Use of the noninvasive components of the mayo score to assess clinical response in Ulcerative Colitis Coated mesalazine (5-aminosalicylic acid) versus sulphasalazine in the treatment of active ulcerative colitis: a randomised trial. 5-Aminosalicylic acid enema in the treatment of distal ulcerative colitis, proctosigmoiditis, and proctitis. Fecal Calprotectin in Assessing Endoscopic and Histological Remission in Patients with Ulcerative Colitis Cyclosporine in severe ulcerative colitis refractory to steroid therapy. Clinical application of faecal calprotectin in ulcerative colitis patients Clinical Activity and Quality of Life Indices Are Valid Across Ulcerative Colitis But Not Crohn’s Disease Phenotypes Clinical, biological, and histologic parameters as predictors of relapse in ulcerative colitis. Development, validation, and evaluation of a pediatric ulcerative colitis activity index: a prospective multicenter study. Ulcerative colitis: Correlation of the Rachmilewitz endoscopic activity index with fecal calprotectin, clinical activity, C‐reactive protein, and blood leukocytes Coated oral 5-aminosalicylic acid therapy for mildly to moderately active ulcerative colitis. A randomized study. Validation of the ulcerative colitis colonoscopic index of severity and its correlation with disease activity measures. Evaluation of disease activity in IBD at the time of diagnosis by the use of clinical, biochemical, and fecal markers
Background : The Mayo score and a noninvasive 9‐point partial Mayo score are used as outcome measures for clinical trials assessing therapy for ulcerative colitis ( UC ) . There are limited data assessing what defines a clinical ly relevant change in these indices . We sought to assess what constitutes a clinical ly meaningful change in these indices using data from a recently completed placebo‐controlled clinical trial . Methods : In all , 105 patients were enrolled in a 12‐week r and omized , placebo‐controlled trial assessing rosiglitazone for treatment of mild to moderate UC . We compared the change in  the Mayo score , the partial Mayo score , and a 6‐point score composed just of the stool frequency and bleeding components of the Mayo score to the patient 's perception of disease activity at week 0 and week 12 . Optimal cutpoints were calculated as the maximal product of sensitivity and specificity . Results : Each index was strongly correlated with the patient 's rating of disease activity at week 12 ( Spearman correlations 0.61–0.71 , P < 0.0001 for all correlations ) . The maximal product of sensitivity and specificity to identify patient reported improvement of disease activity was achieved using cutpoints for change of 2.5 for the Mayo score ( sensitivity 88 % , specificity 80 % ) , 2.5 for the partial Mayo score ( sensitivity 88 % , specificity 87 % ) , and 1.5 for the 6‐point score ( sensitivity 88 % , specificity 80 % ) . Conclusions : The partial Mayo score and the 6‐point score composed solely of the stool frequency and bleeding components performed as well as the full Mayo score to identify patient perceived clinical response OBJECTIVE --To assess the safety and efficacy of a preparation of mesalazine ( 5-aminosalicylic acid ) coated with a pH dependent resin ( Eudragit L ) as compared with sulphasalazine in patients with active mild to moderate ulcerative colitis . DESIGN --Eight week r and omised double blind parallel group study . SETTING --Forty six gastroenterology outpatient clinics in seven countries . PATIENTS --Two hundred and twenty patients aged 18 - 70 who met the following criteria : clinical activity index greater than or equal to 6 and endoscopic index greater than or equal to 4 ; no concomitant treatment for ulcerative colitis ; no hypersensitivity to salicylates or sulphonamides . Of the 164 patients eligible for efficacy analysis , 87 received the coated preparation of mesalazine and 77 sulphasalazine . Most of the remaining patients ( 28 in each group ) were ineligible for the efficacy analysis because of treatment with steroid enemas . All pretrial