Comparative Effectiveness of Biologic Therapies in Preventing Penetrating Complications in Patients With Crohn's Disease.

BACKGROUND & AIMS: Comparative effectiveness of biologics in preventing penetrating disease (PD) in Crohn's disease (CD) is not well established. We compared the risk of developing luminal and perianal PD (LPD and PPD) between biologics used as first-line therapies. METHODS: Adults (>17 years) with CD who initiated their first biologic (anti-tumor necrosis factor [anti-TNF], ustekinumab [UST], or vedolizumab [VDZ]) were identified from Merative Commercial Database (2006 and 2020). We excluded preexisting PD using a minimum look-back period of 1 year. Cohorts were balanced by inverse probability of treatment weighting based on age, sex, comorbidities, prior CD surgery, and CD severity. Pairwise comparisons were performed by Cox proportional hazards models, adjusted for immunomodulator exposure, and with biologic exposure treated as a time-dependent variable based on a medication possession ratio of 0.8. RESULTS: Our analysis included 40,693 patients: 93% anti-TNF, 3% UST, and 4% VDZ. After inverse probability of treatment weighting all comparisons were well balanced. Anti-TNF was protective against LPD (hazard ratio, 0.66; 95% confidence interval, 0.55-0.78; P < .0001) and PPD (hazard ratio, 0.88; 95% confidence interval, 0.80-0.96; P = .0045) compared with VDZ and LPD (hazard ratio, 0.37; 95% confidence interval, 0.30-0.46; P < .0001) compared with UST. There were no significant differences in the risk of LPD and PPD between VDZ and UST. These results were similar after limiting the study period to after 2016. CONCLUSIONS: Anti-TNF therapy was associated with a lower risk of LPD and PPD compared with VDZ, and lower risk of LPD compared with UST. Further studies are needed to validate these findings and to determine potential reasons for these differences.

Comparative Efficacy of Advanced Therapies for Achieving Endoscopic Outcomes in Crohn's Disease: A Systematic Review and Network Meta-Analysis.

BACKGROUND & AIMS: We conducted a network meta-analysis to compare the efficacy of advanced therapies for achieving endoscopic outcomes in patients with moderate-to-severely active Crohn's disease. METHODS: MEDLINE, Embase, and Cochrane CENTRAL databases were searched from inception to August 2, 2023 to identify phase II and III randomized controlled trials (RCTs) in adults (≥18 years) with moderate-to-severe Crohn's disease treated with tumor necrosis factor (TNF) antagonists, etrolizumab, vedolizumab, anti-interleukin (IL)12/23p40, anti-IL23p19, or Janus kinase-1 (JAK1) inhibitors, compared with placebo/active comparator, for induction and/or maintenance of remission and reported endoscopic outcomes. Primary outcome was endoscopic response after induction therapy, and endoscopic remission after maintenance therapy. We performed a random-effects network meta-analysis using a frequentist approach, and estimated relative risk (RRs), 95% confidence interval (CI) values, and P score for ranking agents. We used GRADE to ascertain certainty of evidence. RESULTS: A total of 20 RCTs (19 placebo-controlled and 1 head-to-head trial; 5592 patients) were included out of which 12 RCTs reported endoscopic outcomes for the induction phase, 5 reported for the maintenance phase, and 3 reported for both induction and maintenance phases. JAK1 inhibitors (RR, 3·49 [95% CI, 1·48-8·26]) and anti-IL23p19 (RR, 2·30 [95% CI, 1·02-5·18]) agents were more efficacious than etrolizumab (moderate certainty of evidence), and JAK1 inhibitors (RR, 2·34 [95% CI, 1·14-4·80]) were more efficacious than anti-IL12/23p40 agents for inducing endoscopic response (moderate certainty of evidence). JAK1 inhibitors and anti-IL23p19 ranked highest for induction of endoscopic response. There was paucity of RCTs of TNF antagonists reporting endoscopic outcomes with induction therapy. On network meta-analysis of 6 RCTs, all agents except vedolizumab (RR, 1.89 [95% CI, 0.61-5.92]) were effective in maintaining endoscopic remission compared with placebo. TNF antagonists, IL12/23p40, and JAK1 inhibitors were ranked highest. CONCLUSIONS: On network meta-analysis, JAK1 inhibitors and anti-IL23p19 agents may be the most effective among non-TNF-targeting advanced therapies for inducing endoscopic response. Future head-to-head trials will further inform positioning of different therapies for the management of Crohn's disease.

