Biologics, small molecule therapies and surgery in small bowel Crohn's disease.

PURPOSE OF REVIEW: The terminal ileum and small bowel (SB) are involved in 30-45% of patients with Crohn's disease, while 20% have both small and large bowel involvement. Ileal Crohn's is associated with higher risk of progression to stricturing and penetrating disease 1 , hence it's imperative to utilize effective therapies to induce and maintain clinical and endoscopic remission and prevent intestinal complications. We review the available data of biologics and upadacitinib in small bowel disease, and the emerging data on the role of surgery as first line therapy for isolated Crohn's ileitis. RECENT FINDINGS: Most trials assessing drug efficacy do not report efficacy by disease location, and robust data on efficacy of therapies in isolated small bowel Crohn's is sparse. Several studies indicate that small bowel disease is generally less responsive to biologics, and could require higher drug trough levels to achieve endoscopic healing. SUMMARY: Current therapies for induction and maintenance of remission in moderate to severe Crohn's disease include several classes of monoclonal antibodies and a Janus Kinase inhibitor, upadacitinib. While small bowel Crohn's disease is generally less responsive to treatment, anti-TNFs are still preferred as first line therapy, and the option of early ileocecal resection in early limited ileal disease is gaining interest.

@MondayNightIBD and the Expanding Gastroenterology Twitterverse: A Study on Continuing Medical Education on #GITwitter.

INTRODUCTION: @MondayNightIBD provides weekly continuing medical education (CME) activities focused on inflammatory bowel diseases to clinicians on Twitter. Given its novelty, we assessed whether @MondayNightIBD improves learner knowledge and leads to practice change. We also examined whether inflammatory bowel disease topics addressed in @MondayNightIBD are aligned with entrustable professional activities (EPA) set forth by national gastroenterology societies. METHODS: @MondayNightIBD CME sessions from February 2020 (date the handle was accredited to provide CME) to May 2021 were analyzed. Preactivity and postactivity knowledge was assessed for average score improvement using the Student t test and Cohen d effect size. Postactivity surveys examined for learners' perceptions of whether activities met educational goals and affected willingness to change clinical practice using descriptive percentages. In addition, activities from April 2019 (date of @MondayNightIBD inception) to May 2021 were assessed for whether they address EPA set forth by national gastroenterology societies. RESULTS: Learners' knowledge improved after @MondayNightIBD activities with average preactivity correct answers of 58% to a postactivity average of 79% ( P < 0.001). Greater than 95% of learners found that activities met learning objectives and enhanced knowledge. A total of 92% of learners were committed to practice change because of their @MondayNightIBD participation. Finally, 78% of EPA set forth by a national gastroenterology society have been covered by @MondayNightIBD since its inception. DISCUSSION: @MondayNightIBD is a Twitter-based CME activities platform for gastroenterologists and other clinicians that is embraced by learners, improves knowledge, and encourages practice change. Topics covered during @MondayNightIBD are aligned with EPA set forth by national gastroenterology societies. @MondayNightIBD is a successful model of social media medical education and a novel approach to effectively provide evidence-based CME.

The Toronto Upper Gastrointestinal Cleaning Score: a prospective validation study.

BACKGROUND : Assessment of mucosal visualization during esophagogastroduodenoscopy (EGD) can be improved with a standardized scoring system. To address this need, we created the Toronto Upper Gastrointestinal Cleaning Score (TUGCS). METHODS : We developed the TUGCS using Delphi methodology, whereby an international group of endoscopy experts iteratively rated their agreement with proposed TUGCS items and anchors on a 5-point Likert scale. After each Delphi round, we analyzed responses and refined the TUGCS using an 80 % agreement threshold for consensus. We used the intraclass correlation coefficient (ICC) to assess inter-rater and test-retest reliability. We assessed internal consistency with Cronbach's alpha and item-total and inter-item correlations with Pearson's correlation coefficient. We compared TUGCS ratings with an independent endoscopist's global rating of mucosal visualization using Spearman's ρ. RESULTS : We achieved consensus with 14 invited participants after three Delphi rounds. Inter-rater reliability was high at 0.79 (95 %CI 0.64-0.88). Test-retest reliability was excellent at 0.83 (95 %CI 0.77-0.87). Cronbach's α was 0.81, item-total correlation range was 0.52-0.70, and inter-item correlation range was 0.38-0.74. There was a positive correlation between TUGCS ratings and a global rating of visualization (r = 0.41, P = 0.002). TUGCS ratings for EGDs with global ratings of excellent were significantly higher than those for EGDs with global ratings of fair (P = 0.01). CONCLUSION : The TUGCS had strong evidence of validity in the clinical setting. The international group of assessors, broad variety of EGD indications, and minimal assessor training improves the potential for dissemination.

Biologic Therapies for the Treatment of Post-ileal Pouch Anal Anastomosis Surgery Chronic Inflammatory Disorders: Systematic Review and Meta-analysis.

