Postoperative Ustekinumab Drug Levels and Disease Activity in Patients with Crohn's Disease.

AIMS: This study investigated how post-operative ustekinumab levels relate to surgery type, endoscopic, biochemical, and clinical outcomes in patients with Crohn's Disease. METHODS: A retrospective study of patients with Crohn's Disease with a disease-related operation between 2016 and 2022 assessed outcomes based on ustekinumab levels. Patients were included if they had an ustekinumab trough level within two years post-operatively. Patients were separated into groups based on whether their ustekinumab trough levels were adequate, defined as ≥ 4 µg/mL, or suboptimal < 4 µg/mL. A subset of patients with ustekinumab levels taken within two years both before and after surgery was compared to non-surgical treatment-escalated controls outside the initial patient set. Harvey-Bradshaw index was used to evaluate clinical disease activity. Rutgeert's and Simple Endoscopic Score for Crohn's Disease was used to evaluate endoscopic disease activity. C-reactive protein and fecal calprotectin values were collected to evaluate the molecular inflammatory disease state. CBC data were used to evaluate anemia. RESULTS: Forty-four patients were identified, which had ustekinumab levels after Crohn's Disease-related surgery. Twelve of these patients had pre-operative levels and were compared to 26 non-surgical treatment-escalated controls. No relationship between ustekinumab levels and endoscopic or clinical disease activity post-operatively was found. This also held true when looking at different surgery types. Adequate levels of ustekinumab post-operatively yielded lower risk of anemia. Surgery itself did not have an impact on ustekinumab levels. CONCLUSIONS: This study provided new insights into how post-operative ustekinumab levels impact several factors in patients having undergone Crohn's disease-related surgery.

Therapeutic drug monitoring in patients with inflammatory bowel disease on ustekinumab.

OBJECTIVE: Therapeutic drug monitoring is used clinically to guide anti-tumor necrosis factor (TNF) therapy for inflammatory bowel disease (IBD), but its use for ustekinumab (UST) remains unclear. This study aimed to determine predictive variables of UST levels. METHODS: In this retrospective cohort of patients with IBD, UST trough levels were drawn at maintenance dosing. Relationships between UST trough levels and demographics, therapy, and outcomes were analyzed. Machine-learning models were used to infer combinatorial traits predictive of UST levels. RESULTS: Altogether 177 patients with IBD on UST had a mean UST trough level of 4.742 µg/mL. The injection schedule correlated significantly (P < 0.001) with UST levels. Naiveté to anti-TNFs correlated with higher UST levels (P = 0.048). Univariate analysis revealed that higher inflammatory biomarkers significantly correlated to lower UST levels and a lower Simple Endoscopic Score to Crohn's Disease to adequate UST levels (P = 0.018). Multivariate analysis identified body mass index (BMI), previous anti-TNF failure, and laboratory flare as predictors of UST levels with an area under the receiver operating characteristic curve (AUROC) of 0.72. The UST cut-off level of 5.77 µg/mL yielded a 0.79 AUROC, 80% sensitivity, and 81% specificity for predicting endoscopic remission of Crohn's disease. For the clinical remission end-point in ulcerative colitis, UST level of 4.73 µg/mL yielded a 0.69 AUROC, 53% sensitivity, and 86% specificity. CONCLUSIONS: Higher UST levels correlated with less disease activity. BMI was an important consideration for UST response as well. Therefore, UST dose adjustments to reach target levels may optimize response.

Risk of Infection in Patients With Inflammatory Bowel Disease Treated With Interleukin-Targeting Agents: A Systematic Review and Meta-Analysis.

