Biological treatment approach to inflammatory bowel disease is similar in academic and nonacademic centres - prime time for decentralisation of inflammatory bowel disease care?

BACKGROUND: With the increasing number of inflammatory bowel disease (IBD) patients, it is difficult to manage them within specialised IBD teams in academic medical centres: many are therefore treated in nonacademic IBD centres. It is unclear whether the time to introducing biologics is the same in both settings. AIM: We aimed to compare treatment approach with biologics in academic vs. nonacademic centres. METHODS: We analysed Slovenian national IBD registry data (UR-CARE Registry, supported by the European Crohn's and Colitis Organisation), which included 2 academic (2319 patients) and 4 nonacademic IBD (429 patients) centres. RESULTS: The disease phenotype was similar in both settings. In total, 1687 patients received 2782 treatment episodes with biologics. We observed no differences in treatment episodes with TNF-alpha inhibitors (60% vs. 61%), vedolizumab (24% vs. 23%), or ustekinumab (17% vs. 16%) in academic compared to nonacademic centres (P = 0.949). However, TNF inhibitors were less often the first biologic in academic centres (TNF inhibitors: 67.5% vs. 74.0%, vedolizumab: 20.3% vs. 17.9%, ustekinumab: 12.1% vs. 8.1%; P = 0.0096). Consequently, more patients received ustekinumab (29.8% vs. 18.3%) and vedolizumab (17.4% vs. 13.5%) and fewer TNF inhibitors (52.7% vs. 68.2%) for Crohn's disease in academic compared to nonacademic centres, with no such differences for ulcerative colitis. The time to initiation of the first biologic from diagnosis was short and similar in both settings (11.3 vs. 10.4 months, P = 0.2). CONCLUSION: In this nationwide registry analysis, we observed that biological treatment choice was similar in academic and nonacademic settings. These findings support the decentralisation of IBD care.

Remission Is Maintained after Switch from Dose-Optimised Intravenous Treatment to Subcutaneous Treatment with Vedolizumab in Inflammatory Bowel Disease.

Background and Objectives: The subcutaneous (SC) formulation of vedolizumab has proven to be effective for the maintenance of remission after intravenous induction. Little is known about the efficacy of switching from intravenous maintenance treatment to SC. We aimed to assess the real-world efficacy of switching to SC treatment and to assess the impact of a baseline treatment regimen. Materials and Methods: In this observational cohort study, adult patients with inflammatory bowel disease who were switched to SC vedolizumab maintenance treatment were enrolled. Patients after intravenous induction and patients who switched from intravenous maintenance treatment (every 8 weeks or every 4 weeks) were included. The SC vedolizumab dosing was 108 mg every 2 weeks, regardless of the previous regimen. The clinical, biochemical, and endoscopic disease activity parameters and vedolizumab serum concentrations at the time of the switch and at the follow-up were assessed. Results: In total, 135 patients (38% Crohn's disease, 62% ulcerative colitis) were switched to SC vedolizumab treatment. The median time to the first follow-up (FU) was 14.5 weeks (IQR 12-26), and the median time to the second FU was 40 weeks (IQR 36-52). Nine patients (7%) discontinued SC vedolizumab treatment, with two-thirds of them discontinuing due to active disease. In all dosing regimens, there were no significant changes in the clinical scores and CRP at the baseline and first and second FUs. Clinical and biochemical remission appeared to be maintained irrespective of the previous dosing regimen. Conclusions: The results of this real-world study suggest that the maintenance of clinical and biomarker remission can be achieved in patients who switched from intravenous to SC vedolizumab. The baseline vedolizumab dosing regimen (every 4 weeks versus every 8 weeks) did not have an impact on outcomes.

Upadacitinib for the treatment of moderate-to-severe Crohn's disease.