Background: Chronic inflammatory disorders after ileal pouch-anal anastomosis (IPAA) surgery are common. These include chronic pouchitis (CP), Crohn's disease (CD) of the pouch, prepouch ileitis (PI) and rectal cuff inflammation (cuffitis). The aim of this study was to evaluate the efficacy of biologic therapies in treating these disorders. Method: Systematic review of all published studies from inception to August 1, 2021 was performed to investigate the efficacy of biologic therapies for post-IPAA chronic inflammatory disorders. The primary outcome was the efficacy of biologic therapies in achieving complete clinical response in patients with IPAA. Results: A total of 26 studies were identified including 741 patients. Using a random-effect model, the efficacy of infliximab in achieving complete clinical response in patients with CP was 51% (95% CI, 36 to 66), whereas the efficacy of adalimumab was 47% (95% CI, 31 to 64). The efficacies of ustekinumab and vedolizumab were 41% (95% CI, 06 to 88) and 63% (95% CI, 35 to 84), respectively. In patients with CD/PI, the efficacy of infliximab in achieving complete clinical response was 52% (95% CI, 33 to 71), whereas the efficacy of adalimumab was 51% (95% CI, 40 to 61). The efficacies of ustekinumab and vedolizumab were 42% (95% CI, 06 to 90) and 67% (95% CI, 38 to 87), respectively. Only one study involved patients with cuffitis. Conclusion: Ustekinumab, infliximab, vedolizumab and adalimumab are effective in achieving complete clinical response in post-IPAA surgery chronic inflammatory disorders. More studies are needed to determine the efficacy of biologics in cuffitis.

Management of Crohn's stricture: medical, endoscopic and surgical therapies.

Patients with Crohn's disease are at high risk of presenting with or developing a bowel stricture during the course of their disease. The available therapeutic options to manage a symptomatic Crohn's stricture include medical therapy (mainly biologics), surgical resection and endoscopic interventions. The choice of therapeutic modality depends on the clinical presentation of the stricture, the nature of the stricture (inflammatory vs fibrotic, primary vs anastomotic) and its anatomical characteristics on endoscopy and imaging (length, number, location of strictures and severity of obstruction). The aim herein is to provide an overview of the comprehensive assessment of a Crohn's stricture and to review the indications of the different therapeutic modalities, their success rates and their limitations to help clinicians properly evaluate and manage Crohn's strictures.

Endoscopic submucosal dissection for colorectal dysplasia in inflammatory bowel disease: a US multicenter study.

Background and study aims In patients with inflammatory bowel disease (IBD), endoscopically visible lesions with distinct borders can be considered for endoscopic resection. The role of endoscopic submucosal dissection (ESD) for these lesions is not well defined because of a paucity of data. We aimed to evaluate the outcomes of colorectal ESD of dysplastic lesions in patients with IBD across centers in the United States. Patients and methods This was a retrospective analysis of consecutive patients with IBD who were referred for ESD of dysplastic colorectal lesions at nine centers. The primary endpoints were the rates of en bloc resection and complete (R0) resection. The secondary endpoints were the rates of adverse events and lesion recurrence. Results A total of 45 dysplastic lesions (median size 30mm, interquartile range [IQR] 23 to 42 mm) in 41 patients were included. Submucosal fibrosis was observed in 73 %. En bloc resection was achieved in 43 of 45 lesions (96 %) and R0 resection in 34 of 45 lesions (76 %). Intraprocedural perforation occurred in one patient (2.4 %) and was treated successfully with clip placement. Delayed bleeding occurred in four patients (9.8 %). No severe intraprocedural bleeding or delayed perforation occurred. During a median follow-up of 18 months (IQR 13 to 37 months), local recurrence occurred in one case (2.6 %). Metachronous lesions were identified in 11 patients (31 %). Conclusions ESD, when performed by experts, is safe and effective for large, dysplastic colorectal lesions in patients with IBD. Despite the high prevalence of submucosal fibrosis, en bloc resection was achieved in nearly all patients with IBD undergoing ESD. Careful endoscopic surveillance is necessary to monitor for local recurrence and metachronous lesions after ESD.

The present and future of gastroenterology and hepatology: an international SWOT analysis (the GASTROSWOT project).

GASTROSWOT is a strategic analysis of the current and projected states of the different subspecialties in gastroenterology that aims to provide guidance for research, clinical, and financial planning in gastroenterology. We executed a consensus-based international strengths, weaknesses, opportunities, and threats (SWOT) analysis. Four general coordinators, six field coordinators, and 12 experts participated in the study. SWOTs were provided for the following fields: neurogastroenterology, functional gastrointestinal disorders, and upper gastrointestinal diseases; inflammatory bowel disease; pancreatology and biliary diseases; endoscopy; gastrointestinal oncology; and hepatology. The GASTROSWOT analysis highlights the following in the current state of the field of gastroenterology: the incidence and complexity of several gastrointestinal diseases, including malignancies, are increasing; the COVID-19 pandemic has affected patient care on several levels; and with the advent of technical innovations in gastroenterology, a well trained workforce and strategic planning are required to optimise health-care utilisation. The analysis calls attention to the following in the future of gastroenterology: artificial intelligence and the use of big data will speed up discovery and smarter health-care provision in the field; the growth and diversification of gastroenterological specialties will improve specialised care for patients, but could promote fragmentation of care and health system inefficiencies; and furthermore, thoughtful planning is needed to reach an effective balance between the need for subspecialists and the value of general gastroenterology services.