Development of an MRI-Based Prediction Model for Anti-TNF Treatment Failure in Perianal Crohn's Disease: A Multicenter Study.

BACKGROUND & AIMS: Clinical and radiologic variables associated with perianal fistula (PAF) outcomes are poorly understood. We developed prediction models for anti-tumor necrosis factor (TNF) treatment failure in patients with Crohn's disease-related PAF. METHODS: In a multicenter retrospective study between 2005 and 2022 we included biologic-naive adults (>17 years) who initiated their first anti-TNF therapy for PAF after pelvic magnetic resonance imaging (MRI). Pretreatment MRI studies were prospectively reread centrally by blinded radiologists. We developed and internally validated a prediction model based on clinical and radiologic parameters to predict the likelihood of anti-TNF treatment failure, clinically, at 6 months. We compared our model and a simplified version of MRI parameters alone with existing imaging-based PAF activity indices (MAGNIFI-CD and modified Van Assche MRI scores) by De Long statistical test. RESULTS: We included 221 patients: 32 ± 14 years, 60% males, 76% complex fistulas; 68% treated with infliximab and 32% treated with adalimumab. Treatment failure occurred in 102 (46%) patients. Our prediction model included age at PAF diagnosis, time to initiate anti-TNF treatment, and smoking and 8 MRI characteristics (supra/extrasphincteric anatomy, fistula length >4.3 cm, primary tracts >1, secondary tracts >1, external openings >1, tract hyperintensity on T1-weighted imaging, horseshoe anatomy, and collections >1.3 cm). Our full and simplified MRI models had fair discriminatory capacity for anti-TNF treatment failure (concordance statistic, 0.67 and 0.65, respectively) and outperformed MAGNIFI-CD (P = .002 and < .0005) and modified Van Assche MRI scores (P < .0001 and < .0001), respectively. CONCLUSIONS: Our risk prediction models consisting of clinical and/or radiologic variables accurately predict treatment failure in patients with PAF.

Serrated Polyps in Inflammatory Bowel Disease Indicate a Similar Risk of Metachronous Colorectal Neoplasia as in the General Population.

BACKGROUND: The risk of metachronous advanced neoplasia after diagnosing serrated polyps in patients with IBD is poorly understood. METHODS: A retrospective multicenter cohort study was conducted between 2010 and 2019 at three tertiary centers in Montreal, Canada. From pathology databases, we identified 1587 consecutive patients with serrated polyps (sessile serrated lesion, traditional serrated adenoma, or serrated epithelial change). We included patients aged 45-74 and excluded patients with polyposis, colorectal cancer, or no follow-up. The primary outcome was the risk of metachronous advanced neoplasia (advanced adenoma, advanced serrated lesion, or colorectal cancer) after index serrated polyp, comparing patients with and without IBD. RESULTS: 477 patients with serrated polyps were eligible (mean age 61 years): 37 with IBD, totaling 45 serrated polyps and 440 without IBD, totaling 586 serrated polyps. The median follow-up was 3.4 years. There was no difference in metachronous advanced neoplasia (HR 0.77, 95% CI 0.32-1.84), metachronous advanced adenoma (HR 0.54, 95% CI 0.11-2.67), and metachronous advanced serrated lesion (HR 0.76, 95% CI 0.26-2.18) risk. When comparing serrated polyps in mucosa involved or uninvolved with IBD, both groups had similar intervals from IBD to serrated polyp diagnosis (p > 0.05), maximal therapies (p > 0.05), mucosal inflammation, inflammatory markers, and fecal calprotectin (p > 0.05). CONCLUSION: The risk of metachronous advanced neoplasia after serrated polyp detection was similar in patients with and without IBD. Serrated polyps in IBD occurred independently of inflammation. This helps inform surveillance intervals for patients with IBD diagnosed with serrated polyps.

