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To date, there are limited real-world studies published on the use of infliximab-dyyb, a biosimilar to reference product (RP) infliximab approved for the treatment of moderate to severe inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC) in North America. This study examined utilization patterns and the effects of infliximab-dyyb on clinical outcomes, patient-reported outcomes (PROs), and healthcare resource use (HCRU) in IBD patients in a real-world setting.In this prospective, observational study, adult IBD patients in the US and Canada were recruited to initiate treatment with infliximab-dyyb and followed for 12 months. Patients included biologic-naïve users of infliximab-dyyb and patients switching from RP infliximab or other biologics to infliximab-dyyb. Partial Mayo (pMAYO) and Harvey Bradshaw Index (HBI) scores measured clinical outcomes for the UC and CD cohorts, respectively. Key PRO measures included the SIBDQ, EQ-VAS, and psychological outcomes. In addition, work productivity, HCRU, and adverse events (AEs) were assessed.A total of 67 CD and 48 UC patients were enrolled (51% female; mean age 44 years; 87% Caucasian; mean BMI 27.9). Thirty-nine patients were biologic-naïve, 57 switched from RP infliximab, and 19 switched from other biologics. Among UC biologic-naïve users, pMAYO decreased from 5.67 to 1.09 (p 0.0001) and the remission rate increased from 5.6 to 90.9% (p = 0.0015). For UC patients switching from RP infliximab, pMAYO decreased from 1.38 to 0.29 (p = 0.0103). For CD biologic-naïve users, HBI scores and remission rates did not significantly change. The scores on all the PROs significantly improved from baseline to 12 months. A total of 22 AEs occurred consistent with the known AE profile for infliximab.Clinical outcomes among biologic-naïve users of infliximab-dyyb improved for UC and were maintained for CD patients. Biologic-naïve users of infliximab-dyyb showed significant improvements in PROs. Patients switching from RP infliximab to infliximab-dyyb maintained their clinical outcomes and PROs.ClinicalTrials.gov Registration Number: NCT03801928 (February 23, 2018).

Summary Pouchitis, Crohn's disease of the pouch, cuffitis, polyps, and extraintestinal manifestations of inflammatory bowel disease are common inflammatory disorders of the ileal pouch. Acute pouchitis is treated with oral antibiotics and chronic pouchitis often requires anti-inflammatory therapy, including the use of biologics. Aetiological factors for secondary pouchitis should be evaluated and managed accordingly. Crohn's disease of the pouch is usually treated with biologics and its stricturing and fistulising complications can be treated with endoscopy or surgery. The underlying cause of cuffitis determines treatment strategies. Endoscopic polypectomy is recommended for large, symptomatic inflammatory polyps and polyps in the cuff. The management principles of extraintestinal manifestations of inflammatory bowel disease in patients with pouches are similar to those in patients without pouches.

Purpose of review This review addresses the selection of biologic and small molecule therapy for patients with moderate to severe ulcerative colitis (UC). With several new treatment options approved within the past few years, an update in positioning is timely and relevant. Recent findings Updates on the safety and comparative efficacy of approved therapeutic agents for UC are presented. Newly approved therapies including tofacitinib and ustekinumab, as well as where to position these treatments are discussed. Data on the first-ever head-to-head trial of biologic therapy in UC are examined. This review provides an evidence-based overview of the optimal management strategies of patients in both the inpatient and outpatient settings. Summary As we move closer towards the goal of personalized therapy for our patients with UC, we hope to better select appropriate and effective treatment options. Newly approved therapies provide us with additional options for management. Future advancements in predictive serologic, mucosal, genetic, and fecal markers can enable us to tailor therapy to an individual patient.

