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.

Superior Efficacy of Infliximab Versus Adalimumab for First-Line Treatment of Crohn's Perianal Fistulae.

BACKGROUND: Crohn's disease perianal fistulae (CD-PAF) occur in 25% of patients and are notoriously challenging to manage. Tumor necrosis factor inhibitors are first line agents. AIMS: The aim of this study was to compare infliximab (IFX) versus adalimumab (ADA) efficacy in CD-PAF healing over time. METHODS: A retrospective study at two large-tertiary medical centers was performed. Inclusion criteria were actively draining CD-PAF and initial treatment with IFX or ADA following CD-PAF diagnosis. The primary endpoints were perianal fistula response and remission at 6 and 12 months. Secondary endpoints included biologic persistence over time and dose escalation at 6 and 12 months. RESULTS: Among 151 patients included in the study, 92 received IFX and 59 received ADA as first line agents after CD-PAF diagnosis. At 6 months, the 64.9% of the IFX group and 34.8% of the ADA group demonstrated CD-PAF clinical improvement (p < 0.01). Univariate and multivariate analyses demonstrated significant differences among the IFX and ADA groups for clinical response at 6-months and 12-months (p = 0.002 and p = 0.042, respectively). There were no factors that predicted response, with the exception of concomitant immunomodulator affecting the 6-month clinical response (p = 0.021). Biologic persistence, characterized by Kaplan Meier methods, was significantly longer in the IFX group compared to the ADA group (Log-rank p = 0.01). CONCLUSION: IFX induction and maintenance is associated with higher rates of response and remission in CD-PAF healing as well as higher treatment persistence compared to ADA. Additionally, our study supports the use of concomitant immunomodulator therapy for CD-PAF healing and remission.

Assessing Family Leave Policies and Pregnancy Outcomes Among Gastroenterologists: A Survey of Physicians in the American College of Gastroenterology.

INTRODUCTION: Given variability in parental leave policies in gastroenterology (GI) with little data on outcomes, the American College of Gastroenterology conducted a survey to assess policies and outcomes. METHODS: A survey was distributed to American College of Gastroenterology members with questions on demographics, fertility, pregnancy outcomes, and parental leave policies. RESULTS: There were 796 responses, with 52.5% female individuals. Many (57%) delayed parenting. High rates of infertility (21%) and pregnancy complications (68%) were observed. Satisfaction with parental leave policies in GI was low (35%). DISCUSSION: Our survey highlights the need for policies that support the well-being of our GI colleagues and families.

Pregnancy and Crohn's disease: concerns and assurance of medical therapy.

Approximately 50% of patients with inflammatory bowel disease including both Crohn's disease and ulcerative colitis are female with many being diagnosed and treated during their reproductive years. It is important for women to be in remission prior to and during pregnancy. There have been many advances in the treatment of inflammatory bowel disease, including new therapies. In this review, we summarize the currently approved medications for Crohn's disease and their safety in pregnancy and postpartum. The totality of evidence suggests that the majority of therapies are low-risk before and during pregnancy, and should be continued to control maternal disease.

Advanced endoscopic resection for colorectal dysplasia in inflammatory bowel disease: a meta-analysis.

Background and study aims Little is known about outcomes of advanced endoscopic resection (ER) for patients with inflammatory bowel disease (IBD) with dysplasia. The aim of our meta-analysis was to estimate the safety and efficacy of endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) for dysplastic lesions in patients with IBD. Methods We performed a systematic review through Jan 2021 to identify studies of IBD with dysplasia that was treated by EMR or ESD. We estimated the pooled rates of complete ER, adverse events, post-ER surgery, and recurrence. Proportions were pooled by random effect models. Results Eleven studies including 506 patients and 610 lesions were included. Mean lesion size was 23 mm. The pooled rate of complete ER was 97.9 % (95 % confidence interval [CI]: 95.3 % to 99.7 %). The pooled rate of endoscopic perforation was 0.8 % (95 % CI:0.1 % to 2.2 %) while bleeding occurred in 1.6 % of patients (95 %CI:0.4 % to 3.3 %). Overall, 6.6 % of patients (95 %CI:3.6 % to 10.2 %) underwent surgery after an ER. Among 471 patients who underwent surveillance, local recurrence occurred in 4.9 % patients (95 % CI:1.0 % to 10.7 %) and metachronous lesions occurred in 7.4 % patients (95 %CI:1.5 % to 16 %) over a median follow-up of 33 months. Metachronous colorectal cancer (CRC) was detected in 0.2 % of patients (95 %CI:0 % to 2.2 %) during the surveillance period. Conclusions Advanced ER is safe and effective in the management of large dysplastic lesions in IBD and warrants consideration as first-line therapy. Although the risk of developing CRC after ER is low, meticulous endoscopic surveillance is crucial to monitor for local or metachronous recurrence of dysplasia.

