***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 
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    ***EXAMPLES*** 
    Input: BACKGROUND Biomarkers of intestinal inflammation , such as faecal calprotectin and C-reactive protein , have been recommended for monitoring patients with Crohn 's disease , but whether their use in treatment decisions improves outcomes is unknown . We aim ed to compare endoscopic and clinical outcomes in patients with moderate to severe Crohn 's disease who were managed with a tight control algorithm  , using clinical symptoms and biomarkers , versus patients managed with a clinical management algorithm .  METHODS CALM was an open-label , r and omised , controlled phase 3 study , done in 22 countries at 74 hospitals and outpatient centres , which evaluated adult patients ( aged 18 - 75 years ) with active endoscopic Crohn 's disease ( Crohn 's Disease Endoscopic Index of Severity [ CDEIS ] > 6 ; sum of CDEIS subscores of > 6 in one or more segments with ulcers ) , a Crohn 's Disease Activity Index ( CDAI ) of 150 - 450 depending on dose of prednisone at baseline , and no previous use of immunomodulators or biologics . Patients were r and omly assigned at a 1:1 ratio to tight control or clinical management groups , stratified by smoking status ( yes or no ) , weight ( < 70 kg or ≥70 kg ) , and disease duration ( ≤2 years or > 2 years ) after 8 weeks of prednisone induction therapy , or earlier if they had active disease . In both groups , treatment was escalated in a stepwise manner , from no treatment , to adalimumab induction followed by adalimumab every other week , adalimumab every week , and lastly to both weekly adalimumab and daily azathioprine . This escalation was based on meeting treatment failure criteria , which differed between groups ( tight control group before and after r and om assignment : faecal calprotectin ≥250 μg/g , C-reactive protein ≥5mg/L , CDAI ≥150 , or prednisone use in the previous week ; clinical management group before r and om assignment : CDAI decrease of < 70 points compared with baseline or CDAI > 200 ; clinical management group after r and om assignment : CDAI decrease of < 100 points compared with baseline or CDAI ≥200 , or prednisone use in the previous week ) . De-escalation was possible for patients receiving weekly adalimumab and azathioprine or weekly adalimumab alone if failure criteria were not met . The primary endpoint was mucosal healing ( CDEIS < 4 ) with absence of deep ulcers 48 weeks after r and omisation . Primary and safety analyses were done in the intention-to-treat population . This trial has been completed , and is registered with Clinical Trials.gov , number NCT01235689 . FINDINGS Between Feb 11 , 2011 , and Nov 3 , 2016 , 244 patients ( mean disease duration : clinical management group , 0·9 years [ SD 1·7 ] ; tight control group , 1·0 year [ 2·3 ] ) were r and omly assigned to monitoring groups ( n=122 per group ) . 29 ( 24 % ) patients in the clinical management group and 32 ( 26 % ) patients in the tight control group discontinued the study , mostly because of adverse events . A significantly higher proportion of patients in the tight control group achieved the primary endpoint at week 48 ( 56 [ 46 % ] of 122 patients ) than in the clinical management group ( 37 [ 30 % ] of 122 patients ) , with a Cochran-Mantel-Haenszel test-adjusted risk difference of 16·1 % ( 95 % CI 3·9 - 28·3 ; p=0·010 ) . 105 ( 86 % ) of 122 patients in the tight control group and 100 ( 82 % ) of 122 patients in the clinical management group reported treatment-emergent adverse events ; no treatment-related deaths occurred . The most common adverse events were nausea ( 21 [ 17 % ] of 122 patients ) , nasopharyngitis ( 18 [ 15 % ] ) , and headache ( 18 [ 15 % ] ) in the tight control group , and worsening Crohn 's disease ( 35 [ 29 % ] of 122 patients ) , arthralgia ( 19 [ 16 % ] ) , and nasopharyngitis ( 18 [ 15 % ] ) in the clinical management group . INTERPRETATION CALM is the first study to show that timely escalation with an anti-tumour necrosis factor therapy on the basis of clinical symptoms combined with biomarkers in patients with early Crohn 's disease results in better clinical and