Lemann Index for assessing bowel damage in Crohn's disease: a real world study.

BACKGROUND & AIMS: The Lemann Index (LI), an endpoint to measure cumulative structural bowel damage in Crohn's disease (CD), has been recently updated and validated. We applied this to investigate predictors of bowel damage in a real-world cohort. METHODS: We performed a retrospective study (2008-2022) involving two tertiary referral IBD centers in the US. MR or CT enterographies were reviewed by study radiologists and endoscopy reports by study gastroenterologists, to calculate LI. Baseline and follow-up LI were calculated. We defined high bowel damage as LI ≥2. Factors associated with high LI were identified in patients with ≥2 LI scores using multivariate logistic regression and then assessed for a change in LI (increase vs. no change/decrease) using a multivariate linear mixed-effects model. RESULTS: 447 patients with CD had a median first LI of 7 [IQR, 1.25-14.55]. Median LI scores were significantly different when categorized by disease duration; 2.0 [IQR, 0.6-5.9] for <2 years, 2.6 [IQR, 0.6-9.6] for ≥2 and <10 years, and 12.5 [IQR, 6.4-21.5] for ≥10 years with a p <0.01. Disease duration, presence of perianal disease, elevated C-reactive protein, and Harvey-Bradshaw index, were associated with a high LI at inclusion and increase in LI during follow-up (all p <0.01). CONCLUSIONS: The updated LI quantified cross-sectional and longitudinal cumulative bowel damage in a real-world cohort of patients with CD with predictors identified for a longitudinal increase in LI. Further studies for prospective validation of LI and identification of multi-omic predictors of bowel damage are needed.

Perianal Fistulizing Crohn's Disease-Associated Anorectal and Fistula Cancers: Systematic Review and Expert Consensus.

BACKGROUND & AIMS: Perianal fistulizing Crohn's disease (PFCD)-associated anorectal and fistula cancers are rare but often devastating diagnoses. However, given the low incidence and consequent lack of data and clinical trials in the field, there is little to no guidance on screening and management of these cancers. To inform clinical practice, we developed consensus guidelines on PFCD-associated anorectal and fistula cancers by multidisciplinary experts from the international TOpClass consortium. METHODS: We conducted a systematic review by standard methodology, using the Newcastle-Ottawa Scale quality assessment tool. We subsequently developed consensus statements using a Delphi consensus approach. RESULTS: Of 561 articles identified, 110 were eligible, and 76 articles were included. The overall quality of evidence was low. The TOpClass consortium reached consensus on 6 structured statements addressing screening, risk assessment, and management of PFCD-associated anorectal and fistula cancers. Patients with long-standing (>10 years) PFCD should be considered at small but increased risk of developing perianal cancer, including squamous cell carcinoma of the anus and anorectal carcinoma. Risk factors for squamous cell carcinoma of the anus, notably human papilloma virus, should be considered. New, refractory, or progressive perianal symptoms should prompt evaluation for fistula cancer. There was no consensus on timing or frequency of screening in patients with asymptomatic perianal fistula. Multiple modalities may be required for diagnosis, including an examination under anesthesia with biopsy. Multidisciplinary team efforts were deemed central to the management of fistula cancers. CONCLUSIONS: Inflammatory bowel disease clinicians should be aware of the risk of PFCD-associated anorectal and fistula cancers in all patients with PFCD. The TOpClass consortium consensus statements outlined herein offer guidance in managing this challenging scenario.

Early Biologic Treatment Decreases Risk of Surgery in Crohn's Disease but not in Ulcerative Colitis: Systematic Review and Meta-Analysis.