BACKGROUND: Patients with inflammatory bowel disease (IBD) are at increased risk of infection. The aim of this study was to assess the cumulative incidence and risk of infection in patients with IBD treated with interleukin (IL)-targeting agents. METHODS: We searched PubMed, EMBASE, and Web of Science for randomized controlled trials including patients with IBD receiving IL-targeting agents compared with patients receiving placebo or treatment that only differed from the intervention arm in the absence of an IL-targeting agent. The primary outcome of interest was the relative risk (RR) of any-grade and severe infection during the induction phase. RESULTS: There was no difference in risk of any-grade (RR, 0.98; 95% confidence interval [CI], 0.89-1.09) or severe (RR, 0.64; 95% CI, 0.38-1.10) infection in patients receiving any IL-targeting agent compared with the control group. During the maintenance period, the cumulative incidence of any-grade infection in patients receiving IL-12/23p40-targeting agents (mean follow-up 29 weeks) was 34.82% (95% CI, 26.78%-43.32%), while the cumulative incidence of severe infection was 3.07% (95% CI, 0.93%-6.21%). The cumulative incidence of any-grade infection in patients receiving IL-23p19-targeting agents (mean follow-up 40.9 weeks) was 32.16% (95% CI, 20.63%-44.88%), while the cumulative incidence of severe infection was 1.75% (95% CI, 0.60%-3.36%). During the maintenance phase of the included studies, the incidence of infection was 30.66% (95% CI, 22.12%-39.90%) for any-grade and 1.59% (95% CI, 0.76%-2.63%) for severe infection in patients in the control group. CONCLUSIONS: There was no difference in risk of infection between patients with IBD who received IL-targeting agents compared with the control group. Case registries and randomized controlled trials reporting the safety of IL inhibitors should provide detailed information about the risk of specific infectious complications in patients with IBD receiving IL-targeting agents.

Patients with inflammatory bowel disease treated with interleukin-targeting agents are not more likely to develop any-grade or severe infection compared with patients with inflammatory bowel disease receiving placebo or treatment that only differs in the absence of an interleukin-targeting agent.

The Role of Vitamin D in Patients with Inflammatory Bowel Disease Treated with Vedolizumab.

BACKGROUND: Many clinical factors can contribute to the efficacy of medical therapy in Inflammatory Bowel Disease (IBD). We assessed their effects on the efficacy of vedolizumab therapy in a cohort of patients with IBD. METHODS: We conducted a retrospective study on patients between 18 and 80 years of age with ulcerative colitis (UC) or Crohn's disease (CD) who were seen in the IBD program at Houston Methodist in Houston, TX and treated with vedolizumab for at least 6 months from 2018 to 2022. We investigated factors prior to the initiation of therapy that best predicted treatment response, with an emphasis on vitamin D levels and examined several variables including patients' demographics and clinical information on disease location and severity and nutritional status before and after the initiation of vedolizumab. Post-treatment data were gathered after a minimum of 6 months of vedolizumab therapy. The clinical parameters used for the study were the Harvey-Bradshaw Index for CD and the Activity Index for UC. RESULTS: There were 88 patients included in our study of whom 44 had CD and 44 had UC.; median age was 39.5 (31.0, 53.25) years; 34% patients were male; and 80.7% were Caucasian. All patients received an induction dosing of 300 mg vedolizumab at 0, 2, and 6 weeks then maintenance dosing as standard of care every 8 weeks. Among UC patients with vitamin D ≥ 30 ng/mL at the initiation of vedolizumab therapy, UC Endoscopic Index of Severity (UCEIS) scores after 6 months of therapy were significantly lower than in those who had low pre-treatment vitamin D levels (1.5 vs. 3.87, p = 0.037). After treatment, vitamin D levels improved more significantly in the higher pre-treatment vitamin D group, with a median level of 56 ng/mL, than in the lower pre-treatment vitamin D group, with a median level of only 31 ng/mL (p = 0.007). In patients with CD with vitamin D ≥ 30 ng/mL at the initiation of vedolizumab therapy, we found higher iron saturation (12 vs. 25%, p = 0.008) and higher vitamin B12 levels (433.5 vs. 885 pg/mL, p = 0.003) than in those with vitamin D < 30 ng/mL. After treatment, CD patients with high pre-treatment vitamin D levels had significantly higher vedolizumab levels (27.35 vs. 14.35 µg/mL, p = 0.045) than those with low pre-treatment vitamin D. Post-treatment scores and inflammatory markers in CD patients (HBI, CRP, ESR, and SES-CD) were lower in those who had lower baseline vitamin D. CONCLUSIONS: Our results show higher pre-treatment vitamin D levels predicted significant endoscopic improvement in patients with ulcerative colitis (UC). Improving vitamin D levels lowered C-reactive protein levels significantly in CD patients. Higher vitamin D levels were seen after treatment in both UC and CD patients. Vitamin D can play a role in clinical and endoscopic outcomes and should be assessed routinely and optimized in patients with IBD.