Despite an increasing number of therapies for Crohn's disease (CD), half of patients do not respond to initial treatment or lose response over time, highlighting the need for novel therapies. Inhibition of Janus kinases (JAKs) has emerged as an important therapeutic target for CD. Upadacitinib is an orally administered selective JAK1 inhibitor, which is effective for the induction and maintenance of remission in moderately-to-severely active CD, including in patients with prior failure of biological therapy. Nonselective JAK inhibition has been associated with thromboembolic disease, cardiovascular events and malignancy in patients older than 50 years with rheumatoid arthritis and pre-existing cardiovascular risk factors, which should be considered upon prescription. Upadacitinib is the first and currently only oral advanced therapy for CD.

Not all patients with Crohn's disease (CD) get better with treatment. Blocking Janus kinases (JAKs), enzymes that promote inflammation in the gut, could help these patients. The treatment upadacitinib blocks JAK1 (an enzyme transmitting inflammatory signals) and decreases inflammation in the gut. It eases symptoms. It also resolves gut inflammation in patients with CD. Regarding side effects, JAK inhibitors can cause blood clots in veins, and in the lungs, heart attacks, cancer and infections. Further studies are needed, but caution is advised. Upadacitinib is the first advanced therapy for CD given by mouth.

Determining the optimal treatment target in patients with ulcerative colitis: rationale, design, protocol and interim analysis for the randomised controlled VERDICT trial.

INTRODUCTION: Symptoms, endoscopy and histology have been proposed as therapeutic targets in ulcerative colitis (UC). Observational studies suggest that the achievement of histologic remission may be associated with a lower risk of complications, compared with the achievement of endoscopic remission alone. The actiVE ulcerative colitis, a RanDomIsed Controlled Trial (VERDICT) aims to determine the optimal treatment target in patients with UC. METHODS AND ANALYSIS: In this multicentre, prospective randomised study, 660 patients with moderate to severe UC (Mayo rectal bleeding subscore [RBS] ≥1; Mayo endoscopic score [MES] ≥2) are randomly assigned to three treatment targets: corticosteroid-free symptomatic remission (Mayo RBS=0) (group 1); corticosteroid-free endoscopic remission (MES ≤1) and symptomatic remission (group 2); or corticosteroid-free histologic remission (Geboes score <2B.0), endoscopic remission and symptomatic remission (group 3). Treatment is escalated using vedolizumab according to a treatment algorithm that is dependent on the patient's baseline UC therapy until the target is achieved at weeks 16, 32 or 48. The primary outcome, the time from target achievement to a UC-related complication, will be compared between groups 1 and 3 using a Cox proportional hazards model. ETHICS AND DISSEMINATION: The study was approved by ethics committees at the country level or at individual sites as per individual country requirements. A full list of ethics committees is available on request. Study results will be disseminated in peer-reviewed journals and at scientific meetings. TRIAL REGISTRATION NUMBER: EudraCT: 2019-002485-12; NCT04259138.

Baseline Data and Measurement Instruments Reported In Observational Studies In Inflammatory Bowel Disease: Results From A Systematic Review.

BACKGROUND: Heterogeneity in demographic and outcomes data with corresponding measurement instruments (MI) creates barriers for data pooling and analysis. Several core outcome sets developed in inflammatory bowel disease (IBD) homogenise outcomes data. A parallel Minimum Data Set (MDS) for baseline characteristics is lacking. We conducted a systematic review to develop the first MDS. METHODS: A systematic review of observational studies from 3 databases (2000 to 2021). Titles and abstracts were screened; full-text articles reviewed, and data extracted by two reviewers. Baseline data were grouped into 10 domains: demographics, clinical features, disease behaviour/complications, biomarkers, endoscopy, histology, radiology, healthcare utilisation and patient-reported data. Frequency of baseline data and MI within respective domains are reported. RESULTS: From 315 included studies (600,552 subjects), most originated from Europe (196; 62%), and North America (59; 19%), and were published between 2011 and 2021 (251; 80%). The most frequent domains were demographics (311; 98.7%) and clinical (289; 91.7%); 224 (71.1%) studies reported on the triad of sex (306; 97.1%), age (289; 91.7%) and disease phenotype (231; 73.3%). Few included baseline data for radiology 19; 6%), healthcare utilisation (19; 6%) and histology (17; 5.4%). Ethnicity (19; 6%), race (17; 5.4%) and alcohol/drug consumption (6; 1.9%) were least reported demographics. From 25 MI for clinical disease activity, Harvey Bradshaw Index (n=53) and Mayo score (n=37) were most frequently used. CONCLUSIONS: Substantial variability exists in baseline population data reporting. These findings will inform a future consensus for MDS in IBD to enhance data harmonisation and credibility of real-world evidence.

