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IntroductionCrohn’s disease (CD), one of the main phenotypes of inflammatory bowel disease (IBD), can affect any part of the gastrointestinal tract. It can impact the function of gastrointestinal secretions, as well as increasing the intestinal permeability leading to an aberrant immunological response and subsequent intestinal inflammation. Studies have reported anatomical and functional brain changes in Crohn’s Disease patients (CDs), possibly due to increased inflammatory markers and microglial cells that play key roles in communicating between the brain, gut, and systemic immune system. To date, no studies have demonstrated similarities between morphological brain changes seen in IBD and brain morphometry observed in older healthy controls..MethodsFor the present study, twelve young CDs in remission (M = 26.08 years, SD = 4.9 years, 7 male) were recruited from an IBD Clinic. Data from 12 young age-matched healthy controls (HCs) (24.5 years, SD = 3.6 years, 8 male) and 12 older HCs (59 years, SD = 8 years, 8 male), previously collected for a different study under a similar MR protocol, were analyzed as controls. T1 weighted images and structural image processing techniques were used to extract surface-based brain measures, to test our hypothesis that young CDs have different brain surface morphometry than their age-matched young HCs and furthermore, appear more similar to older HCs. The phonemic verbal fluency (VF) task (the Controlled Oral Word Association Test, COWAT) (Benton, 1976) was administered to test verbal cognitive ability and executive control.Results/DiscussionOn the whole, CDs had more brain regions with differences in brain morphometry measures when compared to the young HCs as compared to the old HCs, suggesting that CD has an effect on the brain that makes it appear more similar to old HCs. Additionally, our study demonstrates this atypical brain morphometry is associated with function on a cognitive task. These results suggest that even younger CDs may be showing some evidence of structural brain changes that demonstrate increased resemblance to older HC brains rather than their similarly aged healthy counterparts.

BACKGROUND: Crohn’s disease (CD) is a subtype of inflammatory bowel disease (IBD) caused by immune-mediated inflammation in the gastrointestinal tract. The extent of morphologic brain alterations and their associated cognitive and affective impairments remain poorly characterized. AIMS: We used magnetic resonance imaging (MRI) to identify structural brain differences between patients with Crohn’s disease in remission compared to age-matched healthy controls and evaluated for structural-behavioral correlates. METHODS: 20 patients and 20 healthy, age-matched controls were recruited in the study. Group differences in brain morphometric measures and correlations between brain measures and performance on a cognitive task, the verbal fluency task, were examined. Correlations between brain measures and cognitive measures as well as self-reported measures of depression, personality, and affective scales were examined.RESULTS: Patients showed significant cortical thickening in the left superior frontal region compared to controls. Significant group differences were observed in sub-cortical volume measures in both hemispheres. Investigation of brain-behavior correlations revealed significant group differences in the correlation between cortical surface area and verbal fluency performance, although behavioral performance was equivalent between the two groups. The left middle temporal surface area was a significant predictor of verbal fluency performance with controls showing a significant positive correlation between these measures, and patients showing the opposite effect.CONCLUSIONS: Our results indicate key differences in structural brain measures in patients with CD compared to controls. Additionally, correlation between brain measures and behavioral responses suggest there may be a neural basis to the alterations in patients’ cognitive and affective responses.

