine, or placebo: a 2-year trial. Early post-operative endoscopic recurrence in Crohn's disease patients: data from an Italian Group for the study of inflammatory bowel disease (IG-IBD) study on a large prospective multicenter cohort. Infliximab prevents Crohn's disease recurrence after ileal resection. Ineffectiveness of probiotics in preventing recurrence after curative resection for Crohn's disease: a randomised controlled trial with Lactobacillus GG Therapy of metronidazole with azathioprine to prevent postoperative recurrence of Crohn's disease: a controlled randomized trial. Ineffectiveness of Lactobacillus johnsonii LA1 for prophylaxis of postoperative recurrence in Crohn’s disease: a randomised, double blind, placebo controlled GETAID trial Prevention of postoperative recurrence with azathioprine or infliximab in patients with Crohn's disease: an open-label pilot study. Postoperative treatment with corticosteroids and salazosulphapyridine (Salazopyrin) after radical resection for Crohn's disease. Low serum trough levels are associated with post-surgical recurrence in Crohn's disease patients undergoing prophylaxis with adalimumab. Postoperative therapy with infliximab for Crohn’s disease: a 2-year prospective randomized multicenter study in Japan Adalimumab Is More Effective Than Azathioprine and Mesalamine at Preventing Postoperative Recurrence of Crohn's Disease: A Randomized Controlled Trial Prophylaxis of postoperative relapse in Crohn's disease with mesalamine: European Cooperative Crohn's Disease Study VI. Placebo‐controlled clinical trial of mesalazine in the prevention of early endoscopic recurrences after resection for Crohn's disease [Maintenance effect of polyglycosides of Tripterygium wilfordii on remission in postoperative Crohn disease]. Scheduled infliximab monotherapy to prevent recurrence of Crohn's disease following ileocolic or ileal resection: A 3‐year prospective randomized open trial Ornidazole for prophylaxis of postoperative Crohn's disease recurrence: a randomized, double-blind, placebo-controlled trial. A randomized, placebo-controlled, double-blind trial of mesalamine in the maintenance of remission of Crohn's disease. The Canadian Mesalamine for Remission of Crohn's Disease Study Group. The role of leukopenia in the 6-mercaptopurine-induced remission of refractory Crohn's disease. Mesalamine in the prevention of endoscopic recurrence after intestinal resection for Crohn's disease. Italian Cooperative Study Group. Low-dose budesonide treatment for prevention of postoperative recurrence of Crohn's disease: a multicentre randomized placebo-controlled trial. German Budesonide Study Group. Prevention of postoperative recurrence of Crohn’s disease: Tripterygium wilfordii polyglycoside versus mesalazine Application of a stopping rule based on total treatment failures: the postoperative Crohn's disease trial. Comparison of the effectiveness of infliximab and adalimumab in preventing postoperative recurrence in patients with Crohn’s disease: an open-label, pilot study [Efficacy of polyglycosides of Tripterygium wilfordii in preventing postoperative recurrence of Crohn disease]. Adalimumab for the prevention and/or treatment of post-operative recurrence of Crohn's disease: a prospective, two-year, single center, pilot study. Prophylactic mesalamine treatment decreases postoperative recurrence of Crohn's disease. The probiotic VSL#3 has anti-inflammatory effects and could reduce endoscopic recurrence after surgery for Crohn's disease. Impact of infliximab therapy after early endoscopic recurrence following ileocolonic resection of Crohn's disease: A prospective pilot study Oral mesalazine (5‐aminosalicylic acid; Asacol) for the prevention of post‐operative recurrence of Crohn's disease Two mesalazine regimens in the prevention of the post‐operative recurrence of Crohn's disease: a pragmatic, double‐blind, randomized controlled trial Azathioprine and mesalamine for prevention of relapse after conservative surgery for Crohn's disease. Addition of Metronidazole to Azathioprine for the Prevention of Postoperative Recurrence of Crohn’s Disease: A Randomized, Double-Blind, Placebo-Controlled Trial Ciprofloxacin for the Prevention of Postoperative Recurrence in Patients with Crohn's Disease: A Randomized, Double-blind, Placebo-controlled Pilot Study Risk and significance of endoscopic/radiological evidence of recurrent Crohn's disease. Infliximab Reduces Endoscopic, but Not Clinical, Recurrence of Crohn's Disease After Ileocolonic Resection. Postoperative therapy with infliximab prevents long-term Crohn's disease recurrence.
Complications of Crohn ’s disease ( CD ) lead to surgery in about 70–90 % of patients . The majority of patients suffer from relapse of the disease . Colonic bacteria are essential to the development of CD . Therefore , a rationale exists in trying to prevent relapse by manipulation of gut microflora . This is feasible by treatment with probiotics or antibiotics . Synbiotic 2000 is a cocktail containing 4 probiotic species and 4 prebiotics . It is rational to pursue that it could be effective in preventing postoperative disease . We sought to check weather treatment with Synbiotic 2000 could prevent postoperative recurrence in patients with CD . This was a prospect i ve multicenter , r and omized study . Patients were r and omized to active treatment or placebo in a 2:1 ratio . Follow-up consisted of endoscopic , clinical , and laboratory parameters . Thirty patients were enrolled . No differences were found between the 2 treatment groups regarding gender , age at diagnosis , age at surgery , weight , smoking status , type of disease , length of the resected segment , or medical treatment prior to surgery . No difference in either endoscopic or clinical relapse rate was found between patients treated with once daily dose of Synbiotic 2000 or placebo . In our small study , Synbiotic 2000 had no effect on postoperative recurrence of patients with CD . Larger studies in patients with the inflammatory type of CD undergoing surgery , using higher doses of probiotics cocktail might prove effective 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 Infliximab is effective treatment for Crohn ’s disease and has been associated with rare , but serious infectious complications . Emerging data suggest a benefit of infliximab in preventing postoperative Crohn ’s disease recurrence . It is not known whether administration of infliximab shortly after resective surgery for Crohn ’s disease increases postoperative complications . Aims To evaluate the risk of developing postoperative complications among Crohn ’s disease patients receiving infliximab within 4 weeks of intestinal resection . Methods As part of a r and omized placebo-controlled infliximab postoperative prevention study , adverse events were prospect ively monitored . Crohn ’s disease patients undergoing intestinal resection were r and omized to placebo or infliximab 2–4 weeks after surgery . Study infusions were administered at 0 , 2 , and 6 weeks then every 8 weeks for 1 year . To evaluate whether infliximab increased postoperative complications , we analyzed all adverse events for 1 year after surgery . Results Twenty-four patients were r and omized to infliximab or placebo after intestinal resection for Crohn ’s disease . Mean time to first postoperative infusion was 20 days ( range 14–25 days ) . Over the course of 1 year , there were 22 total adverse events , but no difference between infliximab and placebo patients ( 12 versus 10 , respectively , P = 1.0 ) . In the immediate postoperative period , within 8 weeks of surgery , the number of adverse events was also similar between the two groups ( 3 infliximab and 5 placebo patients , P = 0.68 ) . There were no serious adverse events and no complications related to wound healing or infection . Conclusions Initiation of infliximab within 4 weeks of intestinal resection was not associated with postoperative complications BACKGROUND & AIMS Prevention of postoperative recurrence after resection for Crohn 's disease ( CD ) would be of great clinical benefit . The efficacy of oral budesonide for prevention of endoscopic recurrence was evaluated in patients undergoing resection for ileal or ileocecal CD . METHODS Sixty-three patients received budesonide and 66 received placebo  in a double-blind , r and omized trial with parallel groups . Ileocolonoscopy , including biopsy , was performed after 3 and 12 months . Indications for surgery were fibrostenosis ( 78 patients ) , disease activity ( 41 ) , and other reasons ( 10 ) . RESULTS The frequency of endoscopic recurrence did not differ between the groups at 3 and 12 months . In patients with disease activity as indication for surgery , the endoscopic recurrence rate at the anastomosis was lower in the budesonide group at 3 months , although not significantly ( 21 % vs. 47 % ; P = 0.11 ) , and at 12 months ( 32 % vs. 65 % ; P = 0.047 ) . There was no such difference with respect to fibrostenosis as indication for surgery . No differences in adverse event patterns were found between the two groups . CONCLUSIONS Oral budesonide , 6 mg daily , offered no benefit in prevention of endoscopic recurrence after surgery for ileal/ileocecal fibrostenotic CD but decreased the recurrence rate in patients who had undergone surgery for disease activity 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 Summary Background Up to 60 % of patients with Crohn 's disease need intestinal resection within the first 10 years of diagnosis , and postoperative recurrence is common . We investigated whether mercaptopurine can prevent or delay postoperative clinical recurrence of Crohn 's disease . Methods We did a r and omised , placebo-controlled , double-blind trial at 29 UK secondary and tertiary hospitals of patients ( aged > 16 years in Scotl and or > 18 years in Engl and and Wales ) who had a confirmed diagnosis of Crohn 's disease and had undergone intestinal resection . Patients were r and omly assigned ( 1:1 ) by a computer-generated web-based r and omisation system to oral daily mercaptopurine at a dose of 1 mg/kg bodyweight rounded to the nearest 25 mg or placebo ; patients with low thiopurine methyltransferase activity  received half the normal dose . Patients and their carers and physicians were masked to the treatment allocation . Patients were followed up for 3 years . The primary endpoint was clinical recurrence of Crohn 's disease ( Crohn 's Disease Activity Index > 150 plus 100-point increase in score ) and the need for anti-inflammatory rescue treatment or primary surgical intervention . Primary and safety analyses were by intention to treat . Subgroup analyses by smoking status , previous thiopurines , previous infliximab or methotrexate , previous surgery , duration of disease , or age at diagnosis were also done . This trial is registered with the International St and ard R and omised Controlled Trial Register ( IS RCT N89489788 ) and the European Clinical Trials Data base ( EudraCT number 2006 - 005800 - 15 ) . Findings Between June 6 , 2008 , and April 23 , 2012 , 240 patients with Crohn 's disease were r and omly assigned : 128 to mercaptopurine and 112 to placebo . All patients received at least one dose of study drug , and no r and omly assigned patients were excluded from the analysis . 16 ( 13 % ) of patients in the mercaptopurine group versus 26 ( 23 % ) patients in the placebo group had a clinical recurrence of Crohn 's disease and needed anti-inflammatory rescue treatment or primary surgical intervention ( adjusted hazard ratio [ HR ] 0·54 , 95 % CI 0·27–1·06 ; p=0·07 ; unadjusted HR 0·53 , 95 % CI 0·28–0·99 ; p=0·046 ) . In a subgroup analysis , three ( 10 % ) of 29 smokers in the mercaptopurine group and 12 ( 46 % ) of 26 in the placebo group had a clinical recurrence that needed treatment ( HR 0·13 , 95 % CI 0·04–0·46 ) , compared with 13 ( 13 % ) of 99 non-smokers in the mercaptopurine group and 14 ( 16 % ) of 86 in the placebo group ( 0·90 , 0·42–1·94 ; pinteraction=0·018 ) . The effect of mercaptopurine did not significantly differ from placebo for any of the other planned subgroup analyses ( previous thiopurines , previous infliximab or methotrexate , previous surgery , duration of disease , or age at diagnosis ) . The incidence and types of adverse events were similar in the mercaptopurine and placebo groups . One patient on placebo died of ischaemic heart disease . Adverse events caused discontinuation of treatment in 39 ( 30 % ) of 128 patients in the mercaptopurine group versus 41 ( 37 % ) of 112 in the placebo group . Interpretation Mercaptopurine is effective in preventing postoperative clinical recurrence of Crohn 's disease , but only in patients who are smokers . Thus , in smokers , thiopurine treatment seems to be justified in the postoperative period , although smoking cessation should be strongly encouraged given that smoking increases the risk of recurrence . Funding Medical Research Council Background and Aims Postoperative recurrence of Crohn 's disease [ POR-CD ] is almost certain if no prophylaxis is administered . Evidence for optimal treatment is lacking . Our aim was to compare the efficacy of adalimumab [ ADA ] and azathioprine [ AZA ] in this setting . Methods We performed a phase 3 , 52-week , multicentre , r and omised , superiority study [ APPRECIA ] , in which patients with ileocolonic resection were r and omised either to  ADA 160 - 80 - 40 mg subcutaneously [ SC ] or AZA 2.5 mg/kg/day , both associated with metronidazole . The primary endpoint was endoscopic recurrence at 1 year [ Rutgeerts i2b , i3 , i4 ] , as evaluated by a blinded central reader . Results We recruited 91 patients [ median age 35.0 years , disease duration 6.0 years , 23.8 % smokers , 7.1 % previous resections ] . The study drugs were administered to 84 patients . Treatment was discontinued owing to adverse events in 11 patients [ 13.1 % ] . Discontinuation was significantly less frequent in the ADA [ 4.4 % ] than in the AZA group [ 23.2 % ] ( dif . : 18.6 % [ 95 % CI 4.1 - 33.2 ] , p = 0.011 ) . According to the intention-to-treat analysis , therapy failed in 23/39 patients in the AZA group [ 59 % ] and 19/45 patients in the ADA group [ 42.2 % ] [ p = 0.12 ] . In the per- protocol analysis [ 61 patients with central ly evaluable images ] , recurrence was recorded in 8/24 [ 33.3 % ] patients in the AZA and 11/37 [ 29.7 % ] in the ADA group [ p = 0.76 ] . No statistically significant differences between the groups were found for recurrence in magnetic resonance images , biological markers of activity , surgical procedures , or hospital admissions . Conclusions ADA has not demonstrated a better efficacy than AZA [ both associated with metronidazole ] for prophylaxis of POR-CD in an unselected population , although tolerance to ADA is significantly better . Clinical Trials.gov NCT01564823 BACKGROUND Most patients with Crohn 's disease need an intestinal resection , but a majority will subsequently experience disease recurrence and require further surgery . This study aim ed to identify the optimal strategy to prevent postoperative disease recurrence . METHODS In this r and omised trial , consecutive patients from 17 centres in Australia and New Zeal and undergoing intestinal resection of all macroscopic Crohn 's disease , with an endoscopically accessible anastomosis , received 3 months of metronidazole therapy . Patients at high risk of recurrence also received a thiopurine , or adalimumab if they were intolerant to thiopurines . Patients were r and omly assigned to parallel groups : colonoscopy at 6 months ( active care ) or no colonoscopy ( st and ard care ) . We used computer-generated block r and omisation to allocate patients in each centre to active or st and ard care in a 2:1 ratio . For endoscopic recurrence ( Rutgeerts score ≥i2 ) at 6 months , patients stepped-up to thiopurine , fortnightly adalimumab with thiopurine , or weekly adalimumab . The primary endpoint was endoscopic recurrence at 18 months . Patients and treating physicians were aware of the patient 's study group and treatment , but central reading of the endoscopic findings was undertaken blind to the study group and treatment . Analysis included all patients who received at least one dose of study drug . This trial is registered with Clinical Trials.gov , number NCT00989560 . FINDINGS Between Oct 13 , 2009 , and Sept 28 , 2011 , 174 ( 83 % high risk across both active and st and ard care groups ) patients were enrolled and received at least one dose of study drug . Of 122 patients in the active care group , 47 ( 39 % ) stepped-up treatment . At 18 months , endoscopic recurrence occurred in 60 ( 49 % ) patients in the active care group and 35 ( 67 % ) patients in the st and ard care group ( p=0.03 ) . Complete mucosal normality was maintained in 27 ( 22 % ) of 122 patients in the active care group versus four ( 8 % ) in the st and ard care group ( p=0.03 ) . In the active care arm , of those with 6 months recurrence who stepped up treatment , 18 ( 38 % ) of 47 patients were in remission 12 months later ; conversely , of those in remission at 6 months who did not change therapy recurrence occurred in 31 ( 41 % ) of 75 patients 12 months later . Smoking ( odds ratio [ OR ] 2.4 , 95 % CI 1.2 - 4.8 , p=0.02 ) and the presence of two or more clinical