Utility of the Endoscopic Healing Index in Identifying Active Inflammation in Patients with Crohn's Disease: Real World Data from a Tertiary Center.

BACKGROUND: The Endoscopic Healing Index (EHI) analyzes biomarkers in a patient's peripheral blood to assess mucosal healing. We aimed to characterize the effectiveness of the EHI as a predictor of disease activity in a real world clinical setting. METHODS: This retrospective study looked at patients treated and followed up at the University of Chicago Medicine IBD center who had EHI tests done as part of routine clinical care. The results of the EHI were compared with radiological imaging or endoscopy performed within 3 months of the EHI in order to determine accuracy at diagnosing active inflammation. RESULTS: Fifty-five patients with CD and with an available EHI were included in this study. Four (50%) patients with an EHI of < 20 (n = 8) had evidence of objective inflammation. A cutoff of ≤ 20 had a sensitivity of 89% and specificity of 23.5% for predicting no evidence of any objective inflammation with an AUROC of 0.69. This score had a negative predictive value (NPV) of 50% and positive predictive value (PPV) of 72.3%. A cutoff EHI of 30 tended to classify patients as either having objective evidence of inflammation or not more often than FCAL (Correctly classifying inflammation: 89% vs 64%, respectively; p = 0.32). CONCLUSION: In this real world analysis, the EHI showed poor predictive value for the absence of active inflammation as assessed by imaging or endoscopy, has limited utility in confirming deep remission and should be used with another objective modality.

Extensive Disease and Exposure to Multiple Biologics Precolectomy Is Associated with Endoscopic Cuffitis Post-Ileal Pouch-Anal Anastomosis in Patients With Ulcerative Colitis.

INTRODUCTION: To better inform the risk of cuffitis in patients with ulcerative colitis (UC), we aimed to identify its occurrence and associated precolectomy factors in a large multicenter cohort of patients who underwent restorative proctocolectomy (RPC) with stapled ileal pouch-anal anastomosis (IPAA). METHODS: This study was a retrospective cohort analysis of individuals diagnosed with UC or indeterminate colitis who underwent RPC with IPAA for refractory disease or dysplasia at Mount Sinai Hospital or the University of Chicago followed by at least 1 pouchoscopy with report of the pouch-anal anastomosis. The primary outcome was cuffitis defined as ulceration of the cuff as reported in each pouchoscopy report. RESULTS: The pouch-anal anastomosis was mentioned in the pouchoscopy reports of 674 patients, of whom 525 (77.9%) had a stapled anastomosis. Among these, cuffitis occurred in 313 (59.6%) patients a median of 1.51 (interquartile range 0.59-4.17) years after final surgical stage. On multivariable analysis, older age (hazard ratio [HR], 1.01; 95% confidence interval [CI], 1.01-1.02), extensive disease (HR, 1.34; 95% CI, 1.01-1.78), exposure to biologics before colectomy (HR, 2.51; 95% CI, 1.93-3.27), and exposure to at least 2 or more biologics before colectomy (HR, 2.18; 95% CI, 1.40-3.39) were significantly associated with subsequent cuffitis. CONCLUSIONS: In this multicenter study of patients who underwent RPC with stapled IPAA and at least 1 follow-up pouchoscopy, cuffitis occurred in approximately 60% and was significantly associated with extensive disease and exposure to multiple biologics precolectomy.

In this multicenter study of patients who underwent restorative proctocolectomy with stapled ileal pouch­anal anastomosis and at least 1 subsequent pouchoscopy, endoscopic cuffitis occurred in 60% and was significantly associated with extensive disease and exposure to multiple biologics.

Real World Clinical Effectiveness and Safety of Ozanimod in the Treatment of Ulcerative Colitis: 1-Year Follow-Up from a Tertiary Center.