Background and Aims Vedolizumab is an anti-α4β7 biologic approved for ulcerative colitis [UC] and Crohn's disease [CD]. We aimed to examine the association of maintenance vedolizumab concentrations with remission. Methods We performed a cross-sectional multi-centre study of inflammatory bowel disease [IBD] patients on maintenance vedolizumab. A homogeneous mobility shift assay [HMSA] was used to determine trough serum concentrations of vedolizumab and anti-drug antibodies [ATVs]. The primary outcome was corticosteroid-free clinical and biochemical remission defined as a composite of clinical remission, normalized C-reactive protein [CRP] and no corticosteroid use in 4 weeks. Secondary outcomes included corticosteroid-free endoscopic and deep remission. Vedolizumab concentrations were compared between patients in remission and with active disease. Logistic regression, adjusting for confounders, assessed the association between concentrations and remission. Results In total, 258 IBD patients were included [55% CD and 45% UC]. Patients in clinical and biochemical remission had significantly higher vedolizumab concentrations [12.7 µg/mL vs 10.1 µg/mL, p = 0.002]. Concentrations were also higher among patients in endoscopic and deep remission [14.2 µg/mL vs 8.5 µg/mL, p = 0.003 and 14.8 µg/mL vs 10.1 µg/mL, p = 0.01, respectively]. After controlling for potential confounders, IBD patients with vedolizumab concentrations >11.5 µg/mL were nearly 2.4 times more likely to be in corticosteroid-free clinical and biochemical remission. Only 1.6% of patients had ATVs. Conclusions In a large real-world cohort of vedolizumab maintenance concentrations, IBD patients with remission defined by objective measures [CRP and endoscopy] had significantly higher trough vedolizumab concentrations and immunogenicity was uncommon. [ABSTRACT FROM AUTHOR]

We sought to assess the association between intra-abdominal visceral adipose tissue (IA-VAT) and response to 3 different biologic drugs in patients with inflammatory bowel disease (IBD) and to investigate its effects on inflammatory cytokine expression, pharmacokinetics, and intestinal microbiota. We prospectively enrolled subjects with active IBD initiating infliximab, vedolizumab, or ustekinumab and a healthy control group. Baseline body composition (including IA-VAT as percent of total body mass [IA-VAT%]) was measured using GE iDXA scan. Primary outcome was corticosteroid- free deep remission at weeks 14–16, defined as Harvey Bradshaw Index <5 for Crohn's disease and partial Mayo score <2 for ulcerative colitis, with a normal C-reactive protein and fecal calprotectin. Secondary outcomes were corticosteroid-free deep remission and endoscopic remission (Endoscopic Mayo Score ≤1 in ulcerative colitis or Simple Endoscopic Score for Crohn's disease ≤2) at weeks 30–46. A total of 141 patients with IBD and 51 healthy controls were included. No differences in body composition parameters were seen between the IBD and healthy control cohorts. Patients with higher IA-VAT% were less likely to achieve corticosteroid-free deep remission (P <.001) or endoscopic remission (P =.02) vs those with lower IA-VAT%. Furthermore, nonresponders with high IA-VAT% had significantly higher serum interleukin-6 and tumor necrosis factor at baseline compared with responders and patients with low IA-VAT%. Drug pharmacokinetic properties and microbiota diversity were similar when comparing high and low IA-VAT% groups. Higher IA-VAT% was independently associated with worse outcomes. This association could be driven at least partially by discrete differences in inflammatory cytokine expression. [Display omitted] Patients with moderate to severe inflammatory bowel disease; a high intra-abdominal visceral adipose tissue burden; and who started infliximab, vedolizumab, or ustekinumab had a lower rate of clinical and endoscopic response compared with those with a lower intra-abdominal visceral adipose tissue burden. These findings could be related to high tumor necrosis factor and interleukin-6 overexpression, but does not seem to be explained by differences in drug pharmacokinetics or changes in the microbiota. [ABSTRACT FROM AUTHOR]

