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.

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.

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.

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.

Impact of medical therapies for inflammatory bowel disease on the severity of COVID-19: a systematic review and meta-analysis.

BACKGROUND: During COVID-19 pandemic, the safety of medical therapies for inflammatory bowel disease (IBD) in relation to COVID-19 has emerged as an area of concern. This study aimed to evaluate the association between IBD therapies and severe COVID-19 outcomes. METHOD: We performed a systematic review and meta-analysis of all published studies from December 2019 to August 2021 to identify studies that reported severe COVID-19 outcomes in patients on current IBD therapies including 5-aminosalicylic acid (5-ASA), immunomodulators, corticosteroids, biologics, combination therapy, or tofacitinib. RESULTS: Twenty-two studies were identified. Corticosteroids (risk ratio (RR) 1.91 (95% CI 1.25 to 2.91, p=0.003)) and 5-ASA (RR 1.50 (95% CI 1.17 to 1.93, p=0.001)) were associated with increased risk of severe COVID-19 outcomes in patients with IBD patients. However, possible confounders for 5-ASA use were not controlled for. Sub-analysis showed that corticosteroids increased the risk of intensive care unit (ICU) admission but not mortality. Immunomodulators alone (RR 1.18 (95% CI 0.87 to 1.59, p=0.28)) or in combination with anti-TNFs ((RR 0.96 (95% CI 0.80 to 1.15, p=0.63)), tofacitinib (RR 0.81 (95% CI 0.49 to 1.33, p=0.40)) and vedolizumab ((RR 1.02 (95% CI 0.79 to 1.31, p=0.89)) were not associated with severe disease. Anti-TNFs (RR 0.47 (95% CI 0.40 to 0.54, p<0.00001)) and ustekinumab (RR 0.55 (95% CI 0.43 to 0.72, p<0.00001)) were associated with decreased risk of severe COVID-19. CONCLUSION: In patients with IBD, the risk of severe COVID-19 is higher among patients receiving corticosteroids. Corticosteroid use was associated with ICU admission but not mortality. The risk is also higher among patients receiving 5-ASAs. However, patient-level data were lacking and insufficient data existed for meta-regression analyses to adjust for confounding. Vedolizumab, tofacitinib, and immunomodulators alone or in combination with anti-TNF were not associated with severe disease. Anti-TNFs, and ustekinumab were associated with favourable outcomes.

Outcomes of Immune Checkpoint Inhibitor-related Diarrhea or Colitis in Cancer Patients With Superimposed Gastrointestinal Infections.

BACKGROUND AND OBJECTIVE: Immune-mediated diarrhea and colitis (IMDC) is a common adverse event in cancer patients receiving immune checkpoint inhibitors (ICIs). Gastrointestinal (GI) infections can co-occur with IMDC, and its impact on the course and outcome of IMDC remains unclear. PATIENTS AND METHODS: We retrospectively reviewed cancer patients who received ICIs and developed IMDC between January 2015 and September 2019. GI multiplex panel is used to assess GI infection. The study group included patients with positive infection except those who are only positive for Clostridioides difficile or cytomegalovirus. The control group is IMDC patients with negative infection using frequency matching. Patients' disease course and outcome were compared between groups. RESULTS: A total of 72 patients with IMDC were included: 22 in the study group and 50 as control. Escherichia coli of different pathotypes was observed in 17 patients. Five patients had viral infections, for example, adenovirus, norovirus, and sapovirus. Patients with GI infections more frequently had grade 3 or 4 colitis (43% vs. 18%, P=0.041). Overall, GI infections were not associated with different risks of IMDC recurrence or overall survival. Antibiotics treatment did not affect the requirement for infliximab or vedolizumab but relate to a higher risk of IMDC recurrence (50.0% vs. 0.0%, P=0.015). CONCLUSIONS: In our study, concomitant GI infections are associated with more severe symptoms in IMDC patients. Antimicrobial treatment did not circumvent the need for immunosuppressive therapy for IMDC or improve the clinical outcome. Concomitant GI infection was not associated with a higher risk of IMDC recurrence or poor overall survival.