BACKGROUND: Ozanimod is a first-in-class Sphingosine-1-phosphate (S1P) receptor modulator approved for the treatment of moderately to severely active ulcerative colitis (UC). Real world data describing use of ozanimod are limited. AIM: To provide 1-year follow-up results of our UC patient cohort treated with ozanimod. METHODS: This prospective, observational cohort study includes consecutive patients who initiated ozanimod at the University of Chicago IBD Center between 5/2021 and 12/2022. We collected demographic, clinical, and laboratory data. Clinical disease activity was prospectively assessed using the Simple Clinical Colitis Activity Index. RESULTS: Forty-five patients with UC initiated ozanimod therapy and were included in the effectiveness analysis. The median age was 35 years (interquartile range (IQR) 28-52), median disease duration of 6 years (IQR 3-13), 26 (58%) were male, 23 (51%) had extensive colitis, 34 (76%) had previous advanced therapy exposure. Thirty-four patients had clinically active UC at the time of ozanimod initiation; week 10 clinical response and remission rates were 58% and 53%, respectively. By week 52, the rates were 25% for both clinical response and remission. In the 12 (39%) patients with a > 75% reduction in absolute lymphocyte count, numerically greater induction clinical response and remission rates were observed (80% vs 54%, p = 0.4 and 75% vs 53%, p = 0.4, respectively). There were no episodes of symptomatic bradycardia and no other new safety signals. CONCLUSION: Ozanimod effectively induced clinical response and remission patients with largely treatment refractory UC, however, had modest long-term effectiveness. The safety profile was favorable with no new signals.

Ozanimod-Exposed Patients with Ulcerative Colitis Undergoing Total Colectomy Exhibit Unique Lymph Node Histologic Changes.

INTRODUCTION: Ozanimod regulates lymphocyte egress from the spleen and lymph nodes into the systemic circulation. The histologic changes which occur in the lymph nodes of patients on ozanimod is unknown. MATERIALS AND METHODS: This retrospective study included patients with UC undergoing total colectomy for treatment-refractory disease who received ozanimod and a cohort of patients with UC undergoing colectomy who did not have ozanimod exposure. Histology of the lymph nodes from the mesentery of colectomy specimens was reviewed and multiple features were scored by experienced pathologists. RESULTS: Six (13%) ozanimod-treated patients with UC required surgery for treatment-refractory disease. Colectomy specimen data were available for 5 patients (1 patient had surgery at an outside center). Lymph node specimens from 6 control patients with UC who had colectomy were examined. Histologic examination of lymph nodes showed that patients treated with ozanimod had significantly greater extent of dilated sinuses (p=0.03) and greater degrees of sinus histiocytosis (p=0.03) compared with control patients. In addition, there was a trend towards more Castleman-like angiotrophic hyperplasia, plasma cell infiltration and subcortical interfollicular expansion in ozanimod treated patients. CONCLUSION: This study identifies unique histologic changes in the lymph nodes of patients with UC treated with ozanimod. The presence of sinus histiocytosis and dilated sinuses is in keeping with the known mechanism of action of ozanimod and suggests that blocking lymphocyte egression from lymph nodes was insufficient to ameliorate disease severity in these patients. The possibility of Castleman-like features identified in several of the cases, needs to be further investigated.

Salvage Therapy in Acute Severe Ulcerative Colitis: Current Practice and a Look to the Future.

The risk of urgent bowel resection increases significantly among patients hospitalized with acute severe ulcerative colitis. In-hospital management requires quick diagnostic, therapeutic, and decision-making, combined with a multi-disciplinary approach and accessibility to multiple therapeutic options. However, the optimal strategy is still debatable. We performed a review of the current options for salvage therapy as well as novel therapy options emerging. We reviewed studies reporting outcomes of hospitalized steroid-refractory acute severe ulcerative colitis treated with salvage therapy (calcineurin inhibitors, infliximab) as well as studies using novel biologic, small molecules, antibiotics, and artificial intelligence to optimize therapy. We collected statistical data about patient factors that impact clinical management and how these can be applied to the real-life practice in order to prescribe a more personalized medicine. Several new drugs and approaches have shown benefits during the last decades for the management of acute severe ulcerative colitis. This effort is driven by the necessity of more effective, safe, and rapidly active therapeutic options with better convenient routes of administration, in order to improve therapeutic outcomes and quality of life for patients. The next step will be tailored medicine according to patients' profiles, taking into account disease characteristics, laboratory parameters, and patients' preferences.