The aim of this study was to assess how 6-thioguanine nucleotide (6-TGN) levels and use of oral methotrexate relate to the pharmacokinetics of biologics. This was a prospective cohort study including patients with inflammatory bowel diseases on maintenance doses of infliximab, vedolizumab, or ustekinumab on monotherapy or combination with a thiopurine or oral methotrexate. We collected 6-TGN concentrations, biomarker levels, and clinical and endoscopic disease activity. The primary outcomes were infliximab, vedolizumab, and ustekinumab concentrations as well as anti-drug antibodies (ADAs). A total of 369 patients were recruited (113 infliximab, 133 vedolizumab, and 123 ustekinumab). Patients with 6-TGN levels ≥146 pmol per 8 × 108 red blood cells (RBCs), and those receiving combination therapy with thiopurine or oral methotrexate had significantly higher infliximab concentrations when compared with monotherapy (median levels of 17.4 μg/mL on thiopurine with 6-TGN ≥146 pmol per 8 × 108 RBCs, 17.1 on methotrexate, and 3.9 on infliximab monotherapy; P =.001 for both comparisons). However, there was no association between the use of immunomodulators and 6-TGN concentrations with vedolizumab (median levels of 8.8 on thiopurine with 6-TGN ≥152 pmol per 8 × 108 RBCs, 6.8 on methotrexate, and 10.5 on vedolizumab monotherapy; P >.05 for both comparisons) or ustekinumab median concentrations (median levels of 5.0 on thiopurine with 6-TGN ≥154 pmol per 8 × 108 RBCs, 5.2 on methotrexate and 7.0 on ustekinumab monotherapy; P >.05 for both comparisons). Fourteen (12%) patients had anti-infliximab antibodies, while 1 patient had ADAs in each of the other drug cohorts. Achieving higher 6-TGN levels or the use of methotrexate improved the pharmacokinetics of infliximab. Conversely, these data do not support the use of combination therapy to augment pharmacokinetics with vedolizumab or ustekinumab. ▪ [ABSTRACT FROM AUTHOR]

The safety and efficacy of tofacitinib in Crohn's disease (CD) has been studied in 2 phase II trials in patients with moderate-to-severe CD with no new safety signals observed, but no significant difference from placebo in the primary efficacy endpoint of clinical response.1–3 However, post hoc analyses and smaller studies have observed clinical and biologic response to tofacitinib in patients with CD.2,4,5 There is a paucity of real-world effectiveness and safety data for tofacitinib in non–Food and Drug Administration label usage in patients with CD and patients with inflammatory bowel disease–unclassified (IBD-U). [ABSTRACT FROM AUTHOR]

Adverse events (AEs) including reactivation of herpes zoster (HZ) and venous thromboembolism (VTE) have been reported from clinical trials of tofacitinib in ulcerative colitis (UC). We investigated the incidence rates of AEs in a real-world study of UC patients given tofacitinib. We collected data from 260 patients with UC in the Tofacitinib Real-world Outcomes in Patients with ulceratIve colitis and Crohn's disease consortium study, performed at 6 medical centers in the United States. Patients were followed up for a median of 6 months (interquartile range, 2.7–11.5 mo). AEs were captured using a standardized data collection instrument before study initiation and at weeks 8, 16, 26, 39, and 52. Serious AEs were defined as life-threatening or resulting in a hospitalization, disability, or discontinuation of therapy. Logistic regression was performed to examine risk factors for AEs. AEs occurred in 41 patients (15.7%); most were infections (N = 13; 5.0%). The incidence rate of any AE was 27.2 (95% CI, 24.4–30.7 per 100 patient-years of follow-up evaluation). Fifteen were serious AEs (36.6% of AEs), and tofacitinib was discontinued for 12 patients (4.6% of cohort). The incidence rates of serious AEs was 10.0 (95% CI, 8.9–11.2 per 100 patient-years of follow-up evaluation). Five patients developed HZ infection and 2 developed VTE (all receiving 10 mg tofacitinib, twice per day). Real-world safety signals for tofacitinib are similar to those for clinical trials, with AEs reported from almost 16% of patients. HZ infection and VTE occurred in patients receiving 10 mg tofacitinib twice per day. These results support dose de-escalation after induction therapy, to reduce the risk of AEs. [Display omitted] [ABSTRACT FROM AUTHOR]

