key: cord-0764996-v0pk7e88
authors: Atreja, Ashish; Fasihuddin, Farah; Garge, Shashank; Davidoff, Liana; Rubin, Jonathan; Kakkar, Sarthak; Wedel, Nicole; Madisetty, Divya; Singhania, Rohit; Jain, Charu Madhwani; Kurra, Sravya; Sands, Bruce
title: A POPULATION-BASED APPROACH TO DIGITAL OUTREACH, TRIAGE, AND MONITORING OF IBD PATIENTS DURING THE COVID-19 PANDEMIC
date: 2021-02-28
journal: Gastroenterology
DOI: 10.1053/j.gastro.2021.01.049
sha: c3c6c926b733e546bd1184e577c8357b068a6ae8
doc_id: 764996
cord_uid: v0pk7e88

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anti-tumor necrosis factor (TNF)-a agent (infliximab, adalimumab, golimumab or certolizumab) following 12-months of continuous enrollment in Medicare fee-for-service Parts A/B/D without either study drug. Patients were required to be !65 years old and have !2 international classification of disease (ICD) codes of Crohn's disease (CD) or ulcerative colitis (UC). We excluded patients who received other biologic therapies and/or those who had !2 codes for other immunologic conditions. Pertinent co-variates included were age, sex, race Charlson Co-morbidity Index (CCI), predicted probability of frailty, healthcare utilization and baseline IBD medications. The outcomes of interest were hospitalizations, IBD-related surgery and new corticosteroid use ! 60 days after drug initiation. We described the study population, assessed health care utilization and use of other IBD medications. We estimated crude incidence rates and hazard ratios (HR) adjusted for the covariates using standardized mortality ratio (SMR) weights. RESULTS: We identified 488 vedolizumab users and 2,213 anti-TNF users. The median age was 72 years in the vedolizumab cohort and 71 years in the anti-TNF cohort; 12% of both cohorts were aged !80 years. Differences in the two cohorts existed with regards to sex, race, baseline healthcare utilization and IBDrelated medications, but all the baseline differences were balanced by weighting measured by a standardized mean difference (SMD) <0.1 (Table 1) . After weighting, vedolizumab users were less likely to be hospitalized in the 12 months after biologic initiation (HR: 0.81, 95% CI: 0.68 -0.96). While there was no significant difference in IBD related hospitalizations, older adults with IBD were less likely to have an infection-related hospitalization (HR: 0.39, 95% CI: 0.23 -0.65). There were no significant differences in IBD related surgery and steroid use after induction (Table 2) . CONCLUSIONS: In this large, retrospective cohort study of older IBD patients who were new users of vedolizumab and anti-TNF agents, we found that older patients initiated on vedolizumab were significantly less likely to have an infection-related hospitalization. However, there were no significant differences in IBD-related hospitalizations, IBD-related surgery or corticosteroid use after biologic induction. Inflammatory Bowel Disease (IBD) center reported an increase in telephone call volume, with many IBD patients expressing anxiety about being on immunosuppressive agents during the COVID-19 pandemic. Consistent with GI society and CDC recommendations, we leveraged the Rx.Universe platform (Rx.Health, New York, NY) to rapidly design and deliver a population-based digital navigation program (DNP) to provide outreach, remote COVID-19 symptom monitoring, triage, and Telehealth to IBD patients. METHODS: After identifying all IBD patients seen in our IBD center from Electronic Health Records (Epic Systems), we "bulk prescribed" the DNP (Rx.Health, New York NY) to 6100 patients' smartphones. Patients were asked to reply to the prompt if they had new or worsening COVID-19 symptoms and opted-in to regular digital monitoring through an electronic patient reported outcome (ePRO) instrument. Patient data was screened by our clinical coordinators, who directly contacted patients via phone calls and scheduled testing and Telehealth visits with IBD practitioners when appropriate. RESULTS: Of the 6100 patients who were sent the DNP, 1829 patients opted-in to be regularly monitored using text-based electronic patient reported outcome (ePRO) instruments. Of those who responded affirmatively, 145 patients were identified requiring additional medical attention and were triaged using Telehealth visits. Compared to patients who chose not to opt-in, patients who opted-in were more likely to be female, white, married, on biologics, and had high inflammatory markers (Table 1) . CONCLUSION: As demonstrated by the 30% of patients who opted-in to regular COVID-19 symptom monitoring, a digital navigation program population approach is an effective and efficient approach to provide continuity of care and to mitigate COVID-19 exposure in a high-risk, immunosuppressed IBD population. This scalable approach serves as a model for providing high quality, remote monitoring to patients during COVID-19 and beyond, as well as achieving "Treat to Target" goals.