Perianal Fistulas Are Associated with Persistently Higher Direct Health Care Costs in Crohn's Disease: A Population-Based Study.

BACKGROUND: The economic impact of perianal fistulas in Crohn's disease (CD) has not been formally assessed in population-based studies in the biologic era. AIM: To compare direct health care costs in persons with and without perianal fistulas. METHODS: We performed a longitudinal population-based study using administrative data from Ontario, Canada. Adults (> 17 years) with CD were identified between 2007 and 2013 using validated algorithms. Perianal fistula positive "cases" were matched to up to 4 "controls" with CD without perianal fistulas based on age, sex, geographic region, year of CD diagnosis and duration of follow-up. Direct health care costs, excluding drug costs from private payers, were estimated annually beginning 5 years before (lookback) and up to 9 years after perianal fistula diagnosis (study completion) for cases and a standardized date for matched controls. RESULTS: A total of 581 cases were matched to 1902 controls. The annual per capita direct cost for cases was similar at lookback compared to controls ($2458 ± 6770 vs $2502 ± 10,752; p = 0.952), maximally greater in the first year after perianal fistulas diagnosis ($16,032 ± 21,101 vs $6646 ± 13,021; p < 0.001) and remained greater at study completion ($11,358 ± 17,151 vs $5178 ± 9792; p < 0.001). At perianal fistula diagnosis, the cost difference was driven primarily by home care cost (tenfold greater), publicly-covered prescription drugs (threefold greater) and hospitalizations (twofold greater), whereas at study completion, prescription drugs were the dominant driver (threefold greater). CONCLUSION: In our population-based cohort, perianal fistulas were associated with significantly higher direct healthcare costs at the time of perianal fistulas diagnosis and sustained long-term.

Effectiveness of Tofacitinib for Hospitalized Patients with Acute Severe Ulcerative Colitis: Case Series.

BACKGROUND: Treatment options for acute severe ulcerative colitis (ASUC) are limited. Tofacitinib, an approved treatment for moderate to severe ulcerative colitis, could be a potential rescue therapy for ASUC given its rapid onset of action. OBJECTIVE: To evaluate the effectiveness of tofacitinib in hospitalized patients with ASUC refractory to standard therapy in a real-world setting. METHODS: Retrospective observational study of hospitalized adult patients with ASUC treated with tofacitinib between January 2019 and September 2020 at five Canadian centers. We extracted patient demographics, clinical status, biomarkers (C-reactive protein and fecal calprotectin), endoscopic findings, and colectomy-free rate at admission, 30 days, 90 days, and 6 months after tofacitinib initiation. RESULTS: Eight patients with symptoms refractory to standard rescue therapy (corticosteroids ± infliximab if infliximab-naïve prior to admission) were treated with tofacitinib. During index hospitalization, clinical response was observed in 5/8 patients. The median time to discharge post-tofacitinib initiation was 5 days (IQR 5.0-6). At 30 and 90 days, all five responders were in clinical remission. At 6 months, only 3/5 responders remained in clinical remission. The colectomy-free rate was 37.5% during the follow-up period (two colectomies occurred within 30 days; one occurred within 90 days). No drug-related adverse reaction occurred. CONCLUSION: In this small case-series, tofacitinib was an effective rescue therapy in patients with refractory ASUC. These findings need to be evaluated in a randomized controlled trial.

Surgery and the Subtype of Inflammatory Bowel Disease Impact the Risk of Venous Thromboembolism After Hospital Discharge.