risk factors including smoking ( OR 2.8 , 95 % CI 1.01 - 7.7 , p=0.05 ) increased the risk of endoscopic recurrence . The incidence and type of adverse and severe adverse events did not differ significantly between patients in the active care and st and ard care groups ( 100 [ 82 % ] of 122 vs 45 [ 87 % ] of 52 ; p=0.51 ) and ( 33 [ 27 % ] of 122 vs 18 [ 35 % ] of 52 ; p=0.36 ) , respectively . INTERPRETATION Treatment according to clinical risk of recurrence , with early colonoscopy and treatment step-up for recurrence , is better than conventional drug therapy alone for prevention of postoperative Crohn 's disease recurrence . Selective immune suppression , adjusted for early recurrence , rather than routine use , leads to disease control in most patients . Clinical risk factors predict recurrence , but patients at low risk also need monitoring . Early remission does not preclude the need for ongoing monitoring . FUNDING AbbVie , Gutsy Group , G and el Philanthropy , Angior Foundation , Crohn 's Colitis Australia , and the National Health and Medical Research Council AIM To investigate the effects of probiotic on intestinal mucosae of patients with ulcerative colitis ( UC ) , and to evaluate the role of probiotic in preventing the relapse of UC . METHODS Thirty patients received treatment with sulphasalazine ( SASP ) and glucocorticoid  and then were r and omly administered bifid triple viable capsule ( BIFICO ) ( 1.26 g/d ) , or an identical placebo ( starch ) for 8 wk . Fecal sample s were collected for stool culture 2 wk before and after the r and omized treatments . The patients were evaluated clinical ly , endoscopically and histologically after 2 mo of treatment or in case of relapse of UC . p65 and IkappaB expressions were determined by Western blot analysis . DNA-binding activity of NF-kappaB in colonic nuclear extracts was detected by electrophoretic mobility shift assay ( EMSA ) . mRNA expressions of cytokines were identified by semi-quantitative assay , reverse transcriptase- polymerase chain reaction ( RT-PCR ) . RESULTS Three patients ( 20 % ) in the BIFICO group had relapses during 2-mo follow-up period , compared with 14 ( 93.3 % ) in placebo group ( P<0.01 ) . The concentration of fecal lactobacilli , bifidobacteria was significantly increased in BIFICO-treated group only ( P<0.01 ) . The expressions of NF-kappaB p65 and DNA binding activity of NF-kappaB were significantly attenuated in the treatment group than that in control ( P<0.05 ) . The mRNA expression of anti-inflammatory cytokines was elevated in comparison with the control group . CONCLUSION The probiotic could impede the activation of NF-kappaB , decrease the expressions of TNF-alpha and IL-1beta and elevate the expression of IL-10 . These results suggest that oral administration of this new probiotic preparation is effective in preventing flare-ups of chronic UC . It may become a prophylactic drug to decrease the relapse of UC 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 INTRODUCTION The incidence of endoscopic recurrence ( ER ) in Crohn 's disease following curative resection is up to 75 % at 1 year . Endoscopy is the most sensitive method to detect the earliest mucosal changes and the severe ER at 1 year seems to predict a clinical relapse . METHODS The aim of this prospect i ve study was to evaluate the incidence of early ER 6 months after curative resection . Secondary outcome was to evaluate the role of  5-aminosalicylic acid ( 5-ASA ) in the prevention of ER at 6 months . A total of 170 patients were included in the study . They were carried-out from the evaluation of the appearance of ER during a trial performed to assess the role of azathioprine vs. 5-ASA as early treatment of severe ER . All the patients started 5-ASA treatment 2 weeks after surgery . RESULTS Six months after surgery ER was observed in 105 patients ( 62 % ) . The endoscopic score was reported as severe in 78.1 % of them ( 82 out of 105 ) . At univariable analysis only ileo-colonic disease influenced the final outcome associating to a lower risk of severe ER ( p=0.04 ; OR 0.52 , 95 % CI 0.277 - 0.974 ) . CONCLUSION In this prospect i ve Italian multicenter IG-IBD study a great proportion of ER occur within 6 months from ileo-colonic resection , with a significant rate of severe ER . Furthermore this study confirms the marginal role of 5-ASA in the prevention of ER . This suggests that post-surgical endoscopic evaluation should be performed at 6 months instead of 1 year to allow an adequate early treatment BACKGROUND & AIMS Crohn 's disease commonly recurs after intestinal resection . We evaluated whether the administration of infliximab after resective intestinal surgery for Crohn 's disease reduces postoperative recurrence . METHODS We r and omly assigned 24 patients with Crohn 's disease who had undergone ileocolonic resection to receive intravenous infliximab ( 5 mg/kg ) , administered within 4 weeks of surgery and continued for 1 year , or placebo . The primary end point was the proportion of patients with endoscopic recurrence at 1 year . Secondary end points were clinical recurrence and remission and histologic recurrence . RESULTS The rate of endoscopic recurrence at 1 year was significantly lower in the infliximab group ( 1 of 11 patients ; 9.1 % ) compared with the placebo group ( 11 of 13 patients ; 84.6 % ) ( P = .0006 ) . There was a nonsignificant higher proportion of patients in clinical remission in the infliximab group ( 8 of 10 ; 80.0 % ) compared with the placebo group ( 7 of 13 ; 53.8 % ) ( P = .38 ) . The histologic recurrence rate at 1 year was significantly lower in the infliximab group ( 3 of 11 patients ; 27.3 % ) compared with the placebo group ( 11 of 13 patients ; 84.6 % ) ( P = .01 ) . The occurrence of adverse events was similar between the placebo and infliximab groups , and none occurred in the immediate postoperative period . CONCLUSIONS Administration of infliximab after intestinal resective surgery was effective at preventing endoscopic and histologic recurrence of Crohn 's disease Background and aims : Experimental studies have shown that luminal bacteria may be involved in Crohn 's disease . Probiotics are a possible alternative to antibiotics . The aim of this r and omised placebo controlled study was to determine if Lactobacillus GG , given by mouth for one year , could prevent Crohn 's recurrent lesions after surgery or to reduce their severity . Methods : Patients operated on for Crohn 's disease in whom all of the diseased gut had been removed were r and omly allocated to receive 12 billion colony forming units of Lactobacillus or identical placebo for one year . Ileocolonoscopy was performed at the end of the trial or at the onset of symptoms . Endoscopic recurrence was defined as grade 2 or higher of Rutgeerts scoring system . Results : Eight of 45 patients were excluded from the trial ( three for non-compliance and five for protocol violations ) .  Clinical recurrence was ascertained in three ( 16.6 % ) patients who received Lactobacillus and in two ( 10.5 % ) who received placebo . Nine of 15 patients in clinical remission on Lactobacillus ( 60 % ) had endoscopic recurrence compared with six of 17 ( 35.3 % ) on placebo ( p=0.297 ) . There were no significant differences in the severity of the lesions between the two groups . Conclusions : Lactobacillus GG seems neither to prevent endoscopic recurrence at one year nor reduce the severity of recurrent lesions BACKGROUND & AIMS More than 80 % of Crohn 's disease ( CD ) patients undergoing resection suffer recurrence of their disease . Therapy with aminosalicylates , antimetabolites , or antibiotics leads to a modest reduction in the incidence of recurrence . GOAL We sought to examine whether metronidazole for 3 months together with azathioprine ( AZA ) for 12 months is superior to metronidazole alone to reduce recurrence of postoperative CD in " high-risk " patients . METHODS CD patients undergoing curative ileocecal resection with > or=1 risk factor for recurrence received metronidazole ( 3 months ) and AZA/placebo ( 12 months ) . The primary end point was the proportion of patients with significant endoscopic recurrence 3 and 12 months after surgery . Secondary end points included clinical recurrence , safety , and tolerability of treatment . RESULTS Eighty-one patients were r and omized ; 19 discontinued the study early .  