Challenges in IBD Research 2024: Pragmatic Clinical Research.

Pragmatic clinical research is 1 of the 5 focus areas of the Challenges in IBD Research 2024, a multidisciplinary effort by scientists, clinicians, patients, and funders to identify priorities for patient-centric research. This summary provides a comprehensive overview of current gaps in inflammatory bowel disease (IBD) clinical research and actionable approaches to address them. This review is focused on identifying research that is needed to achieve the best outcomes for patients in clinical practice. Research gaps include understanding the needs of understudied patient groups and addressing barriers to care so all patients receive optimal care, validating and using biomarkers to enable early diagnosis and result in better outcomes for adults and children with IBD, and determining the optimal sequencing of treatments (medical, surgical, adjunct) in children and adults. Inclusive pragmatic research is needed to address these gaps and lead to improvements in patient care and outcomes for all populations of patients with IBD.

Pragmatic clinical research focuses on improving evidence for how to best treat patients to improve quality of life and disease outcomes in real-world practice. This includes evaluating and improving healthcare delivery and decreasing barriers for all patients.

Risk of Adverse Cardiovascular Outcomes in Postmenopausal Women with Inflammatory Bowel Disease.

BACKGROUND: Individuals with inflammatory bowel disease (IBD) who lack traditional cardiovascular disease (CVD) risk factors, such as young females, are observed to experience adverse CVD outcomes. Whether women with IBD have increased CVD risk after the menopause transition is unclear. METHODS: We conducted a survival analysis of Women's Health Initiative (WHI) participants and excluded those with missing IBD diagnosis, model covariate data, follow-up data, or a baseline history of the following CVD outcomes: coronary heart disease (CHD), ischemic stroke, venous thromboembolism (VTE), peripheral arterial disease (PAD). Risk of outcomes between IBD and non-IBD women was performed using Cox proportional hazard models, stratified by WHI trial and follow-up. Models were adjusted for age, socio-demographics, comorbidities (e.g., hypertension, diabetes, hypercholesterolemia, etc.), family history, and lifestyle factors (e.g., smoking, alcohol, physical activity, body mass index, etc.). RESULTS: Of 134,022 WHI participants meeting inclusion criteria, 1367 (1.0%) reported IBD at baseline. Mean baseline age was 63.4 years. After adjusting for age and other confounders, no significant difference was observed between IBD and non-IBD women for the risk of CHD (HR 0.96, 95% CI 0.73-1.24), VTE (HR 1.11, 95% CI 0.81-1.52) or PAD (HR 0.64, 95% CI 0.28-1.42). After adjusting for age, risk of ischemic stroke was significantly higher (HR 1.41, 95% CI 1.06-1.88) in IBD than non-IBD women. With further adjustment, the excess risk of ischemic stroke among IBD women was attenuated and no longer statistically significant (HR 1.31, 95% CI 0.98-1.76). CONCLUSIONS: Among postmenopausal women with IBD, risk of ischemic stroke may be higher than in non-IBD women.

Feasibility and Acceptability of Digital Behavioral Interventions Among Black and Hispanic Patients With Inflammatory Bowel Disease: A Randomized Pilot Study.

The use of digital behavioral interventions was tested among patients with inflammatory bowel disease with a predominately low-income, Black/Hispanic background who had elevated symptoms of anxiety/depression. Both mood-tracking and cognitive behavioral self-management applications were feasible and acceptable to use, with opportunities for improvement identified.

Medical Cannabis Use Patterns and Adverse Effects in Inflammatory Bowel Disease.

GOALS: To investigate medical cannabis (MC) use patterns and adverse effects in patients with inflammatory bowel disease (IBD). BACKGROUND: MC is now legal in many states. Although previous studies suggest improvement in disease activity among IBD patients using MC, use patterns and adverse effects are unclear. STUDY: A cross-sectional anonymous survey was conducted (October 23, 2020 to January 24, 2021) among patients accessing MC dispensaries in New York and Minnesota. Eligibility criteria: age 18 years or older, selfreported IBD diagnosis, MC dispensary purchase. Survey questions included IBD characteristics, MC and healthcare utilization, and MC effects/adverse events. Participant characteristics were analyzed with descriptive statistics. Utilization patterns and symptoms before and after MC use were compared using the Stuart Maxwell test. RESULTS: Of 236 respondents, overall IBD disease activity was mild-to-moderate. Most respondents (61.0%) took a biological. Median frequency of MC use was at least once within the past week. Most respondents used products with high Δ9-tetrahydrocannabinol content (87.5%) through vape pens/cartridges (78.6%). Respondents reported fewer emergency room visits in the 12 months after versus before MC use (35.2 vs 41.5%, P <0.01) and less impact of symptoms on daily life. Most respondents reported euphoria with MC use (75.4%). The other common side effects were feeling drowsy, groggy, or with memory lapses (4.2%), dry mouth/eyes (3.4%), and anxiety/depression or paranoia (3.4%). Few respondents reported MC diversion (1.3%). CONCLUSIONS: MC users with IBD perceive symptom benefits and report decreased emergency room visits without serious adverse effects. Further studies are needed to confirm these results with objective measures of healthcare utilization and disease activity.