Upadacitinib Is Effective and Safe in Both Ulcerative Colitis and Crohn's Disease: Prospective Real-World Experience.

BACKGROUND & AIMS: Upadacitinib is a novel selective Janus kinase 1 inhibitor that has shown efficacy in the treatment of moderate to severe ulcerative colitis (UC) and Crohn's disease (CD), and has received Food and Drug Administration approval for UC. We report a large real-world experience with upadacitinib in UC and CD. METHODS: We performed a prospective analysis of clinical outcomes on upadacitinib in patients with UC and CD using predetermined intervals at weeks 0, 2, 4, and 8 as part of a formalized treatment protocol at our institution. We used the Simple Clinical Colitis Activity Index and the Harvey-Bradshaw index, as well as C-reactive protein and fecal calprotectin to assess efficacy, and also recorded treatment-related adverse events and serious adverse events. RESULTS: A total of 105 patients were followed up for 8 weeks on upadacitinib, 84 of whom (44 UC patients, 40 CD patients) were initiated because of active luminal or perianal disease and included in the analysis. One hundred percent previously received anti-tumor necrosis factor therapy, and 89.3% had received 2 or more advanced therapies. At 4 and 8 weeks of treatment for UC, 19 of 25 (76.0%) and 23 of 27 (85.2%) achieved clinical response and 18 of 26 (69.2%) and 22 of 27 (81.5%) achieved clinical remission, respectively. Of those who previously were tofacitinib-exposed, 7 of 9 (77.8%) achieved clinical remission by 8 weeks. In CD, 13 of 17 (76.5.%) achieved clinical response and 12 of 17 (70.6%) achieved clinical remission by 8 weeks. Of those with increased fecal calprotectin and C-reactive protein levels, 62% and 64% normalized by week 8, respectively. Results were seen as early as week 2 in both UC and CD, with clinical remission rates of 36% and 56.3.%, respectively. Acne was the most commonly reported adverse event, occurring in 24 of 105 patients (22.9%). CONCLUSIONS: In this large real-world experience in medically resistant patients with UC or CD, we report that upadacitinib is rapidly effective and safe, including in those who had prior tofacitinib exposure. This study was approved by the Institutional Review Board at the University of Chicago (IRB20-1979).

Delays in Therapy Associated With Current Prior Authorization Process for the Treatment of Inflammatory Bowel Disease.

Despite a high approval rate, there were unnecessary delays in therapy due to prior authorizations. This study identified the impact of type of IBD, FDA-labeled indication, and dose escalations on approvals.

Endoscopic Transoral Outlet Reduction for the Treatment of Biliary Reflux Symptoms in Patients After One-Anastomosis Gastric Bypass-a Case Series.

PURPOSE: OAGB is the third most common bariatric surgery. Biliary reflux (BR) is an inherent complication of this unique anatomy, although there is still controversy regarding its significance and long-term risks including carcinogenesis. To date, there is no effective treatment for BR with conversion to RYGB reserved for refractory patients. TORe is an effective treatment for weight-regain and dumping syndrome after RYGB. We hypothesized that narrowing the anastomosis would decrease the amount of bile refluxate entering the stomach and esophagus in patients with BR symptoms after OAGB and alleviate symptoms. The purpose of this study is to evaluate the efficacy of TORe for the treatment of BR symptoms after OAGB. MATERIALS AND METHODS: BR was diagnosed clinically in patients after OAGB using the gastroesophageal reflux disease health-related quality of life (GERD-HRQL) instrument after treatment with high-dose proton pump inhibitor (PPI) excluded possible acid reflux. TORe was carried out using a suture pattern that narrowed and elongated the anastomosis. All patients were prospectively followed. RESULTS: Twelve patients, post-OAGB, underwent TORe for BR. Symptoms resolved in 9 (75%) patients. GERD-HRQL score at 6 months declined from an average of 33.7 (SD 1.9) before the procedure to 16.1 (SD 10, p < 0.001). In one case, a small perforation was identified during the procedure and was immediately sutured with no further sequela. DISCUSSION: TORe appears a safe and effective treatment for BR symptoms after OAGB, at least in the short term. Accurate tools for BR diagnosis, a larger cohort, and longer follow-up periods are needed to better show the effectiveness and durability of this treatment option.