Medical Treatment Options for Ulcerative Colitis.

The landscape of management of ulcerative colitis, a type of inflammatory bowel disease, continues to change with advancement in pharmaceutical options as well as clinical treatment targets. Ulcerative colitis primarily involves the superficial layers of the large bowel, and cause active inflammation that can affect the colon from the rectum to the cecum in a relapsing and a remitting course. In this review, we provide evidence-based guidance on the selection of appropriate medical therapies based on individual patient and disease characteristics, with a focus on biologics and small molecules. We also review the role of surgery and management of acute severe ulcerative colitis.

Living With Inflammatory Bowel Disease: Online Surveys Evaluating Patient Perspectives on Treatment Satisfaction and Health-Related Quality of Life.

Background: The quality of life of persons living with inflammatory bowel disease (IBD) is impacted by the physical and psychosocial burdens of disease, as well as by their satisfaction with the quality of care they receive. We sought to better understand (1) the drivers of satisfaction with treatment, including treatment goals, treatment selection, and attributes of patient/health care professional (HCP) interactions, and (2) how IBD symptoms affect aspects of daily life and overall quality of life. Methods: Two online questionnaires were accessed via MyCrohnsAndColitsTeam.com. The Treatment Survey assessed desired treatment outcomes, past and present therapies, and experiences with the patient's primary treating HCP. The Quality of Life survey assessed respondents' most problematic IBD symptoms and their influence on family and social life, work, and education. Respondents had Crohn's disease (CD) or ulcerative colitis (UC), were 19 years or older, and resided in the United States. All responses were anonymous. Results: The Treatment Experience survey was completed by 502 people (296 CD, 206 UC), and the Quality of Life survey was completed by 302 people (177 CD, 125 UC). Reduced pain, diarrhea, disease progression, and fatigue were the most desired goals of treatment. Biologics and 5-aminosalicylates were reported as a current or past treatment by the greatest proportion of patients with CD and UC, respectively. A numerically lower proportion of respondents with UC than CD reported use of biologic or small molecule therapy; conversely, a numerically greater proportion of respondents with UC than CD reported these drugs to be very or extremely effective. The HCP was key in the decision to switch to, and in the selection of, biologic or small molecule therapy. Overall satisfaction with an HCP was greatly driven by the quality and quantity of the communication and of the time spent with the HCP. Troublesome abdominal symptoms most impacted aspects of social and family life. Emotional challenges associated with IBD were experienced by most respondents. Conclusions: Treatment goals of respondents seem to align with HCPs overall treatment goals, including control of gastrointestinal symptoms and prevention of disease progression. Persons with UC might be offered biologic and small molecule therapies less often, despite reported high efficacy by users. Feeling heard and understood by the HCP are key drivers of treatment satisfaction. Quality communication in the patient/HCP relationship enables a better understanding of the patients' goals, disease burden, and emotional needs, which are all key factors to consider when developing a personalized and comprehensive treatment plan and optimizing quality of life.

Efficacy and safety of vedolizumab and infliximab treatment for immune-mediated diarrhea and colitis in patients with cancer: a two-center observational study.

BACKGROUND: Current treatment guidelines for immune-mediated diarrhea and colitis (IMDC) recommend steroids as first-line therapy, followed by selective immunosuppressive therapy (SIT) (infliximab or vedolizumab) for refractory cases. We aimed to compare the efficacy of these two SITs and their impact on cancer outcomes. METHODS: We performed a two-center, retrospective observational cohort study of patients with IMDC who received SITs following steroids from 2016 to 2020. Patients' demographic, clinical, and overall survival data were collected and analyzed. RESULTS: A total of 184 patients (62 vedolizumab, 94 infliximab, 28 combined sequentially) were included. The efficacy of achieving clinical remission of IMDC was similar (89% vs 88%, p=0.79) between the two groups. Compared with the infliximab group, the vedolizumab group had a shorter steroid exposure (35 vs 50 days, p<0.001), fewer hospitalizations (16% vs 28%, p=0.005), and a shorter hospital stay (median 10.5 vs 13.5 days, p=0.043), but a longer time to clinical response (17.5 vs 13 days, p=0.012). Longer durations of immune checkpoint inhibitors treatment (OR 1.01, p=0.004) and steroid use (OR 1.02, p=0.043), and infliximab use alone (OR 2.51, p=0.039) were associated with higher IMDC recurrence. Furthermore, ≥3 doses of SIT (p=0.011), and fewer steroid tapering attempts (p=0.012) were associated with favorable overall survival. CONCLUSIONS: Treatment with vedolizumab as compared with infliximab for IMDC led to comparable IMDC response rates, shorter duration of steroid use, fewer hospitalizations, and lower IMDC recurrence, though with slightly longer time to IMDC response. Higher number of SIT doses was associated with better survival outcome, while more steroid exposure resulted in worse patient outcomes.