Anti-drug antibodies against anti-TNF in patients with inflammatory bowel disease: an evaluation of possible strategies.

OBJECTIVE: Immunogenicity against anti-TNF antibodies usually leads to loss of response. We aimed to evaluate the efficacy of clinical strategies to improve clinical remission and pharmacokinetics upon detection of anti-drug antibodies (ADA). METHODS: Inflammatory bowel disease (IBD) patients with ADA against infliximab or adalimumab were identified through a single centre database search covering 2004-2022. Criteria for successful intervention upon ADA detection (baseline) were clinical remission after 1 year without further change in strategy. RESULTS: Two-hundred-and-fifty-five IBD patients (206 Crohn's disease) were identified. At baseline, median ADA level was 77 AU/ml; 50.2% of patients were in clinical remission. Implemented strategies were: (1) 81/255 (32%) conservative management, (2) 102/255 (40%) anti-TNF optimisation, (3) 72/255 (28%) switch within or out of class. Switching was the most successful strategy for clinical remission (from 19% at baseline to 69% at 1 year, p < 0.001). Patients that continued the same dose anti-TNF or discontinued biological therapy were often in clinical remission, but deteriorated significantly (-22.7%, p = 0.004). Anti-TNF dose intensification with immunomodulator optimisation was the fastest (median 3.0 months, p = 0.009) and most effective (65% ADA suppression, p < 0.001) strategy to suppress ADA compared to solely anti-TNF or immunomodulator optimisation. CONCLUSIONS: Switching therapy, within or out of class, is the most successful strategy to regain and maintain clinical remission upon immunogenicity. When switching to another anti-TNF, concomitant immunomodulatory therapy should be started or continued to prevent repeated immunogenic loss of response. Anti-TNF dose escalation with concomitant immunomodulator optimisation is the fastest and most effective strategy to suppress ADA.

Immunogenicity against anti-TNF antibodies is associated with loss of response in patients with inflammatory bowel diseases and remains a clinical challenge. We investigated potential therapeutic strategies in a retrospective patient cohort focusing on clinical efficacy and pharmacokinetics.

Performance of European and American Societies of Gastrointestinal Endoscopy Guidelines for Prediction of Choledocholithiasis in Patients with Acute Biliary Pancreatitis.

Background and Objectives: Up to one-third of patients with acute biliary pancreatitis also present with choledocholithiasis. Guidelines from the European Society of Gastrointestinal Endoscopy (ESGE) and the American Society for Gastrointestinal Endoscopy (ASGE) for investigating suspected choledocholithiasis suggest endoscopic retrograde cholangiopancreatography in patients with high-likelihood (ESGE)/high-probability (ASGE) predictors and endoscopic ultrasound in those with intermediate-likelihood (ESGE)/intermediate-probability (ASGE) predictors. Although both guidelines are similar, they are not identical. Furthermore, these algorithms were mainly developed from cohorts of patients without pancreatitis and are therefore poorly validated in a subset of patients with acute pancreatitis. We aimed to assess the performance of the ESGE and ASGE algorithms for the prediction of choledocholithiasis in patients with acute biliary pancreatitis. Materials and Methods: This was a retrospective analysis of 86 consecutive patients admitted to a tertiary referral centre in the year 2020 due to acute biliary pancreatitis. Results: Choledocholithiasis was confirmed in 29/86 (33.7%) of patients (13 with endoscopic retrograde cholangiopancreatography and 16 with endoscopic ultrasound). All 10/10 (100%) ESGE high-likelihood and 14/19 (73.7%) ASGE high-probability patients had choledocholithiasis. Only 19/71 (26.8%) patients with ESGE intermediate likelihood and 15/67 (22.4%) with ASGE intermediate probability had choledocholithiasis. Only 8/13 (61.5%) patients with the ASGE high-probability predictor of dilated common bile duct plus bilirubin > 68.4 µmol/mL had choledocholithiasis. Since this predictor is not considered high likelihood by ESGE, this resulted in a superior specificity of the European compared to the American guideline (100% vs. 91.2%). Following the American instead of the European guidelines would have resulted in five unnecessary endoscopic retrograde cholangiopancreatographies and five unnecessary endoscopic ultrasound examinations. Conclusions: This retrospective analysis suggests that the European guidelines may perform better than the American guidelines at predicting choledocholithiasis in the setting of acute pancreatitis. This was because dilated common bile duct plus bilirubin > 68.4 µmol/mL was not a reliable predictor for persistent bile duct stones.