Background: The aim of the study was to investigate the risk factors associated with the development of small bowel obstruction (SBO) in Crohn's disease (CD) after small bowel resection (SBR) that are not due to active/recurrent inflammation., Methods: We conducted a retrospective cohort study of patients who had SBR for active or complicated CD. Abstracted data included demographics, phenotype, therapies for CD, endoscopic disease recurrence, and several surgical variables. The primary outcome was the development of non-inflammatory SBO (NI-SBO) within 5 years after SBR., Results: A total of 335 patients were included. The cumulative rates of NI-SBO at 6 months, 1 year, and 5 years were 5 (1.5%), 8 (2.4%), and 29 (8.9%), respectively. Variables associated with the development of NI-SBO were active macroscopic or microscopic inflammation in the surgical margins (13 (56%) vs. 65 (27%), P = 0.004), open resection (vs. laparoscopic resection) (12 (41.4%) vs. 60 (19.5%), P = 0.0006) and a higher median number of previous resections (2 (interquartile range (IQR) 2 - 3) vs. 1 (IQR 1 - 2), P = 0.0002). Only 21% of patients who developed NI-SBO required surgical intervention., Conclusions: The incidence of NI-SBO after SBR in CD is low and associated with inflammation at the margins of the resected bowel, previous bowel resections, and an open laparotomy approach. Most NI-SBOs resolve with medical management., Competing Interests: M. Zulqarnain: no conflict; F. Jaber: no conflict, V. Jahagirdar: no conflict; S. Alsakarneh: no conflict; A. Stanton: no conflict; N. Patel: no conflict; J. Gomez: no conflict; P. Beniwal-Patel: no conflict; D. Stein: AbbVie: consulting, speaking and teaching; Allergan: speaking; Bristol Myers Squibb: speaking and teaching; Pfizer: speaking and teaching; Takeda: speaking and teaching; M. F. Otterson: no conflict; A. Yarur: consultant Takeda, Bristol Myers Squibb, Pfizer, Arena., (Copyright 2024, Zulqarnain et al.)

Background: Pivotal trials have shown that ustekinumab is effective in ulcerative colitis (UC). However, the population included in these trials do not represent the cohort of patients treated in the real world. In this study, we aimed to describe the effectiveness and safety of ustekinumab in a clinical cohort of patients with UC., Methods: We performed a multicenter retrospective cohort study and included patients with active UC starting ustekinumab. Variables collected included demographics, clinical data, and disease activity (measured using partial Mayo score [PMS] and endoscopic Mayo score) at follow-up. The primary outcomes were cumulative rates of steroid-free clinical and biochemical remission (SFCBR), defined as a PMS <2 while off steroids and a normal C-reactive protein and/or fecal calprotectin., Results: A total of 245 patients met inclusion criteria. The median time of follow-up was 33 (interquartile range, 17-53) weeks, and 214 (87.3%) had previous exposure to a biologic and/or tofacitinib. Rates of SFCBR, clinical remission, and endoscopic remission at 6 and 12 months were 12.0% (n = 16 of 139), 29.0% (n = 71 of 175), and 18.0% (n = 7 of 39), and 23.8% (n = 15 of 63), 54.3% (n = 57 of 105), and 31.0% (n = 9 of 29), respectively. Non-Hispanic White race, higher baseline PMS, and the use of concomitant corticosteroids were independently associated with failure to achieve SFCBR. Of the 73 that were dose escalated, 28.4% did not respond, 49.3% experienced a benefit, and 21.6% achieved remission., Conclusions: In a population enriched with refractory UC, ustekinumab was well tolerated and induced remission in a significant number of patients. Larger studies with a longer follow-up are warranted., (© The Author(s) 2024. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Introduction: There is a paucity of data on the real-world effectiveness of therapies in patients with Crohn's disease of the pouch., Methods: This was a prospective multicenter study evaluating the primary outcome of remission at 12 months of therapy for Crohn's disease of the pouch., Results: One hundred thirty-four patients were enrolled. Among the 77 patients with symptoms at baseline, 35 (46.7%) achieved remission at 12 months. Of them, 12 (34.3%) changed therapy. There was no significant association between therapy patterns and remission status., Discussion: Approximately 50% with symptoms at enrollment achieved clinical remission at 12 months, most of whom did so without a change in therapy., (Copyright © 2024 by The American College of Gastroenterology.)