Katherine Huang, Ruishu Deng, Ta-Chiang Liu, Anas Gremida, Parakkal Deepak, Chien-Huan Chen, Nicholas Davidson, Randal Kaufman, Matthew Ciorba BACKGROUND: Emerging evidence has demonstrated that protein misfolding in the endoplasmic reticulum (ER), i.e., ER stress, plays fundamental roles in IBD development in humans. Patients with active Crohn's disease and ulcerative colitis exhibit signs of ER stress in their ileal and/or colonic epithelium. Human genetic studies of IBD have identified primary genetic abnormalities in several genes that encode proteins associated with ER stress. We recently reported that oral delivery of tauroursodeoxycholic acid (TUDCA), a naturally occurring bile salt proven to reduce ER stress both in vitro and in vivo, dramatically decreases the clinical, histological and biochemical signs of inflammation in four different IBD mouse models through reducing ER stress in colonic epithelial cells. AIM: Based on this, our aim was to test the efficacy and safety of TUDCA in an open label, Phase I trial for patients with symptomatic ulcerative colitis. METHODS: TUDCA was administered at 2000 mg divided TID for 6 weeks. Baseline and 6 week colonoscopy/flexible sigmoidoscopy with biopsy was performed. Outcome measures include safety, tolerability, Mayo score, and change in markers of ER stress from colon biopsies. RESULTS: To date, complete data is available on 9 of a planned 12 patients. TUDCA was well tolerated and safe with no Grade 3 or greater CTCAE adverse events and no Serious Adverse Events. A significant reduction of 4.6 points on the complete Mayo score was observed from baseline to week 6 (Avg. 8.6 AE 2.5 / 4.00 AE 2.7, P¼0.004) with 100% of patients seeing a decrease. Clinical remission, clinical response and mucosal healing were observed in 22%, 67% and 56% respectively. Fecal calprotectin decreased in 67% of patients. As diarrhea can be a side effect of TUDCA treatment at these doses, we also assessed the Partial Mayo Score at two weeks after completion of the trial (8 weeks from baseline). At this time point the Partial Mayo Score significantly decreased by 3.8 points (Avg. 6.2 AE 2.1 / 2.4 AE 1.9, P¼0.004) with 67% achieving clinical response and 56% remission. The Robarts Histopathology Index decreased in 8 of 9 patients with a mean reduction of 2.67 points (Avg. 6.4 AE 3.2 / 3.8 AE 2.9, P¼0.003). Total serum bile acid profiles changed, but not significantly so, from Wk0 to Wk6. ER stress markers Bip, eIF2a and p-eIF2a were increased in inflamed colon tissue and were lowered post TUDCA treatment in a subset of patients. CONCLUSIONS: Preliminary results from a Phase I clinical trial demonstrate that the dietary supplement TUDCA is safe, well tolerated and is associated with significant clinical improvement in a majority of patients with moderate to severely active ulcerative colitis. Mucosal healing and reductions in markers of ER stress were observed in a subset of patients. Study completion and analysis of gene expression and microbiome are underway.

Sarah Harris INTRODUCTION: Efficacy and safety of ozanimod, an oral sphingosine-1-phosphate (S1P) receptor modulator selectively targeting S1P 1 and S1P 5 , was previously demonstrated in the double-blind phase 2 TOUCHSTONE study (NCT01647516) in patients with moderate-to-severe ulcerative colitis. Here we report the effect of ozanimod on levels of fecal calprotectin (FCP) and fecal lactoferrin (FLF), two markers of intestinal inflammation. METHODS: Patients in TOUCHSTONE were randomized 1:1occurred at baseline and weeks 8 and 32 to measure levels of FCP and FLF

Median baseline levels of FCP were 1272