BACKGROUND AND AIMS: Inflammatory bowel disease (IBD) can lead to long-term complications that significantly impact patients' quality of life and healthcare resource utilization. Prior studies have demonstrated improved short-term outcomes to early exposure of biologics in patients with Crohn's disease (CD) but not in patients with ulcerative colitis (UC). However, there are conflicting data on impact of early intervention on longer-term adverse events. Therefore, we conducted a systematic review and meta-analysis assessing the impact of early biologic treatment on rates of IBD-related surgery. METHODS: A systematic search was conducted in April 2022. Studies were included if biologic initiation was compared between patients starting early (<3 years of diagnosis or top-down treatment) vs later (>3 years of diagnosis or step-up treatment). Studies with <1 year of follow-up were excluded. The outcomes were colectomy and CD-related surgery for patients with UC and CD, respectively. Random-effects analyses were conducted to compare rates of IBD surgery between early and late biologic treatment. RESULTS: Eighteen studies were included in the meta-analysis. Three studies included patients with UC and 15 studies included patients with CD. In patients with CD, early biologic therapy was associated with lower odds of surgery (odds ratio, 0.63; 95% confidence interval, 0.48-0.84) compared with late treatment. Conversely, in patients with UC, the odds of colectomy were increased (odds ratio, 2.86; 95% confidence interval, 1.30-6.30). CONCLUSIONS: Early biologic treatment is associated with lower rates of surgery in patients with CD. In contrast, early biologic therapy appears to be associated with higher rates of colectomy in patients with UC, which may be confounded by disease severity.

A critical review of upadacitinib for the treatment of adults with moderately to severely active ulcerative colitis.

INTRODUCTION: Upadacitinib is a selective janus kinase 1 inhibitor. In March 2022, upadacitinib was approved by the US Food and Drug Administration for the management of moderately to severely active ulcerative colitis (UC) in those who have had an inadequate response or intolerance of tumor necrosis factor inhibitors. It is also approved for the treatment of psoriatic arthritis, atopic dermatitis, rheumatoid arthritis, ankylosing spondylitis, and non-radiographic axial spondyloarthritis. AREAS COVERED: The aim of this article is to review the mechanism of action of upadacitinib, clinical data regarding its efficacy in treating UC, and safety information. EXPERT OPINION: Upadacitinib is superior to placebo in inducing and maintaining both clinical and endoscopic remission in moderately to severely active UC. Its strengths include once daily oral route of administration, low risk of immunogenicity, rapid onset, and efficacy in patients with previous failure of biologic therapy. The use of upadacitinib has been limited due to safety concerns surrounding JAK inhibitors. Phase 3 clinical trials recorded more cases of herpes zoster infection and venous thromboembolism in patients with UC treated with upadacitinib compared to placebo. Ongoing long-term safety studies will provide much needed clarity. Further research is also required to define the positioning of upadacitinib in treatment algorithms.

High Diagnostic Yield of Endoscopic Retrograde Cholangiopancreatography Brush Cytology for Indeterminate Strictures.

Background: Endoscopic retrograde cholangiopancreatography (ERCP) brush cytology is used frequently for sampling indeterminate biliary strictures. Studies have demonstrated that the diagnostic yield of brush cytology for malignant strictures is estimated to be 6%-70%. With improved diagnostic tools, sampling techniques and specimen processing, the yield of ERCP brush cytology may be higher. This study aimed to assess the yield of brush cytology and determine factors associated with a positive diagnosis. Methods: This was a cohort study of patients who underwent ERCP brush cytology from October 2017 to May 2020. Patient demographics, clinical, procedural and pathological data were collected using chart review. Sampling data were captured up to 3 months post-index ERCP to capture repeat brushings, biopsies or surgical resections. Outcomes included the diagnostic yield, true/false positive values and true/false negative values of malignancy detection using ERCP brush cytology. Results: A total of 126 patients underwent a brush cytology, 58% were male and 79% had a stricture in the extrahepatic region. Ninety-three patients were diagnosed with a malignancy, of which 78 had positive brush cytology results and 15 had a negative brush cytology result. The diagnostic yield, sensitivity, specificity, positive predictive value, negative predictive value and accuracy were 84%, 83%, 97%, 99%, 68% and 87% respectively. Conclusion: ERCP brush cytology performed using updated sampling technique is associated with high diagnostic yield. This allows for earlier malignancy diagnosis, timely treatment and decreased need for further investigation.

Risk of Postoperative Infectious Complications From Medical Therapies in Inflammatory Bowel Disease: A Systematic Review and Meta-Analysis.

