Efficacy of biologic and small molecule agents as second-line therapy after exposure to TNF inhibitors in patients with ulcerative colitis: A propensity-matched cohort study.

BACKGROUND: There is limited real-world data on comparative effectiveness of different biologic or small molecule agents as second-line therapies in patients with ulcerative colitis (UC) with prior exposure to a tumour necrosis factor inhibitor (TNFi). METHODS: We conducted a retrospective cohort study using TriNetX, a multi-institutional database to assess the efficacy of tofacitinib, vedolizumab and ustekinumab in patients with ulcerative colitis (UC) with prior exposure to a TNFi. Failure of medical therapy was defined as a composite outcome of intravenous steroids or colectomy within 2 years. One-to-one propensity score matching was performed for demographics, disease extent, mean haemoglobin, C-reactive protein, albumin and calprotectin, prior IBD medications and steroid use between cohorts. RESULTS: Among 2141 patients with UC and prior exposure to TNFi, 348 (16.2%), 716 (33.4%) and 1077 (50.3%) were switched to tofacitinib, ustekinumab and vedolizumab, respectively. After propensity-score matching, there was no difference in the composite outcome (aOR: 0.77, 95% CI: 0.55-1.07) but higher risk of colectomy (aOR: 2.69, 95% CI: 1.31-5.50) in the tofacitinib cohort than the vedolizumab cohort. There was no difference in the risk of composite outcome (aOR: 1.29, 95% CI: 0.89-1.86) but higher risk of colectomy (aOR: 2.63, 95% CI: 1.24-5.58) in the tofacitinib cohort than the ustekinumab cohort. The vedolizumab cohort had a higher risk of composite outcome (aOR: 1.67, 95% CI: 1.29-2.16) than the ustekinumab cohort. CONCLUSION: Ustekinumab might be the preferred second-line therapy over tofacitinib and vedolizumab in patients with UC that were previously exposed to a TNFi.

Management of pouch neoplasia: consensus guidelines from the International Ileal Pouch Consortium.

Surveillance pouchoscopy is recommended for patients with restorative proctocolectomy with ileal pouch-anal anastomosis in ulcerative colitis or familial adenomatous polyposis, with the surveillance interval depending on the risk of neoplasia. Neoplasia in patients with ileal pouches mainly have a glandular source and less often are of squamous cell origin. Various grades of neoplasia can occur in the prepouch ileum, pouch body, rectal cuff, anal transition zone, anus, or perianal skin. The main treatment modalities are endoscopic polypectomy, endoscopic ablation, endoscopic mucosal resection, endoscopic submucosal dissection, surgical local excision, surgical circumferential resection and re-anastomosis, and pouch excision. The choice of the treatment modality is determined by the grade, location, size, and features of neoplastic lesions, along with patients' risk of neoplasia and comorbidities, and local endoscopic and surgical expertise.

Treatment of pouchitis, Crohn's disease, cuffitis, and other inflammatory disorders of the pouch: consensus guidelines from the International Ileal Pouch Consortium.

Pouchitis, Crohn's disease of the pouch, cuffitis, polyps, and extraintestinal manifestations of inflammatory bowel disease are common inflammatory disorders of the ileal pouch. Acute pouchitis is treated with oral antibiotics and chronic pouchitis often requires anti-inflammatory therapy, including the use of biologics. Aetiological factors for secondary pouchitis should be evaluated and managed accordingly. Crohn's disease of the pouch is usually treated with biologics and its stricturing and fistulising complications can be treated with endoscopy or surgery. The underlying cause of cuffitis determines treatment strategies. Endoscopic polypectomy is recommended for large, symptomatic inflammatory polyps and polyps in the cuff. The management principles of extraintestinal manifestations of inflammatory bowel disease in patients with pouches are similar to those in patients without pouches.

Diagnosis and classification of ileal pouch disorders: consensus guidelines from the International Ileal Pouch Consortium.

Restorative proctocolectomy with ileal pouch-anal anastomosis is an option for most patients with ulcerative colitis or familial adenomatous polyposis who require colectomy. Although the construction of an ileal pouch substantially improves patients' health-related quality of life, the surgery is, directly or indirectly, associated with various structural, inflammatory, and functional adverse sequelae. Furthermore, the surgical procedure does not completely abolish the risk for neoplasia. Patients with ileal pouches often present with extraintestinal, systemic inflammatory conditions. The International Ileal Pouch Consortium was established to create this consensus document on the diagnosis and classification of ileal pouch disorders using available evidence and the panellists' expertise. In a given individual, the condition of the pouch can change over time. Therefore, close monitoring of the activity and progression of the disease is essential to make accurate modifications in the diagnosis and classification in a timely manner.