Scoring indices for perianal fistulizing Crohn's disease: A systematic review.

BACKGROUND & AIMS: In this systematic review we summarize existing scoring indices for assessing disease activity and quality of life in perianal fistulizing Crohn's disease (PFCD) and highlight gaps in the literature. METHODS: MEDLINE, EMBASE, and CENTRAL were searched from 24 August 2022 to identify studies evaluating clinical, radiological, or patient-reported outcome measures (PROMS) in PFCD. The primary objective was to identify all available scoring indices and describe the operating properties of these indices. RESULTS: Fifty-three studies reported on the use of one clinical index (Perianal Disease Activity Index: PDAI), three PROMs and ten radiological indices. Twenty-five studies evaluated the operating properties of these indices. The PDAI demonstrated content validity, construct validity and responsiveness but criterion validity or reliability were not assessed. The Van Assche index (VAI), modified VAI and the Magnetic Resonance Index for Assessing Fistulas in Patients with CD (MAGNIFI-CD) were the most studied radiological indices. These indices demonstrated responsiveness and reliability. The VAI and MAGNIFI-CD demonstrated construct validity. Criterion and content validity and feasibility have not been assessed. Among the three PROMs, the Crohn's Anal Fistula Quality of Life index demonstrated content and construct validity, inter-observer reliability and responsiveness. Criterion validity, intra-observer reliability and feasibility have not been assessed for this index. CONCLUSIONS: There are no fully valid, reliable, and responsive clinical disease or radiological indices for PFCD. Although the radiological indices demonstrated responsiveness and reliability, well-defined cut-offs for response and remission are lacking. Future research should focus on establishing standardized definitions and thresholds for outcomes.

Early versus Late Use of Vedolizumab in Ulcerative Colitis: Clinical, Endoscopic, and Histological Outcomes.

BACKGROUND AND AIMS: We explored the potential for differential efficacy of vedolizumab between "early" and "late" ulcerative colitis (UC) with evaluation of clinical, endoscopic, and histological endpoints. METHODS: This was a multicentre, multinational open-label study in patients with moderately-to-severely active UC, defining "early" UC by a disease duration <4 years and bio-naïve and "late" UC by a disease duration >4 years and additional exposure to tumour necrosis factor antagonists. Patients received standard treatment with intravenous vedolizumab for 52 weeks (300 mg weeks 0-2-6, every 8 weeks thereafter without escalation). The primary endpoint was corticosteroid-free clinical remission with endoscopic improvement (total Mayo score ≤2 with no subscore >1) at both week 26 and 52. RESULTS: A total of 121 patients were included: in the "early" group 25/59 (42.4%) achieved the primary endpoint versus 19/62 (30.6%) in the "late" group (P = 0.18). There were no significant differences between the two groups in endoscopic improvement (week 26: "early" 32/59 [54.2%] vs. "late" 29/62 [46.8%]; P = 0.412; week 52: 27/59 [45.8%] vs. 25/62 [40.3%]; P = 0.546) or histological remission (Robarts Histopathology Index <3 without neutrophils in the epithelium and lamina propria) (week 26: 24/59 [40.7%] vs. 21/62 [33.9%]; P = 0.439; week 52: 22/59 [37.3%] vs. 22/62 [35.5%]; P = 0.837). CONCLUSIONS: No significant differences in clinical, endoscopic, and histological outcomes were observed between "early" and "late" disease.