Significant endoscopic recurrence was observed in 14 of 32 ( 43.7 % ) patients in the AZA group and in 20 of 29 ( 69.0 % ) patients in the placebo group at 12 months postsurgery ( P = .048 ) . Intention-to-treat analysis revealed endoscopic recurrence in 22 of 40 ( 55 % ) in the AZA group and 32 of 41 ( 78 % ) in the placebo group at month 12 ( P = .035 ) . At month 12 , 7 of 32 patients had no endoscopic lesions in the AZA group , versus 1 of 29 in the placebo group ( P = .037 ) . CONCLUSIONS Despite the enhanced risk of recurrence , the overall incidence of significant recurrence was rather low , probably owing to the metronidazole treatment that all patients received . Concomitant AZA result ed in lower endoscopic recurrence rates and less severe recurrences 12 months postsurgery , predicting a more favorable clinical outcome . This combined treatment seems to be recommendable to all operated CD patients with an enhanced risk for recurrence Background and aims : Early endoscopic recurrence is frequent after intestinal resection for Crohn ’s disease . Bacteria are involved , and probiotics may modulate immune responses to the intestinal flora . Here we tested the probiotic strain Lactobacillus johnsonii LA1 in this setting . Patients and methods : This was a r and omised , double blind , placebo controlled study . Patients were eligible if they had undergone surgical resection of < 1 m , removing all macroscopic lesions within the past 21 days . Patients were r and omised to receive two packets per day of lyophilised LA1 ( 2 × 109 cfu ) or placebo for six months ; no other treatment was allowed . The primary endpoint was endoscopic recurrence at six months , with grade > 1 in Rutgeerts ’ classification or an adapted classification for colonic lesions . Endoscopic score was the maximal grade of ileal and colonic lesions . Analyses were performed primarily on an intent to treat basis . Results : Ninety eight patients were enrolled ( 48 in the LA1 group ) . At six months , endoscopic recurrence was observed in 30/47 patients ( 64 % ) in the placebo group and in 21/43 ( 49 % ) in the LA1 group ( p = 0.15 ) . Per protocol analysis confirmed this result . Endoscopic score distribution did not differ significantly between the LA1 and placebo groups . There were four clinical recurrences in the LA1 group and three in the placebo group . Conclusion : L johnsonii LA1 ( 4 × 109 cfu/day ) did not have a sufficient effect , if any , to prevent endoscopic recurrence of Crohn ’s disease BACKGROUND AND AIMS Patients with Crohn 's disease ( CD ) often require surgery over their clinical course . However , endoscopic and clinical recurrence of disease appear respectively in up to 80 % and 30 % of patients after one year . Thus , a prophylactic treatment is needed to reduce the possibility of recurrence . Both azathioprine and infliximab have been demonstrated to be effective , but head to head studies have not been performed so far . Aim of this open-label prospect i ve study was to analyse endoscopic , histological and clinical recurrence after one year of treatment with azathioprine or infliximab as postoperative therapies in CD patients with " high risk " of recurrence . METHODS Consecutive CD patients who underwent curative ileocolonic resection were r and omized ( 1:1 ) to receive infliximab ( st and ard induction and maintenance schedule ) or azathioprine ( 2.5 mg/kg/day ) for 1 year . Co- primary endpoints were endoscopic , histological and clinical recurrence after 12 months of therapy . RESULTS Twenty-two consecutive CD patients ( 15 male ; median age 32 years , IQR 22 - 38 ) were enrolled after curative ileocolonic resection . Eleven patients were treated with infliximab and 11 received azathioprine . Among patients treated with azathioprine , 4/10 ( 40 % ) had endoscopic recurrence compared to 1/11 ( 9 % ) in the infliximab group ( p=0.14 ) . Eight out of 10 ( 80 % ) among those who received azathioprine had severe histological activity , whereas 2/11 ( 18 % ) in the infliximab group presented histological recurrence ( p=0.008 ) . No significant clinical differences were found between the two groups . CONCLUSIONS Infliximab was more effective than azathioprine in reducing histological , but not endoscopic and clinical recurrence after curative ileocolonic resection in " high risk " CD 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 Whether therapeutic drug monitoring of biologic therapy can predict the efficacy of adalimumab to prevent postoperative Crohn 's disease recurrence is unknown . AIM To investigate whether  adalimumab trough levels and anti-adalimumab antibodies correlate with endoscopic and clinical outcomes in a series of patients treated with prophylactic adalimumab monotherapy after resective surgery . METHODS Post hoc analysis of a r and omized , mesalamine-controlled trial . Adalimumab trough levels and antibodies were analysed every 8 weeks for 2 years using an homogeneous mobility shift assay . RESULTS At two years , 1/6 patient had clinical recurrence and 1/6 patient had endoscopic and clinical recurrence . At baseline ( 9.5 vs. 14.4 mcg/mL ) and during follow-up [ 7.5 ( 4.4 - 9.8 ) vs. 13.9 (8.9 - 23.6)mcg/mL , p<0.01 ] , median adalimumab trough levels in patients with clinical or endoscopic recurrence were lower than in those who maintained remission . Persistent antibodies-against-adalimumab were detected in the patient with both endoscopic and clinical recurrence . CONCLUSION Measurement of  adalimumab trough levels and anti-adalimumab antibodies after surgery could be useful to further reduce postoperative recurrence Purpose The prevention of postoperative recurrence is a critical issue in surgery for Crohn ’s disease . Prospect i ve r and omized trials in Western countries have shown that the postoperative use of anti-tumor necrosis factor α-antibodies was effective in reducing the recurrence rate . We investigated the efficacy of infliximab ( IFX ) for the prevention of postoperative Crohn ’s disease recurrence . Methods We performed a prospect i ve r and omized multicenter study . Patients who underwent intestinal resection were assigned to groups treated with or without IFX . Immediately after surgery , patients in the IFX group received IFX at 5 mg/kg at 0 , 2 , and 6 weeks , followed by every 8 weeks for 2 years . The primary study outcome was the proportion of patients with endoscopic and /or clinical recurrence at 2 years after surgery . Results Thirty-eight eligible patients participated in this study : 19 in the IFX group and 19 in the non-IFX group .  The disease recurrence rate in the IFX group was 52.6 % ( 10/19 ) , which was significantly lower than that in the non-IFX group ( 94.7 % [ 18/19 ] ) . Conclusion The postoperative use of IFX is effective in preventing Crohn ’s disease recurrence for 2 years OBJECTIVES : Postsurgical recurrence of Crohn 's disease ( CD ) is very frequent and , to date , only infliximab has been shown to be useful in preventing it . The efficacy of adalimumab ( ADA ) is poorly known . We evaluated whether the administration of ADA after resective intestinal surgery reduces postoperative CD recurrence . METHODS : We r and omly assigned 51 patients with CD who had undergone ileocolonic resection to receive after 2 weeks from surgery  ADA at the dose of 160/80/40 mg every two weeks , azathioprine ( AZA ) at 2 mg/kg/day , or mesalamine at 3 g/day , and they were followed up for 2 years . The primary end point was the proportion of patients with endoscopic and clinical recurrence . Secondary end point was the assessment of quality of life by means of a previously vali date d question naire . RESULTS : The rate of endoscopic recurrence was significantly lower in ADA ( 6.3 % ) compared with the AZA ( 64.7 % ; odds ratio (OR)=0.036 ( 95 % confidence interval ( CI ) 0.004–0.347 ) ) and mesalamine groups ( 83.3 % ; OR=0.013 ( 95 % CI 0.001–0.143 ) ) . There was a significantly lower proportion of patients in clinical recurrence in the ADA group ( 12.5 % ) compared with the AZA ( 64.7 % ; OR=0.078 ( 95 % CI 0.013–0.464 ) ) and mesalamine groups ( 50 % ; ( OR=0.143 ( 95 % CI 0.025–0.819 ) ) . The quality of life was higher in the ADA ( 202 ) than in the AZA ( 90 ; OR=0.028 ( 95 % CI 0.004–0.196 ) ) and mesalamine groups ( 98 ; OR=0.015 ( 95 % CI 0.002–0.134 ) ) . CONCLUSIONS : The administration of ADA after intestinal resective surgery was greatly effective in preventing endoscopic and clinical recurrence of CD . Further larger studies are necessary to confirm the therapeutic advantage and to show the economic implication s of biologic therapy in this field 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 Objective : Endoscopic postoperative recurrences occur early after ' curative ' surgery for Crohn 's disease .  