Antibody Response 3 Months After 2-Dose SARS-CoV-2 mRNA Vaccination in Patients With Inflammatory Bowel Disease.

INTRODUCTION: The response to SARS-CoV-2 vaccination of patients with inflammatory bowel disease (IBD) on immune-modifying therapies requires further investigation because previous studies indicate that patients on immune therapy might have decreased antibody concentrations. METHODS: We present the antireceptor binding domain antibody response over a period of 3 months in 217 patients with IBD who completed standard 2-dose SARS-CoV-2 mRNA vaccine series. RESULTS: Almost all (98.6%) IBD vaccine recipients had a positive antireceptor binding domain antibody response at least 3 months after vaccination. Decreased antibody titers at 3 months were seen in a subset of patients on antitumor necrosis factor-alpha. Approximately 10% of the participants with high-titer antibodies at 1 month had a decrease to low-positive titers at 3 months, which was mostly observed in those on combination therapy and antitumor necrosis factor-alpha monotherapy. DISCUSSION: Larger longitudinal studies are required to define the response in IBD population and its clinical impact.

Antibody Response Six Months after SARS-CoV-2 mRNA Vaccination in Patients with Inflammatory Bowel Disease.

Patients with inflammatory bowel disease (IBD) are recommended to receive vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), regardless of their immunosuppression status. Immunosuppressive medications represent a mainstay of therapy in moderate to severe IBD; however, their impact on the SARS-CoV-2 vaccine response remains unclear. Studies thus far have shown that patients with IBD on various therapies had detectable antibody responses after standard vaccinations.1-5 To date, one study has examined the kinetics of antibody response at 3 months after vaccination in patients with IBD, but data beyond this time point are not yet available.6 The aim of this study was to assess anti-spike antibody response 6 months after completion of standard SARS-CoV-2 vaccination in patients with IBD. Secondarily, we observed antibody kinetics over 6 months in a subset of patients post-vaccination.

Serrated Epithelial Change Is Associated With High Rates of Neoplasia in Ulcerative Colitis Patients: A Case-controlled Study and Systematic Review With Meta-analysis.

BACKGROUND: Patients with long-standing ulcerative colitis (UC) are at an increased risk of colorectal cancer. Risk stratification is important to identify patients who require more frequent endoscopic surveillance. Serrated epithelial change (SEC) found in patients with long-standing colitis may be associated with neoplasia and serve as a marker to stratify patients at higher risk of colorectal cancer (CRC). METHODS: A case-control study was performed to compare the rates of neoplasia between UC patients with SEC and UC patients without SEC who were matched for age, disease duration, and disease extent. Paired tests, conditional logistic regression, and Kaplan-Meier analyses were used to compare groups. A systematic review with meta-analysis was performed, combining our local data with previously published data. RESULTS: This study included 196 UC patients without prior neoplasia, 98 with SEC and 98 without SEC. Ulcerative colitis patients with SEC had a significantly higher rate of synchronous or metachronous neoplasia than UC patients without SEC (26.5% vs 3.1%; P < 0.001). Synchronous or metachronous high-grade dysplasia and CRC were found more frequently in UC patients with SEC than UC patients without SEC (11.2% vs 2.0%; P = 0.02). A meta-analysis was consistent with these findings, showing a higher rate of neoplasia in patients with SEC compared with those without SEC (16.4% vs 3.9%; P < 0.001). CONCLUSION: Serrated epithelial change is associated with a significantly increased risk of synchronous and metachronous neoplasia including high-grade dysplasia and CRC in patients with UC. Histopathological findings of SEC should warrant closer endoscopic surveillance for CRC.

