Longer Colonoscopy Withdrawal Time Is Associated With the Detection of Visible Dysplasia in Patients With Inflammatory Bowel Disease.

Background: Colonoscopy withdrawal time (CWT) of at least 6-9 minutes is the minimum time needed for adequate adenoma detection in the general population. The ideal CWT in patients with inflammatory bowel disease (IBD) has not been determined. We aimed to identify the optimal CWT associated with the detection of visible dysplasia in patients with IBD. Methods: This is a retrospective study from 1/1/2017 to 9/1/2022 of adult patients with IBD in endoscopic healing undergoing surveillance via high-definition white light colonoscopy. The primary outcome was the association of CWT with visible dysplasia detection. Results: A total of 259 patients (mean age 56 ±â€…14.8 years; 51.3% female, 68% with ulcerative colitis; 8.9% with primary sclerosing cholangitis) underwent 330 colonoscopies. Patients with visible dysplasia were more likely to be older (P < .001) and have a personal history of visible dysplasia (P < .001) and invisible dysplasia (P = .023). The mean CWT was significantly longer in the visible dysplasia group at 26 minutes (interquartile range [IQR] 20-38.5) vs. 21 minutes (IQR 15-28) in procedures without visible dysplasia (P < .001). On multivariable analysis, increased age (P < .001), increased CWT (P = .001), and personal history of visible dysplasia (P = .013) were independently associated with the detection of visible dysplasia. A CWT of ≥15 minutes (odds ratio [OR] 2.71; 95% confidence interval [CI], 1.11-6.6; P = .02] and not ≥9 minutes (OR 2.57; 95% CI, 0.33-20.2; P = .35) is significantly associated with detection of visible dysplasia. Conclusions: For patients with IBD undergoing surveillance via high-definition white light colonoscopy, the mean CWT was independently associated with the detection of visible dysplasia.

Early Flexible Sigmoidoscopy Improves Clinical Outcomes in Acute Severe Ulcerative Colitis.

Objectives: Guidelines recommend performing a flexible sigmoidoscopy in patients hospitalized with acute severe ulcerative colitis (ASUC). However, it is unclear if time to sigmoidoscopy affects relevant clinical outcomes. We aimed to assess the impact of early sigmoidoscopy on clinical outcomes using a well-characterized cohort of patients with ASUC. Methods: This is a single-center, retrospective study of all patients hospitalized with ASUC from January 1, 2012 to November 1, 2021. Early sigmoidoscopy was defined as occurring within 72 hours of admission while delayed sigmoidoscopy was defined as occurring >72 hours after admission. Primary outcomes were cumulative days of intravenous (IV) corticosteroid (CS) use, length of hospital stay, and colectomy rates. Secondary outcomes were time to infliximab (IFX) rescue and inpatient opioid medication use. Results: A total of 112 patients hospitalized with ASUC who underwent sigmoidoscopy were included in the analysis. Eighty-seven patients (78%) had early sigmoidoscopy and 25 (22%) had delayed sigmoidoscopy. Patients in the early sigmoidoscopy group were exposed to significantly fewer days of IV CS (4.5 vs 9.2 days; P < .001), had shorter hospital stays (6.4 vs 19.3 days; P < .001), and shorter time to IFX rescue (3.5 vs 6.4 days; P = .004). Rates of colectomy in the early and delayed sigmoidoscopy groups were 17% versus 28%, respectively (P = .23). Longer time to sigmoidoscopy was associated with a 16% increased risk of colectomy (HR = 1.16, P = .002). Conclusions: In this well-characterized cohort, early sigmoidoscopy in ASUC was associated with favorable clinical outcomes. These findings highlight the benefits of early sigmoidoscopy in patients with ASUC. Larger prospective studies are needed to corroborate these findings.

Impact of thiopurine dose in anti-tumor necrosis factor combination therapy on outcomes in inflammatory bowel disease.