Real-world impact of infliximab precision-guided dosing on management of patients with IBD.

OBJECTIVES: Evaluate the clinical utility of a precision-guided dosing test for infliximab (IFX) and its impact on treatment decision-making for inflammatory bowel disease (IBD). STUDY DESIGN: Prospective, multisite, clinical experience program. METHODS: Health care providers were given access to PredictrPK IFX, a precision-guided dosing test, for their patients with IBD on maintenance IFX therapy. Blood samples were drawn 20 to 56 days post infusion. A Bayesian data assimilation tool used clinical and serologic data to generate individual pharmacokinetic profiles and forecast trough IFX. Results were reported to providers to aid in-therapy management decisions and the decision-making process was assessed through questionnaires. Relationships between forecasted IFX concentration, disease activity, and therapy management decisions were analyzed by logistic regression. RESULTS: PredictrPK IFX was used for 275 patients with IBD by 37 providers. In 58% of cases, providers modified treatment plans based on the results, including dose modifications (41%; of these, one-third decreased dose) and discontinuation (8%) of IFX. Of the 42% where treatment was not modified, 97.5% had IFX levels of 5 µg/mL or greater. Patients with IFX concentrations less than 5 µg/mL were 3 and 7.3 times more likely to have active disease or discontinue IFX, respectively. There was unanimous agreement among providers who completed a postprogram survey that PredictrPK IFX was beneficial in guiding treatment decisions and added more value to their practice than routine therapeutic drug monitoring. CONCLUSIONS: PredictrPK IFX enables earlier and more precise dose optimization of IFX in patients with IBD, exerting a substantial impact on treatment decisions that may result in improved health outcomes and overall cost savings.

Integrating Intestinal Ultrasound into an Inflammatory Bowel Disease Practice: How to Get Started.

Intestinal ultrasound (IUS) offers a safe, noninvasive, point-of-care tool for diagnosing and monitoring disease activity in patients with inflammatory bowel disease (IBD). IUS is used widely in Europe and Canada for IBD, but it remains underutilized in the United States. Growing interest in IUS in the United States has prompted many IBD centers to train their faculty in IUS. This, however, raises questions about how to effectively use this new tool in the United States, which does not use a social medicine model like those implemented in Europe and Canada. Here, we provide a practical framework for incorporating IUS in an IBD practice in the United States, including training requirements, equipment, and protocols for implementing IUS in daily practice.

Utility of Intestinal Ultrasound in Clinical Decision-Making for Inflammatory Bowel Disease.

Background: There is a clinical need to improve the monitoring of inflammatory bowel disease (IBD) activity. Despite being used regularly in European countries, intestinal ultrasound (IUS) has been implemented less in the United States for unclear reasons. Aims: The aim of this study is to illustrate how IUS can be used as a clinical decision-making tool in an American IBD cohort. Methods: This retrospective cohort analysis evaluated patients with IBD seen at our institution who underwent IUS as part of routine evaluation of their IBD from July 2020 to March 2022. To evaluate the clinical utility of IUS for different patient populations and against more frequently used measures of inflammation, we compared patient demographics, inflammatory markers, clinical scores, and medications between patients in remission and those with active inflammation. Treatment plans between the 2 groups were compared and we analyzed patients with follow-up IUS visits to validate treatment plan decisions at initial evaluation. Results: Out of 148 total patients with IUS, we found that 62.1% (N = 92) of our patients had active disease and 37.9% (N = 56) were in remission. Ulcerative colitis activity index and Mayo scores were both significantly correlated with IUS findings. The treatment plan was significantly correlated with IUS findings (P = .004). At follow-up, we observed an overall decrease in intestinal thickening, improvements in vascular flow, and mural stratification. Conclusions: Clinical decisions incorporating IUS findings effectively reduced inflammation in our IBD patients. IUS should be strongly considered by IBD clinicians in the United States for monitoring disease activity in IBD.

