Dietary patterns are not associated with disease activity among patients with inflammatory conditions of the pouch in a prospective cohort

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\u27s 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

Treatment patterns and standardized outcome assessments among patients with inflammatory conditions of the pouch in a prospective multicenter registry

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\u27s 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 ( 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

Combination Therapy With Immunomodulators Improves the Pharmacokinetics of Infliximab But Not Vedolizumab or Ustekinumab

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.

Structural imaging changes and behavioral correlates in patients with Crohn’s disease in remission.

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

PATIENTS WITH INFLAMMATORY BOWEL DISEASES AND HIGHER VISCERAL ADIPOSE TISSUE BURDEN MAY BENEFIT FROM HIGHER INFLIXIMAB CONCENTRATIONS TO ACHIEVE REMISSION

INTRODUCTIONIn patients with inflammatory bowel diseases (IBD), high visceral adipose tissue burden is associated with lower response to infliximab, potentially through alterations in volume distribution and/or clearance. Differences in visceral adipose tissue may also explain heterogenicity in target trough levels of infliximab associated with favorable outcomes. The aim of this study was to assess whether visceral adipose tissue burden may be associated with infliximab cutoffs associated with efficacy in patients with IBD.METHODSWe 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. Secondary outcome was endoscopic remission within 8 weeks of infliximab level measurement.RESULTSOverall, 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 two visceral adipose tissue % quartiles (<1.2%) while optimal infliximab level cutoffs associated with steroid free deep remission for those patients in the highest two visceral adipose tissue % quartiles was 15.3 mcg/mL (J:0.63). In a multivariable analysis, only visceral adipose tissue % and infliximab level remained independently associated with steroid free deep remission (OR per % of VAT:0.3 [95%CI: 0.17-0.64], p<0.001 and OR per μg/ml:1.11 [95%CI: 1.05-1.19], p<0.001).CONCLUSIONSThe results may suggest that patients with higher visceral adipose tissue burden may benefit of achieving higher infliximab levels to achieve remission