Background: Combination therapy with thiopurines and anti-tumor necrosis factor (TNF) is superior to monotherapy in Crohn's disease (CD) and ulcerative colitis (UC). The optimal dose of thiopurines in combination therapy remains unclear. We investigated the impact of thiopurine dose in combination therapy on outcomes in inflammatory bowel disease (IBD). Methods: This was a single-center, retrospective study of patients with IBD treated with thiopurine and anti-TNF combination therapy between 1/2012 and 11/2020. A therapeutic dose of thiopurines was defined as ≥1 mg/kg for 6-mercaptopurine and ≥2 mg/kg for azathioprine. The primary outcome was anti-drug antibody (ADA) formation in patients on a therapeutic thiopurine dose vs. a lower thiopurine dose group. Secondary outcomes included steroid-free clinical remission, endoscopic healing (absence of ulcers/erosions in CD and Mayo endoscopic score ≤1 for UC), and normal serum C-reactive protein (CRP) in patients who were on combination therapy. Results: A total of 108 patients were included (median age 31.5 years; 58.3% male). A therapeutic dose of thiopurine was used in 19%. In the therapeutic thiopurine dose group, 23.8% developed ADA vs. 29.9% (P=0.58) in the lower dose group. No significant differences were noted between the therapeutic and lower dose thiopurine groups in terms of steroid-free clinical remission (57.1% vs. 60.9%, P=0.75), endoscopic healing (55% vs. 60%, P=0.69), and normal CRP (52.4% vs. 52.9%, P=0.27). Conclusion: In our cohort of patients with IBD on anti-TNF combination therapy, thiopurine dose was not associated with significant differences in anti-TNF immunogenicity and clinical outcomes.

Outcomes of immunomodulator and advanced therapies for primary sclerosing cholangitis-associated inflammatory bowel disease.

BACKGROUND: Inflammatory bowel disease (IBD) coexists in up to 80% of patients with primary sclerosing cholangitis (PSC). The aim of this study is to investigate the outcomes of immunomodulator (IMM)/advanced therapies for the treatment of PSC-IBD. METHODS: This was a single-center, retrospective study of patients with PSC from 1 January 2012 to 1 April 2021. Adult patients (age ≥ 18 years) with PSC-IBD were included. Primary outcomes were rates and predictors of IMM/advanced therapies to treat PSC-IBD. Secondary outcomes included rates of cholangitis, PSC-IBD clinical remission, and endoscopic healing. RESULTS: A total of 106 patients with PSC were reviewed and 72 (68%) with confirmed PSC-IBD were included in the study. The median age was 48 years (IQR, 33-59.5) and 69.4% were male. Overall, 28 patients (38.9%) required IMM/advanced therapies to treat PSC-IBD (22 biologic/small molecule therapy and six thiopurine monotherapy). Patients in the IMM/advanced therapies group were more likely to have small bowel involvement (32.1% vs. 4.6%; P = 0.002). In the IMM/advanced therapies group, clinical remission was achieved in 78.6% but endoscopic healing in only 50%. The rate of acute ascending cholangitis was 42.9% in the IMM/advanced therapies group compared with 31.8% in the non-IMM/advanced therapies group (P = 0.34). CONCLUSION: In our cohort, up to a third of patients with PSC-IBD required IMM/advanced therapies with only 50% of these patients achieving endoscopic healing. The use of IMM/advanced therapies was not associated with a higher risk of cholangitis, but larger studies are needed to investigate the risk with different classes of advanced therapies.

Effect of obesity on vedolizumab response in inflammatory bowel disease.

