Preoperative Use of Multiple Advanced Therapies Is Not Associated With Endoscopic Inflammatory Pouch Diseases.

BACKGROUND: Patients with an ileal pouch-anal anastomosis (IPAA) can experience pouch inflammation postoperatively. The use of antitumor necrosis factor (anti-TNF) biologics may be associated with pouch inflammation, but limited data exist on the impact of multiple advanced therapies on development of subsequent pouch inflammation. The aim of this study was to assess for an association between preoperative use of multiple advanced therapies and risk of endoscopically detected inflammatory pouch diseases (EIPDs). METHODS: We performed a retrospective analysis of ulcerative colitis (UC) and indeterminate colitis (IBDU) patients who underwent an IPAA at a quaternary care center from January 2015 to December 2019. Patients were grouped based on number and type of preoperative drug exposures. The primary outcome was EIPD within 5 years of IPAA. RESULTS: Two hundred ninety-eight patients were included in this analysis. Most of these patients had UC (95.0%) and demonstrated pancolonic disease distribution (86.1%). The majority of patients were male (57.4%) and underwent surgery for medically refractory disease (79.2%). The overall median age at surgery was 38.6 years. Preoperatively, 68 patients were biologic/small molecule-naïve, 125 received anti-TNF agents only, and 105 received non-anti-TNF agents only or multiple classes. Ninety-one patients developed EIPD. There was no significant association between type (P = .38) or number (P = .58) of exposures and EIPD, but older individuals had a lower risk of EIPD (P = .001; hazard ratio, 0.972; 95% confidence interval, 0.956-0.989). CONCLUSION: Development of EIPD was not associated with number or type of preoperative advanced therapies.

Crohn's disease shared decision making intervention leads to more patients choosing combination therapy: a cluster randomised controlled trial.

BACKGROUND: Crohn's disease requires effective patient-clinician communication for successful illness and medication management. Shared decision making (SDM) has been suggested to improve communication around early intensive therapy. However, effective evidence-based SDM interventions for Crohn's disease are lacking, and the impact of SDM on Crohn's disease decision making and choice of therapy is unclear. AIM: To test the impact of SDM on choice of therapy, quality of the decision and provider trust compared to standard Crohn's disease care. METHODS: We conducted a multi-site cluster randomised controlled trial in 14 diverse gastroenterology practices in the US. RESULTS: A total of 158 adult patients with Crohn's disease within 15 years of their diagnosis, with no prior Crohn's disease complications, and who were candidates to receive immunomodulators or biologics, participated in the study. Among these, 99 received the intervention and 59 received standard care. Demographics were similar between groups, although there were more women assigned to standard care, and a slightly shorter disease duration among those in the intervention group. Participants in the intervention group more frequently chose combination therapy (25% versus 5% control, p < 0.001), had a significantly lower decisional conflict (p < 0.05) and had greater trust in their provider (p < 0.05). CONCLUSIONS: With rapidly expanding medication choices for Crohn's disease and slow uptake of early intensive therapy, SDM can personalise treatment strategies and has the potential to move the field of Crohn's disease management forward with an ultimate goal of consistently treating this disease early and intensively in appropriate patients. TRIAL REGISTRATION: Evaluating a Shared Decision Making Program for Crohn's Disease, ClinicalTrials.gov Identifier NCT02084290 https://clinicaltrials.gov/ct2/show/NCT02084290.

Risk Prediction and Comparative Efficacy of Anti-TNF vs Thiopurines, for Preventing Postoperative Recurrence in Crohn's Disease: A Pooled Analysis of 6 Trials.

BACKGROUND & AIMS: The superiority of anti-TNF-α agents to thiopurines for the prevention of postoperative recurrence of Crohn's disease (CD) after ileocolonic resection remains controversial. In this meta-analysis of individual participant data (IPD), the effect of both strategies was compared and assessed after risk stratification. METHODS: After a systematic literature search, IPD were requested from randomized controlled trials investigating thiopurines and/or anti-TNF-α agents after ileocolonic resection. Primary outcome was endoscopic recurrence (ER) (Rutgeerts score ≥i2) and secondary outcomes were clinical recurrence (Harvey-Bradshaw Index/Crohn's Disease Activity Index score) and severe ER (Rutgeerts score ≥i3). A fixed effect network meta-analysis was performed. Subgroup effects were assessed and a prediction model was established using Poisson regression models, including sex, smoking, Montreal classification, CD duration, history of prior resection and previous exposure to anti-TNF-α or thiopurines. RESULTS: In the meta-analysis of IPD, 645 participants from 6 studies were included. In the total population, a superior effect was demonstrated for anti-TNF-α compared with thiopurine prophylaxis for ER (relative risk [RR], 0.52; 95% confidence interval [CI], 0.33-0.80), clinical recurrence (RR, 0.50; 95% CI, 0.26-0.96), and severe ER (RR, 0.41; 95% CI, 0.21-0.79). No differential subgroup effects were found for ER. In Poisson regression analysis, previous exposure to anti-TNF-α and penetrating disease behavior were associated with ER risk. The advantage of anti-TNF-α agents as compared with thiopurines was observed in low- and high-risk groups. CONCLUSIONS: Anti-TNF-α is superior to thiopurine prophylaxis for the prevention of endoscopic and clinical postoperative CD recurrence after ileocolonic resection. The advantage of anti-TNF-α agents was confirmed in subgroup analysis and after risk stratification.