Racial Difference in Efficacy of Golimumab in Ulcerative Colitis.

BACKGROUND: Observational studies have described racial differences in inflammatory bowel disease (IBD) genetics, clinical manifestations, and outcomes. Whether race impacts response to biologics in IBD is unclear. We conducted a post hoc analysis of phase 2 and 3 randomized clinical trials in ulcerative colitis to evaluate the effect of race on response to golimumab. METHODS: We analyzed pooled individual-level data from induction and maintenance trials of golimumab through the Yale Open Data Access Project. The primary outcome was clinical response. Secondary outcomes were clinical remission and endoscopic healing. Multivariable logistic regression was performed comparing White vs racial minority groups (Asian, Black, or other race), adjusting for potential confounders. RESULTS: There were 1006 participants in the induction (18% racial minority) and 783 participants in the maintenance (17% racial minority) trials. Compared with White participants, participants from racial minority groups had significantly lower clinical response (adjusted odds ratio [aOR], 0.43; 95% confidence interval [CI], 0.28-0.66), clinical remission (aOR, 0.41; 95% CI, 0.22-0.77), and endoscopic healing (aOR, 0.48; 95% CI, 0.31-0.74) at week 6. Participants from racial minority groups also had significantly lower clinical remission (aOR, 0.46; 95% CI, 0.28-0.74) and endoscopic healing (aOR, 0.63; 95% CI, 0.41-0.96) at week 30. There were no racial differences in placebo response rates. CONCLUSIONS: Ulcerative colitis participants from racial minority groups were less likely to achieve clinical response, clinical remission, and endoscopic healing with golimumab compared with White participants in induction and maintenance trials. Further studies are needed to understand the impact of race on therapeutic response in IBD.

Racial disparities exist in inflammatory bowel disease, but the influence of race on response to biologic therapy is unclear. In pooled analysis of golimumab clinical trials, participants from racial minority groups were less likely to achieve clinical efficacy compared with White participants.

National Prevalence of Psychological Distress and Use of Mental Health Care in Inflammatory Bowel Disease.

BACKGROUND: Individuals with inflammatory bowel disease (IBD) have elevated symptoms of anxiety and depression. The burden of such symptoms, accompanied by functional impairment in IBD, is not well documented, nor is utilization of mental health care in this population. METHODS: Adults ≥18 years were identified in the cross-sectional 2015-2016 National Health Interview Survey. Responses from the Kessler Index were used to estimate the national prevalence of psychological distress with impairment and mental health-care use in IBD. Factors associated with psychological distress with impairment in IBD were analyzed using logistic regression. RESULTS: The prevalence of psychological distress with impairment was significantly higher in IBD than non-IBD adults (7.69% vs. 3.50%, respectively; P < .01). Among those with IBD and psychological distress with impairment, only a third (36.29%) had seen or talked to a mental health provider in the preceding 12 months. About half of these found the cost of mental health care unaffordable. On multivariable analysis, factors associated with psychological distress in IBD included increasing emergency room visits and trouble finding a health provider. CONCLUSIONS: A significant number of adults with IBD in the United States have psychological distress accompanied by functional impairment. However, mental health care is underutilized in this population. Many of these individuals find the cost of mental health care unaffordable, struggle to find a health provider, and experience repeated emergency room visits. Ongoing efforts to improve mental health care in IBD should address issues of access and cost. Additionally, these efforts should seek to understand other barriers to mental health-care use.

Untreated psychological distress is associated with worse outcomes in inflammatory bowel disease (IBD). This study reveals low utilization of mental health care despite increased odds of psychological distress accompanied by functional impairment in a nationally representative IBD population.

Behavioral Digital Therapeutics in Gastrointestinal Conditions: Where Are We Now and Where Should We Go?

Behavioral digital therapeutics represents a diverse range of health technology tools that can offer beneficial options for patients with gastrointestinal disorders, particularly with the shortage of mental health providers. Challenges to the uptake of behavioral digital interventions exist and can be addressed with mobile device applications, improved interoperability of technology platforms, and flexible integration into clinical practice.

