Faculty Bibliography

OBJECTIVE:The objective of this study was to determine if dual-energy computed tomography enterography (DECTE)-obtained iodine density can predict medical management change or surgery in Crohn disease patients. METHODS:The most active-appearing bowel segment on DECTE in 21 Crohn disease patients was retrospectively interrogated with prototype software determining the percentage of bowel wall (I) in specified ranges. Patients were categorized into 3 groups after DECTE: (1) no management change, (2) outpatient medication change, and (3) inpatient admission or surgery. Crohn's disease activity index was calculated. Group 3's percentage iodine density of >3 mg/mL and Crohn's disease activity index were compared with group 1/2. Crohn's disease activity index and percentage iodine density of >2 mg/mL were compared for groups 2/3 versus group 1 patients. RESULTS:There were 5 group 1, 6 group 2, and 10 group 3 patients. Group 3 patients had higher frequency of iodine density >3 mg/mL (27%) compared with groups 1/2 patients (12.6%) (P < 0.05). Crohn's disease activity index was similar (P = 0.98). Groups 2/3 patients had 60.5% iodine density of >2 mg/mL, whereas group 1 patients had 31.7% iodine density of >2 mg/mL (P < 0.05). Crohn's disease activity index was similar (P = 0.12). CONCLUSIONS:Iodine density from DECTE may predict medical or surgical Crohn disease management.

BACKGROUND:Several routes of fecal microbiota transplantation (FMT) administration are available for treating recurrent Clostridioides difficile infections (CDI), the most recent of which are capsules. AIM/OBJECTIVE:To assess the efficacy of colonoscopy, capsule, enema, and nasogastric tube (NGT) FMT for the treatment of recurrent CDI. METHODS:We reported clinical outcomes of colonoscopy, capsule, enema, and NGT FMT for the treatment of recurrent CDI according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. During January 2000 to January 2018, three databases were searched: PubMed, EMBASE, and CINAHL. Primary outcome was overall cure rate which was assessed using a random effects model; secondary outcomes included adverse effects as well as subgroup analyses comparing donor relationship, sample preparation, and study design. RESULTS:0%). On subgroup analysis of colonoscopy FMT, sample preparation methods had comparable cure rates: fresh 94.9% compared to 94.5%. Similarly, cure rates were unaffected by donor relationship: mixed 94.5% compared to unrelated donor 95.7%. CONCLUSION/CONCLUSIONS:CDI cure rates with FMT performed with colonoscopy are superior to enema and NGT FMT, while those with FMT with colonoscopy and capsule are comparable.

Background: 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 real-world outcomes are limited. We describe the effectiveness and safety of ustekinumab in patients with UC from 2 US tertiary inflammatory bowel disease centers. Methods: Patients with moderately to severely active UC treated with ustekinumab at NYU Langone Health (New York, New York) and University of Chicago Medical Center (Chicago, Illinois) 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. Results: Sixty-six UC patients were included. Ninety-two percent of patients had prior exposure to biologics or tofacitinib. Forty-three percent and 45% of patients achieved clinical remission by 3 and 12 months, respectively. Anti-TNF nonresponse and endoscopic Mayo score of 3 were negative predictors of clinical remission. Thirty-three percent of those followed for a year achieved concurrent endoscopic and histologic healing, which was significantly associated with lower partial Mayo score (P < 0.01) and lower stool frequency (P = 0.02). Serious adverse events occurred in 4 (6%) patients (3 UC exacerbations, 1 vasculitis). Conclusions: In this cohort of mostly biologic-refractory UC patients, treatment with ustekinumab 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.

Pouchitis is the most common complication in patients who have undergone restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA). Up to 81% of IPAA patients experience pouchitis, with 40% of patients presenting within the first year of surgery. Common risk factors include genetic mutations, extensive colitis, rheumatologic disorders, and primary sclerosing cholangitis. Currently, there are no medications with approved indications for pouchitis. As such, the conventional treatment of pouchitis is entirely off-label. This paper is intended to be a practical and up-to-date review of available therapies used for the management of pouchitis. The mainstay of treatment for acute pouchitis remains antibiotics, but newer therapeutics have also shown promise in the treatment of chronic pouchitis. Common lifestyle considerations that may play a role in pouchitis are also reviewed.

BACKGROUND & AIMS:We created and validated a clinical decision support tool (CDST) to predict outcomes of vedolizumab therapy for ulcerative colitis (UC). METHODS:We performed logistic regression analyses of data from the GEMINI 1 trial, from 620 patients with UC who received vedolizumab induction and maintenance therapy (derivation cohort), to identify factors associated with corticosteroid-free remission (full Mayo score of 2 or less, no subscore above 1). We used these factors to develop a model to predict outcomes of treatment, which we called the vedolizumab CDST. We evaluated the correlation between exposure and efficacy. We validated the CDST in using data from 199 patients treated with vedolizumab in routine practice in the United States from May 2014 through December 2017. RESULTS:Absence of exposure to a tumor necrosis factor (TNF) antagonist (+3 points), disease duration of 2 y or more (+3 points), baseline endoscopic activity (moderate vs severe) (+2 points), and baseline albumin concentration (+0.65 points per 1 g/L) were independently associated with corticosteroid-free remission during vedolizumab therapy. Patients in the derivation and validation cohorts were assigned to groups of low (CDST score, 26 points or less), intermediate (CDST score, 27-32 points), or high (CDST score, 33 points or more) probability of vedolizumab response. We observed a statistically significant linear relationship between probability group and efficacy (area under the receiver operating characteristic curve, 0.65), as well as drug exposure (P < .001) in the derivation cohort. In the validation cohort, a cutoff value of 26 points identified patients who did not respond to vedolizumab with high sensitivity (93%); only the low and intermediate probability groups benefited from reducing intervals of vedolizumab administration due to lack of response (P = .02). The vedolizumab CDST did not identify patients with corticosteroid-free remission during TNF antagonist therapy. CONCLUSIONS:We used data from a trial of patients with UC to develop a scoring system, called the CDST, which identified patients most likely to enter corticosteroid-free remission during vedolizumab therapy, but not anti-TNF therapy. We validated the vedolizumab CDST in a separate cohort of patients in clinical practice. The CDST identified patients most likely to benefited from reducing intervals of vedolizumab administration due to lack of initial response. ClinicalTrials.gov no: NCT00783718.