The Role of Fecal Microbiota Transplantation in the Induction of Remission in Ulcerative Colitis.

BACKGROUND: Considerable research supports an important role for the microbiome and/or microbiome-host immune system interactions in the pathogenesis of inflammatory bowel disease (IBD). Consequently, microbiota-modulating interventions, such as fecal microbiota transplantation (FMT), have attracted interest in the management of IBD, including ulcerative colitis (UC). SUMMARY: While the clinical response to FMT in UC has varied between different studies, results to date may offer guidance toward optimal use of FMT. Thus, increased microbiome biodiversity, the presence of short-chain fatty acid-producing bacteria, Clostridium clusters IV and XIVa, Odoribacter splanchnicus, and reduced levels of Caudovirales bacteriophages have been identified as characteristics of the donor microbiome that predict a positive response. However, inconsistency in FMT protocol between studies confounds their interpretation, so it is currently difficult to predict response and premature to recommend FMT, in general, as a treatment for UC. Additional randomized controlled trials designed based on previous findings and employing a standardized protocol are needed to define the role of FMT in the management of UC. KEY MESSAGES: There is a well-developed rationale for the use of microbiome-modulating interventions in UC. Despite variations in study protocol and limitations in study design that confound their interpretation, FMT seems to benefit patients with UC, overall. Available data identify factors predicting FMT response and should lead to the development of optimal FMT study protocols.

Clinical Evaluation of Upadacitinib in the Treatment of Adults with Moderately to Severely Active Ulcerative Colitis (UC): Patient Selection and Reported Outcomes.

This review addresses appropriate patient selection for upadacitinib, a Janus kinase inhibitor approved by the FDA and EMA for treatment of moderately to severely active ulcerative colitis (UC). Janus kinase molecules can contribute to the inflammatory pathway, so inhibiting certain of them may prove efficacious in treating UC and may reduce safety concerns. Upadacitinib is the newest Janus kinase inhibitor to be approved for UC, so it is timely and relevant to review patient selection and when to consider this medication. We will discuss efficacy and safety data from the pivotal clinical trials on upadacitinib. These data can be shared with patients and can inform the use of these agents in clinical practice.

The Current State of Care for Black and Hispanic Inflammatory Bowel Disease Patients.

Research on the care of inflammatory bowel disease (IBD) patients has been primarily in populations of European ancestry. However, the incidence of IBD, which comprises Crohn's disease and ulcerative colitis, is increasing in different populations around the world. In this comprehensive review, we examine the epidemiology, clinical presentations, disease phenotypes, treatment outcomes, social determinants of health, and genetic and environmental factors in the pathogenesis of IBD in Black and Hispanic patients in the United States. To improve health equity of underserved minorities with IBD, we identified the following priority areas: access to care, accurate assessment of treatment outcomes, incorporation of Black and Hispanic patients in therapeutic clinical trials, and investigation of environmental factors that lead to the increase in disease incidence.

In this comprehensive review, we examine the epidemiology, clinical presentations, disease phenotypes, treatment outcomes, social determinants of health, and genetic and environment factors in the pathogenesis of IBD in Black and Hispanic patients in the United States.

Biological Therapies for the Management of Enteric Disease: Considerations for the Clinician.