Introduction: Crohn's disease (CD), one of the main phenotypes of inflammatory bowel disease (IBD), can affect any part of the gastrointestinal tract. It can impact the function of gastrointestinal secretions, as well as increasing the intestinal permeability leading to an aberrant immunological response and subsequent intestinal inflammation. Studies have reported anatomical and functional brain changes in Crohn's Disease patients (CDs), possibly due to increased inflammatory markers and microglial cells that play key roles in communicating between the brain, gut, and systemic immune system. To date, no studies have demonstrated similarities between morphological brain changes seen in IBD and brain morphometry observed in older healthy controls.., Methods: For the present study, twelve young CDs in remission (M = 26.08 years, SD = 4.9 years, 7 male) were recruited from an IBD Clinic. Data from 12 young age-matched healthy controls (HCs) (24.5 years, SD = 3.6 years, 8 male) and 12 older HCs (59 years, SD = 8 years, 8 male), previously collected for a different study under a similar MR protocol, were analyzed as controls. T1 weighted images and structural image processing techniques were used to extract surface-based brain measures, to test our hypothesis that young CDs have different brain surface morphometry than their age-matched young HCs and furthermore, appear more similar to older HCs. The phonemic verbal fluency (VF) task (the Controlled Oral Word Association Test, COWAT) (Benton, 1976) was administered to test verbal cognitive ability and executive control., Results/discussion: On the whole, CDs had more brain regions with differences in brain morphometry measures when compared to the young HCs as compared to the old HCs, suggesting that CD has an effect on the brain that makes it appear more similar to old HCs. Additionally, our study demonstrates this atypical brain morphometry is associated with function on a cognitive task. These results suggest that even younger CDs may be showing some evidence of structural brain changes that demonstrate increased resemblance to older HC brains rather than their similarly aged healthy counterparts., Competing Interests: Dr. Saha is a consultant for UCB Biosciences, Inc. All the other authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. All authors further declare that the research was conducted in the absence of any non-financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Yeske, Hou, Chu, Adluru, Nair, Beniwal-Patel, Saha and Prabhakaran.)

Background and Aims: Racial and ethnic disparities exist in the treatment of IBD. These disparities exist in adult vaccine uptake among the general population and may extend to patients with IBD. The primary aim of this study was to determine whether racial, ethnic, or geographic disparities existed in influenza vaccine uptake among patients with IBD., Methods: We performed a multicenter, retrospective cohort study evaluating adult vaccine uptake among patients with IBD seen at two tertiary referral centers between September 2019 and February 2020. The primary outcome was to determine if racial/ethnic and geographic disparities existed in influenza vaccine uptake for the two prior seasons. Our secondary outcomes were to determine if disparities existed for pneumococcal, zoster, or hepatitis B vaccines., Results: Among the 2453 patients who met the inclusion criteria, most identified as non-Hispanic White (89.9%), were on immunosuppressive therapy (74.5%), and received the influenza vaccine in both seasons (56.0%). Older age (prevalence ratio (PR) 0.98; 95% confidence interval (95%CI) 0.98-0.99; P  < .001) and non-Hispanic White patients (PR 0.76, 95%CI 0.59-0.98, P  < 0.03) were significantly more likely to be immunized. Black patients (PR 1.37; 95%CI 1.18-1.59; P  < .001) and those living in underserved geographic areas (PR 1.35; 95%CI 1.17-1.56; P  < 0.001) were less likely to be immunized. Racial/ethnic and geographic disparities were identified for pneumococcal, zoster, and hepatitis B vaccine uptake., Conclusions: Racial and ethnic vaccination uptake disparities exist among patients with IBD; patients from medically underserved