BACKGROUND: Surgery for inflammatory bowel disease (IBD) is associated with an increased risk of venous thromboembolism (VTE) during hospitalization. It is unclear whether this association persists after hospital discharge. AIMS: We assessed the association between surgery and VTE following hospital discharge in IBD. METHODS: We conducted a population-based cohort study between 2002 and 2016 in Ontario, Canada. Adults with IBD hospitalized for ≥ 72 h who underwent an intra-abdominal surgery were compared to hospitalized, nonsurgical IBD patients. Multivariable Cox proportional hazard models were used to compare VTE risk within 12 months of discharge. RESULTS: A total of 80,445 hospital discharges were analyzed: 60% Crohn's disease (CD) and 40% ulcerative colitis (UC). The median time to VTE was three times longer for nonsurgical patients with CD and 1.6 times longer for nonsurgical patients with UC. Compared with nonsurgical patients, surgery for CD was associated with a lower cumulative risk of VTE in the 2 weeks after discharge and persisted through to 12 months after discharge (adjusted HR 0.24; 95% CI 0.15-0.40). In contrast, urgent surgery for UC was associated with an increased risk of VTE. The increased risk was greatest at 2 weeks after discharge (aHR, 1.80; 95% CI 1.26-2.57) and declined progressively over the course of 12 months. CONCLUSIONS: Surgery was associated with a greater risk of VTE after hospital discharge in UC but not CD. In patients with UC who have undergone urgent surgery, healthcare providers should consider an extended period of prophylaxis after hospital discharge.

Introduction of anti-TNF therapy has not yielded expected declines in hospitalisation and intestinal resection rates in inflammatory bowel diseases: a population-based interrupted time series study.

OBJECTIVES: To better understand the real-world impact of biologic therapy in persons with Crohn's disease (CD) and ulcerative colitis (UC), we evaluated the effect of marketplace introduction of infliximab on the population rates of hospitalisations and surgeries and public payer drug costs. DESIGN: We used health administrative data to study adult persons with CD and UC living in Ontario, Canada between 1995 and 2012. We used an interrupted time series design with segmented regression analysis to evaluate the impact of infliximab introduction on the rates of IBD-related hospitalisations, intestinal resections and public payer drug costs over 10 years among patients with CD and 5 years among patients with UC, allowing for a 1-year transition. RESULTS: Relative to what would have been expected in the absence of infliximab, marketplace introduction of infliximab did not produce significant declines in the rates of CD-related hospitalisations (OR at the last observation quarter 1.06, 95% CI 0.811 to 1.39) or intestinal resections (OR 1.10, 95% CI 0.810 to 1.50), or in the rates of UC-related hospitalisations (OR 1.22, 95% CI 1.07 to 1.39) or colectomies (OR 0.933, 95% CI 0.54 to 1.61). The findings were similar among infliximab users, except that hospitalisation rates declined substantially among UC patients following marketplace introduction of infliximab (OR 0.515, 95% CI 0.342 to 0.777). There was a threefold rise over expected trends in public payer drug cost among patients with CD following infliximab introduction (OR 2.98,95% CI 2.29 to 3.86), suggesting robust market penetration in this group, but no significant change among patients with UC (OR 1.06, 95% CI 0.955 to 1.18). CONCLUSIONS: Marketplace introduction of infliximab has not yielded anticipated reductions in the population rates of IBD-related hospitalisations or intestinal resections, despite robust market penetration among patients with CD. Misguided use of infliximab in CD patients and underuse of infliximab in UC patients may largely explain our study findings.

Tumor Necrosis Factor Inhibitors May Have Limited Efficacy for Complex Perianal Fistulas Without Luminal Crohn's Disease.

BACKGROUND: Complex perianal fistulas occurring in the absence of luminal inflammation (isolated perianal disease, IPD) may represent a specific phenotype of Crohn's disease (CD). AIM: We assessed the effectiveness of tumor necrosis factor (TNF)-antagonists in patients with IPD compared to those with perianal CD (PCD) with luminal inflammation. METHODS: Patients were identified through our institutional radiology database and were classified as PCD or IPD based on the presence or absence of luminal inflammation by ileocolonoscopy and abdominal enterography. Consecutive adults (> 17 years) with recurrent IPD who were treated with TNF antagonists were matched by age and gender to patients with complex PCD (1:2 ratio). Fistula remission was defined as an absence of fistula drainage. Surgery-free survival was assessed by Cox proportional hazard models. RESULTS: Twenty-two patients with IPD treated with a TNF antagonist were compared with 44 matched patients with PCD. A similar proportion of patients with IPD and PCD were treated with concomitant immunomodulators (55% vs. 66%) and underwent examinations under anesthesia prior to therapy (36% vs. 46%). Fistula remission at 3, 6, and 12 months was lower for the IPD cohort: 9.5% versus 34%; 19% versus 39%; and 19% versus 43%. Surgical intervention after initiating anti-TNF therapy was more common for patients with IPD (HR 3.99: 95% CI, 1.62-9.83; p = 0.0026). CONCLUSIONS: Fewer patients with IPD achieved fistula remission, and more required surgical intervention after anti-TNF therapy, suggesting that TNF antagonists may not be as effective in these patients.