COVID-19 and Canadian Gastroenterology Trainees.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has impacted endoscopy services and education worldwide. This study aimed to characterize the impact of COVID-19 on gastroenterology trainees in Canada. METHODS: An analysis of Canadian respondents from the international EndoTrain survey, open from April 11 to May 2 2020 and distributed by program directors, trainees, and national and international gastroenterology societies' representatives, was completed. The survey included questions on monthly endoscopy volume, personal protective equipment availability, trainee well-being and educational resources. The primary outcome was change in procedural volume during the COVID-19 pandemic. Secondary outcomes included trainee's professional and personal concerns, anxiety and burnout. RESULTS: Thirty-four Canadian trainees completed the survey. Per month, participants completed a median of 30 esophagogastroduodenoscopies (interquartile range 16 to 50) prior to the pandemic compared to 2 (0 to 10) during the pandemic, 20 (8 to 30) compared to 2 (0 to 5) colonoscopies and 3 (1 to 10) compared to 0 (0 to 3) upper gastrointestinal bleeding procedures. There was a significant decrease in procedural volumes between the pre-COVID-19 and COVID-19 time periods for all procedures (P < 0.001). Thirty (88%) trainees were concerned about personal COVID-19 exposure, 32 (94%) were concerned about achieving and/or maintaining clinical competence and 24 (71%) were concerned about prolongation of training time due to the pandemic. Twenty-six (79%) respondents experienced some degree of anxiety, and 10 (31%) experienced some degree of burnout. CONCLUSION: The COVID-19 pandemic has substantially impacted gastroenterology trainees in Canada. As the pandemic eases, it important for gastrointestinal programs to adapt to maximize resident learning, maintain effective clinical care and ensure development of endoscopic competence.

P033 Moving the Needle on Speaker Diversity at AIBD.

BACKGROUND: Diversity of invited speakers at academic conferences is a topic of increased focus in recent years. While there have been efforts to improve speaker diversity, an evaluation of this in the IBD field has not been undertaken to date. We aimed to address gaps in knowledge of speaker gender, race, and experience at a major annual IBD conference over time. METHODS: AIBD program brochures from 2014 to 2020 were reviewed by two providers to evaluate speaker demographic information including gender, race, topic of discussion, institutional affiliation, and, for those trained in gastroenterology, years post-fellowship. In addition, the proportion of all-male panels was calculated. As a comparator, the proportion of female speakers and all-male panels was then compared to a control conference run by the same CME organization (Personalized Therapies in Thoracic Oncology). RESULTS: The percentage of female speakers of any specialty at AIBD increased from 25% in 2016 to 39% in 2020. Female adult gastroenterologist speakers increased from 12% in 2015 to 27% in 2020. The percentage of all gastroenterologists that are female in the US is 19%. All-male panels also decreased from an average of 47% in 2014-2017, to 11% in 2018-2020. As a comparator, 47% of speakers at the control conference were female and there were no all-male panels in 2020. For race, in any given year an average of 13% of speakers were Asian, 5% Hispanic/Latinx, and 1% Black. This remained static over time. The percentage of Asian, Hispanic/Latinx, and Black gastroenterologists in the US is 29%, 5%, and 6%, respectively. Average years of experience of speakers at AIBD appeared relatively static, with a mean of 15 years since fellowship training per speaker. CONCLUSION: From 2014-2020, the proportion of female speakers at AIBD has increased to over one third in main programming. There remains room for improvement, particularly in increasing the racial and ethnic diversity of speakers and inviting more gastroenterologists in the early stages of their careers.

Impact of COVID-19 on endoscopy trainees: an international survey.

BACKGROUND AND AIMS: Although coronavirus disease 2019 (COVID-19) has affected endoscopy services globally, the impact on trainees has not been evaluated. We aimed to assess the impact of COVID-19 on procedural volumes and on the emotional well-being of endoscopy trainees worldwide. METHODS: An international survey was disseminated over a 3-week period in April 2020. The primary outcome was the percentage reduction in monthly procedure volume before and during COVID-19. Secondary outcomes included potential variation of COVID-19 impact between different continents and rates and predictors of anxiety and burnout among trainees. RESULTS: Across 770 trainees from 63 countries, 93.8% reported a reduction in endoscopy case volume. The median percentage reduction in total procedures was 99% (interquartile range, 85%-100%), which varied internationally (P < .001) and was greatest for colonoscopy procedures. Restrictions in case volume and trainee activity were common barriers. A total of 71.9% were concerned that the COVID-19 pandemic could prolonged training. Anxiety was reported in 52.4% of respondents and burnout in 18.8%. Anxiety was independently associated with female gender (odds ratio [OR], 2.15; P < .001), adequacy of personal protective equipment (OR, 1.75; P = .005), lack of institutional support for emotional health (OR, 1.67; P = .008), and concerns regarding prolongation of training (OR, 1.60; P = .013). Modifying existing national guidelines to support adequate endoscopy training during the pandemic was supported by 68.9%. CONCLUSIONS: The COVID-19 pandemic has led to restrictions in endoscopic volumes and endoscopy training, with high rates of anxiety and burnout among endoscopy trainees worldwide. Targeted measures by training programs to address these key issues are warranted to improve trainee well-being and support trainee education.