endoscopic outcomes than symptom-driven decisions alone . Future studies should assess the effects of such a strategy on long-term outcomes such as bowel damage , surgeries , hospital admissions , and disability . FUNDING AbbVie BACKGROUND & AIMS Few prospect i ve data are available to support the clinical relevance of mucosal healing in patients with Crohn 's disease . This study examined whether complete healing , determined by endoscopy , predicts a better outcome in Crohn 's disease . METHODS One-hundred thirty-three newly diagnosed and treatment-naïve Crohn 's disease patients were given either a combination of immunosuppressive therapy ( azathioprine ) and 3 infusions of infliximab or treatment with conventional corticosteroids . Patients given azathioprine were given repeated doses of infliximab for relapses , patients given corticosteroids were given azathioprine in cases of corticosteroid dependency and infliximab only if azathioprine failed . A representative subset of 49 patients from the initially r and omized cohort underwent ileocolonoscopy after 2 years of therapy . Correlation analysis was performed between different clinical parameters including endoscopic activity ( Simple Endoscopic Score ) and clinical outcome 2 years after this endoscopic examination . Data were available from 46 patients 3 and 4 years after therapy began . RESULTS Complete mucosal healing , defined as a simple endoscopic score of 0 after 2 years of therapy , was the only factor that predicted sustained , steroid-free remission 3 and 4 years after therapy was initiated ; it was observed in 17 of 24 patients ( 70.8 % ) vs 6 of 22 patients with lesions detected by endoscopy ( 27.3 % , Simple Endoscopic Score > 0 ) ( P = .036 ; odds ratio = 4.352 ; 95 % confidence interval , 1.10 - 17.220 ) . Fifteen of 17 patients with mucosal healing at year 2 maintained in remission without further infliximab infusions during years 3 and 4 ( P = .032 ; odds ratio = 4.883 ; 95 % confidence interval , 1.144 - 20.844 ) . CONCLUSIONS Complete mucosal healing in patients with early-stage Crohn 's disease is associated with significantly higher steroid-free remission rates 4 years after therapy began Objectives : We aim ed to compare the efficacy of remission maintenance between infliximab “ top-down ” and “ step-up ” strategies in moderate to severe pediatric Crohn disease during 3 years . We also aim ed to determine prognostic factors that may influence the relapse-free rate in these patients . Methods : The present study was a retrospective review of a prospect i ve cohort , based on an infliximab treatment protocol for pediatric Crohn disease used at Samsung Medical Center . A total of 31 patients ( group A ) were treated with early infliximab induction ( “ top-down ” strategy ) and 20 patients ( group B ) refractory to conventional therapy  underwent infliximab treatment ( “ step-up ” strategy ) . The efficacy of infliximab treatment was assessed by relapse-free rate and remission period rate for 3 years . A total of 11 prognostic factors that may influence the relapse-free rate were further analyzed . Results : The relapse-free rates at 3 years were 35.5 % ( 95 % confidence interval [ CI ] 0.194–0.519 ) in group A and 15.0 % ( 95 % CI 0.037–0.335 ) in group B ( P = 0.0094 ) . Overall remission period rate for 3 years also showed a significant difference between the 2 groups ( 92.1 % ± 7.2 % vs 78.3 % ± 16.6 % ; P = 0.005 ) . Multivariable analysis revealed that the duration from the initial diagnosis to infliximab infusion was the only factor associated with relapse-free remission for 3 years ( hazard ratio = 1.077 ; 95 % CI 1.025–1.131 ) . Conclusions : “ Top-down ” strategy had a longer remission period compared with the “ step-up ” strategy in pediatric Crohn disease during a study period of 3 years , based on relapse-free rate and remission period rate . Earlier introduction of infliximab is recommended in pediatric patients with moderate to severe Crohn disease OBJECTIVES : We sought to analyze the efficacy ( response and remission ) and safety data from the PRECiSE 2 trial of certolizumab pegol according to duration of Crohn 's disease since diagnosis at baseline . METHODS : Responders to induction