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.

History of malignancy and relevant symptoms may predict a positive computed tomography enterography in obscure gastrointestinal bleeds.

BACKGROUND AND AIM: This study aimed to assess the clinical utility of computed tomography enterography (CTE) and identify factors associated with a diagnostic CTE for patients with obscure gastrointestinal bleeding (OGIB). METHODS: A retrospective observational study was performed at a Canadian tertiary care center from 2005 to 2015. A total of 138 patients underwent a CTE for OGIB. Univariate and multivariate logistic regressions were performed to determine factors associated with a diagnostic CTE. A highly sensitive clinical rule was then developed to help identify OGIB patients for whom a CTE may be beneficial in their clinical work-up. RESULTS: A possible bleeding source was identified in 30 (22%) cases. The presence of abdominal or constitutional symptoms as well as history of colorectal cancer was significantly associated with a positive CTE in univariate and multivariate analyses (P < 0.05). A positive CTE could be predicted based on the presence of abdominal or constitutional symptoms and history of colorectal cancer with 90% sensitivity (95% CI 74-98%) in our population. CONCLUSION: CTE identified a possible source of OGIB in one in five cases. In patients with the presence of abdominal or constitutional symptoms and a personal history of colorectal cancer, CTE may contribute to their diagnostic work-up.

Strategies to Optimize Anti-tumor Necrosis Factor Therapy for Perianal Fistulizing Crohn's Disease: A Systematic Review.

Tumor necrosis factor (TNF) antagonists are considered the cornerstone therapy for fistulizing perianal Crohn's disease (PCD), yet a substantial proportion of patients fail to achieve healing. Therefore, we reviewed the evidence for strategies to enhance the efficacy of TNF antagonists for PCD. A systematic search of electronic databases through July 2018 was performed to identify studies that assessed the effectiveness of TNF antagonists combined with another medical or surgical intervention for PCD; or assessed the association between anti-TNF serum concentrations and fistula healing. Twelve studies compared anti-TNF therapy alone versus a combined approach: four with surgery, three with antibiotics, and five with immunomodulators. Only two studies, both with antibiotics, were rated high quality. The addition of antibiotics to anti-TNF therapy resulted in significantly higher rates of fistula response and healing in one study, and a trend toward reduction in fistula drainage in the other. Three of four studies found higher rates of fistula healing when surgery was combined with TNF antagonists. In contrast, one of five studies found a trend toward higher rates of fistula healing in patients treated concomitantly with immunomodulators. Five observational studies assessed the association between anti-TNF concentration and fistula healing. Higher infliximab serum concentrations were consistently associated with fistula healing. In conclusion, few high-quality studies assessing strategies to optimize anti-TNF therapy for PCD exist. Although antibiotics, possibly surgery, and higher serum infliximab concentrations appear to improve fistula healing, future prospective studies are needed to determine the optimal treatment strategy.

Corticosteroids and Thiopurines, But Not Tumor Necrosis Factor Antagonists, are Associated With Cytomegalovirus Reactivation in Inflammatory Bowel Disease: A Systematic Review and Meta-Analysis.