Chronic inflammatory diseases including human immunodeficiency virus infection, psoriasis, rheumatoid arthritis, and systemic lupus erythematosus predispose to atherosclerotic cardiovascular disease (ASCVD). Inflammatory bowel disease (IBD) is a common chronic inflammatory condition, and the United States has the highest prevalence worldwide. IBD has so far been overlooked as a contributor to the burden of ASCVD among young and middle-age adults, but meta-analyses of cohort studies suggest that IBD is an independent risk factor for ASCVD. This review discusses the epidemiological links between IBD and ASCVD and potential mechanisms underlying these associations. ASCVD risk management of patients with IBD is challenging because of their young age and the inability of current risk scores to fully capture their increased risk. The role of IBD in current primary prevention guidelines is evaluated, and strategies for enhanced ASCVD risk reduction in patients with IBD are outlined. Finally, the authors discuss knowledge gaps and future research directions in this innovative field.

Background Therapeutic efficacy of biologics has remained at about 50% for 2 decades. In Crohn’s disease (CD) patients, we examined the predictive value of an epithelial cell biomarker, ileal microvillar length (MVL), for clinical response to ustekinumab (UST) and vedolizumab (VDZ) and its relationship to another biomarker, intestinal epithelial cell (IEC) pyroptosis, with respect to response to VDZ. Method Ileal biopsies from the UNITI-2 randomized controlled trial were analyzed for MVL as a predictor of clinical response to UST. In a 5-center academic retrospective cohort of CD patients, ileal MVL was analyzed to determine its predictive value for response to VDZ. Correlation between ileal MVL and IEC pyroptosis was determined, and the discriminant ability of the combination of 2 biomarkers to VDZ was examined. Results Clinical response in UST was significantly higher than placebo (65% vs 39%; P = 0.03), with patients with normal MVL (>1.7 µm) having the greatest therapeutic effect: 85% vs 20% (P = 0.02). For VDZ, clinical response with MVL of 1.35 to 1.55 µm was 82% vs 44% (1.55 µm; P = 0.038). There was no correlation between ileal MVL and IEC pyroptosis. The combination criteria of ileal pyroptosis Conclusion Ileal MVL was predictive of response to UST and VDZ in prospective and retrospective CD cohorts. It was independent of ileal IEC pyroptosis, and combination of the 2 biomarkers enhanced the discriminate ability of responders from nonresponders to VDZ.

Inflammatory bowel diseases (IBD), namely, Crohn’s disease (CD) and ulcerative colitis (UC) are idiopathic chronic, relapsing, inflammatory diseases of the gastrointestinal (GI) tract. Triggers for disease flares include medications, infection, acute stress, and the menstrual cycle. Varying ovarian hormone levels i.e. prostaglandins and progesterone may exaggerate GI symptoms in IBD. We aimed to determine the relationship between quality of life, endoscopic and clinical disease activity and the menstrual cycle among females with IBD through a questionnaire based cross-sectional study. The first 75 women of child-bearing age seen at IBD clinic completed a questionnaire incorporating the short IBD questionnaire (SIBDQ). Menstrual symptoms were evaluated using the validated Moos Menstrual Distress Questionnaire (MDQ) to measure cyclical peri-menstrual symptoms. Endoscopic disease severity was assessed using the Rutgeert’s score (post ileo-cecal resection patients) or Simple Endoscopic Score for CD and the Mayo score for UC. There was a statistically negative correlation between MDQ and SIBDQ scores (p

Inflammatory bowel disease (IBD) is a chronic immune-mediated disease affecting the gastrointestinal tract. IBD consists of 2 subtypes: ulcerative colitis and Crohn disease. IBD is thought to develop as a result of interactions between environmental, microbial, and immune-mediated factors in a genetically susceptible host. Of late, the potential role of the microbiome in the development, progression, and treatment of IBD has been a subject of considerable interest and enquiry. Indeed, studies in human subjects have shown that the gut microbiome is different in patients with IBD compared with that in healthy control subjects. Other evidence in support of a fundamental role for the microbiome in patients with IBD includes identification of mutations in genes involved in microbiome-immune interactions among patients with IBD and epidemiologic observations implicating such microbiota-modulating risk factors as antibiotic use, cigarette smoking, levels of sanitation, and diet in the pathogenesis of IBD. Consequently, there has been much interest in the possible benefits of microbiome-modulating interventions, such as probiotics, prebiotics, antibiotics, fecal microbiota transplantation, and gene manipulation in the treatment of IBD. In this review we will discuss the role of the gut microbiome in patients with IBD; our focus will be on human studies.