Assessment of the Degree of Variation of Histologic Inflammation in Ulcerative Colitis.

INTRODUCTION: Treatment of ulcerative colitis (UC) now includes mucosal healing. Adoption of histologic end points is hindered by a lack of evidence guiding optimal sampling, interpretation, and reproducibility of results. METHODS: We analyzed biopsy fragments from colonoscopies in 92 patients with UC. Fragments were scored using 6-point histologic inflammatory activity (HIA) scale. Variability was determined using ordinal representations of HIA scores. The most frequently observed score and percentage of biopsy fragments with that score were determined for each biopsy, each segment, and across all 3 segments for each colonoscopy. Mean percentages and 95% confidence intervals (CIs) were calculated. RESULTS: We reviewed 1802 biopsy fragments. The mean percentages of intrasegment biopsy fragments with the same HIA score were 85.5% (95% CI, 80.9% to 92.9%), 79.6% (95% CI, 76.0% to 87.3%), and 82.7% (95% CI, 79.1% to 90.0%) for the rectum, left colon, and right colon, respectively. The mean percentage of intersegment biopsy fragments with the same HIA score was 70.2% (95% CI, 65.7% to 82.5%). The mean percentages of intrabiopsy fragments with the same HIA score were 83.3% (95% CI, 77.6% to 93.5%), 83.6% (95% CI, 80.1% to 89.7%), and 90.2% (95% CI, 87.6% to 94.7%) for the rectum, left colon, and right colon, respectively. All 3 analyses revealed increased variation when a greater degree of histologic inflammation was present in the biopsies (mean HIA score ≥2). CONCLUSIONS: We found minimal variability between degree of inflammation among biopsy fragments within and among different colorectal segments in UC, suggesting that even a single biopsy would adequately reflect the inflammation of the entire colorectum. These findings have significant implications for the use of histology as a clinical target and trial end point in UC.

Serum Cytomegalovirus Polymerase Chain Reaction Test Is a Valuable Negative Predictor of Infection in Acute Severe Ulcerative Colitis.

BACKGROUND: Diagnosis of cytomegalovirus (CMV) colitis in the setting of severe ulcerative colitis (UC) remains a clinical challenge. This study aimed to determine the utility of serum CMV polymerase chain reaction (PCR) as a non-invasive test for the diagnosis of CMV superinfection in patients hospitalized with UC. METHODS: This retrospective study included consecutive admitted patients with UC who had serum testing for CMV completed as part of standard hospital procedure and CMV colitis diagnosed by expert pathologists. RESULTS: Two hundred and six patients with UC were included; 13 patients (6%) had histologically confirmed CMV colitis. Eleven of 13 patients with CMV colitis (84%) and 3 of 193 (1.5%) patients without CMV colitis had a positive serum PCR test (p < 0.0001). ROC analysis showed that a CMV PCR level of 259 IU/mL had a sensitivity and specificity of 77% and 99%, respectively, for diagnosis of CMV colitis with an AUC of 0.9 (p < 0.0001). Serum CMV PCR level significantly correlated to the number of inclusion bodies on biopsy specimens with data available (n = 8) (r = 0.8, p = 0.02). CMV positivity did not predict the need for salvage therapy, admission or 1-year colectomy rates. CONCLUSION: Serum CMV PCR has an excellent negative predictive value and demonstrates a strong correlation with CMV positivity on histology. This work supports a rationale for serum CMV PCR testing on admission to assess the risk of CMV colitis in patients with severe UC.