areas are also vulnerable to these disparities Studies identifying patient, provider, and system-level opportunities to address these disparities are needed., Competing Interests: F.C. has received research support from Takeda Pharmaceuticals. He has been a consultant for Takeda, Arena Pharmaceuticals, GSK, and Celgene. F.A.F. is a consultant for AbbVie, BMS, Braintree Labs, Fresenius Kabi, GI Reviewers, GSK, IBD Educational Group, Iterative Health, Janssen, Pharmacosmos, Pfizer,Sebela and Viatris. He sits on a DSMB for Eli Lilly. M.S.H. is a consultant for GSK Vaccines and Seqirus and has received research support from Takeda Pharmaceuticals and Dynavax. P.B.P. has been a consultant for Takeda Pharmaceuticals. Guarantor of the article: F.C., D.O., M.S. F.C.—study concept and design, acquisition of data, analysis and interpretation of data, drafting of the manuscript, and critical revision of manuscript. M.S.H—study concept and design, acquisition of data, analysis, and interpretation of data, drafting of the manuscript, and critical revision of manuscript. P.B.P.—study concept and design, acquisition of data, and interpretation of data, drafting of the manuscript, and critical revision of manuscript. G.W.—study concept and design, acquisition of data, analysis and interpretation of data, drafting of the manuscript, and critical revision of manuscript. F.A.F.—critical revision of manuscript. J.W.—study concept and design and critical revision of manuscript. K.B.—acquisition of data and critical revision of manuscript. A.U.—acquisition of data and critical revision of manuscript. T.L.S.—acquisition of data and critical revision of manuscript. R.S.—acquisition of data and critical revision of manuscript. A.H.—acquisition of data and critical revision of manuscript. L.H.—acquisition of data and critical revision of manuscript. K.E.D.—acquisition of data and critical revision of manuscript. S.D.—acquisition of data and critical revision of manuscript. N.S.—acquisition of data and critical revision of manuscript. K.R.S.—acquisition of data and critical revision of manuscript. R.K.R.—data analysis and critical revision of manuscript. M.A.M.—acquisition of data and critical revision of manuscript. F.O.—statistical analysis., (© The Author(s) 2023. Published by Oxford University Press on behalf of Crohn's & Colitis Foundation.)

Introduction: In patients with inflammatory bowel diseases (IBDs), high visceral adipose tissue (VAT) burden is associated with a lower response to infliximab, potentially through alterations in volume distribution and/or clearance. Differences in VAT may also explain the heterogeneity in target trough levels of infliximab associated with favorable outcomes. The aim of this study was to assess whether VAT burden may be associated with infliximab cutoffs associated with efficacy in patients with IBD., Methods: We conducted a prospective cross-sectional study of patients with IBD receiving maintenance infliximab therapy. We measured baseline body composition parameters (Lunar iDXA), disease activity, trough levels of infliximab, and biomarkers. The primary outcome was steroid-free deep remission. The secondary outcome was endoscopic remission within 8 weeks of infliximab level measurement., Results: Overall, 142 patients were enrolled. The optimal trough levels of infliximab cutoffs associated with steroid-free deep remission and endoscopic remission were 3.9 mcg/mL (Youden Index [J]: 0.52) for patients in the lowest 2 VAT % quartiles (<1.2%) while optimal infliximab level cutoffs associated with steroid-free deep remission for those patients in the highest 2 VAT % quartiles was 15.3 mcg/mL (J: 0.63). In a multivariable analysis, only VAT % and infliximab level remained independently associated with steroid-free deep remission (odds ratio per % of VAT: 0.3 [95% confidence interval: 0.17-0.64], P < 0.001 and odds ratio per μg/mL: 1.11 [95% confidence interval: 1.05-1.19], P < 0.001)., Discussion: The results may suggest that patients with higher visceral adipose tissue burden may benefit from achieving higher infliximab levels to achieve remission., (Copyright © 2023 by The American College of Gastroenterology.)

