Faculty Bibliography

INTRODUCTION: Ustekinumab has been recently approved for the treatment of moderately to severely active ulcerative colitis (UC). The registry trials for ustekinumab in UC demonstrated efficacy and safety, but data on the effectiveness and safety in the real world are limited. We describe the effectiveness and safety of ustekinumab in patients with UC from two US tertiary IBD centers.
METHOD(S): Patients with moderately to severely active UC treated with ustekinumab at NYU Langone Medical Center (New York, NY) and University of Chicago Medical Center (Chicago, IL) between January 2016 and March 2020 were retrospectively included. The primary outcome was clinical remission at 3 and 12 months, defined as a partial Mayo score of 2, with a combined rectal bleeding and stool frequency subscore of #1.
RESULT(S): Sixty-six UC patients were included (Table 1). 61% of patients had extensive colitis and overall mean total Mayo score was 6.5 +/- 2.4. 92% of patients had prior exposure to biologics or tofacitinib. 43% and 45% of patients achieved clinical remission by 3 and 12 months, respectively (Figure 1). Anti-TNF non-response and endoscopic Mayo score of 3 were negative predictors of clinical remission at 3 months (Table 2). At 1 year, 50% of patients achieved endoscopic remission and 33% achieved mucosal and histo-endoscopic healing. The achievement of histo-endoscopic healing was significantly associated with lower partial Mayo score (0.5 +/- 0.6 vs. 3.5 +/- 1.7; P < 0.01) and lower stool frequency (0.3 +/- 0.5 vs. 1.4 +/- 0.7; P = 0.02). Serious adverse events occurred in 4 (6%) patients (3 UC exacerbations, 1 vasculitis).
CONCLUSION(S): In this cohort of mostly biologic-refractory UC patients, treatment with usteki-numab achieved remission in nearly half of them at 12 months, and was associated with an overall favorable safety profile. These results are modestly better than the pivotal trials

INTRODUCTION: Current guidelines recommend preoperative risk stratification to guide postoperative prophylactic biologic therapy for the prevention of Crohn's disease (CD) recurrence1. Few data have corroborated the quantified risk of postoperative recurrence (POR) and validated the proposed risk stratification. We aimed to assess the impact of biologic therapy on POR based on guideline-recommended risk stratification.
METHOD(S): CD patients who underwent an ileocolic resection from 1992-2019 were identified at two tertiary referral centers. Patients were stratified into cohorts with high-risk features (smoking, age < 30 years, and >=2 prior surgeries) and low-risk features (nonsmokers, age >50 years, resection length < 10 cm, and disease duration < 10 years). POR, defined as endoscopic (Rutgeerts . i1) or radiographic evidence of disease at least >6 months after surgery, was compared between groups. Recurrence-free survival analysis using Cox proportional hazard modeling and Kaplan-Meier curves were used to estimate POR and the impact of biologic prophylaxis.
RESULT(S): A total of 950 patients with ileocolic resection for CD were included (mean age 37.9, 47%): 785 (82.6%) high-risk and 165 (17.4%) low-risk patients. In the high-risk group, the majority (58.2%) received biologic prophylaxis (43.4% anti-TNF, 7.1% vedolizumab, and 7.8% ustekinumab) while 41.8% had no therapy. In contrast, 60% of low-risk patients had no therapy while 40% received biologic prophylaxis (32.7% anti-TNF, 8% vedolizumab, and 2.4% ustekinumab). In the high-risk group, biologic prophylaxis was significantly associated with earlier POR compared to no therapy (P < 0.001). In the low-risk group, there was no significant difference between biologic and no therapy in time to POR (P = 0.10; Figure 1). When assessing specific risk factors on multivariable analysis, >=2 prior surgeries was the only independent risk factor for POR (P < 0.05) (Table 1).
CONCLUSION(S): The risk stratification proposed for POR in current guidelines may have limited utility in predicting disease recurrence. Low-risk individuals are unlikely to benefit from postoperative biologic prophylaxis. Multiple prior surgeries is the strongest risk factor for POR and these patients may benefit from postoperative biologic prophylaxis