Older Adult Patients Use More Aminosalicylate Monotherapy Compared With Younger Patients With Inflammatory Bowel Disease: TARGET-IBD.

GOAL: The goal of this study was to describe medication utilization patterns in older inflammatory bowel disease (IBD) patients. BACKGROUND: Despite a growing population of older patients with Crohn's disease (CD) and ulcerative colitis (UC), questions remain regarding medication utilization patterns in comparison to younger populations. MATERIALS AND METHODS: We collected data from the 34 sites in TARGET-IBD, a multicenter, observational cohort. The primary outcome in this study was the IBD-specific therapy utilized among older patients with IBD compared with younger age groups. Therapy use was analyzed using pairwise comparisons and then the odds of IBD-specific therapy use among patients older than age 65 were evaluated using multivariable logistic regression models. RESULTS: We identified 2980 patients with IBD (61% CD). In multivariable analysis, younger patients with UC were significantly less likely to utilize aminosalicylate monotherapy when compared with patients above 65 years [age 18 to 29: adjusted odds ratio (aOR)=0.51, 95% confidence interval (CI): 0.33-0.78]. In patients with CD, younger patients were significantly less likely to use aminosalicylate monotherapy when compared with patients above 65 (greatest difference age 18 to 29: aOR=0.31, 95% CI: 0.18-0.52). Younger patients with CD and UC were significantly more likely to use anti-tumor necrosis factor monotherapy than patients above 65 years (age 18 to 29: aOR=3.87, 95% CI: 2.47-6.06 and aOR=2.68, 95% CI: 1.29-5.58, respectively). CONCLUSIONS: Older patients with IBD demonstrate significant differences in medication utilization, including more aminosalicylate monotherapy and less anti-tumor necrosis factor monotherapy compared with younger age groups. Given the aging population in the United States, these utilization patterns may have long-term implications for disease control.

Optimal inflammatory bowel disease management during the global coronavirus disease 2019 pandemic.

PURPOSE OF REVIEW: This review aims to summarize the current evidence regarding the risks and implications of coronavirus disease 2019 (COVID-19) in patients with inflammatory bowel disease (IBD) and discuss optimal management of IBD during this pandemic. RECENT FINDINGS: Patients with IBD are not at increased risk of COVID-19 but several risk factors for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 infection) have been identified, such as active IBD, obesity, and corticosteroid use. COVID-19 outcomes are similar among patients with IBD and the overall population. Although biologics have not been shown to increase the risk of severe COVID-19 complications, several risk factors have been associated with negative COVID-19 outcomes in patients with IBD, including older age, obesity, the presence of comorbidities, active disease, and corticosteroid use. IBD therapy should, therefore, be continued with the aim of attaining or maintaining remission, except for corticosteroids, which should be held or reduced to the minimal effective dose. Although it has been recommended that immunosuppressive therapy be held during a case of COVID-19, the half-lives of these drugs and data on the timing of restarting therapy limit the strength of these recommendations. We recommend COVID-19 vaccination for IBD patients whenever available, as benefits to the individual and to society outweigh the risks. SUMMARY: As our understanding of SARS-CoV-2 and COVID-19 continues to evolve, we are learning more about its impact in patients with IBD and how to better manage patients in this setting. Managing IBD during this pandemic has also highlighted the importance of restructuring services in order to adapt to current and potential future outbreaks. The COVID-19 pandemic has transformed IBD care through the expansion of telemedicine and development of novel approaches to remote monitoring.

Hypoalbuminaemia, Not Biologic Exposure, Is Associated with Postoperative Complications in Crohn's Disease Patients Undergoing Ileocolic Resection.

