Search

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: Vedolizumab, an α4β7 integrin antagonist, is an effective therapy for Crohn's disease (CD). Biomarkers are needed to guide therapy and predict outcomes. This study evaluated biomarker concentrations and outcomes in patients with CD undergoing vedolizumab treatment. Methods: Sera at weeks 0, 2, 6, 14, and ⩾26 were collected from vedolizumab-treated, refractory CD patients. Concentrations of soluble (s)-Vascular Cell Adhesion Molecule (VCAM)-1, s-Intercellular Cell Adhesion Molecule (ICAM)-1, s-Mucosal Addressin Cell Adhesion Molecule (MAdCAM)-1, and s-α4β7 integrin were evaluated for associations with achieving endoscopic remission. Results: A total of 22 patients with CD were included. In all patients, s-MAdCAM-1 decreased significantly and s-α4β7 increased compared with baseline. s-VCAM-1 and s-ICAM-1 changed differentially in patients who achieved remission. At week 6, median s-VCAM-1 (859.6 ng/ml versus 460.3 ng/ml, p = 0.03) and s-ICAM-1 (545.7 ng/ml versus 286.2 ng/ml, p = 0.03) concentrations were higher in patients who achieved endoscopic remission compared with those who did not, and similar differences were observed for s-ICAM-1 concentrations in patients who achieved clinical remission, compared with those who did not (669.1 ng/ml versus 291.0 ng/ml, p = 0.04). Week 14 s-α4β7 concentrations were lower in patients who achieved endoscopic remission, compared with those who did not (7.5 ng/ml versus 17.6 ng/ml, p = 0.020). Conclusion: In all vedolizumab-treated CD patients, s-MAdCAM-1 decreased significantly and s-α4β7 increased. However, higher concentrations of s-ICAM-1 and s-VCAM-1 at week 6 and lower concentrations of s-α4β7 at week 14 differentiated patients who achieved endoscopic remission. These findings may help identify early predictors of response to vedolizumab treatment in patients with CD. Further validation in less refractory CD patients is needed. [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.)