INTRODUCTION: Tofacitinib is a Janus kinase inhibitor approved for moderate to severe ulcer-ative colitis (UC). Prospective real-world data on tofacitinib in UC patients are limited. Using an electronic system to evaluate patient reported outcomes (PROs) in real time, we measured clinical response and PROs during the induction phase of tofacitinib.
METHOD(S): An initial 65 patients initiating tofacitinib were recruited from 13 academic and community gastroenterology practices. Demographic information, disease and medication histories were obtained. Patients completed PRO surveys on days 1-14, and at week 6, 10 and 14. Outcome data included the simple clinical colitis activity index (SCCAI), and PRO measurement information system (PROMIS) measures of depression, anxiety and social satisfaction. A score of < 4 with a decrease by >1.5 points is considered response. PROMIS measures are calibrated using a T score (mean of the US population equal to 50, standard deviation (SD) of 10). A higher PROMIS score equates to more of the measure (higher scores worse for depression, anxiety and better for social satisfaction).
RESULT(S): A total of 62/65 (95%) completed electronic PRO data through week 6. Mean age was 38.4 (SD 14.9), 61.5% were male, mean disease duration was 9.6 years and 58.5% were on concomitant steroids at baseline. Mean disease activity at baseline (n = 65) was active (SCCAI of 5.6 (SD 3.2)), with reductions in mean disease activity to SCCAI 3.1 on day 14, 2.7 on week 14 (Figure 1). At the time of first in-person clinical visit (week 2-6), only 18.2% remained on steroids. Among patients initiating tofacitinib without concomitant corticosteroid use (n = 27), early reductions in SCCAI were seen (mean SCCAI 5.4 at baseline, reduced to SCCAI 3.8 by day 4). Improvements in all PROMIS measures (anxiety, depression, social satisfaction) were seen through week 14 (Figure 2). A total of 54.2% met criteria for response at day 14, with 52.2% at week 6.
CONCLUSION(S): Real time electronic PRO data capture provided the ability to assess cessation of steroids and time to response to tofacitinib via important PRO outcomes. Tofacitinib was associated with a rapid response in this ongoing prospective multi-center real-world cohort, independent of steroid use. Continued enrollment and long-term data, planned through week 30, will enhance our understanding of UC

INTRODUCTION: Guidelines recommend testing inflammatory bowel disease (IBD) patients hospitalized with flare for Clostridioides difficile infection (CDI), though little is known about whether a delay in testing for CDI is related to adverse outcomes. We examined the relationship between time to C. difficile PCR test order, collection, and result with adverse IBD outcomes.
METHOD(S): We performed a retrospective cohort study of IBD patients hospitalized with flare through the emergency department (ED) between 2013 and January 2020 at an urban academic medical center. The time from ED presentation to CDI test order (time-to-order), sample collection (time-to-collection), and test result (time-to-result) were collected. Time-to-result was stratified by within+/-hours, 6-24 hours, and 24 hours or longer. The primary outcome was length of stay (LOS). Secondary outcomes were inpatient anti-TNF administration and surgery. Separately, we used initial hemodynamic and laboratory values to create an IBD hospitalization severity score for evaluation against LOS and time-dependent variables.
RESULT(S): We identified 122 IBD patients hospitalized with flare. There were no significant differences in baseline characteristics among time-to-result groups. There was no difference in time-toorder between the+/-hours and 6-24 hours groups (Table 1). Despite a shorter time-to-result, the average LOS in the+/-hours group was 7.3 days, longer compared to the 6-24 hours group (4.3 days, P=0.018) and the 24 hours group (4.2 days, P=0.035Table 1). There were no differences in inpatient anti-TNF administration (P=0.10) or surgery (P=0.08) among time-to-result groups. Markers of disease severity correlated with longer LOS and earlier time-to-result (Table 2). A composite of these markers was used to stratify patients by disease severity. Those with more severe disease had earlier times-to-result (12.8 hours vs. 32.2 hours, P=0.014) and had a longer LOS (7.9 vs. 3.4 days, P=0.007) with no difference in time-to-order compared to patients with less severe disease (P=0.09Table 3).
CONCLUSION(S): Earlier time-to-result for CDI is associated with longer LOS in IBD patients hospitalized with flare. This inverse relationship is confounded by disease severity at presentation. Patients with more severe disease have a shorter time-to-result and a longer LOS without any difference in time-to-order. Delay in testing was not associated with higher rates of inpatient anti- TNF administration or surgery

BACKGROUND:Hyperbaric oxygen has been reported to improve disease activity in hospitalised ulcerative colitis (UC) patients. AIM/OBJECTIVE:To evaluate dosing strategies with hyperbaric oxygen for hospitalised UC patients. METHODS:We enrolled UC patients hospitalised for acute flares (Mayo score 6-12). Initially, all patients received 3 days of hyperbaric oxygen at 2.4 atmospheres (90 minutes with two air breaks) in addition to intravenous steroids. Day 3 responders (reduction of partial Mayo score ≥ 2 points and rectal bleeding score ≥ 1 point) were randomised to receive a total of 5 days vs 3 days of hyperbaric oxygen. RESULTS:We treated 20 patients with hyperbaric oxygen (75% prior biologic failure). Day 3 response was achieved in 55% (n = 11/20), with significant reductions in stool frequency, rectal bleeding and CRP (P < 0.01). A more significant reduction in disease activity was observed with 5 days vs 3 days of hyperbaric oxygen (P = 0.03). Infliximab or colectomy was required in only three patients (15%) despite a predicted probability of 80% for second-line therapy. Day 3 hyperbaric oxygen responders were less likely to require re-hospitalisation or colectomy by 3 months vs non-responders (0% vs 66%, P = 0.002). No treatment-related adverse events were observed. CONCLUSION/CONCLUSIONS:Hyperbaric oxygen appears to be effective for optimising response to intravenous steroids in UC patients hospitalised for acute flares, with low rates of re-hospitalisation or colectomy at 3 months. An optimal clinical response is achieved with 5 days of hyperbaric oxygen. Larger phase 3 trials are needed to confirm efficacy and obtain labelled approval.