Effectiveness of recombinant zoster vaccine (RZV) in patients with inflammatory bowel disease.

BACKGROUND AND AIMS: Patients with Inflammatory bowel disease (IBD) are at an increased risk of developing herpes zoster (HZ). The effectiveness of the recombinant zoster vaccine (RZV) in patients with IBD is unknown. METHODS: In this retrospective cohort study using Explorys (October 2017-April 2020; IBM Corporation, Somers, NY, USA), the effectiveness of RZV for the prevention of HZ in patients with IBD ≥ 50 years was compared to general population aged ≥ 50 years. Rates of de-novo HZ were compared between patients with IBD and the general population and stratified by number of RZV doses received. Results are presented as odds ratios (OR) with 95% confidence intervals (CI). RESULTS: The overall proportion of IBD patients ≥ 50 years who received HZ vaccination with the live zoster vaccine (ZVL) or RZV was low (n = 11320, out of 112,200 IBD patients in the cohort). A total of 1670 patients received RZV. Receipt of the RZV resulted in a significantly lower rate of HZ in IBD patients (OR 0.36, 95% CI 0.23-0.56) compared to the general population (OR 0.74, 95% CI 0.59-0.92). However, despite vaccination, patients with IBD who received the RZV were still 3-times more likely to develop HZ during the study follow up period compared to the general population receiving the RZV (OR 3.06, 95% CI 1.87-5.02) and unvaccinated IBD patients were 6-times more likely to develop HZ compared to general population (OR 6.21, 95% CI 6.02-6.41). CONCLUSION: The recombinant zoster vaccine is effective in reducing the risk of HZ in patients with IBD compared to the general population. During our follow up period, patients with IBD, however, still remain at an increased risk for HZ despite vaccination.

Endoscopic evaluation of surgically altered bowel in inflammatory bowel disease: a consensus guideline from the Global Interventional Inflammatory Bowel Disease Group.

The majority of patients with Crohn's disease and a proportion of patients with ulcerative colitis will ultimately require surgical treatment despite advances in diagnosis, therapy, and endoscopic interventions. The surgical procedures that are most commonly done include bowel resection with anastomosis, strictureplasty, faecal diversion, and ileal pouch. These surgical treatment modalities result in substantial alterations in bowel anatomy. In patients with inflammatory bowel disease, endoscopy plays a key role in the assessment of disease activity, disease recurrence, treatment response, dysplasia surveillance, and delivery of endoscopic therapy. Endoscopic evaluation and management of surgically altered bowel can be challenging. This consensus guideline delineates anatomical landmarks and endoscopic assessment of these landmarks in diseased and surgically altered bowel.

Risk of de-novo inflammatory bowel disease among obese patients treated with bariatric surgery or weight loss medications.

BACKGROUND: An association between bariatric surgery and development of de-novo inflammatory bowel disease (IBD) has been observed. AIM: To evaluate further the association among bariatric surgery, weight loss medications, obesity and new-onset IBD. METHODS: Using Explorys, a population-based Health Insurance Portability and Accountability Act compliant database, we estimated the prevalence of de-novo IBD among patients treated with bariatric surgery (Roux-en-Y gastrojejunostomy, laparoscopic sleeve gastrectomy or gastric banding) (n = 60 870) or weight loss medications (orlistat, phentermine/topiramate, lorcaserin, bupropion/naltrexone and liraglutide) (n = 193 790) compared with obese controls (n = 5 021 210), between 1999 and 2018. RESULTS: The prevalence of de-novo IBD was lower among obese patients exposed to bariatric surgery (7.72 per 1000 patients) or weight loss medications (7.22 per 1000 patients) compared with patients with persistent obesity not exposed to these interventions (11.66 per 1000 patients, P < 0.0001). The risk reduction for de-novo IBD was consistent across bariatric surgeries and weight loss medications with the exception of orlistat which was not associated with a reduction in risk for de-novo IBD compared with the persistent obese control cohort. CONCLUSION: Obese patients undergoing treatment with bariatric surgery or weight loss medications are at a lower risk for developing de-novo IBD compared with persistently obese controls not exposed to these interventions. These data suggest that obesity and ineffective management of obesity are risk factors for de-novo IBD. Further research is needed to confirm these observations and understand potential mechanisms.

Practical guidelines on endoscopic treatment for Crohn's disease strictures: a consensus statement from the Global Interventional Inflammatory Bowel Disease Group.