Potential of Electrical Neuromodulation for Inflammatory Bowel Disease.

Inflammatory bowel disease (IBD) is a common chronic inflammatory disease of the digestive tract that is often debilitating. It affects patients' quality of life and imposes a financial burden. Despite advances in treatment with medications such as biologics, a large proportion of patients do not respond to medical therapy or develop adverse events. Therefore, alternative treatment options such as electrical neuromodulation are currently being investigated. Electrical neuromodulation, also called bioelectronic medicine, is emerging as a potential new treatment for IBD. Over the past decade, advancements have been made in electrical neuromodulation. A number of electrical neuromodulation methods, such as vagus nerve stimulation, sacral nerve stimulation, and tibial nerve stimulation, have been tested to treat IBD. A series of animal and clinical trials have been performed to evaluate efficacy with promising results. Although the exact underlying mechanisms of action for electrical neuromodulation remain to be explored, this modality is promising. Further randomized controlled trials and basic experiments are needed to investigate efficacy and clarify intrinsic mechanisms.

Ipilimumab-Induced Enteritis without Colitis: A New Challenge.

INTRODUCTION: Ipilimumab is an immune checkpoint inhibitor targeting cytotoxic T-lymphocyte associated antigen 4 (CTLA4), approved to treat metastatic melanoma. It was the first therapy shown to prolong survival in a large, randomized clinical trial. However, immune-related adverse events are common and can be severe. Enterocolitis is a common adverse event with ipilimumab, but enteritis without colitis has not been previously described. CASE REPORT: An 83-year-old man presented to our hospital with grade 3 diarrhea for 5 days. One month prior, he had started treatment with ipilimumab for metastatic melanoma. On presentation, he was found to have severe electrolyte disturbances, including hyponatremia, hypokalemia, and acute kidney injury. Causes of infectious diarrhea were excluded, and he was treated with corticosteroids for presumed ipilimumab-associated enterocolitis. However, colonoscopy revealed normal mucosa, both grossly and on pathology of random biopsies. Steroids were weaned but his symptoms recurred. He then underwent upper endoscopy with enteroscopy. Biopsy of the duodenum was notable for acute inflammation, villous blunting, and other changes consistent with ipilimumab-associated injury. He was restarted on high-dose steroids and his symptoms resolved. DISCUSSION: Ipilimumab-induced enteritis is a serious and potentially life-threatening immune related adverse event that warrants prompt recognition and aggressive management. As in cases of ipilimumab-associated enterocolitis, steroids are an effective therapy. Enteritis without colitis should be suspected in patients on ipilimumab who present with severe diarrhea but have a normal colonoscopy.

Validation of ICD-9-CM diagnostic codes for inflammatory bowel disease among veterans.

BACKGROUND: Inflammatory bowel disease (IBD) is well described among young whites and less so among the elderly and non-whites. Population-level data is required to assess outcomes among minority groups. AIM: To validate diagnostic codes for IBD from the Department of Veterans Affairs. METHODS: National databases were used to identify local patients with Crohn's disease (CD) and ulcerative colitis (UC), the extra-intestinal manifestations and surgical procedures associated with IBD. Diagnosis was confirmed by manual chart abstraction. Multivariable logistic regression was used to derive diagnostic algorithms for CD and UC, which were then validated in an independent cohort. RESULTS: The test cohort of 3,827 patients (1,316 potential cases, 2,511 random controls) was predominantly male (94%), white (56%), and of age of 58 (standard deviation 15). The positive predictive value (PPV) of CD codes was superior (88-100%) to UC (50-93%). The accuracy of extra-intestinal manifestations and surgeries was poor (PPV 0-29%). ICD-9-CM code 555.x without 560.9 had a PPV of 91% for CD in the validation cohort. Code 556.x with age, gender, and race factors was highly predictive of UC (c-statistic 0.9, PPV of 81%). CONCLUSION: VA administrative data can diagnose elderly and non-white patients with IBD.