***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: 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 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 Introduction Crohn ’s disease ( CD ) and ulcerative colitis ( UC ) , the main forms of inflammatory bowel disease ( IBD ) , are chronic , progressive and disabling disorders of the gastrointestinal tract . Although data from r and omised controlled trials ( RCTs ) provide the foundation of evidence that vali date s medical therapy for IBD , considerable heterogeneity exists in the measured outcomes used in these studies . Furthermore , in recent years , there has been a paradigm shift in IBD treatment targets , moving from symptom-based scoring to improvement or normalisation of objective measures of inflammation such as endoscopic appearance , inflammatory biomarkers and histological and radiographic end points . The abundance of new treatment options and evolving end points poses opportunities and challenges for all stakeholders involved in drug development . Accordingly , there exists a need to harmonise measures used in clinical trials through the development of a core outcome set ( COS ) . Methods and analysis The development of an IBD-specific COS includes four steps . First , a systematic literature review is performed to identify outcomes previously used in IBD RCTs . Second , semistructured qualitative interviews are conducted with key stakeholders , including patients , clinicians , research ers , pharmaceutical industry representatives , healthcare payers and regulators to identify additional outcomes of importance . Using the outcomes generated from literature review and stakeholder interviews , an international two-round Delphi survey is conducted to prioritise outcomes for inclusion in the COS . Finally , a consensus meeting is held to ratify the COS and disseminate findings for application in future IBD trials . Ethics and dissemination Given that over 30 novel therapeutic compounds are in development for IBD treatment , the design of robust clinical trials measuring relevant and st and ardised outcomes is crucial . St and ardising outcomes through a COS will reduce heterogeneity in trial reporting , facilitate valid comparisons of new therapies and improve clinical trial quality BACKGROUND Steroid dependent patients with Crohn 's disease are at high risk of developing glucocorticosteroid induced side effects . AIMS We evaluated the possibility of switching from systemic steroids to budesonide ( Entocort ) in  prednisolone/prednisone dependent patients with inactive Crohn 's disease affecting the ileum and /or ascending colon . PATIENTS Steroid dependent patients with a Crohn 's disease activity index ⩽200 were included . METHODS In a double blind multicentre trial , 120 patients were r and omly assigned to receive budesonide 6 mg once daily or placebo . Prednisolone was tapered to zero during the first 4–10 weeks and budesonide or placebo was given concomitantly and for a further 12 weeks . Relapse was defined as an index > 200 and an increase of 60 points from baseline or withdrawal due to disease deterioration . RESULTS After one and 13 weeks without prednisolone  , relapse rates were 17 % and 32 % , respectively , in the budesonide group , and 41 % and 65 % in the placebo group ( 95 % confidence intervals for the difference in percentages −41 % , −8 % and −51 % , −16 % ; p=0.004 and p<0.001 , respectively ) . The number of glucocorticosteroid side effects was reduced by 50 % by switching from prednisolone and was similar in the budesonide and placebo groups . Basal plasma cortisol increased in both groups . CONCLUSIONS The majority of patients with steroid dependent ileocaecal Crohn 's disease may be switched to budesonide controlled ileal release capsules 6 mg without relapse , result ing in a sharp decrease in glucocorticosteroid side effects similar to placebo , and with an increase in plasma cortisol levels BACKGROUND We did a r and omised controlled trial to assess the benefit of maintenance infliximab therapy in patients with active Crohn 's disease who respond to a single infusion of infliximab .  