Advanced Combination Treatment With Biologic Agents and Novel Small Molecule Drugs for Inflammatory Bowel Disease.

The use of combination therapy with a biologic agent and immunosuppressant has well-established efficacy and safety and is common practice in the management of inflammatory bowel disease (IBD). Current research has shifted focus toward the use of advanced combination treatment (ACT). This term was coined to describe combination therapy using 2 or more advanced treatments (biologic agents and/or oral small molecule drugs) with the aim of achieving optimal disease control in selected patients. An ACT approach may be particularly beneficial in patients with documented medically refractory IBD and in patients with a poor prognosis, extraintestinal manifestations, or concomitant immune-mediated inflammatory diseases. To date, the body of evidence for ACT strategies in IBD is largely comprised of uncontrolled retrospective case series and cohort studies in highly refractory patients. Recently, results from the VEGA trial have suggested that combination induction therapy with guselkumab and golimumab was more effective in ulcerative colitis than either agent alone. However, questions remain about issues such as related costs, ACT duration, and optimal combinations to adopt. Future randomized controlled trials are likely to evaluate rationally selected combinations of agents. This article summarizes the available literature on ACT, including comparisons with traditional combination therapy and the rheumatology field, and discusses practical recommendations, profiles of IBD patients who should be considered for combination approaches in clinical practice, and remaining knowledge gaps.

An unusual case of severe gastrointestinal bleeding.

We present the case of a 58-year-old female with a history of a bleeding duodenal peptic ulcer. Endoscopic hemostasis was unsuccessful; therefore, a transcatheter arterial embolization of a culprit vessel was performed. She was admitted to the hospital two months later because of obstruction of the common bile duct with cholangitis. Attempts to endoscopically place a biliary stent failed. The treating medical team opted for a surgical choledocho-jejunostomy. After 20 months, she presented with a melena and a severe anemia. Diagnostic work-up revealed portal vein thrombosis with portal cavernoma and bleeding choledocho-jejunostomy varices. The case presents and discusses rare complications of duodenal ulcer disease, as well as possible causes and treatment options.

A Comparison of Treatment Effect Sizes in Matched Phase 2 and Phase 3 Trials of Advanced Therapeutics in Inflammatory Bowel Disease: Systematic Review and Meta-Analysis.

INTRODUCTION: Phase 2 trials are fundamental to the rational and efficient design of phase 3 trials. We aimed to determine the relationship of treatment effect size estimates from phase 2 and phase 3 clinical trials on advanced therapeutics in inflammatory bowel disease. METHODS: MEDLINE, EMBASE, CENTRAL, and the Cochrane library were searched from inception to December 19, 2022, to identify paired phase 2 and 3 placebo-controlled induction studies of advanced therapeutics for Crohn's disease (CD) and ulcerative colitis (UC). Treatment effect sizes were expressed as a risk ratio (RR) between the active arm and placebo arm. For the same therapeutics, RRs from phase 2 trials were divided by the RR from phase 3 trial to quantify the relationship of effect sizes between phases. RESULTS: Twenty-two studies (9 phase 2 trials, 13 phase 3 trials) were included for CD and 30 studies (12 phase 2 trials, 18 phase 3 trials) for UC. In UC (pooled RR 0.72; 95% confidence interval: 0.58-0.86; RR <1 indicates smaller treatment effect sizes in phase 2 trials), but not CD (pooled RR 1.01; 95% confidence interval: 0.84-1.18), phase 2 trials systematically underestimated treatment effect sizes for the primary endpoint compared with phase 3 trials. The underestimation was observed for clinical, but not endoscopic, endpoints in UC. DISCUSSION: Treatment effect sizes for the primary and clinical endpoints were similar across clinical trial phases in CD, but not UC, where only endoscopic endpoints were comparable. This will help inform clinical development plans and future trial design.