BACKGROUND: The association between cytomegalovirus (CMV) reactivation and individual immunosuppressive agents in inflammatory bowel disease (IBD) has not been clearly defined. Therefore, we performed a systematic review and meta-analysis to assess this association. METHODS: Multiple electronic databases were searched systematically through July 2015 for observational studies reporting CMV reactivation (based on serum-based or tissue-based tests) in IBD patients stratified by medication exposure. We estimated summary odds ratios (ORs) and 95% confidence intervals (CI) using random-effects model. Study quality was assessed using the Newcastle-Ottawa scale. RESULTS: Sixteen observational studies were identified. As compared with nonexposed patients, exposure to corticosteroids (CS) (12 studies, 1180 patients, 52.3% exposed; OR, 2.05; 95% CI, 1.40-2.99) and thiopurines (14 studies, 1273 patients, 24.1% exposed; OR, 1.56; 95% CI, 1.01-2.39) was associated with increased risk of CMV reactivation. In contrast, as compared with patients not exposed to tumor necrosis factor (TNF) antagonists, exposure to TNF antagonists was not associated with an increased risk of CMV reactivation (7 studies, 818 patients, 18.5% exposed; OR, 1.44; 95% CI, 0.93-2.24). The results remained stable for CS and thiopurines when the analysis was limited to hospitalized patients, and by a tissue-based diagnosis. Studies were limited in the ability to assess the impact of concomitant immunosuppressive therapy, duration of medication exposure, and disease severity. CONCLUSIONS: On the basis of 16 observational studies, exposure to CS or thiopurines, but not TNF antagonists, was associated with an increased risk of CMV reactivation in IBD patients.

A model for identifying cytomegalovirus in patients with inflammatory bowel disease.

BACKGROUND & AIMS: The presentation of cytomegalovirus (CMV) disease in patients with inflammatory bowel disease (IBD) can be similar to that of idiopathic IBD. It is a challenge to identify patients at highest risk for CMV. We investigated risk factors and generated a clinical score to identify patients with IBD at highest risk for CMV disease. METHODS: We performed a retrospective case-control study of 68 patients with IBD (66% with ulcerative colitis, 31% with Crohn's disease, and 3% with unclassified IBD) diagnosed with CMV disease on the basis of tissue analysis from January 2005 through December 2011 at Mayo Clinic, Rochester. The patients were each matched with 3 patients with IBD and suspected CMV disease (controls). An a priori set of the most objective variables was used to create a model to identify those with CMV disease. Scores were assigned to each significant factor from the multivariable analysis. Cutoff values that identified patients with CMV with ≥85% sensitivity and specificity were selected. RESULTS: Patients with medically refractory IBD (odds ratio [OR], 3.69; P < .001) or endoscopic ulcers (OR, 3.06; P < .001) and those treated with corticosteroids (OR, 2.95; P < .001) or immunomodulators (OR, 1.86; P = .030) but not tumor necrosis factor antagonists (OR, 1.30; P = .376) were more likely to have CMV disease than patients with IBD without these features. In a multivariable model, refractory disease, treatment with immunomodulators, and age older than 30 years were independently associated with CMV disease. Use of tumor necrosis factor antagonists was an insignificant factor even after adjustment. CONCLUSIONS: Clinical features can identify patients with IBD at risk for CMV disease. This model may help clinicians stratify patients on the basis of risk when CMV disease is suspected.

Effects of antiviral therapy for patients with inflammatory bowel disease and a positive intestinal biopsy for cytomegalovirus.