Pentasa has been shown to be effective in the maintenance treatment of quiescent Crohn 's disease . The aim of this study was to test the efficacy of a 12-week oral intake of Claversal in the prevention of endoscopic recurrences after ' curative ' resection for ileal , colonic or ileocolonic Crohn 's disease . We conducted a multicentre double-blind controlled trial comparing Claversal ( 1 g tid ) with placebo , starting within 15 days after surgery . The macroscopic normality of the two anastomotic segments was assessed at surgery . Patients were clinical ly and biologically evaluated twice ( 6-week interval ) , and colonoscopy was performed at 12 weeks . Endoscopic relapse was defined by any anastomotic ulcerations or stenosis and staged according to a four- grade score . Results : Between May 1989 and May 1991 12 centres included 126 patients , 70 women and 56 men , aged 33 ± 12 years ( range 16–70 ) in the study . Disease locations were ileal , colonic and ileocolonic in 45 , 6 and 49 % , respectively . Claversal and placebo groups were similar at inclusion , except for ESR ( 37 ± 26 vs. 27 ± 23mm/h in the Claversal and placebo groups , respectively ; P<0.05 ) . Nine patients were withdrawn from the study . Adverse reactions occurred only in six patients . Five patients were excluded for protocol violation . Finally , 106 patients could be evaluated at 12 weeks ( 55 Claversal and 51 placebo ) . An endoscopic relapse was observed in 50 % and 63 % of the Claversal and placebo groups , respectively ( P = 0.16 ) , with a similar grade distribution . Claversal was well tolerated . Conclusions : Our study confirms that a large proportion of endoscopic recurrences occur within 3 months of resection in Crohn 's disease . There was a slight trend towards greater efficacy of Claversal ; it could be worthwhile trying higher dosages and /or 5-ASA compounds with different intestinal release profiles OBJECTIVE To observe the maintenance effect of polyglycosides of Tripterygium wilfordii ( GTW ) on remission in postoperative Crohn disease ( CD ) . METHODS From 2005 to 2007 , 45 adult cases of postoperative Crohn disease were r and omly divided into two groups , GTW group and mesalazine group , which received GTW and mesalazine treatment respectively . CD activity index ( CDAI ) and clinical markers were collected at 0 , 3 , 6 , 12 months or at the onset of symptoms . Ileocolonoscopy was performed at the end of the trial ( 1 year after operation ) or at the onset of symptoms , and recurrence score were recorded . RESULTS No clinical recurrence was ascertained in both groups at 3 months . Four patients ( 18.2 % ) in GTW group relapsed and 5 ( 21.7 % ) in mesalazine group relapsed at 6 months ( P=0.530 ) . Seven patients ( 31.8 % ) in GTW group and 9 ( 39.1 % ) in mesalazine group relapsed at one year ( P=0.421 ) . Ten patients ( 45.5 % ) in GTW group had endoscopic recurrence compared with 14 ( 60.9 % ) in mesalazine group at one year(P=0.231 ) . There were no significant differences between two groups . CONCLUSION GTW is similar to mesalazine in maintenance of remission of postoperative Crohn disease Background : Infliximab ( IFX ) is effective for remission induction and maintenance of  Crohn 's disease ( CD ) . This trial assessed the efficacy of scheduled maintenance IFX monotherapy to prevent postoperative CD recurrence . Methods : Thirty‐one CD patients who had ileocolic resection within the past 4 weeks were r and omly assigned to scheduled IFX at 5 mg/kg intravenously every 8 weeks for 36 months ( n = 15 ) or without IFX ( control , n = 16 ) . All patients were treated without immunomodulator or corticosteroid following surgery . The primary and secondary endpoints were remission rates at 12 and 36 months , defined as CD Activity Index ( CDAI ) ≤150 , an International Organization for the Study of Inflammatory Bowel Disease ( IOIBD ) score < 2 , and C‐reactive protein ( CRP ) < 0.3 mg/dL. Additionally , endoscopic recurrences at 12 and 36 months were evaluated . Results : At 12 and 36 months , 100 % , and 93.3 % of patients in the IFX group were in remission ( IOIBD < 2 ) , respectively vs. 68.8 % and 56.3 % in the control arm ( P < 0.03 ) . Similarly , 86.7 % and 86.7 % of patients in the IFX group maintained serological remission ( CRP < 0.3 mg/dL ) vs. 37.5 % and 37.5 % in the control arm ( P < 0.02 ) . Further , the IFX group achieved higher endoscopic remission at 12 months , 78.6 % vs. 18.8 % ( P = 0.004 ) . However , in the Kaplan – Meier survival analysis the CDAI scores between the two arms were not significantly different either at 12 or at 36 months . No adverse event ( AE ) was observed . Conclusions : An early intervention with IFX monotherapy should prevent clinical , serological , and endoscopic CD recurrence following ileocolic resection . Thiopurine naivety and eliminating the initial loading dose of IFX might minimize serious AEs . ( Inflamm Bowel Dis 2012 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 BACKGROUND & AIMS The efficacy of mesalamine for the maintenance of remission in patients with Crohn 's disease is controversial . The aim of this study was to conduct a double-blind , placebo-controlled study of mesalamine ( 750 mg four times a day for 48 weeks ) in maintaining remission in 293 patients with Crohn 's disease . Patients were stratified according to the method of induction of remission ( medical or surgical ) . METHODS Patients were assessed at weeks 4 , 12 , 24 , 36 , and 48 . Relapse was defined as a Crohn 's Disease Activity Index of > 150 ( + 60 points over baseline ) . RESULTS Of the 293 patients , 246 ( 84 % ) returned for at least 4 weeks of follow-up and were included in the final analysis . Thirty of the 118 ( 25 % ) who received mesalamine had a relapse compared with 47 of 128 ( 36 % ) receiving placebo ( P = 0.056 ) . Among those with relapse , the time to relapse was 119 days for the mesalamine-treated patients compared with 109 days for placebo-treated patients ( P = NS ) . However , 25 % of mesalamine-treated patients had relapsed by 249 days of follow-up compared with 154 days for placebo-treated patients . Subgroup analysis showed that patients with ileocecal-colonic disease or patients who were women had fewer relapses on mesalamine therapy than placebo-treated patients ( 21 % vs. 41 % , P = 0.018 ; and 19 % vs. 41 % , P = 0.003 , respectively ) . CONCLUSIONS Mesalamine treatment reduced relapse compared with placebo treatment , although conventional statistical significance was not achieved OBJECTIVES 1 ) to determine the frequency of induced leukopenia in patients with refractory Crohn 's disease treated with 6-Mercaptopurine ( 6-MP ) .  2 ) to determine the influence of 6-MP-induced leukopenia on achieving remission [ including the three major specific goals of therapy : ( a ) elimination or reduction of steroids , ( b ) healing of abscesses and fistulas , and ( c ) elimination of recurrent intestinal obstruction ] and the effect on the rate and percentage of improvement in the CCFA-IOIBD index of Crohn 's disease activity after 3 months of 6-MP therapy . 3 ) to determine whether an improvement of leukopenia was accomplished by an increased risk of clinical bone marrow depression . METHODS We review ed the course of 98 consecutive patients with refractory Crohn 's disease treated with 6-MP and compared the 51 who developed leukopenia and the 47 who did not , in regard to achievement of remission , length of time until remission , rate of recurrence , and time until recurrence . RESULTS 1 ) The mean time to remission was 8.8 wk for patients with leukopenia versus 14.3 wk for those without leukopenia . 2 ) A strong positive correlation exists between 6-MP induced leukopenia and the achievement and maintenance of remission in refractory Crohn 's disease . This was evident in the analysis of response in specific goals and in the activity index . 3 ) There was no clinical evidence of bone marrow suppression in the 51 patients who developed 6-MP induced leukopenia . CONCLUSIONS 1 ) Increasing the dose of 6-MP in patients with refractory Crohn 's disease who have not yet responded and who have not achieved leukopenia will very likely increase the efficacy of this drug . 