The Management Approach to the Adolescent IBD Patient: Health Maintenance and Medication Considerations.

PURPOSE OF REVIEW: Inflammatory bowel disease (IBD) is often diagnosed during adolescence and can have a deep impact on the physical, hormonal, developmental, and psychosocial changes associated with this life period. The purpose of this review is to address the particular manifestations of IBD (such as growth and pubertal delay), health maintenance issues, and treatment considerations in the adolescent. RECENT FINDINGS: The need for a multidisciplinary approach to recognize and address growth and pubertal delay, bone health, as well as the psychosocial impact of IBD on the adolescent has been increasingly recognized as an integral part of IBD care in this population. Vaccinations schedule, preventive health measures, and promoting compliance with care are particularly important during adolescence. Replacing nutrients deficits is also crucial: in particular, vitamin D has been shown to play a role in the gut immune system, and adequate vitamin D levels might promote IBD remission. Iron replacement should be done by intravenous route since oral iron is poorly absorbed in chronic inflammatory states. Finally, recent data have shed light on the increased risk of particular types of lymphoma in adolescent on thiopurines, whereas biologic therapies, in particular, anti-TNF, now are positioned as a preferred and effective steroid-sparing agents in moderate to severe IBD. Management of adolescents with IBD is not without significant challenges. An early implementation of steroid-sparing therapies, a multidisciplinary treatment approach, and a dynamic physician-patient relationship are essential to achieve remission, prevent disease-related complications but also optimize developmental, physical, and psychosocial health, and encourage compliance and transition to adult care.

Management of Asymptomatic Terminal Ileitis.

Ileal intubation is often performed during screening colonoscopies. This had led to the recognition of mild ileitis in many asymptomatic patients. The natural history and clinical significance of this finding are not well established, and there are no guidelines on whether these patients merit further work-up or an interval surveillance colonoscopy. This conundrum was presented and discussed on @MondayNightIBD. In this article, we review the specific literature on the topic and make reference to the informed opinions of the convo participants. We propose an #IBDAlgorithm for management of asymptomatic ileitis.

A case of checkpoint inhibitor-induced celiac disease.

BACKGROUND: Immune checkpoint inhibitors (ICIs) have now become standard of care treatment for many malignancies. ICIs are associated with unique immune mediated adverse events (irAEs) due to dysregulation of immune activation. As treatment with ICIs is becoming more common, rare irAEs are also being recognized. Here we report a case of ICI-induced celiac disease. CASE: A 74-year-old Caucasian female with metastatic renal carcinoma received second line nivolumab (anti-PD1 antibody) after initial disease progression on sunitinib. Ipilimumab was added after she failed to respond to six cycles of nivolumab monotherapy. One week after her first cycle of combination treatment, she presented with nausea, vomiting, grade 1 diarrhea, and weight loss. She underwent endoscopy, which showed bile stasis in the stomach, normal appearing stomach mucosa, and nonbleeding erythematous mucosa in the duodenal bulb. Stomach biopsy showed moderate active chronic gastritis. Duodenal biopsy showed moderate chronic active duodenitis with focal neutrophilic cryptitis, mucosal erosions, villous atrophy, mildly increased intraepithelial lymphocytes, and moderate chronic inflammation in the lamina propria pathognomonic of celiac disease. Symptoms improved with gluten-free diet, twice-daily omeprazole and anti-emetics and she was able to continue on treatment. CONCLUSIONS: There has been only one published case reporting ICI-induced celiac disease. Our case report highlights a rare irAE (celiac disease) associated with ICI treatment. It is unclear whether the patient had previously undiagnosed celiac disease or whether ICIs triggered her enteritis. Our patient was able to continue treatment with ICIs with dietary modifications, suggesting correct diagnosis is critical for optimal patient outcome.

