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.

Continuous Monitoring of CRP, IL-6, and Calprotectin in Inflammatory Bowel Disease Using a Perspiration-Based Wearable Device.

BACKGROUND: Wearable sensor devices represent a noninvasive technology to continuously track biomarkers linked to inflammatory bowel disease (IBD). We assessed the inflammatory markers associated with IBD in human perspiration. METHODS: Participants with IBD were monitored for 40 to 130 minutes with a proprietary wearable sensor device used to measure C-reactive protein, interleukin-6, and calprotectin. Sensor response using electrochemical impedance spectroscopy and serum samples were measured on the same day. The Mann-Whitney test was used to analyze the relationship between active and remission IBD in serum and perspiration, classified according to endoscopic reports and serum biomarker levels. Asynchronously collected fecal calprotectin from a subset of the population was similarly analyzed. RESULTS: A total of 33 subjects were enrolled. Expression of calprotectin was significantly elevated in the active cohort compared with the remission cohort in perspiration (P < .05; median = 906.69 ng/mL; active 95% confidence interval [CI], 466.0-1833 ng/mL; remission 95% CI, 328.4-950.8 ng/mL), serum (median = 1860.82 ng/mL; active 95% CI, 1705-2985 ng/mL; remission 95% CI, 870.2-1786 ng/mL), and stool (P < .05; median = 126.74 µg/g; active 95% CI, 77.08-347.1 µg/g; remission 95% CI, 5.038-190.4 µg/g). Expression of CRP in perspiration and serum was comparable between the active and remission cohorts (perspiration: P > .05; median = 970.83 pg/mL; active 95% CI, 908.7-992 pg/mL; remission 95% CI, 903.3-991.9 pg/mL; serum: median = 2.34 µg/mL; active 95% CI, 1.267-4.492 µg/mL; remission 95% CI, 1.648-4.287 µg/mL). Expression of interleukin-6 in perspiration was nonsignificant in the active cohort compared with the remission cohort and was significantly elevated in serum (perspiration: P < .05; median = 2.13 pg/mL; active 95% CI, 2.124-2.44 pg/mL; remission 95% CI, 1.661-2.451 pg/mL; serum: median = 1.15 pg/mL; active 95% CI, 1.549-3.964 pg/mL; remission 95% CI, 0.4301-1.257 pg/mL). Analysis of the linear relationship between perspiration and serum calprotectin (R2 = 0.7195), C-reactive protein (R2 = 0.615), and interleukin-6 (R2 = 0.5411) demonstrated a strong to moderate relationship across mediums. CONCLUSIONS: We demonstrate the clinical utility of perspiration as a noninvasive medium for continuous measurement of inflammatory markers in IBD and find that the measures correlate with serum and stool markers across a range of disease activity.

This work establishes the clinical utility of perspiration as a noninvasive, continuous marker for gut inflammation and demonstrates the ability to distinguish between active and inactive inflammatory bowel disease across perspiration, serum, and stool.

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.

Dual-Targeted Therapy with Upadacitinib and Ustekinumab in Medically Complex Crohn's Disease.

BACKGROUND AND AIMS: Ongoing efforts to break the therapeutic ceiling in inflammatory bowel disease include combination therapy approaches. Dual-targeted therapy (DTT) has been reported in case reports and small case series. This report describes our experience with ustekinumab (UST) and upadacitinib (UPA) as DTT in patients with Crohn's disease (CD). METHODS: In this retrospective, observational study, we reviewed medical records of patients with CD treated with combined UST and UPA between April 2021 and July 2022. Clinical remission was defined as Harvey-Bradshaw Index (HBI) ≤ 4, and clinical response was defined as decrease in HBI ≥ 3 or physician's assessment of clinical response. RESULTS: We identified 10 CD patients treated with UST/UPA, with median follow-up period of 10 months (interquartile range (IQR) 7.3-12). Median age was 35.5 years (IQR 28.3-43.8) and median number of prior biologic treatment exposures was 4 (IQR 4-5). Indications for UST/UPA were active CD (n = 6), extraintestinal manifestations (EIM) (n = 2), and both active CD and EIM (n = 2). Five of six patients with active CD achieved clinical remission with UST/UPA. Two patients with active EIM (joint pain) achieved resolution of their symptoms. One patient exhibited improvement in both conditions. Three patients developed mild respiratory symptoms and one experienced bowel obstruction. Two patients developed nausea resulting in de-escalation of treatment interval or discontinuation altogether. CONCLUSION: Based on our case series, combination therapy with UST and UPA may be effective and appears safe in refractory Crohn's disease and for patients with co-existing extraintestinal manifestations.

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.

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).

Factors Associated With Fecal Calprotectin Sample Collection Compliance: An IBD Center Quality Improvement Project.

Background: Fecal calprotectin (Fcal) is a noninvasive, inexpensive biomarker of disease activity. However, patient compliance with this test is variable and incompletely described. We assessed compliance rates with Fcal tests and identified factors associated with noncompliance. Methods: A retrospective chart review of patients with inflammatory bowel disease (IBD) who had a Fcal test ordered through our center between August 2021 and December 2021 was conducted. Demographic, clinical, disease, and test-related information were recorded. Patients with incomplete Fcal orders were sent a survey to better understand their reasons for noncompliance. Simple statistical analysis and and multivariable logistic regression modeling were performed. Results: Of 303 patients, 165 (54.4%) had an order for Fcal. Of the Fcal tests ordered, 55 (33.3%) were not completed. Remission of IBD, no prior Fcal completion, and tests ordered at a distant site were all associated with test noncompletion. A multivariable logistic regression revealed that history of a prior completed Fcal test is associated with subsequent test completion (odds ratio = 2.1, 95% confidence interval 1.9-35.5, P = .004). Patients who did not complete the test described the pandemic and third-party testing center issues as the most common reasons for noncompliance. Conclusions: In this single center experience with Fcal testing in patients with IBD, we identified that a history of incomplete Fcal testing and distant location of lab testing were significantly associated with noncompletion of the test. We provide practical guidance for future utilization and compliance, including the impact of home-based testing.