2 ) Influenced by the results of this study , we have launched a double-blind prospect i ve study to evaluate the relationship between the induction of leukopenia with 6-MP and the achievement of remission BACKGROUND / AIMS Recurrence of lesions of Crohn 's disease of the ileum within 1 year after so-called curative resection was well documented by endoscopy in 73%-93 % of cases . This study investigated the efficacy of mesalamine in reduction of endoscopic recurrence after surgery . METHODS In a double-blind , multicenter clinical trial , 87 patients were treated with 3 g/day mesalamine ( Pentasa ) or with placebo within 1 month after surgery . After 12 months of treatment , severity of endoscopic lesions was recorded with a five-point score ; when it was not possible to reach the anastomosis by endoscopy , a barium enema was performed . RESULTS Seventeen clinical relapses ( seven in the mesalamine group ) were recorded . After 12 months , the endoscopic lesions were less frequent and less severe in the mesalamine group than were those in the placebo group ( chi 2 , 13.5 ; P < 0.008 ) . The overall rate of severe recurrence ( score of 3 - 4 on endoscopy or radiological documentation ) was 24 % in the mesalamine group and 56 % in the placebo group ( chi 2 , 8.57 ; P < 0.004 ; difference 32 % ; 95 % confidence interval , 22 - 52 ) . The odds ratio for active treatment was 4.1 . CONCLUSIONS This study shows that mesalamine is useful in decreasing the rate and severity of endoscopic recurrences after curative surgery for ileal Crohn 's disease OBJECTIVE Endoscopic recurrence of Crohn 's disease frequently occurs within weeks after ' curative ' operation . Treatment with 3 x 1 mg oral pH-modified release budesonide was tried to prevent postoperative recurrence . DESIGN A multicentre r and omized double-blind placebo-controlled trial of 1 year duration was performed . SETTING Departments of surgery , endoscopy and pathology of three university hospitals participated in the trial . PATIENTS Patients with Crohn 's disease who underwent ileal and /or colonic resection and whose anastomosis was accessible to colonoscopy were admitted to the study . Of the 88 r and omized patients , 83 patients were included in the efficacy analysis  ( budesonide n = 43 , placebo n = 40 ) . Treatment was started within 2 weeks after surgery . INTERVENTIONS Colonoscopy was performed 3 and 12 months postoperatively . The anastomosis and the adjacent bowel were evaluated by endoscopy and histology . For follow-up of the clinical course of the disease the Crohn 's disease activity index ( CDAI ) was used . MAIN OUTCOME MEASURES The primary outcome variable was recurrence of Crohn 's disease based on endoscopic findings . Secondary efficacy variables were histology scores , CDAI , time-to-failure and global judgement of well-being of the patient . RESULTS The recurrence rate after 1 year ( endoscopic and /or clinical ) was 57 % ( 20/35 ) in the budesonide group and 70 % ( 19/27 ) in the placebo group ( n.s . ) . Mean time-to-failure was 196 days under budesonide and 154 days under placebo ( n.s . ) . Median CDAI ( relapse 19 % vs. 28 % ) and global patients ' judgement at the end of treatment ( bad 5 % vs. 15 % ) was slightly in favour of budesonide . One patient in each group discontinued the trial because of adverse events . Potentially steroid-related side effects were reported more frequently in the placebo than in the budesonide group ( 32 % vs. 17 % ) ( n.s . ) . SUMMARY AND CONCLUSION Although the effect of budesonide was altogether positive in almost all variables studied in this trial ( e.g. endoscopic and histopathological score , time-to-failure , CDAI , patients ' global judgement and rate of side effects ) , this increase in efficacy was small and the power for detecting differences versus placebo was too low to be statistically significant . According to these results , low-dose oral budesonide can not be recommended to be used for the prevention of postoperative relapse in Crohn 's disease Objectives To explore effectiveness and safety of polyglycosides of Tripterygium wilfordii ( GTW ) and mesalazine ( 5-aminosalicylic acid [ 5-ASA ] ) in preventing postoperative clinical and endoscopic recurrence of Crohn ’s disease . Methods In this prospect i ve , single-centre , single-blind study , postoperative Crohn ’s disease patients in remission were r and omized to receive 1 mg/kg GTW daily , orally , or 4 g 5-ASA daily , orally , for 52 weeks . Patients underwent physical examinations , ileocolonoscopies and biochemical analyses at baseline and weeks 13 , 26 and 52 , or when clinical recurrence was suspected . Outcome measures were proportion of patients showing clinical or endoscopic recurrence at week 52 , and changes in Rutgeerts ’ and Crohn ’s Disease Activity Index ( CDAI ) scores . Results Twenty-one patients were assigned to receive GTW and 18 to 5-ASA ; two patients on GTW and one on 5-ASA were withdrawn . Clinical and endoscopic recurrences were less common in the GTW group ( n = 4 ) versus the 5-ASA group ( n = 9 ) . There were improvements in Rutgeerts ’ scores for those taking GTW .  Mean between-group CDAI scores were similar . No serious adverse events were reported . Conclusion These findings indicate that GTW appears to be an effective , well-tolerated prophylactic regimen , superior to oral 5-ASA , for preventing clinical and endoscopic recurrence in postsurgical Crohn ’s disease The Postoperative Crohn 's Disease Trial ( PCDT ) , a placebo-controlled r and omized trial of Rowasa I in the prevention of postoperative recurrence of Crohn 's disease , is used as an example of how a stopping rule based on total endpoint occurrences can provide considerable advantage over st and ard fixed sample size methods . It can be used when the primary outcome is occurrence or time to occurrence and does not raise the troublesome issues regarding the unblinding of group differences that other sequential methods create . The main advantage of the total endpoint stopping rule is that it provides set power . St and ard fixed sample size design s provide a given power only on average . The power actually achieved in a particular fixed sample size trial is largely determined by the overall observed rate of endpoint occurrences . This cl aim about the total endpoint stopping rule is well established in the statistical literature and , as well as outlining the mathematical details in an Appendix , we use computer simulation of the PCDT to demonstrate that use of the stopping rule will allow termination of the trial while maintaining power and type I error at a predetermined level Background Endoscopic and clinical recurrence of Crohn ’s disease ( CD ) appears in up to 80 and 30 % of patients , respectively , 1 year after surgery . Both infliximab ( IFX ) and adalimumab ( ADA ) have been demonstrated to be effective in reducing the possibility of recurrence after surgery , but head-to-head studies have not been performed so far . The aim of this open-label prospect i ve study was to compare endoscopic , histological and clinical recurrence after 1 year of treatment with IFX or ADA as postoperative prophylaxis in CD patients with a high risk of recurrence . Methods Consecutive CD patients who underwent curative ileocolonic resection  were r and omized to receive IFX or ADA for 1 year . Co- primary endpoints were endoscopic , histological and clinical recurrence after 12 months of therapy . Results Twenty consecutive CD patients ( 9 males and 11 females ; median age 32.5 years , range 20–39 years ) were enrolled after undergoing curative ileocolonic resection . Among the 10 patients treated with IFX , 2 ( 20 % ) had endoscopic recurrence compared to 1 ( 10 % ) in the group of 10 ADA patients ( p = 1.0 ) . Three out of 10 ( 30 % ) IFX patients and 2 out of 10 ( 20 % ) ADA patients had histological recurrence ( p = 1.0 ) . No significant clinical differences were found between the two groups . Conclusions IFX and ADA were similar in preventing histological , endoscopic and clinical recurrence after curative ileocolonic resection in high risk CD patients OBJECTIVE To observe the efficacy of polyglycoside of Tripterygium wilfordii(GTW ) in preventing postoperative recurrence of Crohn disease(CD ) . METHODS Thirty-nine post-operative CD patients in whom all of the diseased gut had been removed from January 2005 to December 2006 were enrolled in a r and omized , placebo-controlled trial . The patients took GTW(21 cases ) or SASP(18 cases ) in two weeks after operation . Crohn disease activity index(CDAI ) , ESR and CRP were collected at week 0 , 13 , 26 , 52 or at the onset of symptoms . Ileocolonoscopy was performed at the end of the trial or at the onset of symptoms . RESULTS One patient in GTW  group and 2 patients in SASP group were lost and 2 patients in GTW were excluded from the trial for non-compliance . Clinical recurrence was ascertained in one patient ( 5.6 % ) received GTW and in four ( 25.0 % ) received SASP . Four of eighteen patients in GTW(22.2 % ) had endoscopic recurrence compared with nine of sixteen(56.2 % ) in SASP . There were significant differences between the two groups(P<0.05 ) . CONCLUSION Tripterygium wilfordii showed good efficacy in preventing