BACKGROUND & AIMS: Cytomegalovirus (CMV) is an opportunistic pathogen; documented tissue involvement of patients with inflammatory bowel disease (IBD) is associated with adverse outcomes. We quantified the density of CMV inclusions in biopsy specimens from patients with IBD and assessed their response to antiviral therapy. METHODS: In a case-control study, we identified all small bowel and colon biopsy specimens collected from 1111 patients with IBD that had been submitted to the Department of Laboratory Medicine and Pathology, Mayo Clinic, to evaluate for CMV in intestinal tissue from 2005 through 2011. All positive cases were reviewed to confirm the diagnosis of CMV in tissue. We determined the number of viral inclusions in each processed biopsy sample. Biopsy specimens with 5 or more inclusions were considered to have high-grade CMV density. We collected data on response to antiviral therapy and history of surgical resection within 1 year after diagnosis of CMV in tissue. CMV-negative samples (controls) were selected from the same IBD population. Primary outcomes included clinical improvement, hospital admission, time to admission, need for surgical procedures, time to surgery, escalation of therapy, and relapse of CMV infection. RESULTS: In our analysis of the biopsy samples, 68 (6%) were found to contain CMV. Follow-up data and treatment outcomes were available from 50 cases, including 16 patients with high-grade CMV density (all treated) and 34 with low-grade CMV density (20 treated). There was no overall difference in survival, free of surgery, between patients with or without CMV 1 year after diagnosis in tissue. Antiviral treatment improved surgery-free survival outcomes of patients with CMV infection­particularly of patients with high-grade CMV density. CONCLUSIONS: Patients with IBD and a high density of CMV inclusions in intestinal biopsy specimens benefit from antiviral therapy. Patients with fewer viral inclusions in biopsy specimens also might benefit, but the severity of the IBD should be the prime consideration in determining treatment strategies.

Temporary Faecal Diversion for Refractory Perianal and/or Distal Colonic Crohn's Disease in the Biologic Era: An Updated Systematic Review with Meta-analysis.

BACKGROUND AND AIMS: We evaluated short- and long-term outcomes of temporary faecal diversion [FD] for management of refractory Crohn's disease [CD], focusing on outcomes in the biologic era. METHODS: Through a systematic literature review until March 15, 2023, we identified 33 studies [19 conducted in the biologic era] that evaluated 1578 patients with perianal and/or distal colonic CD who underwent temporary FD [with intent of restoring bowel continuity] and reported long-term outcomes [primary outcome: successful restoration of bowel continuity, defined as remaining ostomy-free after reconnection at a minimum of 6 months after diversion or at the end of follow-up]. We calculated pooled rates (with 95% confidence interval [CI]) using random effects meta-analysis, and examined factors associated with successful restoration of bowel continuity. RESULTS: Overall, 61% patients [95% CI, 52-68%; 50% in biologic era] experienced clinical improvement after FD. Stoma takedown was attempted in 34% patients [28-41%; 37% in biologic era], 6-18 months after diversion. Among patients where bowel restoration was attempted, 63% patients [54-71%] had successful restoration of bowel continuity, and 26% [20-34%] required re-diversion. Overall, 21% patients [17-27%; 24% in biologic era] who underwent FD were successfully restored; 34% patients [30-39%; 31% in biologic era] required proctectomy with permanent ostomy. On meta-regression, post-diversion biologic use and absence of proctitis was associated with successful bowel restoration after temporary FD in contemporary studies. CONCLUSION: In the biologic era, temporary FD for refractory perianal and/or distal colonic CD improves symptoms in half the patients, and bowel continuity can be successfully restored in a quarter of patients.

Does combined medical and surgical treatment improve perianal fistula outcomes in patients with Crohn's disease? A systematic review and meta-analysis.

BACKGROUND: The optimal treatment of perianal fistulizing Crohn's disease (PFCD) is unknown. We performed a systematic review with meta-analysis to compare combined surgical intervention and anti-TNF therapy (combined therapy) vs. either therapy alone. METHODS: MEDLINE, EMBASE, and Cochrane databases were searched systematically through December 2023. Surgical intervention was defined as an exam under anesthesia ± setons. We calculated weighted risk ratios (RR) with 95% confidence intervals (CI) for our co-primary outcomes: fistula response and healing, defined clinically as a reduction in fistula drainage or number of draining fistulas and fistula closure respectively. RESULTS: Thirteen studies were analysed: 515 patients treated with combined therapy, 330 patients with surgical intervention and 406 patients with anti-TNF therapy with follow-up between 10 weeks and 3 years. Fistula response (RR 1.10; 95% CI, 0.93-1.30, p=0.28) and healing (RR 1.06; 95% CI, 0.86-1.31, p=0.58) was not significantly different when comparing combined therapy with anti-TNF therapy alone. In contrast, combined therapy was associated with significantly higher rates of fistula response (1.25; 95% CI, 1.10-1.41, p<0.001) and healing (RR 1.17; 95% CI, 1.00-1.36, p=0.05) compared with surgical intervention alone. Our results remained stable when limiting to studies that assessed outcomes within 1 year and studies where <10% of patients underwent fistula closure procedures. CONCLUSION: Combined surgery and anti-TNF therapy was not associated with improved PFCD outcomes compared with anti-TNF therapy alone. Due to an inability to control for confounding and small study sizes, future, controlled trials are warranted to confirm these findings.

