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Background and Aims Digital collection of patient-reported outcome measures [PROMs] is largely unexplored as a basis for follow-up for patients with ulcerative colitis [UC]. Our aim was to develop a model to predict the likelihood of escalation of therapy or intervention at an outpatient appointment that may be used to rationalize follow-up. Methods TrueColours-IBD is a web-based, real-time, remote monitoring software that allows longitudinal collection of ePROMs. Data for prediction modelling were derived from a Development Cohort, guided by the TRIPOD statement. Logistic regression modelling used ten candidate items to predict escalation of therapy or intervention. An Escalation of Therapy or Intervention [ETI] calculator was developed, and applied in a Validation Cohort at the same centre. Results The Development Cohort [ n  = 66] was recruited in 2016 and followed for 6 months [208 appointments]. From ten items, four significant predictors of ETI were identified: SCCAI, IBD Control-8, faecal calprotectin, and platelets. For practicality, a model with only SCCAI and IBD Control-8, both entered remotely by the patient, without the need for faecal calprotectin or blood tests was selected. Between 2018 and 2020, a Validation Cohort of 538 patients [1188 appointments] was examined. A 5% threshold on the ETI calculator correctly identified 343/388 [88%] escalations and 274/484 [57%] non-escalations. Conclusions A calculator based on digital, patient-entered data on symptoms and quality of life can predict whether a patient with UC requires escalation of therapy or intervention at an outpatient appointment. This may be used to streamline outpatient appointments for patients with UC. [ABSTRACT FROM AUTHOR]

Background Patient-reported outcome measures [PROMs] are key to documenting outcomes that matter most to patients and are increasingly important to commissioners of health care seeking value. We report the first series of the ICHOM Standard Set for Inflammatory Bowel Disease [IBD]. Methods Patients treated for ulcerative colitis [UC] or Crohn's disease [CD] in our centre were offered enrolment into the web-based TrueColours-IBD programme. Through this programme, e-mail prompts linking to validated questionnaires were sent for symptoms, quality of life, and ICHOM IBD outcomes. Results The first 1299 consecutive patients enrolled [779 UC, 520 CD] were studied with median 270 days of follow-up (interquartile range [IQR] 116, 504). 671 [52%] were female, mean age 42 years (standard deviation [sd] 16), mean body mass index [BMI] 26 [sd 5.3]. At registration, 483 [37%] were using advanced therapies. Median adherence to fortnightly quality of life reporting and quarterly outcomes was 100% [IQR 48, 100%] and 100% [IQR 75, 100%], respectively. In the previous 12 months, prednisolone use was reported by 229 [29%] patients with UC vs 81 [16%] with CD, p  <0.001; 202 [16%] for <3 months; and 108 [8%] for >3 months. An IBD-related intervention was reported by 174 [13%] patients, and 80 [6%] reported an unplanned hospital admission. There were high rates of fatigue [50%] and mood disturbance [23%]. Conclusions Outcomes reported by patients illustrate the scale of the therapeutic deficit in current care. Proof of principle is demonstrated that PROM data can be collected continuously with little burden on health care professionals. This may become a metric for quality improvement programmes or to compare outcomes. [ABSTRACT FROM AUTHOR]