recurrence of postoperative CD which can maintain remission and prevent recurrence BACKGROUND Infliximab has shown efficacy at preventing post operative recurrence ( POR ) of Crohn 's disease ( CD ) . This study aim ed at evaluating whether adalimumab can prevent and treat POR of CD . METHODS This prospect i ve , single-center , open-label , two-year study included 23 patients who had undergone ileocecal resection for refractory or complicated CD and were at high-risk for POR . Patients received adalimumab from post operative day 14 ( Group I , n=8 ) or at 6 months post operatively after confirmation of endoscopic recurrence ( PO-ER ) despite treatment with azathioprine , infliximab , or 5-ASA ( patients intolerant to infliximab and azathioprine , Group II , n=15 ) . Symptom assessment and laboratory tests were performed at monthly visits . Endoscopic findings were grade d using the Rutgeerts score ( RS ) at 6 and 24 months after initiation of adalimumab . Primary end-points were maintenance ( group I ) or achievement of mucosal healing ( Group II ) . Secondary end-points were prevention of post operative clinical recurrence ( PO-CR ) ( Group I ) and endoscopic and clinical improvement ( group II ) . RESULTS In Group I , PO-ER ( RS≥i2 ) was seen in one patient at 6 months PO , whereas a second patient developed PO-ER and PO-CR after 24 months of treatment . In Group II , all patients had PO-ER whereas 9 ( 60 % ) patients had PO-CR at study enrolment ; after 24 months of treatment 9/15 ( 60 % ) patients achieved complete ( RS-i0 , n=3 ) or near complete ( RS-i1 , n=6 ) mucosal healing and 5/9 ( 56 % ) clinical remission . No serious adverse events were reported . CONCLUSIONS This pilot study suggests that adalimumab may prevent PO-ER and treat PO-ER/CR in high risk patients for POR of CD 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 BACKGROUND & AIMS Probiotic formulations of single species of bacteria have not been effective in preventing the recurrence of Crohn 's disease after surgery . We investigated the ability of VSL#3 , a mixture of 8 different bacterial probiotic species , to prevent Crohn 's disease recurrence after surgery in a multicenter , r and omized , double-blind , placebo-controlled trial . METHODS Within 30 days of ileocolonic resection and re-anastomosis , patients with Crohn 's disease were r and omly assigned to groups given 1 sachet of VSL#3 ( 900 billion viable bacteria , comprising 4 strains of Lactobacillus , 3 strains of Bifidobacterium , and 1 strain of Streptococcus salivarius subspecies thermophilus ) ( n = 59 ) or matching placebo ( n = 60 ) . Colonoscopy was performed at days 90 and 365 to evaluate the neoterminal ileum for disease recurrence and obtain mucosal biopsies for cytokine analysis . Patients from both groups with either no or mild endoscopic recurrence at day 90 received VSL#3 until day 365 . The primary outcome was the proportion of patients with severe endoscopic recurrence at day 90 . RESULTS At day 90 , the proportion of patients with severe endoscopic lesions did not differ significantly between VSL#3 ( 9.3 % ) and placebo ( 15.7 % , P = .19 ) . The proportions of patients with non-severe lesions at day 90 who had severe endoscopic recurrence at day 365 were 10.0 % in the early VSL#3 group ( given VSL#3 for the entire 365 days ) and 26.7 % in the late VSL#3 group ( given VSL#3 from days 90 through 365 ) ( P = .09 ) . Aggregate rates of severe recurrence ( on days 90 and 365 ) were not statistically different , 20.5 % of subjects in the early VSL#3 group and 42.1 % in the late VSL#3 group . Patients receiving VSL#3 had reduced mucosal inflammatory cytokine levels compared with placebo at day 90 ( P < .05 ) . Crohn 's disease activity index and inflammatory bowel disease quality of life scores were similar in the 2 groups . CONCLUSIONS There were no statistical differences in endoscopic recurrence rates at day 90 between patients who received VSL#3 and patients who received placebo . Lower mucosal levels of inflammatory cytokines and a lower rate of recurrence among patients who received early VSL#3 ( for the entire 365 days ) indicate that this probiotic should be further investigated for prevention of Crohn 's disease recurrence . Clinical trials.gov number : NCT00175292 Background : The efficacy of infliximab for endoscopic recurrence after resection of Crohn 's disease ( CD ) has not yet been reported . The aim of this prospect i ve study was to investigate the impact of infliximab on early endoscopic lesions after resection for CD . Methods : Twenty‐six patients maintaining clinical remission ( CD activity index [ CDAI ] score < 150 ) with mesalamine ( 3 g/day ) after resection showed endoscopic recurrence in the neoterminal ileum at 6 months postoperatively ( = baseline ) . Over the following 6 months , 10 patients were treated with continuous mesalamine ( 3 g/day ) , 8 patients were treated with azathioprine therapy ( 50 mg/day ) , and the other 8 patients were treated with infliximab therapy ( 5 mg/kg , every 8 weeks ) . During ileocolonoscopy at baseline and 6 months later , mucosal biopsies were taken for cytokine assays . Results : During 6‐month observation , no patients in the infliximab group , 3 ( 38 % ) in the azathioprine group , and 7 ( 70 % ) in the mesalamine group developed clinical recurrence ( CDAI ≥150 ) ( P = 0.01 ) . At 6 months , endoscopic inflammation was improved in 75 % of patients in the infliximab group , 38 % in the azathioprine group , and 0 % in the mesalamine group ( P = 0.006 ) . The mucosal interleukin (IL)‐1&bgr ; , IL‐6 , and tumor necrosis factor‐&agr ; levels significantly decreased in the infliximab group , while they significantly increased in the mesalamine group , and they did not change significantly in the azathioprine group . Conclusions : Infliximab therapy showed clear suppressive effects on clinical and endoscopic disease activity , and mucosal cytokine production in patients with early endoscopic lesions after resection . To confirm our conclusions , r and omized controlled trials with a larger number of patients are necessary Methods : A multicentre r and omized controlled trial was conducted to evaluate the efficacy of oral mesalazine ( 5‐aminosalicylic acid ) for the prevention of post‐operative recurrence in 110 patients operated on for Crohn 's disease by first intestinal resection . Patients were r and omly allocated to receive 2.4 g/day of mesalazine , or no treatment at all . The protocol included colonoscopy with ileoscopy at 6 months and yearly thereafter . Recurrence was denned on the basis of endoscopic criteria and classified as mild or severe Background : The role of mesalazine in preventing the clinical recurrence of Crohn 's disease after surgery has been shown in a meta‐ analysis of all published studies . No clear relationship , however , has been shown between dosage and response 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 Background : Endoscopic recurrence occurs in up to 80 % of patients with Crohn ’s disease 1 year after intestinal resection .  Imidazole antibiotics , thiopurines , and particularly their combination have proven efficacy in preventing endoscopic recurrence . The aim of the study was to compare the efficacy of the addition of metronidazole ( for 3 months after the surgical treatment ) to azathioprine for the prevention of postsurgical endoscopic recurrence . Methods : A pilot study was made of 50 patients with Crohn ’s disease undergoing intestinal resection with ileocolic anastomosis and treated with 2 to 2.5 mg/kg of azathioprine per day for 1 year . The patients were r and omized to receive additional 15 to 20 mg/kg of metronidazole per day or placebo for the first 3 months ( n = 25 per arm ) . Endoscopic assessment was performed 6 and 12 months after the surgical resection . The primary end point was the prevention of endoscopic recurrence as defined by a Rutgeerts score of < 2 at 6 months . The initial sample size had an 80 % statistical power in detecting an absolute risk reduction of ≥30 % . Results : Endoscopic recurrence occurred in 28 % and 44 % of the patients at 6 months ( P = 0.19 ) and in 36 % and 56 % ( P = 0.15 ) at 12 months in the metronidazole and placebo groups , respectively . No statistically significant differences were found between the treatment groups regarding severe endoscopic recurrence ( Rutgeerts score ≥ 3 ) at 6 and 12 months . Likewise , there were no differences in the rate of adverse events between the treatment groups . Conclusions : The addition of metronidazole to azathioprine did not significantly reduce the risk of endoscopic recurrence  beyond azathioprine alone in