Role of colonoscopy in diagnosis of capecitabine associated ileitis: Two case reports.

BACKGROUND: Capecitabine is considered a first line agent in adjuvant therapy for breast and colorectal cancer. However, cases of severe diarrhea have been reported with increasing frequency in recent years. When diarrhea is severe and prolonged, capecitabine associated ileitis should be considered as a possible etiology. CASE SUMMARY: Herein, we present two cases of capecitabine ileitis, specifically involving the terminal ileum and ascending colon. We will demonstrate the disease course and treatment modalities applied to alleviate this condition, as well as discuss the merits of using colonoscopy to aid in diagnosis. CONCLUSION: Ultimately our cases demonstrate that symptomatic management with traditional anti-diarrheal medications is largely ineffective. Prompt recognition and discontinuation of capecitabine is an imperative step in proper management of this condition and colonoscopy with biopsy can be helpful when the diagnosis is unclear.

Early introduction of selective immunosuppressive therapy associated with favorable clinical outcomes in patients with immune checkpoint inhibitor-induced colitis.

BACKGROUND: Current treatment guidelines for immune-mediated colitis (IMC) recommend 4 to 6 weeks of steroids as first-line therapy, followed by selective immunosuppressive therapy (SIT) (infliximab or vedolizumab) in patients who do not respond to steroids. We assessed the effect of early SIT introduction and number of SIT infusions on clinical outcomes. METHODS: We performed a retrospective review of patients with IMC who received SIT at The University of Texas MD Anderson Cancer Center between January and December 2018. Logistic regression analyses were used to assess associations between clinical outcomes and features of IMC. RESULTS: Of the 1459 patients who received immune checkpoint inhibitors, 179 developed IMC of any grade; 84 of these 179 patients received SIT. Of the 84 patients who received SIT, 79% were males, and the mean age was 60 years (standard deviation, 14). Compared with patients who received SIT > 10 days after IMC onset, patients who received early SIT (≤10 days) required fewer hospitalizations (P = 0.03), experienced steroid taper failure less frequently (P = 0.03), had fewer steroid tapering attempts (P < 0.01), had a shorter course of steroid treatment (P = 0.09), and had a shorter duration of symptoms (P < 0.01). Patients who received one or two infusions of SIT achieved histologic remission less frequently (P = 0.09) and had higher fecal calprotectin levels after SIT (P = 0.01) compared with patients who received three or more infusions. Risk factors for IMC recurrence after weaning off steroids included: 1) needing multiple hospitalizations, 2) experiencing steroid taper failure after SIT, 3) receiving infliximab rather than vedolizumab, 4) receiving fewer than three infusions of SIT, 5) having higher fecal calprotectin levels after SIT, and 6) receiving a longer course of steroids, hospitalization and IMC symptoms. Unsuccessful weaning from steroids after SIT was associated with high IMC grades; multiple hospitalizations; steroid-resistant IMC; long interval from IMC to SIT initiation; and long duration of steroids, IMC symptoms, and hospitalization. CONCLUSION: SIT should be introduced early in the disease course of IMC instead of waiting until failure of steroid therapy or steroid taper. Patients who received three or more infusions of SIT had more favorable clinical outcomes.

Immune checkpoint inhibitor-induced colitis: A comprehensive review.

Immune checkpoint inhibitors (ICIs) are monoclonal antibodies that target down-regulators of the anti-cancer immune response: Cytotoxic T-lymphocyte antigen-4, programmed cell death protein-1, and its ligand programmed death-ligand 1. ICIs have revolutionized the treatment of a variety of malignancies. However, many immune-related adverse events have also been described which mainly occurs as the immune system becomes less suppressed, affecting various organs including the gastrointestinal tract and causing diarrhea and colitis. The incidence of immune-mediated colitis (IMC) ranges from 1%-25% depending on the type of ICI and if used in combination. Endoscopically and histologically there is a significant overlap between IMC and inflammatory bowel disease, however more neutrophilic inflammation without chronic inflammation is usually present in IMC. Corticosteroids are recommended for grade 2 or more severe colitis while holding the immunotherapy. About one third to two thirds of patients are steroid refractory and benefit from infliximab. Recently vedolizumab has been found to be efficacious in steroid and infliximab refractory cases. While in grade 4 colitis, the immunotherapy is permanently discontinued, the decision is controversial in grade 3 colitis.