BACKGROUND: There are limited data on the postoperative outcomes in Crohn's disease patients exposed to preoperative ustekinumab or vedolizumab. We hypothesised that preoperative biologic use in Crohn's disease is not associated with postoperative complications after ileocolic resection. METHODS: Crohn's disease patients who underwent ileocolic resection over 2009-2019 were identified at a large regional health system. Preoperative biologic use within 12 weeks of surgery was categorised as no biologic, anti-tumour necrosis factor, vedolizumab, or ustekinumab. The primary endpoint was 90-day intra-abdominal septic complication. Risk factors included preoperative medical therapies, demographics, disease characteristics, laboratory values, and surgical approach. Regression models assessed the association of biologic use with intra-abdominal septic complication. RESULTS: A total of 815 Crohn's disease patients who underwent an ileocolic resection were included [62% no biologic, 31.4% anti-tumour necrosis factor, 3.9% vedolizumab, 2.6% ustekinumab]. Primary anastomosis was performed in 85.9% of patients [side-to-side 48.8%, end-to-side 26%, end-to-end 25%] in primarily a stapled [77.2%] manner. Minimally invasive approach was used in 41.4%. The 90-day postoperative intra-abdominal sepsis rate of 810 patients was 12%, abscess rate was 9.6%, and anastomotic leak rate was 3.2%. Multivariable regression modelling controlling for confounding variables demonstrated that preoperative biologic use with anti-tumour necrosis factor [p = 0.21], vedolizumab [p = 0.17], or ustekinumab [p = 0.52] was not significantly associated with intra-abdominal septic complication. Preoperative albumin < 3.5 g/dl was independently associated with intra-abdominal septic complication (odds ratio [OR] 1.76 [1.03, 3.01]). CONCLUSIONS: In Crohn's disease patients undergoing ileocolic resection, preoperative biologics are not associated with 90-day postoperative intra-abdominal septic complication. Preoperative biologic exposure should not delay necessary surgery.

Altered Expression of the Epithelial Mucin MUC1 Accompanies Endoscopic Recurrence of Postoperative Crohn's Disease.

BACKGROUND: MUC1-glycoprotein is expressed at low levels and in fully glycosylated form on epithelial cells. Inflammation causes MUC1 overexpression and hypoglycosylation. We hypothesized that overexpression of hypoglycosylated MUC1 would be found in postoperative Crohn's disease (CD) recurrence and could be considered an additional biomarker of recurrence severity. METHODS: We examined archived neo-terminal ileum biopsies from patients with prior ileocecal resection who had postoperative endoscopic assessment of CD recurrence and given a Rutgeerts ileal recurrence score. Consecutive tissue sections were stained using 2 different anti-MUC1 antibodies, HMPV that recognizes all forms of MUC1 and 4H5 that recognizes only inflammation-associated hypoglycosylated MUC1. RESULTS: A total of 71 postoperative CD patients were evaluated. There was significant increase in MUC1 expression of both glycosylated/normal (P<0.0001) and hypoglycosylated/abnormal (P<0.0001) forms in patients with severe endoscopic CD recurrence (i3+i4), ileal score i2, compared with patients in endoscopic remission (i0+i1). Results were similar regardless of anti-TNF-α use. Although MUC1 expression and Rutgeerts scores were in agreement when characterizing the majority of cases, there were a few exceptions where MUC1 expression was characteristic of more severe recurrence than implied by Rutgeerts score. CONCLUSIONS: MUC1 is overexpressed and hypoglycosylated in neo-terminal ileum tissue of patients with postoperative CD recurrence. Increased levels are associated with more severe endoscopic recurrence scores, and this is not influenced by anti-TNF-α use. Discrepancies found between Rutgeerts scores and MUC1 expression suggest that addition of MUC1 as a biomarker of severity of postoperative CD recurrence may improve categorization of recurrence status and consequently treatment decisions.

Approach to Latent Tuberculosis Infection Screening Before Biologic Therapy in IBD Patients: PPD or IGRA?

The use of biological agents for the treatment of chronic inflammatory conditions such as inflammatory bowel diseases (IBD) has been on the rise.1,2 Current biological therapies include antitumor necrosis factor-α (anti-TNF-α), anti-interleukin-12/23, and anti-integrin agents. Before initiation of biological drugs, screening for Mycobacterium tuberculosis infection is required to avoid reactivation or worsening of disease after immunosuppression. It has been shown that anti-TNF-α treated patients have a 14-fold increased risk of tuberculosis (TB) infection/reactivation compared with healthy controls.3 The methods for screening for TB have evolved over time and vary from region to region.

Predictors of Suicidal Ideation Among IBD Outpatients.

BACKGROUND: Suicidal ideation (SI) is understudied in inflammatory bowel diseases (IBD). We aim to determine SI rates among IBD outpatients and to evaluate predictors of SI. MATERIALS AND METHODS: This is a prospective observational study of consecutive adult IBD outpatients over 18 months. Patients were screened for depression and SI using patient health questionnaire (PHQ-9). Demographic data were obtained from electronic medical record. Regression modeling was used for predictor analyses. RESULTS: In total, 71 of consecutive 1352 IBD outpatients had SI. Significant correlations between SI and depression severity, tricyclic antidepressants (TCA), IBD-related quality of life, and low vitamin D levels were seen. Univariate regression showed that depression severity, TCA use, and quality of life predicted SI. Multivariate regression showed depression severity (ß=0.46; P=0.002) and TCA use (ß=0.31; P=0.012) made unique contributions. CONCLUSIONS: SI is associated with depressive severity and less directly with IBD activity. Low-dose TCA, often used for chronic abdominal pain, is also a risk factor. Identifying the subset of IBD patients most vulnerable to SI can facilitate proper referrals to behavioral services and prevent progression to completed suicides.