Background: Evidence-based recommendations regarding the influence of diet on inflammatory conditions of the pouch after restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) are limited., Methods: We analyzed dietary patterns at enrollment in a prospective registry of patients with 1 of 4 inflammatory conditions of the pouch (acute pouchitis, chronic antibiotic-dependent pouchitis, chronic antibiotic refractory pouchitis, and Crohn's disease of the pouch). We analyzed dietary intake by disease activity at enrollment and then compared dietary patterns among patients who remained in remission throughout the 12-month follow-up to those patients who experienced a disease relapse. We also compared dietary patterns among patients with inflammatory conditions of the pouch to the United States Department of Agriculture (USDA) recommended daily goals., Results: Among 308 patients, there were no differences in dietary patterns among patients with 1 of the 4 disease states at enrollment. Additionally, among the 102 patients in remission at baseline, there were no significant differences noted among patients who went on to experience a disease flare in the 12 months after enrollment compared to those patients who remained in remission. However, patients with inflammatory conditions of the pouch demonstrated decreased intake of several food groups and macronutrients including dairy, fruits, vegetables, whole grains, and fiber when compared to USDA recommendations., Conclusions: In a prospective cohort, we demonstrated no impact of dietary patterns on disease activity. The relative deficiencies in several food groups and macronutrients among patients after IPAA indicate the potential role of targeted nutritional counseling in this population., Competing Interests: E.L.B. has served as a consultant for AbbVie, Bristol-Meyers Squibb, Eli Lilly, and Target RWE. P.D. has served as a consultant or on an advisory board for Janssen, Pfizer, Prometheus Biosciences, Boehringer Ingelheim, AbbVie, Arena Pharmaceuticals, Takeda Pharmaceuticals LLC, Roche Genentech, Bristol Myers Squibb and Scipher Medicine Corporation. He has also received funding under a sponsored research agreement unrelated to the data in the paper from Takeda Pharmaceutical, Arena Pharmaceuticals, Bristol Myers Squibb-Celgene, Janssen, Landos Pharma, Teva Pharma, Iterative scopes, CorEvitas and Boehringer Ingelheim. P.D. holds the position of Associate Editor for Crohn’s & Colitis 360 and has been recused from reviewing or making decisions for the manuscript. P.B.-P. has received honorarium from the Takeda speaker’s bureau. L.R. has served on an advisory board for Janssen. LR holds the position of Associate Editor for Crohn’s & Colitis 360 and has been recused from reviewing or making decisions for the manuscript. M.D. has served as a consultant or has received advisory board fees from Abbvie, Arena, BMS, Eli Lilly, Gilead, Janssen, Pfizer, Prometheus Labs, Takeda. She has received grant support from Janssen, Abbvie. She also has the following relationships: Licenser of software: Takeda; Co-Founder, Equity ownership and board of director for Trellus Health Shannon Chang has served as a consultant for AbbVie, BMS, and Pfizer. R.K.C. has participated in advisory boards for AbbVie, Bristol Myers Squibb, Fresenius Kabi, and has served as a consultant for Fzata, Magellan Health, Pfizer, and Samsung Bioepis. He is on the Data Safety Monitoring Board for Adiso, is a member of the Executive Committee for the IBD Education Group and is Co-Director of the CorEvitas Registry. M.D.L. has served as a consultant for AbbVie, UCB, Takeda, Janssen, Pfizer, Salix, Valeant, Target Pharmasolutions and has received research support from Pfizer and Takeda. H.H.H. has served as a consultant for Alivio, AMAG, BMS, ExeGI Finch, Gilead, Janssen, Lycera, Merck, Otsuka, Pfizer, PureTech, Seres and has received research support from Pfizer and Artizan Biosciences. M.K., P.D.R.H., J.B., and C.A. have no relevant disclosures., (© The Author(s) 2023. Published by Oxford University Press on behalf of Crohn's & Colitis Foundation.)