Objective Mucosal barrier dysfunction plays a crucial role in intestinal inflammation in Crohn’s disease (CD). Intestinal epithelial cell (IEC) death resulting from innate immune activation, termed pyroptosis, was recently found to be a cause of this barrier defect. The aim of this study was to determine the predictive value of pretreatment ileal biopsy pyroptosis as a biomarker for clinical response to vedolizumab in CD. Design Crohn’s disease patients ranging 18 to 80 years old from 5 IBD centers with pre-vedolizumab ileal biopsies during colonoscopy were enrolled. Biopsies were stained for activated caspases, and levels of ileal IEC pyroptosis levels were quantified. The primary outcome was clinical response 6 months after therapy, defined as a reduction of Harvey-Bradshaw Index (HBI) of ≥5 points from baseline. Secondary outcomes included clinical remission, defined as HBI Results One hundred CD patients (45 male, 55 female), median age 47 (19, 78) years, were included; clinical response rate was 60%, and clinical remission was 36%. The response rate in patients with ileal pyroptosis Conclusions Ileal biopsy IEC pyroptosis was predictive of clinical response and endoscopic improvement to vedolizmab in CD patients.

Antibiotics and probiotics are often used as adjunctive therapy in inflammatory bowel disease. However, data are limited and randomised controlled trials are too inconsistent to provide generalised recommendations for their use in all patients with ulcerative colitis or Crohn’s disease. Antibiotics are best used in the management of infectious complications and fistulas in Crohn’s disease and, perhaps, in reducing the intensity of inflammation in luminal disease. Ciprofloxacin, metronidazole and rifaximin have been most widely used and studied. On the other hand, there appears to be a limited role for antibiotics in ulcerative colitis (UC). Probiotics are most effective in pouchitis, and may have a role in the initial therapy and maintenance of remission in mild UC; the probiotic cocktail VSL#3 has been the most widely studied. There is scant evidence of efficacy for probiotics in Crohn’s disease.

In recent years, extensive studies have been carried out on the synthesis of hybrid inorganic–organic polymers. An important group of these polymers are polyborosiloxanes which have gained importance as oxidation protection coating. Methylborosiloxane (BM) with ceramic residue 85% was synthesized from boric acid and methyltriethoxysilane in 1:2 ratio at 80–85 °C. The effect of carbon addition on the crystallization behaviour of BM was studied using pyrocarbon (PyC) as the carbon source. Ceramic conversion studies of the oligomers were carried out with and without carbon by pyrolysis at 900 °C followed by heat treatment at 1500 °C and 1650 °C in inert atmosphere. The oligomer gave an amorphous SiBOC ceramic at 1500 °C, but with increase in heat treatment temperature to 1650 °C, SiC crystallized out from the SiBOC matrix. With the increase in the PyC concentration, there was an enhancement in the formation of crystalline SiC.

Background With the management of inflammatory bowel disease (IBD) becoming increasingly complex, incorporating preventive care health maintenance measures can be challenging. The aim of developing these updated recommendations is to provide more specific details to facilitate their use into a busy clinical practice setting. Method Fifteen statements were formulated with recommendations regarding the target, timing, and frequency of the health maintenance interventions in patients with IBD. We used a modified Delphi method and a literature review to establish a consensus among the panel of experts. The appropriateness of each health maintenance statement was rated on a scale of 1 to 5 (1–2 as inappropriate, and 4–5 as appropriate) by each panelist. Interventions were considered appropriate, and statements were accepted if ≥80% of the panelists agreed with a score ≥4. Results The panel approved 15 health maintenance recommendations for adults with IBD based on the current literature and expert opinion. These recommendations include explicit details regarding specific screening tools, timing of screening, and vaccinations for adults with IBD. Conclusions Patients with IBD are at an increased risk for infections, malignancies, and other comorbidities. Given the complexity of caring for patients with IBD, this focused list of recommendations can be easily incorporated in to clinical care to help eliminate the gap in preventative care for patients with IBD.