Mirikizumab for the treatment of moderate to severe ulcerative colitis.

Despite a growing number of available therapeutic options for ulcerative colitis (UC), up to 50% of patients do not respond to initial treatment or lose response over time, highlighting the need for novel therapies. The IL-23 pathway has emerged as an important therapeutic target for UC. Mirikizumab is a humanized IgG4 monoclonal antibody against the p19 subunit of IL-23, dosed intravenously during induction and subcutaneously during maintenance. It is effective for the induction and maintenance of remission in moderately to severely active UC, including patients with prior failure of biological or tofacitinib therapy. Like other IL-23 antagonists, mirikizumab has a favorable safety profile. It is the first agent of its class to receive regulatory approval for moderately to severely active UC in Europe.

Despite a growing number of available therapeutic options for ulcerative colitis (UC), up to 50% of patients do not respond to initial treatment or lose response over time, highlighting the need for novel therapies. A molecule promoting inflammation in the colon called IL-23 is a promising target for new drugs that treat UC. Mirikizumab is an antibody that works against a portion of IL-23 and thus suppresses inflammation in the colon. Mirikizumab was shown to be effective in alleviating symptoms and resolving inflammation of the colon in patients with UC. The drug was safe and well tolerated by patients. Mirikizumab is the first drug of its kind to receive approval for UC in Europe.

Targeting IL-23 for IBD: Rationale and Progress to Date.

Inflammatory bowel disease, including Crohn's disease and ulcerative colitis, comprises multiple complex immune-mediated disorders. Early diagnosis and prompt disease control may prevent long-term complications and hospitalization. The therapeutic options have expanded in the last two decades, with the development of biologics and small molecules targeting specific pathways implicated in inflammatory bowel disease pathogenesis. The interleukin (IL)-23/Th-17 axis is one such example. Targeting IL-12/23 is effective for the treatment of both moderate-to-severe Crohn's disease and ulcerative colitis, and ustekinumab (an IL-12/23p40 antagonist) is approved for both indications. In patients with psoriasis, improved clinical outcomes were observed with agents that more selectively targeted IL-23 (IL-23p19 antagonists) compared with those that target both IL-12 and IL-23. Many specific IL-23p19 antagonists are currently being investigated in Crohn's disease and ulcerative colitis, and risankizumab has been recently approved for moderate-to-severely active Crohn's disease. In this review, we summarize the mechanisms of action and the evidence from clinical trials supporting the efficacy and safety of IL-23p19 antagonists for the treatment of inflammatory bowel disease.

Systematic review and meta-analysis of randomised controlled trials: Medical therapies for the treatment and prevention of pouchitis.

BACKGROUND AND AIMS: We conducted a systematic review to assess medical therapy for the treatment and prevention of pouchitis. METHODS: Randomised controlled trials (RCTs) of medical therapy in adults with or without pouchitis were searched to March 2022. Primary outcomes included clinical remission/response, maintenance of remission and prevention of pouchitis. RESULTS: Twenty RCTs (N = 830) were included. Acute pouchitis: One study compared ciprofloxacin with metronidazole. At 2 weeks, 100% (7/7) of ciprofloxacin participants achieved remission, compared with 67% (6/9) of metronidazole participants (RR: 1.44, 95% CI: 0.88-2.35, very low certainty evidence). One study compared budesonide enemas with oral metronidazole. Fifty percent (6/12) of budesonide participants achieved remission compared with 43% (6/14) of metronidazole participants (RR: 1.17, 95% CI: 0.51-2.67, low certainty evidence). Chronic pouchitis: Two studies (n = 76) assessed De Simone Formulation. Eighty-five percent (34/40) of De Simone Formulation participants maintained remission at 9-12 months compared with 3% (1/36) placebo participants (RR: 18.50, 95% CI: 3.86-88.56, moderate certainty evidence). One study assessed vedolizumab. Thirty-one percent (16/51) of vedolizumab participants achieved clinical remission at 14 weeks compared with 10% (5/51) of placebo participants (RR: 3.20, 95% CI: 1.27-8.08, moderate certainty evidence). PROPHYLAXIS: Two studies assessed De Simone Formulation. Ninety percent (18/20) of De Simone Formulation participants did not develop pouchitis compared with 60% (12/20) of placebo participants (RR: 1.50, 95% CI: 1.02-2.21, moderate certainty evidence). CONCLUSIONS: Apart from vedolizumab and the De Simone formulation, the effects of other medical interventions for pouchitis are uncertain.