Several biologic therapies have been approved for enteric diseases. We evaluate each biologic's role based on their mechanism of action in treating these conditions. This review examines data on efficacy and safety, as well as considerations for using these therapies in clinical practice in inflammatory bowel diseases, enteric infections-specifically Clostridioides difficile colitis-and potentially in the increasingly prevalent disorder of eosinophilic esophagitis. When choosing an appropriate therapy, it is important to assess patient severity, as most biologics are approved for those with moderate to severe disease activity. With many years of data from clinical trials and real-world experience, these therapies have been shown to improve outcomes overall in enteric diseases, contributing to more options for our patients.

Systematic Review With Meta-analysis: Safety and Effectiveness of Combining Biologics and Small Molecules in Inflammatory Bowel Disease.

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 to assess the safety and effectiveness of dual biologic therapy (DBT), or small molecule combined with a biologic therapy (SBT) in IBD patients. Methods: We searched MEDLINE, EMBASE, Scopus, Web of Science, Cochrane Database of Systematic Reviews, and Clinical trials.gov until November 3, 2020, including studies with 2 or more IBD patients on DBT or SBT. Main outcome was safety assessed as pooled rates of adverse events (AEs) and serious AEs (SAEs) for each combination. Effectiveness was reported as pooled rates of clinical, endoscopic, and/or radiographic response and remission. The certainty of evidence was rated according to the Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) framework. Results: Of the 3688 publications identified, 13 studies (1 clinical trial, 12 observational studies) involving 266 patients on 7 different combinations were included. Median number of prior biologics ranged from 0 to 4, and median duration of follow-up was 16-68 weeks. Most common DBT and SBT were vedolizumab (VDZ) with anti-tumor necrosis factor (aTNF, n = 56) or tofacitinib (Tofa, n = 57), respectively. Pooled rates of SAE for these were 9.6% (95% confidence interval [CI], 1.5-21.4) for VDZ-aTNF and 1.0% (95% CI, 0.0-7.6) for Tofa-VDZ. The overall certainty of evidence was very low due to the observational nature of the studies, and very serious imprecision and inconsistency. Conclusions: DBT or SBT appears to be generally safe and may be effective in IBD patients, but the evidence is very uncertain.

Day Care Attendance and Infectious Complications in Children Born to Mothers With Inflammatory Bowel Disease.

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.

Ustekinumab Exposure in Pregnant Women From Inflammatory Bowel Disease Clinical Trials: Pregnancy Outcomes Through Up To 5 Years in Crohn's Disease and 2 Years in Ulcerative Colitis.

Background: While no adverse developmental outcomes were observed in preclinical animal studies, limited data exist regarding effects of ustekinumab on human pregnancies. Previously, no data have been reported for women treated with ustekinumab in inflammatory bowel disease (IBD) clinical trials and corresponding pregnancy outcomes. Here, we present pregnancy outcomes from IBD clinical trials, incorporating 5 years of treatment in Crohn's disease (CD) and 2 in ulcerative colitis (UC). Methods: All patients in the clinical trials agreed to use adequate birth control and were discontinued from treatment upon pregnancy confirmation. Nonetheless, 39 pregnancies occurred with maternal ustekinumab exposure from 4 CD and 1 UC study. Maternal and neonatal outcomes and data are presented with summary statistics, where available. Results: Of 1289 women who received ≥1 dose of ustekinumab, 39 maternal pregnancies with outcomes were reported (pregnancy cohort). Median maternal age was 28.0 years and median duration of ustekinumab treatment before pregnancy was 63.7 weeks with the last dose of ustekinumab administered prior to or during the first trimester (terminal half-life of ~3 weeks). Outcomes for the 39 pregnancies were: 26 live births (all normal newborns), 8 spontaneous abortions, and 5 elective abortions. No congenital anomalies were reported among normal newborns and no safety signals emerged with neonatal outcomes. Conclusions: Based on this series of 39 pregnancies with outcomes from IBD clinical trials, mothers treated with ustekinumab (limited to up to the first trimester) did not demonstrate a risk of negative outcomes. More data are needed to characterize the safety profile of ustekinumab use during pregnancy.