OBJECTIVE: To assess the impact of inflammatory bowel disease (IBD) medications on postoperative infection risk within 30 days of surgery. METHODS: We searched multiple electronic databases and reference lists of articles dating up to August 2018 for prospective and retrospective studies comparing postoperative infection risk in patients treated with an IBD medication perioperatively with the risk in patients who were not taking that medication. Outcomes were overall infectious complications and intra-abdominal infections within 30 days of surgery. RESULTS: Sixty-three studies were included. Overall infectious complications were increased in patients who received anti-tumor necrosis factor (TNF) agents (odds ratio [OR] 1.26; 95% confidence interval [CI], 1.07-1.50) and corticosteroids (OR 1.34; 95% CI, 1.25-1.44) and decreased in those who received 5-aminosalicylic acid (OR 0.63; 95% CI, 0.46-0.87). No difference was observed in those treated with immunomodulators (OR 1.08; 95% CI, 0.94-1.25) or anti-integrin agents (OR 1.06; 95% CI, 0.67-1.69). Both corticosteroids and anti-TNF agents were associated with increased intra-abdominal infection risk (OR 1.63; 95% CI, 1.33-2.00 and OR 1.46; 95% CI, 1.08-1.97, respectively), whereas no impact was observed with 5-aminosalicylates, immunomodulators, or anti-integrin therapy. Twenty-two studies had low risk of bias while the remaining studies had very high risk. CONCLUSIONS: Corticosteroids and anti-TNF agents were associated with increased overall postoperative infection risk as well as intra-abdominal infection in IBD patients, whereas no increased risk was observed for immunomodulators or anti-integrin therapy. Although these results may result from residual confounding rather than from a true biological effect, prospective studies that control for potential confounding factors are required to generate higher-quality evidence.

The Impact of Clostridium difficile Infection on Mortality in Patients With Inflammatory Bowel Disease: A Systematic Review and Meta-Analysis.

BACKGROUND AND AIMS: Clostridium difficile infection (CDI) has been associated with an increased mortality risk among patients with inflammatory bowel disease (IBD) in multiple observational studies. We performed a systematic review and meta-analysis to help clearly define the magnitude of risk in IBD patients with and without CDI, and to assess the risk in individual IBD subtypes. METHODS: A systematic search of multiple electronic databases was conducted for observational studies reporting the risk of mortality in IBD, stratified by the presence of CDI. Weighted summary estimates were calculated using generalized inverse variance with random-effects model. Study quality was assessed using the Newcastle-Ottawa scale. RESULTS: Ten observational studies were identified (8 from North America and 2 from Europe) and included 40,700 IBD patients with CDI and 1,320,764 IBD controls without CDI. Overall, IBD patients with CDI had a higher risk of mortality compared with IBD patients without CDI [odds ratios (OR), 4.39; 95% confidence interval (CI), 3.56-5.42; I=93%]. The results were stable in high-quality studies and in hospitalized patients. When patients were stratified by IBD type, CDI was associated with increased mortality in patients with ulcerative colitis (7 studies) (OR, 4.39; 95% CI, 3.44-5.61; I), but not in patients with Crohn's disease (4 studies) (OR, 2.21; 95% CI, 0.84-5.77; I). Individual studies were limited by an inability to control for IBD disease activity and therapeutic interventions. CONCLUSIONS: On the basis of 10 observational studies with at least moderate quality, CDI seems to increase mortality risk in IBD, particularly in ulcerative colitis. These findings are a cause for concern and suggest that CDI should be managed aggressively in patients with IBD.

Systematic Review and Meta-Analysis: Preoperative Vedolizumab Treatment and Postoperative Complications in Patients with Inflammatory Bowel Disease.

BACKGROUND AND AIMS: The impact of vedolizumab, a gut-selective monoclonal antibody, on postoperative outcomes is unclear. This study aimed to assess the impact of preoperative vedolizumab treatment on the rate of postoperative complications in patients with inflammatory bowel disease [IBD] undergoing abdominal surgery. METHODS: A systematic search of multiple electronic databases from inception until May 2017 identified studies reporting rates of postoperative complications in vedolizumab-treated IBD patients compared to no biologic exposure or anti-tumor necrosis factor (anti-TNF) treated IBD patients. Outcomes of interest included postoperative infectious complications and overall postoperative complications. Pooled risk ratios and 95% confidence intervals were estimated using the random-effects model. RESULTS: Five studies comprising 307 vedolizumab-treated IBD patients, 490 anti-TNF-treated IBD patients and 535 IBD patients not exposed to preoperative biologic therapy were included. The risk of postoperative infectious complications (risk ratio [RR] 0.99, 95% confidence interval [CI] 0.37-2.65) and overall postoperative complications [RR 1.00, 95% CI 0.46-2.15] were not significantly different between vedolizumab-treated patients and those who received no preoperative biologic therapy. In addition, the risk of postoperative infectious complications [RR 0.99, 95% CI 0.34-2.90] and overall postoperative complications [RR 0.92, 95% CI 0.44-1.92] were not significantly different between vedolizumab-treated vs anti-TNF-treated patients. CONCLUSIONS: Preoperative vedolizumab treatment in IBD patients does not appear to be associated with an increased risk of postoperative infectious or overall postoperative complications compared to either preoperative anti-TNF therapy or no biologic therapy. Future prospective studies which include perioperative drug level monitoring are needed to confirm these findings.

