***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 and aims : Immunosuppressive therapy with intravenous ciclosporin is an alternative treatment option to total colectomy for patients with ulcerative colitis ( UC ) , while the benefits of oral administration of tacrolimus are not well defined and are based on reports of several uncontrolled studies . Methods : Patients with refractory active UC were r and omly assigned to a high trough concentration ( 10–15 ng/ml ) group ( HT group ) ( n = 21 ) , low trough concentration ( 5–10 ng/ml ) group ( LT group ) ( n = 22 ) , or placebo group ( n = 20 ) . Patients received an initial oral dose of 0.05 mg/kg tacrolimus or placebo twice daily . Efficacy was evaluated in 60 patients based on a disease activity index ( DAI ) score .  Fifty eight patients had additional treatment with tacrolimus  and were evaluated for efficacy in a 10 week open label extension . Results : An improvement in DAI score ( ⩾4 points , all categories improved ) was observed for 68.4 % of cases in the HT group compared with 10.0 % in the placebo group ( p<0.001 ) . In the HT group , 20.0 % of patients had clinical remission and 78.9 % had mucosal healing . In the open label extension , 55.2 % of all patients had an improved DAI score at week 10 . Mean dose of prednisolone  was reduced from 19.7 mg/day at study entry to 7.8 mg/day at week 10 . The incidence of side effects in the HT group was significantly higher than that of the placebo group ( p = 0.043 ) . The most common event was mild finger tremor . Conclusions : Our findings demonstrate dose dependent efficacy and safety of oral tacrolimus for remission-induction therapy of refractory UC . The optimal target range appears to be 10–15 ng/ml in terms of efficacy with two week therapy BACKGROUND & AIMS Thiazolidinedione lig and s for the gamma subtype of peroxisome proliferator-activated receptors ( PPARgamma ) , widely used to treat type 2 diabetes mellitus , have been proposed as novel therapies for ulcerative colitis ( UC ) . METHODS This multicenter , r and omized , double-blind , placebo-controlled clinical trial compared the efficacy of rosiglitazone ( Av and ia ; GlaxoSmithKline , Philadelphia , PA ) 4 mg orally twice daily vs placebo twice daily for 12 weeks in 105 patients with mild to moderately active UC .  Disease activity was measured with the Mayo score . The primary end point was clinical response ( > /=2-point reduction ) at week 12 . Clinical remission ( Mayo score < /=2 ) , endoscopic remission , and quality of life were secondary outcomes . RESULTS After 12 weeks of therapy , 23 patients ( 44 % ) treated with rosiglitazone and 12 patients ( 23 % ) treated with placebo achieved clinical response ( P = .04 ) . Remission was achieved in 9 patients ( 17 % ) treated with rosiglitazone and 1 patient ( 2 % ) treated with placebo ( P = .01 ) . Endoscopic remission was uncommon in either treatment arm ( 8 % rosiglitazone vs 2 % placebo ; P = .34 ) . Clinical improvement was evident as early as 4 weeks after beginning treatment ( P = .049 ) . Quality of life was improved significantly at week 8 ( P = .01 ) , but not at week 4 ( P = .48 ) or week 12 ( P = .14 ) . Serious adverse events were rare . CONCLUSIONS Rosiglitazone was efficacious in the treatment of mild to moderately active UC Background and aims Leucocyte migration to gut mucosa , mediated by integrin binding to mucosal addressin cell adhesion molecule ( MAdCAM ) , is a promising target for therapeutic intervention in inflammatory bowel disease . This first-in-human study of a monoclonal antibody to MAdCAM , PF-00547,659 , aim ed to explore the safety and preliminary efficacy of this gut-specific mechanism in ulcerative colitis . Methods In this r and omised , double-blind placebo-controlled study , 80 patients with active ulcerative colitis received single or  multiple ( three doses , 4-week intervals ) doses of PF-00547,659 0.03–10 mg/kg IV/SC , or placebo . Safety was assessed by adverse events , laboratory tests , and immunogenicity . Exploratory efficacy analyses were based on Mayo score and endoscopic responder rates at weeks 4 and 12 . Faecal calprotectin was quantified as a measure of disease activity , and the number of α4β7 + lymphocytes was measured to demonstrate drug activity . Results No obvious drug-related side effects were observed in the PF-00547,659 group , while patient numbers , especially those fully exposed , were small . Overall responder/remission rates at 4 and 12 weeks were 52%/13 % and 42%/22 % , respectively with combined PF-00547,659 doses compared with 32%/11 % and 21%/0 % , respectively with placebo . Equivalent endoscopic responder rates were 50 % and 42 % versus 26 % and 29 % , respectively . Faecal calprotectin levels decreased to a greater extent with PF-00547,659 than placebo ( week 4 : 63 % vs 18 % ) . Despite variability , there was a trend for an increase in α4β7 + lymphocytes in patients receiving PF-00547,659 . Conclusions The favourable short-term safety profile and preliminary efficacy findings for PF-00547,659 in this first-in-human