Stricture formation is a common complication of Crohn's disease, resulting from the disease process, surgery, or drugs. Endoscopic balloon dilation has an important role in the management of strictures, with emerging techniques, such as endoscopic electroincision and stenting, showing promising results. The underlying disease process, altered bowel anatomy from disease or surgery, and concurrent use of immunosuppressive drugs can make endoscopic procedures more challenging. There is an urgent need for the standardisation of endoscopic procedures and peri-procedural management strategies. On the basis of an extensive literature review and the clinical experience of the consensus group, which consisted of representatives from the Interventional Inflammatory Bowel Disease Group, we propose detailed guidance on all aspects of the principles and techniques for endoscopic procedures in the treatment of inflammatory bowel disease-associated strictures.

College inflammatory bowel disease (C-IBD) day: a targeted approach to shared decision-making in college age students with IBD-a 2-year pilot project.

BACKGROUND: Adherence to treatment is a key therapeutic goal in chronic disorders including diabetes, inflammatory bowel disease (IBD), and hypertension. Non-adherence has been associated with increased health care costs. Previous studies have evaluated adherence to treatment in inflammatory bowel disease, as well as predictors of non-adherence. Higher belief of necessity for medications and membership of IBD patient organizations have been associated with higher medication adherence. AIM: This study aimed to identify patient reported factors that influence understanding of IBD in college age patients with IBD. METHODS: We conducted questionnaire based survey among a group of college age patients with IBD who attended a structured program. The program consisted of a clinical appointment with an IBD physician, lecture by an IBD physician, followed by interactive segment between patients. Educational material was available for patients to review. In addition, opportunity was given to patients to share their story and ask questions in a safe environment. RESULTS: A total of 26 patients participated in the two C-IBD sessions over a 2-year period. Twenty-three were enrolled in college, 1 was a recent graduate, and 2 were of college age but not enrolled. All patients thought the program was beneficial, 96% rated the overall experience as "awesome" or "very good." Seventy-six percent of patients reported sharing their story as the most beneficial. Only 19% found the physician lecture beneficial. CONCLUSION: A targeted approach to a vulnerable population with IBD is an additional useful tool in improving understanding of IBD. This may lead to improved compliance with management plans.

Postoperative infliximab is not associated with an increase in adverse events in Crohn's disease.

BACKGROUND: Infliximab is effective treatment for Crohn's disease and has been associated with rare, but serious infectious complications. Emerging data suggest a benefit of infliximab in preventing postoperative Crohn's disease recurrence. It is not known whether administration of infliximab shortly after resective surgery for Crohn's disease increases postoperative complications. AIMS: To evaluate the risk of developing postoperative complications among Crohn's disease patients receiving infliximab within 4 weeks of intestinal resection. METHODS: As part of a randomized placebo-controlled infliximab postoperative prevention study, adverse events were prospectively monitored. Crohn's disease patients undergoing intestinal resection were randomized to placebo or infliximab 2-4 weeks after surgery. Study infusions were administered at 0, 2, and 6 weeks then every 8 weeks for 1 year. To evaluate whether infliximab increased postoperative complications, we analyzed all adverse events for 1 year after surgery. RESULTS: Twenty-four patients were randomized to infliximab or placebo after intestinal resection for Crohn's disease. Mean time to first postoperative infusion was 20 days (range 14-25 days). Over the course of 1 year, there were 22 total adverse events, but no difference between infliximab and placebo patients (12 versus 10, respectively, P = 1.0). In the immediate postoperative period, within 8 weeks of surgery, the number of adverse events was also similar between the two groups (3 infliximab and 5 placebo patients, P = 0.68). There were no serious adverse events and no complications related to wound healing or infection. CONCLUSIONS: Initiation of infliximab within 4 weeks of intestinal resection was not associated with postoperative complications.

Crohn's disease activity index does not correlate with endoscopic recurrence one year after ileocolonic resection.