Impact of Specialized Inpatient IBD Care on Outcomes of IBD Hospitalizations: A Cohort Study.

BACKGROUND: The management of inflammatory bowel diseases (IBDs; Crohn's disease, ulcerative colitis) is increasingly complex. Specialized care has been associated with improved ambulatory IBD outcomes. AIMS: To examine if the implementation of specialized inpatient IBD care modified short-term and long-term clinical outcomes in IBD-related hospitalizations. METHODS: This retrospective cohort study included IBD patients hospitalized between July 2013 and April 2015 at a single tertiary referral center where a specialized inpatient IBD care model was implemented in July 2014. In-hospital medical and surgical outcomes as well as postdischarge outcomes at 30 and 90 days were analyzed along with measures of quality of in-hospital care. Effect of specialist IBD care was examined on multivariate analysis. RESULTS: A total of 408 IBD-related admissions were included. With implementation of specialized IBD inpatient care, we observed increased frequency of use of high-dose biologic therapy for induction (26% versus 9%, odds ratio 5.50, 95% confidence interval 1.30-23.17) and higher proportion of patients in remission at 90 days after discharge (multivariate odds ratio 1.60, 95% confidence interval 0.99-2.69). Although there was no difference in surgery by 90 days, among those who underwent surgery, early surgery defined as in-hospital or within 30 days of discharge, was more common in the study period (71%) compared with the control period (46%, multivariate odds ratio 2.73, 95% confidence interval 1.22-6.12). There was no difference in length of stay between the 2 years. CONCLUSIONS: Implementation of specialized inpatient IBD care beneficially impacted remission and facilitated early surgical treatment.

Systematic Review and Meta-analysis: Phenotype and Clinical Outcomes of Older-onset Inflammatory Bowel Disease.

BACKGROUND: Little is known of the clinical outcome of patients with older-onset inflammatory bowel disease [IBD]. We performed a systematic review to determine phenotype and outcomes of older-onset IBD compared with younger-onset subjects. METHODS: A systematic search of Embase and Medline up to June 2015 identified studies investigating phenotype and outcomes of older-onset [diagnosed at age ≥ 50 years] Crohn's disease [CD] and ulcerative colitis [UC] subjects. Pooled analyses of disease phenotype, medication use, and disease-related surgery were calculated. RESULTS: We analysed findings from 43 studies comprising 8274 older-onset and 34641 younger-onset IBD subjects. Compared with younger-onset patients, older-onset CD patients were more likely to have colonic disease (odds ratio [OR] 2.56, 95% confidence interval [CI] 1.88 - 3.48) and inflammatory behaviour [OR 1.19, 95% CI 1.07 - 1.33], and less likely to have penetrating disease or perianal involvement. More older-onset UC patients had left-sided colitis [OR 1.49, 95% CI 1.18 - 1.88]. Although fewer older-onset IBD patients received immunomodulators [CD: OR 0.44; UC: OR 0.60] or biologicals [CD: OR 0.34; UC: OR 0.41], older-onset CD was similar in the need for surgery [OR 0.70, 95% CI 0.40 - 1.22] whereas more older-onset UC patients underwent surgery [OR 1.36, 95% CI 1.18 - 1.57]. CONCLUSIONS: Elderly IBD patients present with less complicated disease, but have similar or higher rates of surgery than non-elderly patients. Whether this reflects a non-benign disease course, physicians' reluctance to employ immunomodulators, or both, merits further study which is essential for improving the care of IBD in the elderly.