Background and Aims Endoscopy and histopathology are pivotal for evaluating disease activity in ulcerative colitis [UC]; correlation between validated endoscopic and histological indices has not been examined. We aim to correlate the Ulcerative Colitis Endoscopic Index of Severity [UCEIS] with two new validated histological indices in patients with established UC. Methods This was a single-centre cohort of patients with established UC, who underwent flexible sigmoidoscopy or colonoscopy by a single endoscopist. The UCEIS was scored at the worst affected area in the distal colon, which was biopsied; histological disease activity using Nancy [NI] and Robarts' Histological [RHI] indices was scored by a pathologist blinded to the endoscopy. Spearman correlation between the UCEIS, NI, and RHI, and between NI and RHI, was performed. Results A total of 125 patients, median age 37 years [range 16–81 years], with UCEIS scores [scale 0–8]: 0, n = 21; 1–3, n = 48; 4–6, n = 51; and 7–8, n = 5, were included. Correlation coefficients between UCEIS and NI [scale 0–4] were r = 0.84 (95% confidence interval [CI] 0.76–0.89, p < 0.001) and between UCEIS and RHI [scale 0–33] r = 0.86 [95% CI 0.80–0.90, p < 0.001]. The difference in correlation was not significant [ p = 0.57]. There was excellent correlation between the two histological indices [r = 0.92, 95% CI 0.87–0.95, p < 0.001]. Quiescent disease activity defined as the absence of neutrophils [Nancy 0–1, Robarts 0–3] was most closely correlated with UCEIS = 0. Conclusions The UCEIS strongly correlates with both NI and RHI. Complete mucosal healing is best defined as a UCEIS = 0/8, since this correlates with the absence of microscopic disease activity. [ABSTRACT FROM AUTHOR]

Background and Aims: Vedolizumab, a humanised monoclonal antibody for the treatment of inflammatory bowel disease, selectively blocks gut lymphocyte trafficking. This may reduce the risk of respiratory tract infections [RTIs] compared with systemic immunosuppressive therapies. To assess this possibility, we evaluated the rates of RTIs in clinical trials of vedolizumab. Methods: Patient-level data from Phase 3 randomised controlled trials [RCTs] of vedolizumab in ulcerative colitis [UC; GEMINI 1] and Crohn’s disease [CD; GEMINI 2], and a long-term safety study [UC and CD] were pooled. Cox proportional hazards models were used to estimate the incidence of upper RTIs [URTIs] and lower RTIs [LRTIs] with adjustment for significant covariates. Results: In the RCTs [n = 1731 patients], the incidence of URTIs was numerically higher in patients receiving vedolizumab compared with those receiving placebo, although this difference was not statistically significant (38.7 vs 33.0 patients per 100 patient-years; hazard ratio [HR] 1.12; 95% confidence interval [CI]: 0.83–1.51; p = 0.463). The rate of LRTIs, including pneumonia, was numerically lower in the vedolizumab versus the placebo group: this difference was not statistically significant (7.7 vs 8.5 per 100 patient-years [HR 0.85; 95% CI: 0.48–1.52; p = 0.585]). Both URTIs and LRTIs were more frequent in patients with CD compared with UC. Most RTIs in patients receiving vedolizumab were not serious and did not require treatment discontinuation. Conclusions: Vedolizumab therapy was not associated with an increased incidence of respiratory tract infection compared with placebo. [ABSTRACT FROM AUTHOR]

Introduction: Patients with inflammatory bowel disease (IBD) undergoing polypectomy are recommended by current guidelines to have biopsies taken from adjacent mucosa to determine whether there is dysplasia present. With improvements in endoscopic imaging, it is now possible to characterize colonic lesions with higher levels of confidence than previously. We have reviewed the diagnostic yield of polyp-adjacent biopsies in IBD. Materials and Methods: A systematic search of our histopathology database revealed cases in which polyps had been endoscopically resected or biopsied in patients with IBD. Endoscopy reports and medical records were reviewed, and patient demographic and disease-specific details were recorded, along with details of polyp characteristics and histopathology outcomes. Results: Three hundred and two polyps were biopsied or resected in 131 patients undergoing 178 colonoscopies. The median polyp size was 4 mm (range 1-45), and the predominant morphology was Paris 0-Is (n = 98, 32%). The histology was tubular adenoma in 76 (25%), tubulovillous adenoma in 14 (5%), hyperplastic in 112 (37%), post-inflammatory in 32 (11%), sessile serrated polyp in 31 (10%), traditional serrated adenoma in 2 (0.7%), flat high-grade dysplasia or cancer in 2 (0.7%) and other in 33 (11%). Dysplasia in adjacent biopsies was detected in 2 patients (0.7%), and was endoscopically visible in both cases. The proportion of endoscopically unsuspected dysplasia was 0/300 (0%, 95% CI 0-1.6%). Conclusion: The diagnostic yield for polyp-adjacent biopsies in patients with IBD is negligible. With high-definition technology and chromoendoscopy, it may no longer be necessary to biopsy endoscopically normal adjacent tissue to detect invisible dysplasia. [ABSTRACT FROM AUTHOR]