this study but does not worsen its safety profile Background : The commensal bacterial flora plays a critical role in the postoperative recurrence of Crohn 's disease ( CD ) . We conducted a r and omized , double-blind , placebo-controlled 6-month pilot trial of ciprofloxacin for the prevention of endoscopic recurrence in patients with CD who underwent surgery . Methods : Thirty-three patients with CD , who had undergone surgery with ileocolonic anastomosis within the previous 2 weeks , were r and omized to treatment with ciprofloxacin ( 500 mg twice daily ) or placebo tablets for 6 months . Endpoints were endoscopic recurrence at 6 months and safety and tolerability of long-term ciprofloxacin therapy . Results : Thirty-three patients were r and omized ; 14 patients discontinued the study early . Significant endoscopic recurrence was observed in 3 of 9 patients ( 33 % ) in the ciprofloxacin group and 5 of 10 patients ( 50 % ) in the placebo group at 6 months after surgery ( P < 0.578 ) . The intention-to-treat analysis demonstrated endoscopic recurrence in 11 of 17 patients ( 65 % ) in the ciprofloxacin group and 11 of 16 patients ( 69 % ) in the placebo group at month 6 ( P < 0.805 ) . Thirty-six adverse events occurred in 19 of 33 patients ( 58 % ) . Possible drug-associated adverse events occurred significantly more often in the ciprofloxacin group ( P < 0.043 ) , leading to study drug discontinuation in 24 % ( 4 of 17 ) and 6 % of patients ( 1 of 16 ) in the ciprofloxacin and placebo groups , respectively ( P < 0.166 ) . Conclusions : In this pilot study , ciprofloxacin was not more effective than placebo for the prevention of postoperative recurrence in patients with CD . Long-term ciprofloxacin therapy is limited by drug-associated side effects . Future studies in postoperative prevention of CD should evaluate antibiotic approaches with a more favorable safety profile BACKGROUND & AIMS The aim of this study was to determine the risk of endoscopic/radiological recurrence of Crohn 's disease postoperatively and the long-term outcome . METHODS A r and omized placebo-controlled trial was performed to determine the effectiveness of mesalamine in preventing recurrent Crohn 's disease postoperatively . Patients in the  control group were examined endoscopically/radiologically before entry into and annually during the trial . Findings were classified as minimal or severe . RESULTS There were 76 patients ( 49 men and 37 women ; mean age , 37.1 + /- 13.2 years ) . Fifty ( 61.7 % ) had terminal ileal resections . Overall , 55 endoscopic/radiological recurrences were observed in 51 patients ( 67.1 % ) . Expressed actuarially , the recurrence rate was 27.5 % at 1 year ( 95 % confidence interval [ CI ] , 15.8%-37.6 % ) , 60.8 % at 2 years ( 95 % CI , 46%-71.3 % ) , and 77.3 % at 3 years ( 95 % CI , 62.7%-86.3 % ) . Nineteen ( 37 % ) were symptomatic and 12 ( 24 % ) were initially asymptomatic but later became symptomatic ( mean , 13.0 + /- 8.8 months ) , whereas 20 ( 39 % ) remained asymptomatic ( mean , 16.9 + /- 17.4 months ) . Patients with severe endoscopic/radiological disease were significantly more likely to be or become symptomatic than those with minimal disease ( 23 of 32 vs. 8 of 19 , respectively ; P = 0.0437 ) . CONCLUSIONS This study suggests that postoperative endoscopic/radiological recurrences occur later than previously reported . Furthermore , many of these patients , especially with minimal disease , will remain asymptomatic BACKGROUND & AIMS Most patients with Crohn 's disease ( CD ) eventually require an intestinal resection . However , CD frequently recurs after resection . We performed a r and omized trial to compare the ability of infliximab vs placebo to prevent CD recurrence . METHODS We evaluated the efficacy of infliximab in preventing postoperative recurrence of CD in 297 patients at 104 sites worldwide from November 2010 through May 2012 . All study patients had undergone ileocolonic resection within 45 days before r and omization . Patients were r and omly assigned ( 1:1 ) to groups given infliximab ( 5 mg/kg ) or placebo every 8 weeks for 200 weeks . The primary end point was clinical recurrence , defined as a composite outcome consisting of a CD Activity Index score > 200 and a ≥70-point increase from baseline , and endoscopic recurrence ( Rutgeerts score ≥i2 , determined by a central reader ) or development of a new or re-draining fistula or abscess , before or at week 76 . Endoscopic recurrence was a major secondary end point . RESULTS A smaller proportion of patients in the infliximab group had a clinical recurrence before or at week 76 compared with the placebo group , but this difference was not statistically significant ( 12.9 % vs 20.0 % ; absolute risk reduction [ ARR ] with infliximab , 7.1 % ; 95 % confidence interval : -1.3 % to 15.5 % ; P = .097 ) . A significantly smaller proportion of patients in the infliximab group had endoscopic recurrence compared with the placebo group ( 30.6 % vs 60.0 % ; ARR with infliximab , 29.4 % ; 95 % confidence interval : 18.6 % to 40.2 % ; P < .001 ) . Additionally , a significantly smaller proportion of patients in the infliximab group had endoscopic recurrence based only on Rutgeerts scores ≥i2 ( 22.4 % vs 51.3 % ; ARR with infliximab , 28.9 % ; 95 % confidence interval : 18.4 % to 39.4 % ; P < .001 ) . Patients previously treated with anti-tumor necrosis factor agents or those with more than 1 resection were at greater risk for clinical recurrence . The safety profile of infliximab was similar to that from previous reports . CONCLUSIONS Infliximab is not superior to placebo in preventing clinical recurrence after CD-related resection . However , infliximab does reduce endoscopic recurrence . Clinical Trials.gov ID NCT01190839 BACKGROUND & AIMS A previous r and omized , placebo-controlled study showed that infliximab maintenance therapy prevented recurrence of Crohn 's disease 1 year after an ileocolonic resection . We evaluated recurrence of Crohn 's disease , on the basis of endoscopic examination and /or the need for additional surgical resection , beyond the first postoperative year . METHODS In a prospect i ve , open-label , long-term follow-up study , 24 patients previously r and omly assigned to receive infliximab for 1 year after an ileocolonic resection were given the option to continue , stop , or start infliximab therapy . The primary end point was the time to recurrence of Crohn 's disease , on the basis of endoscopic evidence ( endoscopic recurrence ) , from the initial assignment to postoperative infliximab or placebo . Secondary end points were rate of endoscopic recurrence , time to reoperation , and rate of surgical recurrence in relation to the total time on infliximab . RESULTS All patients were followed for at least 5 years after surgery . Patients assigned to the infliximab group in the first year after surgery had a longer mean time to first endoscopic recurrence ( 1231 ± 747 days ) than patients originally assigned to the placebo group ( 460 ± 121 days , P = .003 ) . Colonoscopies identified Crohn 's disease recurrence in 22.2 % of patients who received long-term infliximab and in 93.9 % of those not on infliximab ( P < .0001 ) . Compared with no infliximab , the adjusted rate ratio for being in endoscopic remission while on infliximab was 13.47 ( 95 % confidence interval , 3.52 - 61.53 ; P = .0001 ) . Patients originally assigned to the infliximab group had a mean longer time to surgery ( 1798 ± 359 days ) than patients originally assigned to the placebo group ( 1058 ± 529 days , P = .04 ) . The rate of surgical recurrence ( required additional surgical resection ) was significantly lower among patients who received infliximab for most of the follow-up period than patients who received it for shorter periods ( 20.0 % vs 64.3 % , P = .047 ) . CONCLUSIONS Postoperative infliximab maintenance beyond 1 year prevents recurrence of Crohn 's disease
BACKGROUND Crohn 's disease ( CD ) is a chronic disease of the gut .
About 75 % of people with CD undergo surgery at least once in their lifetime to induce remission .
However , as there is no known cure for the disease , patients usually experience a recurrence even after surgery .
Different interventions are routinely used in maintaining postsurgical remission .
There is currently no consensus on which treatment is the most effective .
OBJECTIVES To assess the effects and harms of interventions for the maintenance of surgically induced remission in Crohn 's disease and rank the treatments in order of effectiveness .
Adverse events and serious adverse events were not sufficiently or objective ly reported to permit an NMA .