characteristics were comparable in the two treatment groups . INTERVENTIONS --Coated mesalazine ( Mesasal ) 1.5 g daily or sulphasalazine 3.0 g daily for eight weeks . Compliance monitored by pill counts . END POINT-- Clinical and endoscopic remission . MEASUREMENTS AND MAIN RESULTS -- Clinical activity measured by daily diary cards , assessment by investigators , and laboratory findings . Endoscopic evaluation at week 8 . After four weeks 50 of 70 patients ( 71 % ) taking coated mesalazine and 38 of 58 ( 66 % ) taking sulphasalazine had achieved remission of their disease by eight weeks remission rates were 74 % ( 37/50 patients ) and 81 % ( 35/43 ) in the two treatment groups respectively . Endoscopic remission at eight weeks was recorded in 20 of 41 patients ( 49 % ) taking coated mesalazine and 18 of 38 ( 47 % ) taking sulphasalazine . There was a higher incidence of adverse events among patients taking sulphasalazine ( 25/105 ; 24 % ) than among those taking coated mesalazine ( 16/115 ; 14 % ) . CONCLUSION --Mesalazine coated with Eudragit L is a safe , logical alternative to sulphasalazine The efficacy and safety of 4-g 5-aminosalicylic acid enemas were assessed in 153 patients with ulcerative colitis involving up to 50 cm of distal colon . Seventy-six patients received active medication and 77 received a placebo .  There were 20 dropouts ( 6 in the active group and 14 in the placebo group ) during the study because of insufficient efficacy . After 6 wk of therapy , 48 of the 76 patients ( 63 % ) receiving 5-aminosalicylic acid were considered to be " much improved " by the study physician compared to 22 of the 77 patients ( 29 % ) on placebo ( p = 0.001 ) . A disease activity index based on patient symptoms and sigmoidoscopic appearance was used to assess efficacy . Mean disease activity index declined 55 % for patients on 5-aminosalicylic acid and 24 % for patients on placebo ( p = 0.0001 ) . Analysis of subgroups indicated that patients most likely to respond were those with disease confined to the 20 - 40 cm from the anus . Response was not affected by concurrent sulfasalazine , but patients requiring concurrent oral steroids had a diminished response . Rapid onset of efficacy was shown by a significant reduction in rectal bleeding within 3 days of treatment initiation . 5-Aminosalicylic acid enemas are well tolerated and are of benefit in the treatment of ulcerative colitis confined to the distal colon Background Persistent active endoscopic and histological inflammation is associated with poorer outcomes in ulcerative colitis ( UC ) . Fecal calprotectin is a surrogate marker of endoscopic and histological remission . Aims To confirm the correlation between fecal calprotectin and endoscopic or histological disease activity and to define the optimal cutoff value to detect endoscopic and histological remission . Methods From a prospect ively maintained data base , we analyzed 61 UC patients who had fecal calprotectin measurement and endoscopy performed within 1 month .  Endoscopic activity was grade d using the Mayo endoscopic subscore ( MES ) . Histological remission was defined as normal histology or quiescent histological activity . Results Eighteen patients ( 29.5 % ) and five patients ( 8.1 % ) had endoscopic remission defined as MES ≤ 1 or MES = 0 , respectively . We observed a significantly lower median level of fecal calprotectin in patients with endoscopic remission than those with endoscopic activity for both definition of endoscopic remission , i.e. , MES ≤ 1 ( 158 vs 490 µg/g , p = 0.0005 ) or MES = 0 ( 94 vs 414 µg/g , p = 0.013 ) . Seven patients ( 11.5 % ) were in histological remission . They had a lower median level of fecal calprotectin than those with active histological inflammation ( 107 vs 416 µg/g , p = 0.016 ) . Using a ROC curve , fecal calprotectin < 250 µg/g predicted endoscopic remission ( MES ≤ 1 ) with a sensitivity of 67 % and specificity of 77 % , while fecal calprotectin < 200 µg/g predicted histological remission with a sensitivity of 71 % and specificity of 76 % . Conclusion Fecal calprotectin level correlated with both endoscopic activity and histological activity and is a reliable biomarker in assessing mucosal healing in UC BACKGROUND There has been no new effective drug therapy for patients with severe ulcerative colitis since corticosteroids were introduced almost 40 years ago . In an uncontrolled study , 80 percent of 32 patients with active ulcerative colitis refractory to corticosteroid therapy had a response to cyclosporine therapy . METHODS We conducted a r and omized , double-blind , controlled trial in which cyclosporine ( 4 mg per kilogram of body weight per day ) or placebo was administered by continuous intravenous infusion to 20 patients with severe ulcerative colitis whose condition had not improved after at least 7 days of intravenous corticosteroid therapy .  A response to therapy was defined as an improvement in a numerical symptom score ( 0 indicated no symptoms , and 21 severe symptoms ) leading to discharge from the hospital and treatment with oral medications . Failure to respond to therapy result ed in colectomy , but some patients in the placebo group who had no response and no urgent need for surgery were subsequently treated with cyclosporine . RESULTS Nine of 11 patients ( 82 percent ) treated with cyclosporine had a response within a mean of seven days , as compared with 0 of 9 patients who received placebo ( P < 0.001 ) . The mean clinical -activity score fell from 13 to 6 in the cyclosporine group , as compared with a decrease from 14 to 13 in the placebo group . All five patients in the placebo group who later received cyclosporine therapy had a response . CONCLUSIONS Intravenous cyclosporine therapy is rapidly effective for patients with severe corticosteroid-resistant ulcerative colitis Objective Faecal calprotectin ( FC ) is the most relevant noninvasive biomarker for monitoring inflammatory status , response to treatment and for predicting clinical relapse in ulcerative colitis ( UC ) . The aim of this study was to evaluate the role of FC in predicting both clinical /endoscopic activity and clinical relapse in a large UC patient cohort . Patients and methods A two-phase prospect i ve study was carried out . In the first phase , the relationship between FC and clinical /endoscopic activity was evaluated . In the second phase , a cohort of asymptomatic patients with endoscopic mucosal healing was followed up using clinical and FC level determinations . Results One hundred and twenty-one UC patients were enrolled . The  FC concentrations were directly correlated with both clinical and endoscopic activity ( r=0.76 and 0.87 , respectively , P<0.05 ) and were capable of differentiating between different degrees of endoscopic severity ( P<0.01 ) . An FC cut-off value of 110 & mgr;g/g was highly predictive ( 95 % ) of endoscopic activity . Seventy-four patients in clinical remission with mucosal healing were followed up for a year or until relapse and 27 % developed a clinical relapse . The  FC concentration of nonrelapsed patients ( 48 & mgr;g/g ) versus relapsed patients ( 218 & mgr;g/g ) was significantly different ( P<0.01 ) . An FC cut-off value of 193 & mgr;g/g had an accuracy of 89 % in predicting clinical relapse . High FC levels were associated with clinical relapse using survival analysis and multivariate analysis . Conclusion Our data strongly support the use of FC for staging the activity of disease , predicting relapse and leading decision-making in a UC setting Background  Clinical activity and quality of life ( QOL ) indices assess disease activity in Crohn ’s disease ( CD ) and ulcerative colitis ( UC ) . However , a paucity of data exists on the validity of these indices according to disease characteristics . Aims To examine the correlation between QOL and clinical activity indices and endoscopic disease activity according to disease characteristics . Methods We used a prospect i ve registry to identify CD and UC patients ≥18 years old with available information on Short Inflammatory Bowel Disease Question naire scores ( SIBDQ ) , Harvey – Bradshaw Index ( HBI ) and simple endoscopic scores for CD ( SES-CD ) , and Simple Clinical Colitis Activity Index ( SCCAI ) and Mayo endoscopic score for UC . We used Spearman rank correlations to calculate correlations between indices and Fisher transformation to compare correlations across disease characteristics . Results Among 282 CD patients , we observed poor correlation between clinical activity and QOL indices to SES-CD with no differences in correlation according to disease characteristics . Conversely , among 226 UC patients  , clinical activity and QOL had good correlation to Mayo endoscopic score ( r = 0.55 and −0.56 , respectively ) with better correlations observed with left-sided versus extensive colitis ( r = 0.73 vs. 0.45 , p = 0.005 ) and shorter duration of disease ( r = 0.61 vs. 0.37 , p = 0.04 ) . Conclusions Our data suggest good correlation between SCCAI and endoscopic disease activity in UC , particularly in left-sided disease . Poor correlations between HBI or SIBDQ and SES-CD appear to be consistent across different disease phenotypes BACKGROUND & AIMS Ulcerative colitis ( UC ) is a chronic relapsing inflammatory bowel disease . We aim ed to assess whether clinical , biological , and histologic parameters in quiescent UC predict time to clinical relapse . METHODS Seventy-four patients with clinical ly and endoscopically determined inactive UC were followed up for 1 year or for a shorter period if they had a relapse .  Serum erythrocyte sedimentation rate ; C-reactive protein , interleukin (IL)-1beta , IL-6 , and IL-15 values ; anti-neutrophil cytoplasmic antibody titers ; and rectal biopsy specimens  were obtained at baseline , at 6 and 12 months , and /or at relapse . Multivariate survival analysis was performed to determine independent predictors of clinical relapse . RESULTS Twenty-seven patients relapsed  ( 19/42 women ; 8/32 men ) . Multivariate Cox regression analysis retained younger age ( P = 0.003 ; hazard ratio , 0.4 per decade ) , greater number of prior relapses in women ( P < 0.001 ; hazard ratio , 1.6 per prior relapse ) , and basal plasmacytosis ( P = 0.003 ; hazard ratio , 4.5 ) on rectal biopsy specimens as predictors of shorter time to clinical relapse . Kaplan-Meier survival curves showed the 20 - 30-year-old age group and women with more than 5 prior relapses to be groups with shorter times to relapse . CONCLUSIONS Younger age , multiple previous relapses ( for women ) , and basal plasmacytosis on rectal biopsy specimens were independent predictors of earlier relapse . These findings may help identify patients with inactive UC who will require optimal maintenance medical therapy BACKGROUND AND AIMS Colonoscopic appearance , the primary measure of disease activity in adult ulcerative colitis , is less acceptable to children . Our aim was to develop a noninvasive activity index of pediatric ulcerative colitis . METHODS Item selection was performed judgmentally using a Delphi group of 36 experts in pediatric inflammatory bowel disease . Item weighting was performed by regression modeling using a prospect i ve cohort of 157 pediatric ulcerative colitis patients . Validation was assessed on a separate prospect i ve cohort of 48 children with ulcerative colitis undergoing complete colonoscopy .  Responsiveness was evaluated at a follow-up visit of 75 children using effect size statistics and diagnostic utility approaches . RESULTS A list of 41 items was generated and reduced to 11 by rank order . Two physicians completed the  Pediatric Ulcerative Colitis Activity Index ( PUCAI ) on each of the patients in the weighting cohort . Six clinical items were significant in the regression analysis ; the laboratory items and an endoscopic appearance item did not improve the PUCAI performance . In the validation cohort , the PUCAI was highly correlated with the Physician 's Global Assessment ( r = 0.91 , P < .001 ) , Mayo score ( r = 0.95 , P < .001 ) , and colonoscopic appearance ( r = 0.77 , P < .001 ) . Correlations were higher than 2 noninvasive adult