Background: Vedolizumab is used in inflammatory bowel disease (IBD), administered as a non-weight-based fixed dose. A higher body mass index (BMI) is associated with lower serum vedolizumab levels, but it is unclear whether it is associated with an unfavorable response to vedolizumab. We examined the relationship between BMI and the need for dose escalation, and the overall response to vedolizumab in IBD patients. Methods: This was a single-center, retrospective study of IBD patients who received vedolizumab between 1st July 2014 and 1st September 2020. The primary outcome was need for vedolizumab dose escalation or discontinuation. Secondary outcomes were steroid-free clinical remission (SFCR), endoscopic remission, and normal serum C-reactive protein (CRP). Outcomes were compared between patients with BMI <30 kg/m2 (non-obese) or ≥30 kg/m>2 (obese). Results: 190 patients were included, with a median follow-up time of 21 months. Median age was 37 years, 50.5% were male, and median BMI was 24.8 kg/m2 (75.3% of patients had BMI <30 kg/m2). Vedolizumab was dose-escalated in 48.9% of the obese group vs. 42% of the non-obese group (P=0.4). Vedolizumab was discontinued in 31.9% of the obese group vs. 53.2% of the non-obese group (P=0.01). The rate of CRP normalization was significantly lower in the obese group (46.2% vs. 66%, P=0.03). SFCR and endoscopic remission rates were not significantly different between the groups. Conclusions: Obesity was not associated with higher rates of vedolizumab dose escalation. However, it was associated with lower rates of vedolizumab discontinuation and CRP normalization, but not SFCR or endoscopic remission.

Immune Checkpoint Inhibitor-associated Diarrhea and Colitis: A Systematic Review and Meta-analysis of Observational Studies.

BACKGROUND: Immune checkpoint inhibitors (ICIs) have transformed the management of advanced malignancies but are associated with diarrhea and colitis. The objective of our systematic review and meta-analysis was to determine the incidence and outcomes of ICI-associated diarrhea and colitis. Bibliographic databases were searched through August 13, 2019, for observational studies of ICI therapy reporting the incidence and/or treatment of diarrhea or colitis. The primary outcome was ICI-associated diarrhea and colitis. Meta-analyses were performed with random-effects models. Twenty-five studies (N=12,661) were included. All studies had a high risk of bias in at least 1 domain. The overall incidence of diarrhea/colitis was 12.8% [95% confidence interval (CI), 8.8-18.2, I2=96.5]. The incidence was lower in patients treated with anti-programmed cell death 1/programmed death-ligand 1 (4.1%, 95% CI, 2.6-6.5) than in those treated with anti-cytotoxic T-cell lymphocyte-associated antigen 4 (20.1%, 95% CI, 15.9-25.1). The remission of diarrhea and/or colitis was higher in patients treated with corticosteroids plus biologics (88.4%, 95% CI, 79.4-93.8) than in those treated with corticosteroids alone (58.3%, 95% CI, 49.3-66.7, Q=18.7, P<0.001). ICI were permanently discontinued in 48.1% of patients (95% CI, 17.8-79.1). ICI were restarted after temporary interruption in 48.6% of patients (95% CI, 18.2-79.4) of whom 17.0% (95% CI, 6.4-30.0) experienced recurrence. Real-world incidence of ICI-associated diarrhea/colitis exceeds 10%. These events lead to permanent ICI discontinuation in just over 50% of patients, while <20% have recurrence of symptoms if ICI are resumed. Further studies are needed to identify patients who would benefit from early treatment with biologics as well as appropriate patients to resume ICI therapy.

Novel and Emerging Therapies for Inflammatory Bowel Disease.

Inflammatory bowel diseases (IBD) such as ulcerative colitis and Crohn's disease are chronic, relapsing and remitting disorders of intestinal inflammation with potential systemic manifestations. Despite the availability of current biologics, such as anti-tumor necrosis factor (anti-TNF), anti-integrins, anti-interleukins and small molecules such as tofacitinib, the rates of primary and secondary treatment failure remain high in IBD. This highlights the importance of continued development of new therapeutic targets and modifications of existing ones to improve the treatment response rates and to also improve the safety profile and tolerability of these medications. In this review we will discuss novel treatment target agents including selective janus kinase (JAK) inhibitors, anti-interleukin (IL) (IL-12/IL-23), leukocyte trafficking/migrating inhibitors (such as sphingosine-1-phosphate receptor modulator) and other small molecules currently in development.

Sleep Characteristics and Rest-Activity Rhythms Are Associated with Gastrointestinal Symptoms Among Adults with Inflammatory Bowel Disease.