Biopsies from ulcer edge yield higher histological activity scores than biopsies from non-ulcerated mucosa in active ulcerative colitis.

BACKGROUND: The appropriate location for biopsy collection in ulcerative colitis is unknown. OBJECTIVES: We aimed to determine the location for biopsy collection in the presence of ulcers which yields the highest histopathological score. DESIGN AND METHODS: This prospective cross-sectional study enrolled patients with ulcerative colitis and ulcers in the colon. Biopsy specimens were obtained at the edge of the ulcer; at a distance of one open forceps (7-8 mm) from the ulcer edge; at a distance of three open forceps (21-24 mm) from the ulcer edge; further referred to as locations 1, 2 and 3 respectively. Histological activity was assessed using Robarts Histopathology Index and the Nancy Histological Index. Statistical analysis was performed using mixed effects models. RESULTS: A total of 19 patients were included. Decreasing trends with distance from the ulcer edge ( P  < 0.0001) were observed. Biopsies procured from the edge of the ulcer (location 1) yielded a higher histopathological score compared to biopsies procured at locations 2 and 3 ( P  ≤ 0.001). CONCLUSION: Biopsies from the ulcer edge yield higher histopathological scores than biopsies next to the ulcer. In clinical trials with histological endpoints, biopsies should be obtained from the ulcer edge (if ulcers are present) to reliably assess histological disease activity.

Existing Bowel Preparation Quality Scales Are Reliable in the Setting of Centralized Endoscopy Reading.

BACKGROUND: Development of bowel preparation products has been based upon colon cleansing rating by a local endoscopist. It is unclear how bowel preparation scales perform when centrally evaluated. AIMS: To evaluate the reliability of bowel preparation quality scales when assessed by central readers. METHODS: Four central readers evaluated 52 videos in triplicate, 2 weeks apart, during the entire endoscopic procedure (insertion/withdrawal of the colonoscope) and exclusively on colonoscope withdrawal using the Boston Bowel Preparation Scale (BBPS), Chicago Bowel Preparation scale, Harefield Cleansing Scale, Ottawa Bowel Preparation Quality Scale (OBPQS), Aronchick score, a visual analogue scale, and additional items proposed in a modified Research and Development/University of California Los Angeles appropriateness process. Reliability was assessed with intraclass correlation coefficients. RESULTS: Intraclass correlation coefficients (95% confidence interval) for inter-rater reliability of the quality scales ranged from 0.51 to 0.65 (consistent with moderate to substantial inter-rater reliability) during the entire procedure. Corresponding intraclass correlation coefficients for intra-rater reliability ranged from 0.69 to 0.77 (consistent with substantial intra-rater reliability). Reliability was highest in the right colon and lowest in the left colon. No differences were observed in reliability when assessed for the procedure overall (insertion/withdrawal) relative to assessment on withdrawal alone. CONCLUSION: All five bowel preparation quality scales had moderate to substantial inter-rater reliability. Panelists considered the Aronchick score too simplistic for clinical trials and recognized that assessment of residual fluid in the Ottawa Bowel Preparation Quality Scale was not amenable to central assessment.