Ozanimod in the Treatment of Ulcerative Colitis: Initial Real-World Data From a Large Tertiary Center.

Ulcerative colitis (UC) is a chronic inflammatory condition affecting the colon and rectum. Long-term therapy is generally required to achieve and maintain disease control.1 In May 2021 the US Food and Drug Administration approved the use of ozanimod in patients with moderate to severe UC. We describe the first report of the use of ozanimod in real-world clinical practice.

Endo-histologic Normalization Is Achievable with Tofacitinib and Is Associated with Improved Clinical Outcomes.

BACKGROUND: Recent real-world effectiveness studies investigating tofacitinib have been encouraging. Questions remain regarding the long-term effectiveness and safety of tofacitinib, effect on endoscopic remission rates, histologic changes, and alterations in fecal calprotectin levels. METHODS: This retrospective study includes consecutive patients with inflammatory bowel disease (IBD) who initiated tofacitinib therapy. We reviewed electronic medical records for demographic and clinical data, as well as all adverse events and hospitalizations. All patients receiving tofacitinib were included in the safety analysis and only patients with ulcerative colitis (UC) were included in the effectiveness analysis. RESULTS: 119 patients with IBD (97 UC, 12 CD, and 10 pouchitis) seen at our center between 2014 and 2020 were included in this study. Median follow-up was 32 weeks (interquartile range (IQR) 3-252). Clinical response and remission were observed in 70% and 21%, 59% and 33%, and 49%, and 37% at weeks 8, 24, and 52, respectively. Endo-histologic healing was achieved by 11%, 25%, and 37.5% of patients at weeks 8, 24, and 52, respectively. Histologic normalization occurred as early as 24 weeks in this cohort and was achieved by 26% of patients in endoscopic remission. Overall, there were 27 (25%) adverse events with 6 (5%) resulting in treatment discontinuation. There were 11 (10%) infections, none required treatment discontinuation. Ten (10.3%) patients underwent colectomy during the follow-up period. There were no cardiovascular adverse events in the cohort during follow-up. CONCLUSION: This study demonstrates the effectiveness and long-term safety of tofacitinib in patients with UC. Importantly, we show that the endpoint of endo-histologic healing is achievable with tofacitinib and can occur as early as week 8 of therapy.

Trends in Biochemical Parameters, Healthcare Resource and Medication Use in the 5 Years Preceding IBD Diagnosis: A Health Maintenance Organization Cohort Study.

BACKGROUND: Few data describing pre-diagnosis changes in patients with inflammatory bowel disease (IBD) exist. We aimed to determine if there is a pattern of change in use of health resources, medications and laboratory results in the years preceding diagnosis. METHODS: This retrospective study used electronic medical records of Maccabi Health Services (MHS). Patients with IBD ≥ 16 years of age and minimum of 5-years follow-up were identified by entry into the MHS IBD registry and included in the analysis. Demographic, clinical, medication and laboratory data were collected. Generalized estimating equation model was applied to study trends and compare between years. RESULTS: This study included 5643 patients with IBD. Of these, 3039 (53.8%) had Crohn's disease (CD), 2322 (41.1%) had ulcerative colitis (UC) and 282 (5%) had indeterminate colitis (IC). Laboratory parameters including white blood cells, platelets and C-reactive protein showed significant increases while haemoglobin and mean cell volume showed significant decreases in mean values in the 2 years prior to diagnosis with stable values prior to that (p < 0.0001). Parameters such as creatinine, total protein and albumin showed significant, progressive decreases in mean values starting 5 years prior to diagnosis (p < 0.0001). Patients with CD had distinct laboratory trends when compared with patients with UC. CONCLUSIONS: Changes in laboratory parameters, healthcare service and medication use occur during the 5-year period before IBD diagnosis. These data can have future clinical applicability by developing a composite score and referral algorithm introducing red flags into primary care visits and appropriate referral for specialist care.

