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Background and aimsDespite increasing interest in histologic remission as a treatment target in ulcerative colitis (UC), the accuracy of histologic findings in left colon in detecting pancolonic histologic remission is unknown.MethodsIn a retrospective cohort study of patients with endoscopically active pancolitis undergoing treat-to-target interventions, we evaluated the diagnostic accuracy of left-sided (distal to splenic flexure) histologic and endoscopic findings on colonoscopy for detecting histologic and endoscopic healing elsewhere in the colon.ResultsOf 86 patients with moderate to severely active pancolitis who underwent 2 consecutive colonoscopies during treat-to-target interventions, 38% and 51% achieved histologic and endoscopic remission, respectively. Substantial agreement (kappa, 0.67; 95% confidence interval (CI), 0.51-0.83) was observed in histologic findings between left and right colon on follow-up colonoscopy. Histologic, and endoscopic, findings in left colon showed excellent accuracy in detecting pancolonic histologic remission (area under the curve (AUC), 0.96 [95% CI, 0.93-1.0]; misclassification rate, 5.9%), histologic normalization (AUC, 1.0, 0%), endoscopic improvement (AUC, 0.95 [0.96-1.0], 3.5%) and endoscopic remission (AUC, 0.98 [0.96-1.00], 5.8%), respectively.ConclusionsIn patients with active pancolitis undergoing treat-to-target interventions, histologic and endoscopic findings in the left colon on colonoscopy have excellent accuracy for detecting pancolonic histologic remission, histologic normalization, endoscopic improvement, and endoscopic remission. Flexible sigmoidoscopy may suffice for monitoring histologic and endoscopic activity in patients with pancolitis.

Background & aimsHospitalized patients with acute severe ulcerative colitis (ASUC) often require surgery. Although the tumor necrosis factor antagonist infliximab is an effective salvage therapy to prevent colectomy in patients with ASUC, optimal dosing is unclear. Calculated infliximab clearance has been associated with important outcomes in patients with ulcerative colitis, but its utility in patients with ASUC has not been established. We assessed the relationship between calculated the baseline infliximab clearance before infliximab salvage therapy and the requirement for colectomy in patients hospitalized for ASUC.MethodsWe obtained data from hospitalized patients with ASUC who initiated infliximab therapy. We then calculated the baseline infliximab drug clearance in these patients based on an existing formula. The primary aim was to compare clearance between patients who required colectomy 6 months later and patients who did not require colectomy. Receiver operating characteristic curve analyses evaluated clearance thresholds for colectomy. Multivariable logistic regression analysis evaluated factors associated with colectomy.ResultsIn 39 patients with ASUC, the median baseline calculated clearance was higher in patients requiring colectomy at 6 months than in patients without colectomy (0.733 vs 0.569 L/d; P = .005). An infliximab clearance threshold of 0.627 L/d identified patients who required colectomy with 80.0% sensitivity and 82.8% specificity (area under the curve, 0.80). A higher proportion of patients with infliximab clearance of 0.627 L/d or more underwent colectomy within 6 months (61.5%) than patients with lower infliximab clearance values (7.7%) (P = .001). Multivariable analysis identified baseline infliximab clearance as the only factor associated with colectomy. The infliximab dose in the hospital was higher in patients who required colectomy. Results were similar at 30 days and 1 year.ConclusionsIn patients hospitalized with ASUC, higher values of calculated infliximab clearance before infliximab administration is associated with higher rates of colectomy. Although patients who required colectomies received higher doses, data on infliximab concentrations are lacking. Infliximab pharmacokinetic models are needed for patients with ASUC to allow comparative trials on clearance-based vs standard dosing.