indices calculated concurrently . Interobserver and test-retest reliability were excellent ( intraclass correlation coefficient = 0.95 ; 95 % CI : 0.93 - 0.97 ) . Cut-off points were established using receiver operator characteristic curves on the full cohort . Excellent responsiveness was found at repeated visits ( effect size = 1.9 , area under the receiver operator characteristic curve = 0.97 ) . CONCLUSIONS The rigorously developed PUCAI is a noninvasive , valid , highly reliable , and responsive index with which to assess disease activity in pediatric ulcerative colitis Background : The accuracy of noninvasive markers for the detection of endoscopically active ulcerative colitis ( UC ) according the Rachmilewitz Score is so far unknown . The aim was to evaluate the correlation between endoscopic disease activity and fecal calprotectin , Clinical Activity Index , C‐reactive protein ( CRP ) , and blood leukocytes . Methods : UC patients undergoing colonoscopy  were prospect ively enrolled and scored independently according the endoscopic and clinical part of the Rachmilewitz Index . Patients and controls provided fecal and blood sample s for measuring calprotectin , CRP , and leukocytes . Results : Values in UC patients ( n = 134 ) compared to controls ( n = 48 )  : calprotectin : 396 ± 351 versus 18.1 ± 5 μg/g , CRP 16 ± 13 versus 3 ± 2 mg/L , blood leukocytes 9.9 ± 3.5 versus 5.4 ± 1.9 g/L ( all P < 0.001 ) . Endoscopic disease activity correlated closest with calprotectin ( Spearman 's rank correlation coefficient r = 0.834 ) , followed by Clinical Activity Index ( r = 0.672 ) , CRP ( r = 0.503 ) , and leukocytes ( r = 0.461 ) . Calprotectin levels were significantly lower in UC patients with inactive disease ( endoscopic score 0‐3 , calprotectin 42 ± 38 μg/g ) , compared to patients with mild ( score 4‐6 , calprotectin 210 ± 121 μg/g , P < 0.001 ) , moderate ( score 7‐9 , calprotectin 392 ± 246 μg/g , P = 0.002 ) , and severe disease ( score 10‐12 , calprotectin 730 ± 291 μg/g , P < 0.001 ) . The overall accuracy for the detection of endoscopically active disease ( score ≥4 ) was 89 % for calprotectin , 73 % for Clinical Activity Index , 62 % for elevated CRP , and 60 % for leukocytosis . Conclusions : Fecal calprotectin correlated closest with endoscopic disease activity , followed by Clinical Activity Index , CRP , and blood leukocytes . Furthermore , fecal calprotectin was the only marker that reliably discriminated inactive from mild , moderate , and highly active disease , which emphasizes its usefulness for activity monitoring . Inflamm Bowel Dis We assessed oral 5-aminosalicylic acid ( 5-ASA ) prepared with a pH-sensitive polymer coating in 87 patients with mildly to moderately active ulcerative colitis in a double-blind , placebo-controlled trial . Patients were r and omly assigned to receive 5-ASA at a dosage of either 4.8 or 1.6 g per day or placebo for six weeks . The outcome was monitored by flexible proctosigmoidoscopic examinations and physicians ' assessment s at three-week intervals and by patients ' recordings of daily symptoms . Results showed 24 percent complete and 50 percent partial responses in those receiving 4.8 g of 5-ASA per day as compared with 5 percent complete and 13 percent partial responses in those receiving placebo ( P less than 0.0001 , rank-sum test ) . At a dosage of 1.6 g per day , the response was twice as good as with placebo , but the difference did not reach statistical significance ( P = 0.51 ) . Age , sex , duration of disease , duration of active symptoms , or extent of disease did not affect the clinical outcome . We conclude that oral 5-ASA administered in a dosage of 4.8 g per day is effective therapy , at least in the short term , for mildly to moderately active ulcerative colitis BACKGROUND & AIMS Endoscopic healing is likely to become an important goal for treatment of patients with ulcerative colitis ( UC ) . A simple vali date d endoscopic index is needed . We vali date d the previously developed UC Colonoscopic Index of Severity ( UCCIS ) . METHODS In a prospect i ve study , 50 patients with UC were examined by colonoscopy ;  we analyzed videos of rectum and sigmoid , descending , transverse , and cecum/ascending colon .  