Background: This study evaluated the prevalence of adjunctive pharmacotherapies use among ileal pouch-anal anastomosis (IPAA) patients. Methods: The IBD Partners database was queried to compare IPAA patients with and without pouch-related symptoms (PRS). Within the cohort of patients with PRS, patient reported outcomes were compared among opioid, nonsteroidal anti-inflammatory drug (NSAID), and probiotic users. Results: There were no differences in patient reported outcomes based on NSAID or probiotic usage. Opioid users reported increased bowel frequency, urgency, poor general well-being, abdominal pain, and depression (P < 0.05 for all variables). Conclusions: In IPAA patients with PRS, opioid use, but not NSAIDs or probiotics, was associated with a higher burden of PRS.

INTRODUCTION: Tofacitinib is an oral, small molecule JAK inhibitor for the treatment of UC. Changes in liver enzymes, lipids, hemoglobin (Hb), absolute neutrophil count (ANC), and absolute lymphocyte count (ALC) have been observed during 8-wk induction and 52-wk maintenance therapy with tofacitinib in patients (pts) with UC [1]. Monitoring of select parameters is recommended in pts treated with tofacitinib per product labeling [2].
METHOD(S): Changes from baseline in liver enzymes, lipids, ANC, ALC, and Hb were investigated in pts with UC treated with tofacitinib in an ongoing Phase 3, open-label, long-term extension (OLE) study (NCT01470612; data as of May 2019, database not locked). Pts who completed or demonstrated treatment failure in OCTAVE Sustain, or were non-responders after completing OCTAVE Induction 1 or 2, were eligible for the OLE study. Pts in remission at the end of OCTAVE Sustain received tofacitinib 5 mg twice daily (BID); all other pts received tofacitinib 10 mg BID in the OLE study. Proportions of pts with laboratory values meeting protocol discontinuation criteria (Table), proportions of pts with investigator-defined treatment-emergent adverse events (TEAEs) of hyper-lipidemia, and proportions of pts with an addition of or change in lipid-lowering agent (LLA), were also evaluated.
RESULT(S): Changes from OLE study baseline in liver enzymes, lipids, ANC, ALC, and Hb at Months 36 and 48, and the proportion of pts meeting protocol discontinuation criteria, are presented (Table). Findings were generally similar to the previously presented Sep 2018 data cut, which focused on Month 36 [3]. Hyperlipidemia TEAEs occurred in 2.3% and 1.3% of pts treated with tofacitinib 5 and 10 mg BID, respectively. Furthermore, 9.7% and 6.8% of pts treated with tofacitinib 5 and 10 mg BID, respectively, had a new LLA added, and 2.9% and 1.8% of pts treated with tofacitinib 5 and 10 mg BID, respectively, had their LLA dose increased.
CONCLUSION(S): No major changes from OLE study baseline were observed with tofacitinib in laboratory parameters recommended for monitoring up to Month 48. Proportions of pts meeting protocol discontinuation criteria for liver enzymes, ANC, ALC, or Hb, with hyperlipidemia TEAEs, or with a change in LLA, were low. Due to OLE study dose assignment, pt baseline remission status differs across treatment arms

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: Ileal pouch-anal anastomosis (IPAA) is a common surgical procedure in patients with an initial diagnosis of ulcerative colitis (UC), indeterminate colitis (IC), or familial adenomatous polyposis syndrome (FAP). Tobacco smoking has been associated with protection from onset of UC. Smoking has been reported to be both a protective factor and a risk factor for the development of pouchitis. In this systematic review and meta-analysis, we examine the influence of smoking on the risk of pouchitis.
METHOD(S): We identified 16 studies evaluating smoking as a risk factor for developing pouchitis in patients with a history of IPAA in a systematic search performed from inception through May 2020. A meta-analysis was then performed using a random-effects model to generate risk ratios.
RESULT(S): A total of 2,389 IPAA patients were included in the systematic review and meta-analysis. In the included studies, the percentage of patients with a diagnosis of pouchitis ranged from 22% to 72%. The percentage of patients with a history of smoking ranged from 7% to 63%. In total, 919 patients had pouchitis (330 current or former smokers; 589 non-smokers), and 1,470 patients did not have pouchitis (485 current or former smokers; 985 non-smokers). A history of smoking compared with never smoking was not associated with an increased risk of developing pouchitis (RR = 0.96, 95% CI 0.78-1.17, I² 5 68.6%). There was also no significant risk of pouchitis when comparing current smokers versus non-smokers (RR = 1.09, 95% CI 0.93-1.28, I² 5 0%) and former smokers versus non-smokers (RR = 0.95, 95% CI 0.70-1.28, I² 5 79.8%).
CONCLUSION(S): Smoking, past or present, is not associated with an increased risk for the development of pouchitis. This is important to consider when counseling patients on the risks of smoking and pouchitis

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