Correction: ACG Clinical Guideline: Management of Crohn's Disease in Adults.

Since the publication of these Guidelines, the authors have noticed an error in the text on page 15. The incorrect statement is.

Distinct Histopathologic and Molecular Alterations in Inflammatory Bowel Disease-Associated Intestinal Adenocarcinoma: c-MYC Amplification is Common and Associated with Mucinous/Signet Ring Cell Differentiation.

Background: Chronic idiopathic inflammatory bowel disease (IBD) is a significant risk factor for the development of intestinal adenocarcinoma. The underlying molecular alterations in IBD-associated intestinal adenocarcinoma remain largely unknown. Methods: We compared the clinicopathologic and molecular features of 35 patients with 47 IBD-associated intestinal adenocarcinomas with a consecutive series of 451 patients with sporadic colorectal carcinoma identified at our institution and published data on sporadic colorectal carcinoma. Results: c-MYC amplification was the most frequent molecular alteration identified in 33% of IBD-associated intestinal adenocarcinoma that is a significantly higher frequency than in sporadic colorectal carcinoma (8%) (P = 0.0001). Compared to sporadic colorectal carcinoma, IBD-associated intestinal adenocarcinomas more frequently demonstrated mucinous differentiation (60% vs 25%, P < 0.001) and signet ring cell differentiation (28% vs 4%, P < 0.001). Mucinous and signet ring cell differentiation were significantly associated with the presence of c-MYC amplification (both with P < 0.05). HER2 positivity (11%), KRAS exon 2 or 3 mutation (10%), and IDH1 mutation (7%) were less commonly observed in IBD-associated intestinal adenocarcinoma. There was an association between poor survival and HER2 status with 3 of 4 patients having HER2-positive adenocarcinoma dead of disease at last clinical follow-up; however, no statistically significant survival effect was identified for any of the molecular alterations identified. Conclusions: We demonstrate that IBD-associated intestinal adenocarcinomas have a high frequency of c-MYC amplification that is associated with mucinous and signet ring cell differentiation. Many of the identified molecular alterations have potential therapeutic relevance, including HER2 amplification, IDH1 mutation, and low frequency KRAS mutation.

ACG Clinical Guideline: Management of Crohn's Disease in Adults.

Crohn's disease is an idiopathic inflammatory disorder of unknown etiology with genetic, immunologic, and environmental influences. The incidence of Crohn's disease has steadily increased over the past several decades. The diagnosis and treatment of patients with Crohn's disease has evolved since the last practice guideline was published. These guidelines represent the official practice recommendations of the American College of Gastroenterology and were developed under the auspices of the Practice Parameters Committee for the management of adult patients with Crohn's disease. These guidelines are established for clinical practice with the intent of suggesting preferable approaches to particular medical problems as established by interpretation and collation of scientifically valid research, derived from extensive review of published literature. When exercising clinical judgment, health-care providers should incorporate this guideline along with patient's needs, desires, and their values in order to fully and appropriately care for patients with Crohn's disease. This guideline is intended to be flexible, not necessarily indicating the only acceptable approach, and should be distinguished from standards of care that are inflexible and rarely violated. To evaluate the level of evidence and strength of recommendations, we used the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system. The Committee reviews guidelines in depth, with participation from experienced clinicians and others in related fields. The final recommendations are based on the data available at the time of the production of the document and may be updated with pertinent scientific developments at a later time.

White Paper AGA: The Impact of Mental and Psychosocial Factors on the Care of Patients With Inflammatory Bowel Disease.

Patients with chronic medically complex disorders like inflammatory bowel diseases (BD) often have mental health and psychosocial comorbid conditions. There is growing recognition that factors other than disease pathophysiology impact patients' health and wellbeing. Provision of care that encompasses medical care plus psychosocial, environmental and behavioral interventions to improve health has been termed "whole person care" and may result in achieving highest health value. There now are multiple methods to survey patients and stratify their psychosocial, mental health and environmental risk. Such survey methods are applicable to all types of IBD programs including those at academic medical centers, independent health systems and those based within independent community practice. Once a practice determines that a patient has psychosocial needs, a variety of resources are available for referral or co-management as outlined in this paper. Included in this white paper are examples of psychosocial care that is integrated into IBD practices plus innovative methods that provide remote patient management.