BACKGROUND: Sleep disturbance is common in inflammatory bowel disease (IBD) and is associated with poorer quality of life and increased disease activity; however, sleep is a multidimensional process, and little is known about specific sleep characteristics and rest-activity rhythms (RARs) in this population. AIMS: The purposes were to (1) describe sleep characteristics and RARs; (2) compare sleep characteristics and RARs and GI symptoms by disease activity; and (3) describe associations between sleep characteristics, RARs, and GI symptoms among adults with IBD. METHODS: We conducted a cross-sectional study of adults with IBD. We measured sleep characteristics and RARs (continuous wrist actigraphy); GI symptoms (PROMIS-GI); and disease activity (physicians' global assessment). We conducted cosinor and nonparametric analyses to compute RAR variables and bivariate analyses to address the aims. RESULTS: The sample included 37 participants [age M = 38 years (SD = 13.8) and 21 (56.8%) female], of whom 23 (60.6%) were in remission. Sleep efficiency [M = 82.91% (SD 5.35)] and wake after sleep onset (WASO) [M = 42.26 min (SD 18.57)] were not associated with disease activity. Inter-daily stability of the RAR was associated with heartburn/reflux (r = - .491, p = .005) and gas/bloating (r = - .469, p = .008). Intra-daily variability of the RAR was associated with heartburn/reflux (r = .421, p = .018). CONCLUSIONS: People with IBD may have disrupted RARs, which are associated with GI symptoms. Research is needed to improve understanding of these associations and to develop interventions to improve these characteristics in adults with IBD.

The Feasibility of Measuring Sleep and Circadian Characteristics in Adults with Inflammatory Bowel Disease.

Interest in sleep and circadian research in inflammatory bowel disease (IBD) (Crohn's disease and ulcerative colitis) is growing; however, few studies have objectively measured sleep or circadian rhythms in people with these conditions. The purpose was to determine the feasibility of the use of wrist actigraphy, electronic sleep/activity diaries, and participant-collected saliva among adults with both active and inactive IBD. We conducted a 10-day feasibility study of adults aged 18 years to 60 years with IBD. We measured sleep and rest-activity rhythms with wrist actigraphy, self-reported sleep/activity using electronic diaries, and participant-collected saliva to compute salivary dim light melatonin onset. All 37 (100%) participants wore the wrist actigraphs, 91.8% (N = 34) participants completed at least 15 of the 18 electronic diaries, and 34 (91.9%) completed the saliva collection. It is feasible to use wrist actigraphy and electronic sleep/activity diaries in adult participants with inflammatory bowel disease.

Longitudinal Changes in Symptom Cluster Membership in Inflammatory Bowel Disease.

PURPOSE: To describe changes in symptom cluster membership over 1 year and to examine which demographic and clinical factors predict changes in symptom cluster membership among adults with inflammatory bowel disease. DESIGN: A retrospective longitudinal study of the Crohn's & Colitis Foundation of America Partners Cohort from 2012 to 2015. METHODS: We measured symptoms of pain interference, fatigue, sleep disturbance, depression, and anxiety. We used latent transition analysis to describe changes in symptom cluster membership (baseline, 6 months, and 12 months) and multinomial regressions to examine factors associated with symptom cluster membership transition. FINDINGS: Four groups were identified (N = 5,296): high symptom burden (32.3%-35.3%), low symptom burden (24.2%-27.1%), physical symptoms (19.0%-20.9%; pain, fatigue, sleep disturbance), and psychological symptoms (20.0%-21.5%; depression, anxiety). The probability of staying in the same group was .814 to .905. Moving from active disease into remission was associated with moving from the high burden to low burden and psychological symptom groups. CONCLUSIONS: Symptom cluster membership was quite stable over 1 year. Research is needed to understand the underlying etiology of symptom clusters better and to develop interventions to reduce symptom burden in this vulnerable population. CLINICAL RELEVANCE: Careful consideration of symptom management options should be done with patients to select options that are effective and potentially target multiple symptoms.

Knowledge Gaps in the Management of Postoperative Crohn's Disease: A US National Survey.