Patients with inflammatory bowel disease often present to the emergency department due to the chronic relapsing nature of the disease. Previous studies have shown younger patients to have an increased frequency of emergency department visits, resulting in repeated exposure to imaging studies and steroids, both of which are associated with risks. We performed a retrospective cohort analysis of inflammatory bowel disease patients seen at Houston Methodist Hospital’s emergency department from January 2014 to December 2017 using ICD codes to identify patients with Crohn’s disease, ulcerative colitis, or indeterminate colitis from the electronic medical record. Data were collected on demographics, medications, and imaging. Five hundred and fifty-nine patients were randomly selected for inclusion. Older age was associated with decreased risk of CT scan or steroid use. Patients with ulcerative colitis compared to Crohn’s had decreased risk of CT scan, while there was an increased risk of CT in patients on a biologic, immunomodulator, or when steroids were given. Steroid use was also more common in those with inflammatory bowel disease as the primary reason for the visit. Patients in our study frequently received steroids and had CT scans performed. The increased risk of CT in those on a biologic, immunomodulator, or steroids suggests more severe disease may contribute. Guidelines are needed to reduce any unnecessary corticosteroid use and limit repeat CT scans in young inflammatory bowel disease patients to decrease the risk of radiation-associated malignancy over their lifetime.

Restorative proctocolectomy with ileal pouch-anal anastomosis is an option for most patients with ulcerative colitis or familial adenomatous polyposis who require colectomy. Although the construction of an ileal pouch substantially improves patients' health-related quality of life, the surgery is, directly or indirectly, associated with various structural, inflammatory, and functional adverse sequelae. Furthermore, the surgical procedure does not completely abolish the risk for neoplasia. Patients with ileal pouches often present with extraintestinal, systemic inflammatory conditions. The International Ileal Pouch Consortium was established to create this consensus document on the diagnosis and classification of ileal pouch disorders using available evidence and the panellists' expertise. In a given individual, the condition of the pouch can change over time. Therefore, close monitoring of the activity and progression of the disease is essential to make accurate modifications in the diagnosis and classification in a timely manner.