BACKGROUND: Crohn's disease clinical trials utilize the Crohn's Disease Activity Index (CDAI) to measure primary endpoint assessments of clinical recurrence and remission. We evaluated the extent of agreement between clinical recurrence/remission as defined by the CDAI and endoscopic recurrence 1 year after intestinal resection for Crohn's disease (CD). METHODS: Twenty-four CD patients who had been randomly assigned to a postoperative clinical trial had 1 year clinical, endoscopic, and histological assessment for disease recurrence. The primary endpoint was the extent of agreement between endoscopic recurrence and clinical recurrence 1 year after intestinal resection for CD. Secondary endpoints were extent of agreement between endoscopic recurrence and the surrogate markers of CD activity, i.e., histological activity, sedimentation rate, and C-reactive protein (CRP). RESULTS: Twelve of the 24 patients (50%) were in endoscopic remission (i0, i1) and 12 (50%) had endoscopic recurrence (i2, i3, or i4). There was good agreement between endoscopy and histological activity scores (intraclass correlation coefficient = 0.53, kappa coefficient = 0.58). In contrast, there was little to no relationship between endoscopy and CDAI scores; median CDAI scores for endoscopy scores of i0/i1, i2, i3, and i4 were 118, 76, 156, and 78, respectively (P for trend = 0.88). The kappa coefficient (of agreement) between endoscopy score ± 2 and CDAI score ± 150 was 0.12 (exact P = 0.68), indicating poor agreement. Similarly, there was no consistent association observed between endoscopy scores and mean CRP and ESR values at week 54. CONCLUSIONS: The CDAI shows poor agreement with endoscopic recurrence 1 year after intestinal resection. Endoscopic recurrence should be the primary endpoint of future postoperative studies and ileocolonoscopy the gold standard test to detect postoperative recurrence.

Anti-TNF antibody therapy for inflammatory bowel disease during pregnancy: a clinical review.

The incidence of inflammatory bowel disease (IBD; Crohn's disease, ulcerative colitis) is highest during the peak reproductive years, hence the increased concern with the safety of IBD drugs during pregnancy. Over the past 11 years, anti-TNF-alpha antibody therapy has emerged as a treatment approach for refractory IBD patients who have failed to achieve or maintain remission with corticosteroids and immunomodulator agents. The TNF-alpha inhibitors (anti-TNFs; infliximab, adalimumab, certolizumab pegol) have proven successful in inducing and maintaining remission of moderate-to-severe IBD, but recommendations for the use of these compounds during pregnancy have lacked consensus. Balanced against the potential risk of these drugs on the fetus is the well-established fact that high disease activity has been found to poorly affect pregnancy outcomes in IBD, and the potential use of anti-TNF agents may control disease flare and severity during pregnancy. Concerns regarding the effect of anti-TNFs on the pregnancy and fetus have been assuaged by registry data which has demonstrated an overall positive safety record. Both the U.S. Food and Drug Administration and the European Crohn's and Colitis Organization categorize anti-TNF agents as safe during pregnancy. New knowledge regarding the physiologic timing of placental transfer of therapeutic antibody subclasses and pegylated antibody fragments from the mother into the fetus has also helped to allay concerns. This review will examine the present state of knowledge regarding the use of anti-TNFs in pregnant women with IBD.

Postoperative Crohn's disease: prevention and treatment.

Crohn's disease is a chronic, relapsing-remitting inflammatory disease of the intestinal tract that commonly requires surgical treatment. Unfortunately, the majority of patients will ultimately develop postoperative disease recurrence and require subsequent surgery. A number of medications have been researched for the maintenance of postoperative remission. Of these, few have demonstrated consistent efficacy. A recently published randomized, controlled trial indicated that infliximab is effective in the maintenance of postoperative remission.

The use and abuse of antibiotics in elective colorectal surgery: the saga continues....

BACKGROUND: The role of antibiotic prophylaxis in preventing post-operative complications in patients undergoing elective colorectal surgery is well established. Despite evidence that a single-dose prophylaxis is sufficient, the duration of antibiotic use in clinical practice is highly variable and surveys have identified persistent patterns of antibiotic abuse in elective colorectal surgery. MATERIALS AND METHODS: We conducted a retrospective review of all patients who underwent elective colorectal surgery between 1998 and 2002 at the American University of Beirut Medical Center. A survey among general surgeons in Lebanon was also performed to investigate the pattern of antibiotic prophylaxis used in such cases. The MEDLINE database (1966-2004) was searched for English-language articles and abstracts on antimicrobial use in elective colorectal surgery. Papers cited in relevant primary articles were also reviewed. Data were extracted and reviewed by all authors. RESULTS: Two hundred and eleven matching patient-records were identified. A triple regimen including metronidazole, ampicillin and an aminoglycoside was the most commonly used preoperative prophylactic method. Patients received post-operative antibiotics for a mean of 6.66+/-2.62 days. The mean duration of post-operative antibiotic prophylaxis used by the interviewed surgeons was 4.31+/-1.08 days. CONCLUSIONS: Our study confirms that even when strong evidence exists, surgeons fail to adhere to antibiotic prophylaxis guidelines. This pattern is not unique to Lebanon but is shared to a large extent by surgeons around the world. Adherence to published guidelines and improved education of surgeons are essential to the delivery of cost-effective medical practice.