COVID-19 is not associated with worse long-term inflammatory bowel disease outcomes: a multicenter case-control study.

Background: Inflammatory bowel disease (IBD) is not associated with worse coronavirus disease 2019 (COVID-19) outcomes. However, data are lacking regarding the long-term impact of severe acute respiratory syndrome coronavirus 2 infection on the disease course of IBD. Objectives: We aimed to investigate the effect of COVID-19 on long-term outcomes of IBD. Design: We performed a multicenter case-control study of patients with IBD and COVID-19 between February 2020 and December 2020. Methods: Cases and controls were individuals with IBD with presence or absence, respectively, of COVID-19-related symptoms and confirmatory testing. The primary composite outcome was IBD-related hospitalization or surgery. Results: We identified 251 cases [ulcerative colitis (n = 111, 45%), Crohn's disease (n = 139, 55%)] and 251 controls, with a median follow-up of 394 days. The primary composite outcome of IBD-related hospitalization or surgery occurred in 29 (12%) cases versus 38 (15%) controls (p = 0.24) and on multivariate Cox regression, COVID-19 was not associated with increased risk of adverse IBD outcomes [adjusted hazard ratio (aHR): 0.84, 95% confidence interval [CI]: 0.44-1.42]. When stratified by infection severity, severe COVID-19 was associated with a numerically increased risk of adverse IBD outcomes (aHR: 2.43, 95% CI: 1.00-5.86), whereas mild-to-moderate COVID-19 was not (aHR: 0.68, 95% CI: 0.38-1.23). Conclusion: In this case-control study, COVID-19 did not have a long-term impact on the disease course of IBD. However, severe COVID-19 was numerically associated with worse IBD outcomes, underscoring the continued importance of risk mitigation and prevention strategies for patients with IBD during the ongoing COVID-19 pandemic.

Celiac disease.

This review will focus on the pathogenesis, clinical manifestations, diagnosis, and management of celiac disease (CD). Given an increasing awareness of gluten-related disorders, medical professionals of all varieties are encountering patients with a diagnosis of CD or who are thought to have food intolerance to gluten. The prevalence of CD among the general population is estimated to be 1% in Western nations, and there is growing evidence for underdiagnosis of the disease, especially in non-Western nations that were traditionally believed to be unaffected. The development of serologic markers specific to CD has revolutionized the ability both to diagnose and monitor patients with the disease. Additionally, understanding of the clinical presentations of CD has undergone a major shift over the past half century. Although it is well understood that CD develops in genetically predisposed subjects exposed to gluten, the extent of other environmental factors in the pathogenesis of the disease is an area of continued research. Currently, the main therapeutic intervention for CD is a gluten-free diet; however, novel nondietary agents are under active investigation. Future areas of research should also help us understand the relationship of CD to other gluten-related disorders.

Olmesartan, other antihypertensives, and chronic diarrhea among patients undergoing endoscopic procedures: a case-control study.

OBJECTIVE: To investigate a recent association between the use of the angiotensin receptor-blocker (ARB) olmesartan and a severe enteropathy resembling celiac disease. PATIENTS AND METHODS: We searched our endoscopy database for all outpatient esophagogastroduodenoscopy (EGD) or colonoscopy examinations in patients aged at least 50 years during the period January 1, 2007, to March 31, 2013. Cases were those whose examination indication was diarrhea, and controls were those whose examination indication was esophageal reflux (EGD) or colorectal cancer screening (colonoscopy). We compared cases with controls with regard to the proportion of those listing olmesartan among their medications. Secondary exposures were the proportion of those taking nonolmesartan ARBs or other antihypertensive medications. We also examined biopsy results to determine whether there were histologic changes associated with the use of olmesartan. RESULTS: We identified 2088 patients undergoing EGD and 12,428 patients undergoing colonoscopy meeting inclusion criteria. On multivariate analysis, there was no statistically significant association between olmesartan and diarrhea among those undergoing EGD (odds ratio, 1.99; 95% CI, 0.79-5.00) or colonoscopy (odds ratio, 0.63; 95% CI, 0.23-1.74). Review of pathology reports of the EGD and colonoscopy groups showed no association between the use of olmesartan and the histologic diagnosis of celiac disease (P=.61) or microscopic colitis (P=1.0), respectively. CONCLUSION: Our findings suggest that neither olmesartan nor other ARBs were associated with diarrhea among patients undergoing endoscopy. The spruelike enteropathy recently associated with olmesartan is likely a rare adverse effect and milder presentations are unlikely.