BACKGROUND:Ileal pouch-anal anastomosis is a common surgical procedure in patients with an initial diagnosis of ulcerative colitis or indeterminate colitis. Tobacco smoking has been associated with protection from onset of ulcerative colitis. Smoking has been reported to be both a protective factor and a risk factor for the development of pouchitis. AIM/OBJECTIVE:To examine the influence of smoking on the risk of pouchitis. METHODS:We identified 15 studies evaluating smoking as a risk factor for developing pouchitis in ulcerative colitis or indeterminate colitis patients with a history of ileal pouch-anal anastomosis in a systematic search performed from inception through May 4, 2020. A meta-analysis was then performed using a random-effects model to generate risk ratios (RR) and 95% confidence intervals (CI). RESULTS: = 78.5%). CONCLUSIONS:Smoking, past or present, is not associated with an increased risk for the development of pouchitis in patients with ulcerative colitis or indeterminate colitis.

First detected in Wuhan, China, the novel 2019 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an enveloped RNA beta-coronavirus responsible for an unprecedented, worldwide pandemic caused by COVID-19. Optimal management of immunosuppression in inflammatory bowel disease (IBD) patients with COVID-19 infection currently is based on expert opinion, given the novelty of the infection and the corresponding lack of high-level evidence in patients with immune-mediated conditions. There are limited data regarding IBD patients with COVID-19 and no data regarding early pregnancy in the era of COVID-19. This article describes a patient with acute severe ulcerative colitis (UC) during her first trimester of pregnancy who also has COVID-19. The case presentation is followed by a review of the literature to date on COVID-19 in regard to inflammatory bowel disease and pregnancy, respectively.

PURPOSE/OBJECTIVE:For more than half of Crohn's disease patients, strictures will cause bowel obstructions that require surgery within 10 years of their initial diagnosis. This study utilizes computed tomography imaging and clinical data obtained at the initial emergency room visit to create a prediction model for progression to surgery in Crohn's disease patients with acute small bowel obstructions. METHODS:A retrospective chart review was performed for patients who presented to the emergency room with an ICD-10 diagnosis for Crohn's disease and visit diagnosis of small bowel obstruction. Two expert abdominal radiologists evaluated the CT scans for bowel wall thickness, maximal and minimal luminal diameters, length of diseased segment, passage of oral contrast, evidence of penetrating disease, bowel wall hyperenhancement or stratification, presence of a comb sign, fat hypertrophy, and small bowel feces sign. The primary outcome was progression to surgery within 6 months of presentation. The secondary outcome was time to readmission. RESULTS:Forty patients met the inclusion criteria, with 78% receiving medical treatment alone and 22% undergoing surgery within 6 months of presentation to the emergency room. Multivariable analysis produced a model with an AUC of 92% (95% CI 0.82-1.00), 78% sensitivity, and 97% specificity, using gender, body mass index, and the radiographic features of segment length, penetrating disease, and bowel wall hyperenhancement. CONCLUSIONS:The model demonstrates that routine clinical and radiographic data from an emergency room visit can predict progression to surgery, and has the potential to risk stratify patients, guide management in the acute setting, and predict readmission.

Background/UNASSIGNED:Chronic inflammatory diseases (CIDs; ankylosing spondylitis [AS], psoriatic arthritis [PsA], psoriasis [PsO], or rheumatoid arthritis [RA]) and inflammatory bowel disease (IBD; Crohn's disease and ulcerative colitis) are associated with substantial economic burden. The relative increased costs among patients with CIDs and concomitant IBD compared to those without IBD is an important consideration when deciding on the clinical management of patient symptoms. Given the increasing use of novel agents for the treatment of CIDs, including those that may increase the risk of IBD in patients with CIDs, the objective of the study was to describe the incidence of IBD and to quantify healthcare resource utilization (HRU) and costs associated with IBD among patients with CIDs. Methods/UNASSIGNED:The IBM MarketScan® Research Databases (1/2010-7/2017) were used to identify adult patients with ≥2 claims with a diagnosis of either AS/PsA/PsO/RA (index date was a random claim for AS/PsA/PsO/RA). The one-year incidence rate of IBD was calculated following the index date. HRU and healthcare costs were compared between patients developing and not developing IBD in the year following the index date, adjusting for baseline characteristics. Results/UNASSIGNED: < 0.0001). Conclusion/UNASSIGNED:Higher HRU and costs were observed in patients with concomitant CID and IBD compared to patients with CID alone. Consideration should be given to treatment decisions that adequately manage CID and IBD to ensure optimal clinical and economic outcomes.