Background: Combining biologics and small molecules could potentially overcome the plateau of drug efficacy in inflammatory bowel disease (IBD). We conducted a systematic review and meta-analysis (SRMA) to assess the safety and effectiveness of dual biologic therapy (DBT) or small molecule combined with a biologic therapy (SBT) in IBD patients. Methods: MEDLINE, EMBASE, Scopus, Web of Science, Cochrane Database of Systematic Reviews and Clinical trials.gov were reviewed from inception to Nov 3, 2020. Studies with two or more IBD patients on DBT or SBT were included while single-case reports were excluded. The main outcome was safety assessed as pooled rates of adverse events (AEs) and serious AEs (SAEs) for each combination category. Effectiveness was reported as pooled rates of clinical, endoscopic and/or radiographic response and remission. Random-effects modeling was performed for between-study heterogeneity using the I² statistic. The SRMA was registered with PROSPERO (CRD4202018361). Findings: Of the 3,688 publications identified, 13 studies involving 266 patients on seven different combinations were included. Median number of prior biologics ranged from 0-4, and median duration of follow-up was 16-68 weeks. Most common DBT and SBT were vedolizumab (VDZ) with anti-Tumour Necrosis Factor (aTNF, n=56) or tofacitinib (Tofa, n=57), respectively. Pooled rates of SAE for these were 9·6% (95% CI, 1·5 – 21·4; 8 studies; I2 0%) for VDZ-aTNF and 1·0% (95% CI, 0·0 – 7·6; 5 studies; I2 0%) for Tofa-VDZ. Pooled clinical remission rates for these were 55·1% (95% CI, 19·6 – 88·5; 8 studies; 53 TTs; I2 81%) for VDZ-aTNF and 47·8% (95% CI, 19·0 – 77·4; 5 studies; 49 TTs; I2 69%) for Tofa-VDZ. No new safety signal was reported for any combination. There was considerable heterogeneity across studies (I2, 0 to 87%). Interpretation: DBT or SBT appears to be generally safe and effective in IBD patients with conclusions on effectiveness limited by between-study heterogeneity. This data needs to be confirmed in prospective studies. Registration: The SRMA was registered with PROSPERO (CRD4202018361). Funding Statement: None. Declaration of Interests: Kindra Clark-Snustad: Dr. Clark-Snustad reports personal fees from BMS, personal fees from Pfizer, outside the submitted work; Anish Patel: Dr. Patel reports personal fees from JANSSEN, personal fees from TAKEDA, personal fees from ABBVIE, outside the submitted work; Andres Yarur: Dr. Yarur reports personal fees from Takeda, personal fees from Prometheus Bioscience, personal fees from Arena Pharmaceutical, personal fees from Bristol Myers Squibb, during the conduct of the study; Benjamin L. Cohen: Dr. Cohen reports personal fees from Abbvie, personal fees and nonfinancial support from Pfizer, personal fees from Bristol Myers Squibb, personal fees from Janssen, personal fees from Target RWE, personal fees from Sublimity Therapeutics, outside the submitted work; Matthew A. Ciorba: Dr. Ciorba reports grants and personal fees from Pfizer, grants and personal fees from Takeda, outside the submitted work; Scott D. Lee MD: Dr. Lee reports grants and personal fees from Abbvie, grants and personal fees from UCB, grants and personal fees from JANSSEN, grants and personal fees from TAKEDA, grants from BMS, grants from ABGENOMICS, grants and personal fees from ELI LILLY, grants from ARENA, outside the submitted work; Edward V. Loftus, Jr.: Dr. Loftus reports grants and personal fees from AbbVie, personal fees from Allergan, grants and personal fees from Amgen, personal fees from Arena, personal fees from Boehringer Ingelheim, grants and personal fees from Bristol-Myers Squibb, personal fees from Calibr, grants and personal fees from Celgene, personal fees from Celltrion Healthcare, personal fees from Eli Lilly, grants and personal fees from Genentech, grants and personal fees from Gilead, personal fees from Iterative Scopes, grants and personal fees from Janssen, personal fees from Ono Pharma, grants and personal fees from Pfizer, grants from Receptos, grants from Robarts Clinical Trials, personal fees from Sun Pharma, grants and personal fees from Takeda, grants from Theravance, grants and personal fees from UCB, outside the submitted work; David Fudman: Dr. Fudman reports personal fees from Pfizer, outside the submitted work; Bincy P. Abraham: Dr. Abraham reports personal fees from Abbvie, personal fees from Ferring, grants and personal fees from Takeda, personal fees from Janssen, personal fees from Pfizer, personal fees from Medtronics, personal fees from Samsung bioepis, personal fees from Bristol-Myers Squibb, outside the submitted work; Jean-Frederic Colombel: Dr. Colombel reports grants and personal fees from Abbvie, personal fees from Amgen, personal fees from Allergan, personal fees from Arena Phramaceuticals, personal fees from Boehringer Ingelheim, personal fees from Bristol-Myers-Squibb, personal fees from Celgene Corporation, personal fees from Celltrion, personal fees from Eli Lilly, personal fees from Enterome, personal fees from Ferring Phramaceuticals, personal fees from Genentech, personal fees from Gilead, personal fees from Iterative Scopes, personal fees from Ipsen, personal fees from Immunic, personal fees from Imtbio, personal fees from Inotrem, grants and personal fees from Janssen Pharmaceuticals, personal fees from Landos, personal fees from Limmatech, personal fees from Medimmune, personal fees from Merck, personal fees from Novartis, personal fees from OMass, personal fees from Otsuka, personal fees from Pfizer, personal fees from Shire, grants and personal fees from Takeda, personal fees from Tigenix, personal fees from VielaBio, outside the submitted work; Parakkal Deepak: Dr. Deepak reports personal fees from Janssen, personal fees from Pfizer, personal fees from Prometheus Biosciences, other from Boehringer Ingelheim, personal fees from Arena Pharmaceuticals, grants from Takeda Pharmaceuticals, grants from Arena Pharmaceuticals, grants from Bristol Myers Squibb-Celgene, grants from Boehringer Ingelheim, outside the submitted work; All other authors declare no competing interests.