Background and Aims: Early objective markers for failure of intravenous[iv] corticosteroid for acute severe colitis [ASC] can avoid delay in rescue therapy or colectomy. We investigated faecal calprotectin [FC], C-reactive protein [CRP], and endoscopy using the ulcerative colitis endoscopic index of severity [UCEIS] as predictors of steroid failure following intensive therapy of ASC. Methods: Consecutive patients with ASC satisfying Truelove and Witts' criteria, hospitalised at a single centre from May 2015 to November 2016, were included; all received iv corticosteroids. The primary outcome measure was steroid failure defined as colectomy and/or rescue therapy with ciclosporin or infliximab during admission. FC levels were measured at admission and on Day 3 of intensive therapy. UCEIS was scored at admission, and CRP on Day 3 of intensive therapy. Results: Of 49 patients, 21 [43%] failed iv corticosteroids and 15 [31%] underwent surgery. FC levels were significantly higher in steroid failures (2522 [590-9654] μg/g) compared with steroid responders (1530 [352-10 278] μg/g) at admission [p = 0.04], as well as on Day 3 of iv corticosteroid therapy (2718 [222-9175] μg/g vs 727 [218-4062] μg/g, p = 0.001). Steroid failures had a higher median [range] UCEIS score than responders (6 [4-8] vs 5 [4-7] [p = 0.001]). CRP level did not differ significantly between steroid failures and responders. A UCEIS > 6 at admission and FC > 1000 μg/g on Day 3 were independent predictors of steroid failure and need for rescue therapy/colectomy. Conclusions: All patients with UCEIS > 6 and Day 3 FC > 1000 μg/g failed iv corticosteroids. The UCEIS score on admission and Day 3 FC are early predictors of failure of ivcorticosteroid therapy. [ABSTRACT FROM AUTHOR]

Background and Aims: Histological remission and low faecal calprotectin are positive prognostic factors in ulcerative colitis [UC]. Intramucosal calprotectin [iMC], which can be readily determined by immunohistochemistry, has not so far been evaluated as a predictor of outcome in UC. We aimed to investigate the relationship between iMC and clinical, endoscopic, and histological measures of remission in UC, and the independent prognostic value of iMC. Methods: Ambulant patients with UC were recruited for a study comparing clinical activity indices. Sigmoidoscopy and biopsy were performed at the index visit. Clinical, endoscopic, and histological activity were scored and iMC semi-quantitatively measured using immunohistochemistry for the S100A8/9 heterodimer on colonic biopsies, scored as the mean number of positive cells in five high-power fields [HPF]. At the end of follow-up [6 years], data on steroid use, hospitalisation, and colectomy ['adverse outcomes'] were collected. Results: iMC was determined in 83 patients and 20 controls, and correlated with clinical, endoscopic, and histological activity [r = 0.51, 0.65, 0.53, p > 0.001, respectively]. iMC was lowest (median 2.4, interquartile range [IQR]: 5.2-5, p < 0.001) in patients with concordance between clinical, endoscopic, and histological remission. Median iMC > 5/HPF was associated with adverse outcome (hazard ratio [HR] 3.36, confidence interval [CI] 1.58, 7.15, p < 0.001). Only 53%, 33%, and 25% of patients in histological remission with iMC > 5 cells/HPF avoided an adverse outcome after 1, 3, and 6 years, respectively. Conclusions: iMC was lowest in patients with concordant clinical, endoscopic, and histological remission. Median iMC > 5/HPF was associated with adverse outcomes despite histological remission. Therefore iMC is a potentially useful independent marker of activity. [ABSTRACT FROM AUTHOR]