study pave the way for further investigation in larger trials , to establish the role of PF-00547,659 in ulcerative colitis treatment . Trial Register No : NCT00928681 BACKGROUND / AIMS Uncontrolled studies suggest that cyclosporine administered as an enema may be of benefit for left-sided ulcerative colitis and safer than intravenous or oral administration . The efficacy and safety of cyclosporine enemas for left-sided ulcerative colitis in a placebo-controlled trial was assessed . METHODS Steroid and mesalamine enemas were withdrawn before the study . Forty patients were assigned to 1 of 4 strata : no concomitant therapy , oral steroids , oral salicylates , or oral steroids and salicylates . After stratification , patients were r and omized to nightly treatment with 350 mg cyclosporine ( n = 20 ) or placebo ( n = 20 ) enemas . Clinical response was determined at baseline and 4 weeks by endoscopy , physician assessment , and a patient diary of daily symptoms . Trough blood cyclosporine levels were measured by high-performance liquid chromatography . RESULTS At 4 weeks , 8 of 20 patients ( 40 % ) who received cyclosporine showed clinical improvement compared with 9 of 20 patients ( 45 % ) who received placebo . One patient receiving cyclosporine had reversible neutropenia attributable to sulfasalazine , and another patient receiving cyclosporine was unable to tolerate the enema vehicle . No other toxicity was noted during the trial . Blood cyclosporine levels were detectable in only two patients . CONCLUSIONS Cyclosporine enemas administered in a dosage of 350 mg/day for 4 weeks are not efficacious in mildly to moderately active left-sided ulcerative colitis Background : We report a multicenter study of oral tacrolimus ( FK506 ) therapy in steroid‐refractory ulcerative colitis ( UC ) . Methods : In a placebo‐controlled , double‐blind study , 62 patients with steroid‐refractory , moderate‐to‐severe UC were r and omized into either a tacrolimus group or a placebo for 2 weeks . Patients were evaluated using the Disease Activity Index ( DAI ) . As an entry criterion , patients had to have a total DAI score of 6 or more as well as a mucosal appearance subscore of 2 or 3 .  Clinical response was defined as improvement in all DAI subscores . Mucosal healing was defined as mucosal appearance subscore of 0 or 1 . Clinical remission was defined as a total DAI score ≤2 with an individual subscore of 0 or 1 . Results : The mean total DAI score at study entry was 9.8 ± 1.61 in the tacrolimus group and 9.1 ± 1.05 in the placebo group . At week 2 the clinical response rate was 50.0 % ( 16/32 ) in the tacrolimus group and 13.3 % ( 4/30 ) in the placebo group ( P = 0.003 ) . The rate of mucosal healing observed was 43.8 % ( 14/32 ) in the tacrolimus group and 13.3 % ( 4/30 ) in the placebo group ( P = 0.012 ) and the rate of clinical remission observed was 9.4 % ( 3/32 ) in the tacrolimus group and 0.0 % ( 0/30 ) in the placebo group ( P = 0.238 ) . The therapies in this study were well tolerated , with only minor side effects . Conclusions : Oral tacrolimus therapy in patients with steroid‐refractory UC shortened the acute phase and induced rapid mucosal healing . These results suggest that tacrolimus therapy is useful as an alternative therapy for steroid‐refractory UC . ( Inflamm Bowel Dis 2011 ; 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 Objective The aim of this study was to assess the efficacy and safety of adalimumab ( ADA ) , a recombinant human monoclonal antibody against tumour necrosis factor α ( TNF ) , for the induction of clinical remission in anti-TNF naïve patients with moderately to severely active ulcerative colitis . Methods This 8-week , multicentre , r and omised , double-blind , placebo-controlled study ( NCT00385736 ) , conducted at 94 centres in North America and Europe , enrolled ambulatory adult patients with Mayo score of ≥6 points and endoscopic subscore of ≥2 points despite treatment with corticosteroids and /or immunosuppressants . Under the original study protocol , 186 patients were r and omised ( 1:1 ) to subcutaneous treatment with ADA160/80 ( 160 mg at week 0 , 80 mg at week 2 , 40 mg at weeks 4 and 6 ) or placebo . Subsequently , at the request of European regulatory authorities , the protocol was amended to include a second induction group ( ADA80/40 : 80 mg at week 0 , 40 mg at weeks 2 , 4 and 6 ) . The primary efficacy endpoint was clinical remission ( Mayo score ≤2 with no individual subscore > 1 ) at week 8 , assessed in 390 patients r and omised ( 1:1:1 ) to ADA160/80 , ADA80/40 , or placebo . Safety was assessed in all enrolled patients . Patients , study site personnel , investigators , and the sponsor were blinded to treatment assignment . Results At week 8 , 18.5 % of patients in the ADA160/80 group ( p=0 
    Output:
    
Conclusion : In a systematic review , we found that despite recent advances in clinical trials methods , there is a great deal of variation in definitions of endpoints , including response and remission , in r and omized controlled trials of patients with UC .