Introduction: Inflammatory Bowel Disease (IBD), comprised of Ulcerative Colitis (UC) and Crohn’s Disease (CD) is a chronic inflammatory disease with systemic involvement. Inflammation predisposes to atherosclerosis and studies suggest that IBD is associated with premature atherosclerotic cardiovascular disease (ASCVD). There is, however, limited population-based data on cardiovascular risk factor (CRF) burden in IBD among those who have not yet developed clinical ASCVD. We sought to study the association between IBD and CRFs among a nationally representative population with IBD and without established ASCVD. Methods: The study population was derived from the 2015-2016 National Health Interview Survey database. ASCVD was defined as myocardial infarction, angina or stroke; those with ASCVD were excluded. IBD was defined as either CD or UC. We computed weighted prevalence estimates of various traditional CRFs for the US population by IBD status. Univariate and multivariate logistic regression models were used to evaluate associations between CRFs and IBD. Average and poor cardiovascular risk profiles were defined as 2-3 and ≥4 CRFs, respectively. Results: Overall 786 (1.2%) representing 2.6 million ASCVD-free adults reported IBD. Individuals with IBD had higher prevalence of multiple CRFs (Figure, top). In adjusted models those with IBD had significantly higher odds of having prevalent hypertension, diabetes mellitus and hypercholesterolemia (Figure, bottom). These associations were similar among elderly and young participants. Those with IBD were almost 2-fold more likely to have a poor cardiovascular risk profile. Conclusion: Our findings from a nationally representative US population suggest an increased burden and clustering of CRFs among IBD patients without clinical ASCVD. Future efforts are needed to understand the underlying mechanisms, and enhance the detection and treatment of these CRFs to reduce ASCVD risk in IBD patients.

Introduction: Recent blood pressure (BP) guidelines recommend aggressive control of BP to prevent target organ damage, however, no population-level studies have assessed the impact of aggressive BP control on the incidence of Nonalcoholic Fatty Liver Disease (NAFLD). In this study, we investigate the implications of suboptimal BP control for incident NAFLD. Methods: We analyzed data from 6,252 consecutive participants in an employer-mandated routine health evaluation at Hospital Israelita Albert Einstein (São Paulo, Brazil) collected between 2004 to 2016 who were free of NAFLD at baseline. NAFLD was defined as liver ultrasound detected hepatic steatosis among individuals with an alcohol use disorder identification test (AUDIT) score /= 130mmHg and/or diastolic BP >/= 80 mmHg. Multivariate analysis was conducted adjusting for possible confounders as noted in the figure. Results: Over a median follow-up period of 2.9 years (range: 0.6 - 10.6 years), the incidence of NAFLD was 25.8% among individuals with hypertension (N=473) compared to 15.2% among non-hypertensive individuals (N=5,779; p Conclusions: Among persons with known hypertension, suboptimal BP is an independent risk of NAFLD. In addition, among those without known hypertension, suboptimal BP is an independent predictor of future NAFLD. Intervention studies are needed to investigate the role of BP control in the prevention of NAFLD.

ObjectiveTherapeutic efficacy of biologics has remained at about 50% for 2 decades. In Crohn’s disease (CD) patients, we examined the predictive value of an epithelial cell biomarker, ileal microvillar length (MVL), for clinical response to ustekinumab (UST) and vedolizumab (VDZ), and its relationship to another biomarker, intestinal epithelial cell (IEC) pyroptosis with respect to response to VDZ.DesignIleal biopsies from the UNITI-2 randomized controlled trial were analyzed for MVL as a predictor of clinical response to UST. In a 5-center academic retrospective cohort of CD patients, ileal MVL was analyzed to determine its predictive value for response to VDZ. Correlation between ileal MVL and IEC pyroptosis was determined, and the discriminant ability of the combination of two biomarkers to VDZ was examined.ResultsClinical response in UST was significantly higher than placebo (65% vs. 39%, p=0.03), with patients with normal MVL (>1.7 µm) having the greatest therapeutic effect: 85% vs. 20% (p=0.02). For VDZ, clinical response with MVL of 1.35-1.55 µm was 82% vs. 44% (1.55 µm) (p=0.038). There was no correlation between ileal MVL and IEC pyroptosis. The combination criteria of ileal pyroptosis < 14 positive cells/1000 IECs or MVL of 1.35-1.55 µm could identify 84% of responders and 67% of non-responders (p=0.001).ConclusionsIleal MVL was predictive of response to UST and VDZ in prospective and retrospective CD cohorts. It was independent of ileal IEC pyroptosis, combination of the two biomarkers enhanced the discriminate ability of responders from non-responders to VDZ.