Eight gastroenterologists blindly rated 4 mucosal lesions ( for vascular pattern , granularity , friability , ulceration ) and severity of damage to each segment and overall . The global assessment of endoscopic severity ( GAES ) was based on a 4-point scale and 10-cm visual analogue scale . Correlation of the UCCIS score with clinical indexes ( clinical activity index and simple clinical colitis activity index ) , patient-defined remission , and laboratory measures of disease activity ( levels of C-reactive protein , albumin , and hemoglobin and platelet counts ) were estimated by using the Pearson ( r ) or Spearman ( r(s ) ) method . RESULTS Interobserver agreement was good to excellent for the 4 mucosal lesions evaluated by endoscopy and the GAES . The UCCIS calculated for our data accounted for 74 % ( R(2 ) = 0.74 ) and 80 % ( R(2 ) = 0.80 ) of the variation in the GAES and visual analogue scores , respectively ( P < .0001 ) . The UCCIS also correlated with clinical activity index ( r = 0.52 , P < .001 ) , simple clinical colitis activity index ( r = 0.62 , P < .0001 ) , and patient-defined remission ( r = 0.43 , P < .01 ) . The UCCIS also correlated with levels of C-reactive protein ( r(s ) = 0.56 , P < .001 ) , albumin ( r = -0.55 , P < .001 ) , and hemoglobin ( r = -0.39 , P < .01 ) . A rederivation of the equation for the UCCIS by using the data from a previous study combined with those of the current study ( n = 101 ) yielded similar results . CONCLUSIONS The UCCIS is a simple tool that provides reproducible results in endoscopic scoring of patients with UC Abstract Objective . The present population based adult cohort was part of a new prospect i ve study of patients with inflammatory bowel disease ( IBD ) in South-Eastern Norway , the Inflammatory Bowel South-Eastern Norway II study , investigating disease characteristics in an attempt to improve our knowledge regarding factors related to early clinical phenotype and disease activity . Material and methods . Patients suspected to have IBD on the basis of predefined symptoms , including abdominal pain , diarrhea , and /or blood in stool for more than 10 days were examined at the local hospital .  Colonoscopy with biopsies was performed and blood and stool sample s were taken . Results . In ulcerative colitis ( UC ) patients , the median Simple Clinical Colitis Activity Index ( SCCAI ) was 4 ( range 0–10 ) in mild and 6 ( range 0–14 ) in patients with moderate or severe endoscopic activity of inflammation ( p = 0.002 ) . The calprotectin concentration in feces was significantly related to the SCCAI ( p = 0.034 ) and the Mayo endoscopic subscore ( p = 0.031 ) . There was a significant association between the C-reactive protein ( CRP ) value , leucocytes and thrombocytes and the SCCAI , but only leucocytes were significantly associated with the Mayo endoscopic subscore . In Crohn 's disease ( CD ) patients , there was no statistical significant association between the Harvey-Bradshaw Index ( HBI ) and the endoscopic grade of mucosal inflammation ( p = 0.8 ) . The calprotectin concentration in feces was significantly related to the endoscopic activity score ( p = 0.004 ) , but not to the HBI ( p = 0.5 ) . HBI was significantly related to the CRP value ( p = 0.047 ) and thrombocytes ( p = 0.03 ) . Conclusions . In UC , both biochemical and fecal markers are related to disease activity and extent of disease , whereas in CD , the fecal calprotectin concentration is a reliable marker of mucosal affection , but not for systemic disease activity
BACKGROUND & AIMS Optimal management of patients with ulcerative colitis ( UC ) requires assessment of disease activity-usually by endoscopy , which is invasive , costly , and not risk free .
We performed a systematic review to determine whether clinical symptoms correlate with findings from endoscopy assessment s of patients with UC .