Risk Factors for and Frequency of CT Scans, Steroid Use, and Repeat Visits in Inflammatory Bowel Disease Patients Seen at a Single-Center Emergency Department: A Retrospective Cohort Study.

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.

Probiotic VSL#3 Treatment Reduces Colonic Permeability and Abdominal Pain Symptoms in Patients With Irritable Bowel Syndrome.

Background: Little is known regarding the clinical impact of treatment and treatment duration of probiotic VSL#3 on gut and microbiome function in irritable bowel syndrome (IBS). As part of a safety trial, we assessed the effect of VSL#3 treatment duration on abdominal pain, stooling, gut permeability, microbiome composition and function. Methods: Adults with IBS were randomized into an open label trial to receive the probiotic VSL#3 for 4 or 8 weeks. Adverse events, abdominal pain, and stooling patterns were recorded daily. Gut permeability, fecal bile acid levels, and microbiome composition were profiled at baseline and after treatment. Results: Fifteen subjects completed the trial (4-week: n = 8; 8-week: n = 7). Number of pain episodes decreased in both groups (P = 0.049 and P = 0.034; 4- vs. 8-week, respectively). Probiotic organisms contained in VSL#3 were detected in feces by whole shotgun metagenomic sequencing analysis and relative abundances of Streptococcus thermophilus, Bifidobacterium animalis, Lactobacillus plantarum, and Lactobacillus casei subsp. paraccasei correlated significantly with improved abdominal pain symptoms and colonic permeability at study completion. Although abdominal pain correlated significantly with the detection of probiotic species at study completion, a composite view of gut microbiome structure showed no changes in community diversity or composition after VSL#3 treatment. Conclusions: Probiotic organisms identified in stool correlated significantly with improvement in colonic permeability and clinical symptoms, prompting future studies to investigate the mechanistic role of VSL#3 and colonic permeability in IBS pathophysiology in a larger randomized controlled trial. Clinical Trial Registration: www.clinicaltrials.gov, Identifier: NCT00971711.

Vitamin D Receptor Gene Single Nucleotide Polymorphisms and Association With Vitamin D Levels and Endoscopic Disease Activity in Inflammatory Bowel Disease Patients: A Pilot Study.

BACKGROUND: Inflammatory bowel diseases (IBDs) comprise a heterogenous group of chronic gastrointestinal disorders that are multifactorial in etiology. Experimental in vitro and in vivo studies suggest that intestinal vitamin D receptor (VDR) signaling plays a role in modulating the immune response in IBD as a cause and/or a consequence of chronic inflammation. AIM: The aim of this study is to study the associations between vitamin D receptor gene single nucleotide polymorphisms(SNPs), vitamin D levels, and endoscopic disease activity in IBD. METHODS: This is a cross-sectional analysis of IBD patients who underwent endoscopic evaluation at a tertiary care hospital. Demographic variables, IBD disease type and location, medical therapies, vitamin D levels, and endoscopic disease activity were collected. Colonic biopsies obtained were investigated for the presence of VDR SNPs: ApaI, TaqI, BsmI, FokI, and Tru9I. RESULTS: Patients in endoscopic remission had higher vitamin D levels compared with those with inflammation found on endoscopy (P = <0.001). Patients with lower vitamin D levels were homozygous for Fok ancestral alleles (P = 0.0045). With regard to endoscopic disease activity, we found no differences in mutations of any of the VDR SNPs in our sample. CONCLUSIONS: The association between the presence of the ancestral FokI and lower vitamin D levels suggests a multifactorial etiology for vitamin D deficiency in IBD. Higher vitamin D levels in those in endoscopic remission compared with lower levels in those with active inflammation suggests that the impact of VDR gene SNP on disease activity may be overcome with replacement therapy.

Inflammatory Bowel Disease and Atherosclerotic Cardiovascular Disease: JACC Review Topic of the Week.

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.