Active inflammation during pregnancy in women with inflammatory bowel disease (IBD) is a risk factor for clinical relapse.1,2 In utero exposure to biologics is not associated with adverse pregnancy outcomes3 or infections in infants born to mothers with IBD.1,2,4 However, prior studies did not account for day care exposure in the first year of life, which is an established risk factor for infection in the general population. We aimed to determine whether children born to mothers with IBD have an increased rate of infection when attending day care in the first year after exposure to biologic therapy in utero.

Background Intestinal Ultrasound (IUS) has been gaining momentum in the management of patients with inflammatory bowel disease (IBD). Underutilized in the United States(U.S.), we present the impact of IUS in management decisions in a cohort of IBD patients seen at a tertiary center. Methods This retrospective study analyzed all IBD patients seen at our institution undergoing IUS as part of routine clinical evaluation. Patient demographics, disease type, clinical activity, laboratory markers, and therapy was obtained. Patients with evidence of inflammation based on IUS characteristics of bowel wall thickening, with additional parameters of mural stratification, mesenteric fat, doppler flow, lymph nodes, dilated bowel, free fluid used as adjunct measures were compared to those without IUS features of activity. Subsequent management plan based on findings were evaluated. Results Of 148 patients seen for IUS (median age 41 (range 18–81), 67% female), 108(73%) had Crohn’s disease (CD), 39(26.4%) had ulcerative colitis (UC), 1(0.7%) had IBD-undetermined (IBD-U) with 111(75%) Caucasians, 9.5% Blacks, 8.8% Asians, and 6.8% Hispanics. Median disease duration was 8 years, range (0–43) with 113(94.1%) on biologic/small molecule therapy and 7(5.8%) on mesalamines. No differences in BMI were noted in those with active disease vs. those in remission. However, we noted 29(19.3%) had fatty liver on ultrasound, which correlated highly with high BMI (31 vs. 24) in those with normal liver (p On IUS, 110(66%) of our patients had evidence of disease activity and 56(34%) were in remission. Inflammatory markers ESR and CRP did not correlate to IUS activity. In our UC patients Mayo score correlated to IUS findings but not Harvey Bradshaw Index (HBI) for CD. For those with positive findings on IUS, 29.5% escalated therapy for their IBD, and 13.3% required change in drug mechanism. For those in remission, the majority of patients 43(84.3%) continued their therapy while 3(5.9%) successfully de-escalated therapy. Conclusion In our study, IUS was useful in providing management decisions in those with active disease especially as there was a lack of correlation to inflammatory markers and HBI scores.

BACKGROUND Anti-drug antibodies (ADAbs) may decrease the efficacy of biologics and increase the risk of adverse events. A single positive test may not preclude further treatment because of variations in assays used, test timing, and patient variables. We evaluated the longitudinal patterns of immunogenicity during 7 years of antitumor necrosis factor-alpha drug certolizumab pegol (CZP) treatment for moderate-to-severe Crohn's disease. METHODS PRECiSE 3 patients (n = 595) received open-label CZP 400 mg every 4 weeks up to 7 years. CZP-ADAb expression, plasma CZP concentration, Harvey-Bradshaw Index, C-reactive protein, and fecal calprotectin concentrations were measured multiple times. Longitudinal data, examined for CZP-ADAb positivity and categorized as transient (with temporary/no effect on CZP concentration), persistent, or negative, were correlated with clinical and biological variables. RESULTS Of the CZP-ADAb-positive patients, 40 (22.6%) had transient CZP-ADAbs and 94 (77.4%) had persistent CZP-ADAbs. Demographic characteristics were similar between groups. Median C-reactive protein and fecal calprotectin were higher (P < 0.05 at some visits) and plasma CZP concentrations were significantly lower (P < 0.0001 at all visits) in the persistent CZP-ADAb-positive group relative to the CZP-ADAb-negative group. Transient CZP-ADAb-positive and CZP-ADAb-negative patients had similar plasma CZP, C-reactive protein, and fecal calprotectin concentrations. Median Harvey-Bradshaw Index scores and rates of adverse events were similar among groups. CONCLUSIONS This analysis demonstrates that persistent CZP-ADAb has negative effects on drug levels and efficacy, whereas transient expression may not. Serial measurements may be needed to characterize ADAb positivity. www.clinicaltrials.gov, Number NCT00160524.