METHODS 573 patients with a score of at least 220 on the Crohn 's disease activity index ( CDAI ) received a 5 mg/kg intravenous infusion of infliximab at week 0 . After assessment of response at week 2 , patients were r and omly assigned repeat infusions of placebo at weeks 2 and 6 and then every 8 weeks thereafter until week 46 ( group I ) , repeat infusions of 5 mg/kg infliximab at the same timepoints ( group II ) , or 5 mg/kg infliximab at weeks 2 and 6 followed by 10 mg/kg ( group III ) . The prespecified co- primary endpoints were the proportion of patients who responded at week 2 and were in remission ( CDAI < 150 ) at week 30 and the time to loss of response up to week 54 in patients who responded . Analyses of the co- primary endpoints were by intention to treat . FINDINGS 335 ( 58 % ) patients responded to a single infusion of infliximab within 2 weeks . At week 30 , 23 of 110 ( 21 % ) group I patients were in remission , compared with 44 of 113 ( 39 % ) group II ( p=0.003 ) and 50 of 112 ( 45 % ) group III ( p=0.0002 ) patients . Thus , patients in groups II and III combined were more likely to sustain clinical remission than patients in group I ( odds ratio 2.7 , 95 % CI 1.6 - 4.6 ) . Throughout the 54-week trial , the median time to loss of response was 38 weeks ( IQR 15 to > 54 ) and more than 54 weeks ( 21 to > 54 ) for groups II and III , respectively , compared with 19 weeks ( 10 - 45 ) for group I ( p=0.002 and p=0.0002 , respectively ) .  Infliximab safety was consistent with that seen in other trials of infliximab in Crohn 's disease and rheumatoid arthritis . In particular , the incidence of serious infections was similar across treatment groups . INTERPRETATION Patients with Crohn 's disease who respond to an initial dose of infliximab are more likely to be in remission at weeks 30 and 54 , to discontinue corticosteroids , and to maintain their response for a longer period of time , if infliximab treatment is maintained every 8 weeks BACKGROUND & AIMS The aim of this study was to evaluate the usefulness of short-term infliximab combined with azathioprine ( AZA ) or 6-mercaptopurine ( 6-MP ) in steroid-dependent Crohn 's disease patients . METHODS Patients with active disease despite prednisone given for more than 6 months were eligible and were stratified as follows : the failure stratum consisted of patients receiving AZA/6-MP at a stable dose for more than 6 months , and the naive stratum consisted of patients not treated previously with AZA/6-MP . Patients were r and omized to infliximab 5 mg/kg or placebo at weeks 0 , 2 , and 6 . All patients were treated with AZA/6-MP maintained at a stable dose throughout the 52 weeks of the study . The primary end point was remission off steroids at week 24 . RESULTS Among the 113 enrolled patients ( 55 in the failure stratum ) , 57 were assigned to infliximab . At week 24 , the success rate ( intent-to-treat analysis ) was higher in the infliximab group than in the placebo group ( 57 % vs 29 % ; P = .003 ) ; at weeks 12 and 52 , the corresponding rates were 75 % vs 38 % ( P < .001 ) and 40 % vs 22 % ( P = .04 ) , respectively . In each stratum , the success rate was significantly higher in the infliximab group at weeks 12 and 24 , and a trend was found at week 52 . In the failure stratum , only 27 % of the patients in the infliximab group were still in remission off steroids , compared with 52 % in the naive stratum . Steroid resistance was less common and the cumulative dose of prednisone was lower in the infliximab group . CONCLUSIONS Infliximab plus AZA/6-MP is more effective than AZA/6-MP alone in steroid-dependent Crohn 's disease patients Background : Adalimumab induced clinical remission after four weeks in patients with active Crohn ’s disease in the CLASSIC I trial . Objective : To evaluate long term efficacy and safety of adalimumab maintenance therapy in Crohn ’s disease in a follow-on r and omised controlled trial ( CLASSIC II ) . Methods : In the preceding CLASSIC I trial , 299 patients with moderate to severe Crohn ’s disease naive to tumour necrosis factor antagonists received induction therapy with adalimumab 40 mg/20 mg , 80 mg/40 mg , or 160 mg/80 mg , or placebo , at weeks 0 and 2 . In all , 276 patients from CLASSIC I enrolled in CLASSIC II and received open-label adalimumab 40 mg at weeks 0 ( week 4 of CLASSIC I ) and 2 ; 55 patients in remission at both weeks 0 and 4 were re-r and omised to adalimumab 40 mg every other week , 40 mg weekly , or placebo for 56 weeks . Patients not in remission at both weeks 0 and 4 were enrolled in an open-label arm and received adalimumab 40 mg every other week . With non-response or flare , these patients could have their dosages increased to 40 mg weekly . Patients in the r and omised arm with continued non-response or disease flare could switch to open-label adalimumab 40 mg every other week and again to 40 mg weekly . The primary end point was maintenance of remission ( CDAI < 150 ) in r and omised patients through week 56 . Results : Of 55 patients r and omised at week 4 , 79 % who received adalimum 
    Output:
    
Conclusions In this systematic review , we demonstrate heterogeneity in definitions of response and remission , and changes in outcomes reported in RCTs of CD .