***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: Background Endogenous opioid peptides have been shown to play a role in the development and /or perpetuation of inflammation . We hypothesize that the endogenous opioid system is involved in inflammatory bowel disease , and antagonism of the opioid – opioid receptor will lead to reversal of inflammation . Aims A r and omized double-blind placebo-controlled study was design ed to test the efficacy and safety of an opioid antagonist for 12 weeks in adults with active Crohn ’s disease . Methods Forty subjects with active Crohn ’s disease were enrolled in the study . R and omized patients received daily oral administration of 4.5-mg naltrexone or placebo . Providers and patients were masked to treatment assignment . The primary outcome was the proportion of subjects in each arm with a 70-point decline in Crohn ’s Disease Activity Index score ( CDAI ) . The secondary outcome included mucosal healing based upon colonoscopy appearance and histology . Results Eighty-eight percent of those treated with naltrexone had at least a 70-point decline in CDAI scores compared to 40 % of placebo-treated patients ( p = 0.009 ) . After 12 weeks , 78 % of subjects treated with naltrexone exhibited an endoscopic response as indicated by a 5-point decline in the Crohn ’s disease endoscopy index severity score ( CDEIS ) from baseline compared to 28 % response in placebo-treated controls ( p = 0.008 ) , and 33 % achieved remission with a CDEIS score < 6 , whereas only 8 % of those on placebo showed the same change . Fatigue was the only side effect reported that was significantly greater in subjects receiving placebo . Conclusions Naltrexone improves clinical and inflammatory activity of subjects with moderate to severe Crohn ’s disease compared to placebo-treated controls . Strategies to alter the endogenous opioid system provide promise for the treatment of Crohn ’s disease Background and aims : To evaluate the safety , pharmacokinetics and clinical efficacy of the intercellular adhesion molecule‐1 antisense phosphorothioate oligonucleotide alicaforsen ( ISIS 2302 ) at 250–350 mg in Crohn 's disease BACKGROUND Oral budesonide 9 mg/day represents first-line treatment of mild-to-moderately active ileocolonic Crohn 's disease . However , there is no precise recommendation for budesonide dosing due to lack of comparative data . A once-daily ( OD ) 9 mg dose may improve adherence and thereby efficacy . METHODS An eight-week , double-blind , double-dummy r and omised trial compared budesonide 9 mg OD versus 3 mg three-times daily ( TID ) in patients with mild-to-moderately active ileocolonic Crohn 's disease . Primary endpoint was clinical remission defined as CDAI < 150 at week 8 ( last observation carried forward ) . RESULTS The final intent-to-treat population comprised 471 patients ( 238 [ 9 mg OD ] , 233 [ 3 mg TID ] ) . The confirmatory population for the primary endpoint analysis was the interim per protocol population ( n=377 ; 188 [ 9 mg OD ] , 189 [ 3 mg TID ] ) , in which the primary endpoint was statistically non-inferior with budesonide 9 mg OD versus 3 mg TID . Clinical remission was achieved in 71.3 % versus 75.1 % , a difference of -3.9 % ( 95 % CI [ -14.6 % ; 6.4 % ] ; p=0.020 for non-inferiority ) . The mean ( SD ) time to remission was 21.9 ( 13.8 ) days versus 21.4 ( 14.6 ) days with budesonide 9 mg OD versus 3 mg TID , respectively . In a sub population of 122 patients with baseline SES-CD ulcer score ≥1  , complete mucosal healing occurred in 32.8 % ( 21/64 ) on 9 mg OD and 41.4 % ( 24/58 ) on 3 mg TID ; deep remission ( mucosal healing and clinical remission ) was observed in 26.6 % ( 17/64 ) and 32.8 % ( 19/58 ) of patients , respectively . Treatment-emergent suspected adverse drug reactions were reported in 4.6 % of 9 mg OD and 4.7 % of 3 mg TID patients . CONCLUSIONS Budesonide at the recommended dose of 9 mg/day can be administered OD without impaired efficacy and safety compared to 3 mg TID dosing in mild-to-moderately active Crohn 's disease 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 Mucosal ischaemia may contribute to the pathogenesis of Crohn ’s disease .  Microvascular abnormalities have been found in colonic resection specimens , and mucosal levels of constitutive nitric oxide synthase are reduced We studied the efficacy and safety of the topically acting steroid budesonide in an oral preparation for controlled ileal release in an open , uncontrolled trial . Twenty‐one patients with active Crohn 's disease localized to the distal ileum , ileocaecal region or ascending colon , entered the trial . The median age was 36 years and the median duration of Crohn 's disease was 8 years . The patients received budesonide , in a controlled ileal release preparation , in a dose of 3 mg t.d.s . for 12 weeks , followed by a reduction to 2 mg t.d.s . for 6 weeks and finally to 1 mg t.d.s . for an additional 6 weeks . Primary variables were the modified Crohn 's disease activity index ( mCDAI ) , laboratory parameters and plasma cortisol levels . The mean mCDAI at entry was 268 ( ± 71 s.d . ) . dropping to 146 ( ± 91 s.d . ) after 4 weeks of treatment and to 122 ( ± 87 s.d . ) after a total of 12 weeks on 3 mg t.d.s . ( P < 0.001 ) . Following dose reduction , the mean mCDAI increased after 18 and 24 weeks of treatment . The erythrocyte sedimentation rate also fell significantly during the study period . Eighteen patients responded favourably during the first 12‐week treatment period , and 13 completed the trial . Seven patients were withdrawn due to failure of treatment after reduction of dose , and four of those were treated surgically . No serious side‐effects or significant corticosteroid‐related side‐effects occurred . The mean plasma cortisol levels decreased , but remained within normal range . Four patients were markedly suppressed on the highest dose of budesonide . The controlled ileal release of budesonide seems to be beneficial in active ileal and ileocolonic Crohn 's disease without causing important side‐effects 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 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. 
    Output:
    
Many of the common adverse events relate to disease exacerbation or treatment failure .
CONCLUSIONS Trial endpoints vary across studies , over time and are distinct in fistula studies .
Despite growth in reporting of objective measures of inflammation and in patient-reported outcome measures , there is a lack of st and ardisation .
This confirms the need for a core outcome set for comparative effectiveness research in Crohn 's disease