Background: Much of our understanding about the natural history of pouch-related disorders has been generated from selected populations. We designed a geographically diverse, prospective registry to study the disease course among patients with 1 of 4 inflammatory conditions of the pouch. The primary objectives in this study were to demonstrate the feasibility of a prospective pouch registry and to evaluate the predominant treatment patterns for pouch-related disorders., Methods: We used standardized diagnostic criteria to prospectively enroll patients with acute pouchitis, chronic antibiotic-dependent pouchitis (CADP), chronic antibiotic refractory pouchitis (CARP), or Crohn's disease (CD) of the pouch. We obtained detailed clinical and demographic data at the time of enrollment, along with patient-reported outcome (PRO) measures., Results: We enrolled 318 patients (10% acute pouchitis, 27% CADP, 12% CARP, and 51% CD of the pouch). Among all patients, 55% were on a biologic or small molecule therapy. Patients with CD of the pouch were more likely to use several classes of therapy ( P < .001). Among patients with active disease at the time of enrollment, 23% with CARP and 40% with CD of the pouch were in clinical remission at 6 months after enrollment., Conclusions: In a population where most patients had refractory inflammatory conditions of the pouch, we established a framework to evaluate PROs and clinical effectiveness. This infrastructure will be valuable for long-term studies of real-world effectiveness for pouch-related disorders., (© The Author(s) 2022. Published by Oxford University Press on behalf of Crohn's & Colitis Foundation.)

Background: Infliximab is an efficacious therapy for inflammatory bowel disease and may play a role in management of some extraintestinal manifestations. While higher trough levels of infliximab are associated with higher rates of disease remission, the association between trough levels of infliximab and arthralgia activity characterised as an extraintestinal manifestation has yet to be defined., Objective: We aimed to assess the association between serum trough levels of infliximab and peripheral arthralgia activity in patients with inflammatory bowel disease., Design: In this cross-sectional study, we identified patients with inflammatory bowel disease on infliximab therapy with known history of arthralgias attributed to an extraintestinal manifestation. Collected variables included disease phenotype, medications (such as thiopurines or methotrexate), Harvey Bradshaw Index, partial Mayo score, C reactive protein, trough levels of infliximab and anti-infliximab antibodies. The primary outcome was active patient-reported arthralgia., Results: Out of 267 patients included, 65 (24.4%) had active arthralgias at the time the trough level of infliximab was measured. No significant differences in trough levels were seen between those patients with and without arthralgias. Patients on combination therapy with methotrexate or thiopurines or those with detectable anti-infliximab antibodies were not more likely to have inactive arthralgias (OR 0.99, 95% CI 0.57 to 1.74, p=0.99 and OR 1.94, 95% CI 0.9 to 4.1, p=0.09, respectively)., Conclusions: This study suggests that although therapeutic drug monitoring of infliximab can have a role in the management of Crohn's disease and ulcerative colitis, it does not seem to be useful in managing arthralgias associated with inflammatory bowel disease., Competing Interests: Competing interests: DJS: Has speaker honorariums from Abbvie, Takeda, Pfizer and Jansen. AJY: Member of advisory boards for Takeda, Bristol Myers Squibb, Prometheus Laboratories and Arena Pharmaceuticals, (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background and Purpose: In this pilot study, we investigated functional brain activation changes in patients with Crohn's disease (CD) in remission compared to age and gender-matched healthy controls (HCs)., Methods: Data from 20 patients with CD in remission (age range 19-63 years) and 20 HCs (matched in age and gender) were analyzed. Task functional MRI (fMRI) data were collected while participants performed a cognitive (phonemic verbal fluency) task in the scanner. All participants also performed the same task outside the scanner., Results: Task fMRI results showed greater bi-hemispheric activation in CD patients compared to controls. Because this pattern is commonly reported with normal aging, we performed further analyses to investigate fMRI responses in a subset of the younger CD patients (N = 12, age < = 35 years) compared to matched young HCs (age < = 35 years), and an older cohort of HCs (age > = 50 years). Results showed that task activation patterns were similar between young CD patients and older HCs, and that both groups differed significantly from younger HCs. Activation intensity in specific brain regions for patients was associated with disease duration., Conclusions: These results suggest that CD patients in remission may show accelerated signs of aging in terms of brain responses to a typical cognitive task. Future work with larger sample size will need to replicate these results as well as investigate the influence of factors, such as chronicity of the disease and medication effects on task-associated brain activation patterns in this patient population., (© 2019 by the American Society of Neuroimaging.)