Objective There are limited data on using more than one biologic or small molecule drug combined to treat patients with inflammatory bowel disease. The aim of our study was to determine the effectiveness and safety of combination biologic use in inflammatory bowel disease. Methods We identified patients with Crohn's disease or ulcerative colitis who received treatment with a combination of two biologics or a biologic and a small molecule drug from 2015 to 2019 for persistent disease activity or concomitant rheumatological or dermatological disease. The primary end-point was effectiveness, based on improvements in inflammatory markers, clinical, and endoscopic remission. The secondary end-point was safety. Results Of the 50 patients treated with combination therapy there were significantly more patients in clinical and endoscopic remission at follow-up compared to baseline (50% vs 14%, P = 0.0018, delta 36%, 95% confidence interval [CI] 0.13-0.53; and 34% vs 6%, P = 0.0039, delta 28%, 95% CI 0.09-0.47), respectively. Median erythrocyte sedimentation rate (17 mm/h vs 13 mm/h, P = 0.002) and C-reactive protein (5.00 mg/dL vs 2.35 mg/dL, P = 0.002) also decreased posttreatment. There were eight serious adverse events and no deaths CONCLUSIONS: Combination biologic therapy appears to be an effective option for patients with refractory inflammatory bowel disease or concomitant autoimmune disease that is inadequately controlled by biologic monotherapy. There was an increased risk of serious infection compared with biologic monotherapy; however, this risk might be minimized by discontinuing immunomodulators prior to initiating combination therapy. Large prospective studies are needed to confirm these findings.

Due to the lack of cure for inflammatory bowel disease (IBD) and failure of current medical therapies in many patients with IBD, a need exists in finding novel ways to treat inflammation with a high benefit and the lowest risk possible. With current medical therapies, adverse events or risks of cancer/lymphoma and infections prevent patients-and sometimes providers-in using effective therapies for treatment. Some patients develop systemic side effects that preclude them from continuing a therapy that may have been efficacious, or in other cases, current medical therapies are not adequate to control disease. Nanotechnology is an emerging field where particles, in the size of nanometers, can be used to deliver medications directly to the area of inflammation thus avoiding drug-associated systemic side effects. When using nanoparticles (NPs), only a small amount of the drug is needed, and it can be delivered directly to the inflamed site without exposure to the rest of the body. Here we review conventional and unconventional therapies applied in the treatment of IBD underlying how the introduction of NPs has improved their safety and efficacy.

Iron deficiency is the most common etiology of anemia worldwide and is often managed with varying methods of iron supplementation. Although rare, oral iron supplementation can perpetuate iron deficiency anemia by causing gastric ulceration and upper gastrointestinal bleeding in high-risk populations. However, this complication has not been previously described with intravenous iron supplementation. We present a case of a 63-year-old male with severe iron deficiency anemia on biweekly intravenous iron infusions and weekly packed red blood cell transfusions who presented with melena over several months. Upper endoscopy demonstrated a clean-based gastric body ulcer and nonbleeding gastric varices. Histology of the gastric ulcer was suggestive of iron-induced gastric mucosal injury. This case demonstrates that frequent utilization of intravenous iron and packed red blood cell transfusions may predispose certain patients to the development of iron-induced gastritis and ulceration.