Perceived value of computed tomography imaging for patients with inflammatory bowel disease in the emergency department: a Canadian survey.

Background: There are high rates of computed tomography (CT) utilization in the emergency department (ED) for patients with inflammatory bowel disease (IBD), despite guidelines recommending judicious use. We performed a national survey to better understand perceptions and practice patterns of Canadian physicians related to CT imaging in the ED. Methods: Our survey was developed by a multistep iterative process with input from key stakeholders between 2021 and 2022. It evaluated Canadian gastroenterologists', surgeons', and emergency physicians' (1) perceived rates of IBD findings detected by CT, (2) likelihood of performing CT for specific presentations and (3) comfort in diagnosing IBD phenotypes/complications without CT. Results: A total of 208 physicians responded to our survey: median age 44 years (IQR, 37-50), 63% male, 68% academic, 44% emergency physicians, 39% gastroenterologists, and 17% surgeons. Compared with emergency physicians and surgeons, gastroenterologists more often perceived that CT would detect inflammation alone and less often IBD complications. Based on established rates in the literature, 13 (16%) gastroenterologists, 33 (40%) emergency physicians, and 21 (60%) surgeons overestimated the rates of at least one IBD complication. Although most physicians were more comfortable diagnosing inflammation compared to IBD complications without CT, gastroenterologists were significantly less likely to recommend CT imaging for non-obstructive/penetrating presentations compared with emergency physicians and surgeons with results that varied by IBD subtype. Conclusion: This national survey demonstrates differences in physician perceptions and practices regarding CT utilization in the ED and can be used as a framework for educational initiatives regarding appropriate usage of this modality.

Pancolonic Dye Spray Chromoendoscopy to Detect and Resect Ill-Defined Neoplastic Lesions in Colonic Inflammatory Bowel Disease.

Background: Pancolonic dye spray chromoendoscopy (DCE) is used as an adjunct to white light endoscopy (WLE) to enhance the detection and delineation of ill-defined neoplastic (dysplastic) lesions in persons with colonic inflammatory bowel diseases (cIBD). We evaluated the utility of DCE as follow-up to high-definition WLE (HD-WLE) to "unmask" and/or facilitate endoscopic resection of neoplastic lesions. Methods: We retrospectively studied persons with cIBD who underwent DCE as follow-up to HD-WLE between 2013 and 2020. We describe neoplastic findings and management during HD-WLE and DCE exams and report outcomes from post-DCE surveillance exams. Results: Twenty-four persons were studied (mean age 56.7 ± 13.8 years, 50.0% male, 70.8% ulcerative colitis, mean disease duration 18.0 ± 11.0 years). Overall, 32 visible neoplastic lesions were unmasked during DCE, of which 24 were endoscopically resected. DCE facilitated the diagnosis of two cancers. Among 17 persons referred for evaluation of "invisible" neoplasia (detected in non-targeted biopsies) during HD-WLE, DCE identified neoplastic lesions at the same site in eight persons and a different site in four persons. Among seven persons referred for ill-defined visible neoplasia, DCE facilitated complete endoscopic resection in four individuals, whereas two individuals required colectomy for a diagnosis of cancer. Among 19 individuals with post-DCE surveillance, five developed new visible neoplastic lesions, including one high-grade neoplasia which was completely resected. Conclusions: In our cohort, DCE aided in unmasking invisible neoplasia and facilitated endoscopic resection of ill-defined neoplasia, suggesting that it is a useful surveillance tool in selected persons with cIBD. Large prospective studies are needed to validate these findings.