Treat-to-target and sequencing therapies in Crohn's disease.

Crohn's disease (CD) is a chronic immune-mediated inflammatory condition which can negatively impact a patient's quality of life. The traditional management strategy for CD has focused on symptomatic control, however, this approach fails to prevent organ damage and to change the progressive course of this disease. Thus, the field has moved towards a treat-to-target strategy that includes identifying individualized objective targets, choosing a therapy based on individual factors that include disease severity and risk, closely monitoring disease activity at predefined time points, and optimizing therapies as needed. Due to the increasing number of therapies approved for CD, this review explores the various factors which should be considered in the sequencing of treatment options together with using the treat-to-target framework to control disease activity early in its course and provide holistic patient care.

Endoscopic Management of Colitis-Associated Neoplasia.

This article reviews the latest data concerning the use of advanced therapeutic techniques for endoscopically treating colitis-associated neoplastic lesions and discusses factors associated with improved outcomes.

Ozanimod Maintenance Therapy After Cyclosporine Induction in Acute Severe Ulcerative Colitis.

Ozanimod has recently received US Food and Drug Administration approval for moderate-to-severe ulcerative colitis. Treatment of acute severe colitis remains a clinical challenge, and although many patients respond to cyclosporine therapy, there remains a relative paucity of maintenance options. This case report describes the first reported, successful use of ozanimod after hospitalization for acute severe ulcerative colitis and in tandem with cyclosporine. Although a longer follow-up is required, this report shows the feasibility of ozanimod in this clinical setting.

Factors associated with poor compliance amongst hospitalized, predominantly adolescent pediatric Crohn's disease patients.

BACKGROUND: Compliance with medical treatment is vital for the control of inflammatory bowel disease (IBD) and prevention of disease complications and is an issue in paediatric patients. We explored patient-related factors associated with non-compliance in a large database of predominantly adolescent, hospitalized paediatric Crohn's disease (CD) patients. PATIENTS/MATERIALS AND METHODS: We analyzed data from the Kid's Inpatient Database (KID) the largest publicly available all-payer paediatric inpatient care database in the United States. All available paediatric CD patients non-electively admitted in 2016 were included. CD patients were extracted using the standard international classification of diseases (ICD) 10 codes. Data suggesting non-compliance, comorbidities and surgical procedures related to CD were similarly extracted. RESULTS: 2439 paediatric CD patients with non-elective admission were included in the analysis. 2 280 patients (94%) were adolescents. Of the total cohort, 113 patients (4.6%) had a diagnosis of non-compliance. In univariate analyses, smoking (15.9 vs. 5.5%, p < .001), cannabis use (5.3 vs 1.5%, p = .009), and a diagnosis of depression (19.5 vs. 9%, p = .001) or schizoaffective disorder (5.3 vs 0.3%, p < .001) were associated with non-compliance. Multivariable analysis revealed that schizoaffective disorder (odds ratio (OR) 11.6, 95% CI 3.6-37.2), depression (OR 1.9, 95%CI 1.2-3.2) and smoking (OR 2.2, 95%CI 1.25-4) were independently associated with non-compliance. CONCLUSIONS: In this study, mental health disorders and smoking were independently associated with non-compliance to medication in predominantly adolescent, hospitalized paediatric CD patients. A multidisciplinary approach involving paediatric gastroenterologists, psychiatrists and addiction specialists are needed to treat the underlying causes and improve adherence in these patients.KEY MESSAGESMental health disorders and smoking are independent risk factors for medication non-compliance amongst adolescent, paediatric CD patients.A multidisciplinary approach is required to treat underlying causes and improve adherence in paediatric IBD patients.