Background and Aims: Acute severe colitis [ASC] is associated with major morbidity. We aimed to develop and externally validate an index that predicted ASC within 3 years of diagnosis. Methods: The development cohort included patients aged 16-89 years, diagnosed with ulcerative colitis [UC] in Oxford and followed for 3 years. Primary outcome was hospitalization for ASC, excluding patients admitted within 1 month of diagnosis. Multivariable logistic regression examined the adjusted association of seven risk factors with ASC. Backwards elimination produced a parsimonious model that was simplified to create an easy-to-use index. External validation occurred in separate cohorts from Cambridge, UK, and Uppsala, Sweden. Results: The development cohort [Oxford] included 34/111 patients who developed ASC within a median 14 months [range 1-29]. The final model applied the sum of 1 point each for extensive disease, C-reactive protein [CRP] > 10 mg/l, or haemoglobin < 12 g/dl F or < 14 g/dl M at diagnosis, to give a score from 0/3 to 3/3. This predicted a 70% risk of developing ASC within 3 years [score 3/3]. Validation cohorts included different proportions with ASC [Cambridge = 25/96; Uppsala = 18/298]. Of those scoring 3/3 at diagnosis, 18/18 [Cambridge] and 12/13 [Uppsala] subsequently developed ASC. Discriminant ability [c-index, where 1.0 = perfect discrimination] was 0.81 [Oxford], 0.95 [Cambridge], 0.97 [Uppsala]. Internal validation using bootstrapping showed good calibration, with similar predicted risk across all cohorts. A nomogram predicted individual risk. Conclusions: An index applied at diagnosis reliably predicts the risk of ASC within 3 years in different populations. Patients with a score 3/3 at diagnosis may merit early immunomodulator therapy. [ABSTRACT FROM AUTHOR]

Background and Aims: To determine whether clinical information influences endoscopic scoring by central readers using the Ulcerative Colitis Endoscopic Index of Severity [UCEIS; comprising 'vascular pattern', 'bleeding', 'erosions and ulcers']. Methods: Forty central readers performed 28 evaluations, including 2 repeats, from a library of 44 video sigmoidoscopies stratified by Mayo Clinic Score. Following training, readers were randomised to scoring with ['unblinded', n = 20, including 4 control videos with misleading information] or without ['blinded', n 20] clinical information. A total of 21 virtual Central Reader Groups [CRGs], of three blinded readers, were created. Agreement criteria were pre-specified. Kappa [κ] statistics quantified intra- and inter-reader variability. Results: Mean UCEIS scores did not differ between blinded and unblinded readers for any of the 40 main videos. UCEIS standard deviations [SD] were similar [median blinded 0.94, unblinded 0.93; p = 0.97]. Correlation between UCEIS and visual analogue scale [VAS] assessment of overall severity was high [r blinded = 0.90, unblinded = 0.93; p = 0.02]. Scores for control videos were similar [UCEIS: p ≥ 0.55; VAS: p ≥ 0.07]. Intra- [κ 0.47-0.74] and inter-reader [κ 0.40-0.53] variability for items and full UCEIS was 'moderate'-to-'substantial', with no signifcant differences except for intra-reader variability for erosions and ulcers [κ blinded: 0.47 vs unblinded: 0.74; p 0.047]. The SD of CRGs was lower than for individual central readers [0.54 vs 0.95; p < 0.001]. Correlation between blinded UCEIS and patient-reported symptoms was high [stool frequency: 0.76; rectal bleeding: 0.82; both: 0.81]. Conclusions: The UCEIS is minimally affected by knowledge of clinical details, strongly correlates with patient-reported symptoms, and is a suitable instrument for trials. CRGs performed better than individuals. [ABSTRACT FROM AUTHOR]