BACKGROUND: Postoperative recurrence (POR) of Crohn's disease (CD) is common. Guidelines on POR management have recently been issued, but clinical practice may vary. AIMS: To examine the current clinical practice of POR management in the USA METHODS: A web-based survey was sent to all members of the American Gastroenterological Association and the American College of Gastroenterology. The survey consisted of multiple-choice questions with clinical scenarios to assess how participants manage POR. RESULTS: A total of 189 responses were received from practices in 34 states. 44% of participants were from academic settings. The median number of CD patients seen each month was 20-30 patients per participant. The majority of participants considered smoking, prior intestinal surgery, penetrating disease, perianal fistula, early disease onset, and long extent of disease as high-risk factors for POR. To diagnose and grade endoscopic recurrence, 57% of participants used an endoscopic scoring system; 86% defined clinical recurrence using a combination of symptoms and endoscopic findings; and 79% of participants routinely performed colonoscopy after surgery. In high-risk patients, 65% offered medical prophylaxis-most often biologics and/or immunomodulators-immediately after surgery, while 34% offered medical prophylaxis regardless of the patient's risk of POR. 64% of participants never stopped medical prophylaxis once initiated. CONCLUSIONS: Most gastroenterologists routinely perform colonoscopy to guide POR management. The majority of these providers continue medical prophylaxis indefinitely regardless of subsequent endoscopic findings. Further research is needed to determine the risks and benefits of continuing versus deescalating therapy in patients with potentially surgically induced remission.

Symptom clusters in adults with inflammatory bowel disease.

Symptoms (pain, fatigue, sleep disturbance, depression, and anxiety) in inflammatory bowel disease (IBD) are associated with reduced quality of life. Understanding how IBD symptoms cluster and the clinical and demographic factors associated with symptom clusters will enable focused development of symptom management interventions. The study purposes were to (i) identify symptom cluster membership among adults with IBD and (ii) examine associations between demographic (age, gender, race/ethnicity, and education) and clinical factors (smoking status, time since diagnosis, medication type, IBD type, disease activity), and membership in specific symptom cluster groups. We conducted a retrospective study of data from the Crohn's and Colitis Foundation of America's (CCFA) Partners Cohort and used Patient Reported Outcome Measurement Information System (PROMIS) measures to measure pain interference, fatigue, sleep disturbance, anxiety, and depression. The sample included 5,296 participants with IBD (mean age 44, 72% female). In latent class analysis (LCA), four groups of participants were identified based on symptoms: "low symptom burden" (26% of sample), "high symptom burden" (38%), "physical symptoms" (22%), and "psychological symptoms" (14%). In multinomial regression, female gender, smoking, corticosteroids, Crohn's disease, and active disease state were associated with membership in the high symptom burden group. Additional research is needed to test interventions that may be effective at reducing symptom burden for individuals with IBD.

Appendectomy does not decrease the risk of future colectomy in UC: results from a large cohort and meta-analysis.

OBJECTIVES: Early appendectomy is inversely associated with the development of UC. However, the impact of appendectomy on the clinical course of UC is controversial, generally favouring a milder disease course. We aim to describe the effect appendectomy has on the disease course of UC with focus on the timing of appendectomy in relation to UC diagnosis. DESIGN: Using the National Institute of Diabetes and Digestive and Kidney Diseases Inflammatory Bowel Disease Genetics Consortium database of patients with UC, the risk of colectomy was compared between patients who did and did not undergo appendectomy. In addition, we performed a meta-analysis of studies that examined the association between appendectomy and colectomy. RESULTS: 2980 patients with UC were initially included. 111 (4.4%) patients with UC had an appendectomy; of which 63 were performed prior to UC diagnosis and 48 after diagnosis. In multivariable analysis, appendectomy performed at any time was an independent risk factor for colectomy (OR 1.9, 95% CI 1.1 to 3.1), with appendectomy performed after UC diagnosis most strongly associated with colectomy (OR 2.2, 95% CI 1.1 to 4.5). An updated meta-analysis showed appendectomy performed either prior to or after UC diagnosis had no effect on colectomy rates. CONCLUSIONS: Appendectomy performed at any time in relation to UC diagnosis was not associated with a decrease in severity of disease. In fact, appendectomy after UC diagnosis may be associated with a higher risk of colectomy. These findings question the proposed use of appendectomy as treatment for UC.