Background Deep remission in patients with UC has relied on initial achievement of biochemical, endoscopic, and/or histological remission. We evaluated persistent symptomatic remission and endoscopic healing (EH: Mayo endoscopy score [MES] 0 or 1) on consecutive endoscopic examinations as a durable treatment endpoint. Methods In a retrospective cohort study, we estimated and compared cumulative risk of clinical relapse in patients with persistent EH, with and without persistent histological remission and depth of EH, among adults with active UC treated-to-target of symptomatic remission and EH who achieved and maintained symptomatic remission and EH over two serial endoscopic assessments. We also explored risk of relapse in patients with persistent EH whose therapy was de-escalated. Results Of 270 patients who initially achieved EH with treatment-to-target, 89 maintained symptomatic remission and EH on follow-up endoscopy [interval between EH1 and EH2, 16 months]. On follow-up after EH2 [median, 19 months], 1-year cumulative risk of relapse in patients with persistent EH was 11.5%, and with persistent histological remission was 9.5%. Seventeen patients with persistent EH, who underwent de-escalation of therapy, did not have an increased risk of relapse as compared with patients who continued index therapy [5.3% vs 14%, p  = 0.16]. Conclusions Patients with active UC treated-to-target of clinical remission, who achieve and maintain symptomatic remission and EH over consecutive endoscopies, have a low risk of relapse, particularly in a subset of patients who simultaneously achieve histological remission. Persistent EH should be examined as a treatment endpoint suggestive of deep remission. [ABSTRACT FROM AUTHOR]

Summary: Background: Immune checkpoint inhibitors may variably impact patients with pre‐existing autoimmune diseases. Aims: To evaluate the risks and outcomes of adverse events in patients with pre‐existing inflammatory bowel diseases treated with immune checkpoint inhibitors. Methods: Through a systematic literature review up until July 31, 2020, we identified 12 studies reporting the impact of immune checkpoint inhibitors in 193 patients with inflammatory bowel disease. Outcomes of interest were relapse of inflammatory bowel disease, need for corticosteroids and/or biologics to manage inflammatory bowel disease relapse, and discontinuation of immune checkpoint inhibitors. We calculated pooled rates (with 95% confidence intervals [CI]) using random effects meta‐analysis, and examined risk factors associated with adverse outcomes through qualitative synthesis of individual studies. Results: On meta‐analysis, 40% patients (95% CI, 26%‐55%) experienced relapse of inflammatory bowel disease with immune checkpoint inhibitors. Among patients who experienced relapse, 76% (95% CI, 65%‐85%) required corticosteroids, and 37% (95% CI, 22%‐53%) required biologic therapy. Overall, 35% patients (95% CI, 17%‐57%) with inflammatory bowel disease discontinued immune checkpoint inhibitors. Gastrointestinal perforation and abdominal surgery due to immune checkpoint inhibitor complications occurred in <5% patients. In a large study, inhibitors of cytotoxic T‐lymphocyte antigen‐4 (CTLA‐4) were associated with a higher risk of relapse than programmed cell death 1 (PD‐1) and programmed death ligand 1 (PD‐L1) inhibitors. Conclusions: Approximately 40% of patients with pre‐existing inflammatory bowel diseases experience relapse with immune checkpoint inhibitors, with most relapsing patients requiring corticosteroids and one‐third requiring biologics. CTLA‐4 inhibitors may be associated with higher risk of relapse. [ABSTRACT FROM AUTHOR]

Background: The Endoscopic Healing Index (EHI) is a serum biomarker panel that can predict endoscopic inflammation in Crohn's disease (CD)., Methods: Paired serum samples with endoscopies from adult patients participating in a prospective biobank (June 2014 to December 2018) were analyzed post hoc. Diagnostic performance for EHI was assessed against the individual parameters of the Simple Endoscopic Score for CD using previously identified cutoffs. Confounders for EHI performance were identified using logistic regression., Results: A total of 205 CD patients were included (50% male, median age 37 years). An EHI of 20 points was sensitive for ruling out any ulcers (85%; 95% confidence interval [CI], 77%-91%) and large (5-20 mm) or very large (>20 mm) ulcers (93%; 95% CI, 84%-97%). An EHI of 50 points was specific for ruling in any ulcers (86%; 95% CI, 76%-92%) and large or very large ulcers (87%; 95% CI, 79%-92%). After accounting for total extent of inflamed mucosa, strictures, and disease location, each 20-point increase in EHI was associated with a 1.7-fold increased probability for the presence of large or very large ulcers (adjusted odds ratio, 1.7; 95% CI, 1.1-2.6)., Conclusions: The EHI was independently associated with ulcer size and accurately identified large or very large ulcers. A cutoff of 50 points can reliably rule in mucosal ulcers and allow for treatment adjustment. A cutoff of 20 points can reliably rule out mucosal ulcers and signal completion of treatment adjustment algorithms., (© The Author(s) 2022. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)