treatment with certolizumab pegol at week 6 in PRECiSE 2 ( n=425 ) were r and omized to receive certolizumab pegol 400 mg ( n=215 ) or placebo ( n=210 ) until week 26 . Logistic regression analysis identified factors linked to Crohn 's disease history ( short duration , no prior infliximab use , no corticosteroids , no operations ) as prognostics of outcome . Efficacy ( response , remission ) and safety data were reanalyzed according to duration of Crohn 's disease since diagnosis at baseline . RESULTS : The proportions of patients in response at study end were inversely related to duration of Crohn 's disease . Maintenance of response  with certolizumab pegol was achieved in 89.5 % of patients with a diagnosis < 1 year ( P<0.01 vs. placebo ) , compared with 57.3 % of patients with a diagnosis ≥5 years ( P<0.001 vs. placebo ) . Corresponding remission rates were 68.4 % ( P<0.05 vs. placebo ) and 44.3 % ( P<0.001 vs. placebo ) , respectively . Response and remission rates did not differ significantly by disease duration in placebo subgroups . Incidences of adverse events were unaffected by duration of disease at baseline . CONCLUSIONS : These data suggest that patients treated with certolizumab pegol 400 mg earlier rather than later , with a confirmed Crohn 's disease diagnosis , may achieve better treatment outcomes BACKGROUND & AIMS Patients with moderate to severe ileocolonic Crohn 's disease ( CD ) who received adalimumab induction and maintenance therapy  had greater rates of mucosal healing than patients who received placebo after adalimumab induction therapy in a 52-week trial ( EXTend the Safety and Efficacy of Adalimumab Through ENDoscopic Healing ) . We investigated whether this treatment also induced deep remission-a composite clinical and endoscopic end point . METHODS Rates of deep remission , defined as the absence of mucosal ulceration and CD Activity Index scores less than 150 , were compared between patients given continuous adalimumab  and those given only induction therapy followed by placebo .  We assessed the relationships between deep remission and other outcomes among patients who received adalimumab .  The outcomes of patients with deep remission were compared with those of patients with only the absence of mucosal ulceration or only clinical remission . RESULTS Rates of deep remission were 16 % in patients given adalimumab vs 10 % in those given placebo ( P = .34 ) at week 12 , and 19 % vs 0 % ( P < .001 ) at week 52 . Rates of deep remission were greatest among patients who received adalimumab and had CD for 2 years or less ( 33 % at weeks 12 and 52 ) . At week 52 , patients who achieved deep remission at week 12 required significantly fewer adalimumab treatment adjustments , hospitalizations , and CD-related surgeries ; had significantly less activity impairment ; and had better quality of life and physical function compared with patients not achieving deep remission . Deep remission generally was associated with better outcomes than only an absence of mucosal ulceration ; outcomes of patients with deep remission vs only clinical remission were similar . Deep remission was associated with estimated total cost savings of $ 10,360 ( from weeks 12 through 52 ) compared with lack of deep remission . CONCLUSIONS In an exploratory study of patients with moderate to severe ileocolonic CD who received adalimumab induction and maintenance therapy , patients achieving deep remission appeared to have better 1-year outcomes than those not achieving deep remission . These findings should be vali date d in large , prospect i ve trials . Clinical Trials.gov number : NCT00348283 Abstract Objective . Pediatric Crohn ’s disease ( CD ) is often debilitating , with upper gastrointestinal ( GI ) involvement and complications over time . Treatment with tumor necrosis factor ( TNF ) blockers can induce and maintain remission . We wanted to evaluate the outcome of patients medically treated for CD to investigate whether clinical , endoscopic and biochemical factors 
    Output:
    
Early biologic treatment is associated with improved clinical outcomes in both adult and paediatric CD patients , not only in prospect i ve clinical trials but also in real-world setting