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Cross-sectional magnetic resonance enterography (MRE) and intestinal ultrasonography (IUS) provide valuable and noninvasive information to accurately assess disease activity, severity, and extent; detect complications; and monitor the response to treatment, as well as predict the postoperative recurrence of Crohn’s disease and a negative disease course. Therefore, both imaging modalities are emerging as pivotal diagnostic tools to achieve the emerging therapeutic target of transmural healing associated with better disease outcomes. Despite its numerous potential advantages over endoscopy and even MRE and its good availability, IUS is still widely underused to monitor and manage inflammatory bowel disease (IBD) patients and help in making clinical decisions in routine practice. This situation is clearly due to the absence of validated, reliable, and responsive indices, as well as the lack of trained gastroenterologists and radiologists, as IUS is a component of radiologist expertise in several countries but not yet integrated into the training program of gastroenterologists. However, there is an increasing body of evidence in the literature that IUS and MRE are both becoming essential imaging resources to help clinicians in making reliable decisions. Here, we discuss the up-to-date evidence about the usefulness and performance of cross-sectional imaging, focusing on the ability of bowel US and MRE to aid clinical decision-making for the optimal management and monitoring of IBD.

Introduction:Therapeutic drug monitoring (TDM) of intravenous (IV) infliximab is increasingly practiced to improve therapeutic outcomes in patients with inflammatory bowel diseases (IBD). Recently, a subcutaneous (SC) formulation of infliximab was approved for maintenance treatment of IBD. In the present work, we introduce a software tool to guide infliximab dosing by predicting infliximab concentrations after switching to the SC formulation.Methods:An infliximab population pharmacokinetics (popPK) model, published in the European Public Assessment Report (EMA/CHMP/548703/2019), was used in this study. A software tool was developed using the Shiny package (v1.7.4) in R (v4.3.0). Bayesian forecasting was implemented using mapbayr (v0.10.0), which was used to estimate individual PK parameters through maximum a posteriori estimation. External validation data were obtained from the prospective, multicenter REMSWITCH trial [1]. For each patient, a pre-switch infliximab trough concentration (TC) was used to predict a post-switch TC. Predicted and observed post-switch TCs were compared, and absolute and relative prediction errors (PE) were calculated. Relapse was defined as an increase in fecal calprotectin >=150 mg/g from baseline.Results:A total of 76 patients contributed 1 pre/post-switch TC pair each. Three patients had detectable antibodies towards infliximab pre-switch. Three other patients were cotreated with methotrexate pre-switch. The estimated median clearance using TCs pre-switch was 0.31 L/day for the relapse-free cohort, and 0.42 L/day for the relapse cohort ( P < 0.001) (Figure 1A). The estimated median clearance using TCs post-witch was 0.33 L/day for the relapse-free cohort, and 0.46 L/day for the relapse cohort (P < 0.001) (Figure 1B). Furthermore, there is a tendency towards higher positive prediction errors for the relapse group (Figure 1C).Conclusion:The clinically validated software tool (https://lpmx.shinyapps.io/infliximab/) allows interactive simulations and individual predictions to guide infliximab dosing while switching formulations. Predictions for patients without relapse were unbiased yet precision is likely compromised by variable SC bioavailability or time-varying PK. Significantly higher estimated clearance in the relapsed cohort resulted in an overprediction of TC, likely driven by increased disease activity and thus lower-than-expected infliximab observations. These findings serve as an early predictor for relapse, warranting closer monitoring of these patients.

Background: Anti-tumor necrosis factor (TNF) agents are now accepted as the first-line medical treatment for stricturing Crohn’s disease (CD). However, data are lacking about the effectiveness of advanced therapies after anti-TNF failure. Objectives: To compare the effectiveness of ustekinumab and a second-line anti-TNF agent after failing to respond to a first-line anti-TNF for a symptomatic stricturing CD. Design: Multicenter retrospective study. Methods: We included consecutive adult patients with CD treated with ustekinumab or anti-TNF for symptomatic stricture (confirmed on imaging or endoscopy) after prior failure of one anti-TNF for the current stricture. Short-term endpoints were symptomatic remission (composite endpoint) at 6 months, defined as no abdominal pain, no vomiting, no food restriction, no sub-occlusive episode, no steroid, no surgery, and no drug discontinuation or symptomatic response (same definition except for tolerating mild abdominal pain). Long-term endpoints were time to drug discontinuation for treatment failure and to bowel damage progression. The comparisons were performed after using propensity score analysis. Results: Seventy patients were included (34 on ustekinumab, 36 on anti-TNF). After propensity score adjustment, symptomatic remission at 6 months was achieved in 73.9% of patients receiving ustekinumab compared to 42.7% in the anti-TNF group (p = 0.24), while symptomatic response was observed in 84.0% and 49.5%, respectively (p = 0.13). Predictors of remission in the ustekinumab group were prior bowel resection (p = 0.001) and stricture length <12 cm (p = 0.042). The risk of treatment discontinuation (hazard ratio (HR) = 2.86 (1.33–6.15); p = 0.008) and bowel damage progression (HR = 3.90 (1.64–9.24); p = 0.003) were higher in the anti-TNF group. Conclusion: Ustekinumab appears more effective than a second-line anti-TNF in patients with symptomatic stricturing CD after failing to respond to a first-line anti-TNF. Plain language summary USTEKNOSIS study In the USTEKNOSIS study, we showed that ustekinumab appears more effective than a second anti-TNF in patients with symptomatic stricturing Crohn’s disease after failing to a first anti-TNF.

Early ileocolonoscopy within the first year after surgery is the gold standard to evaluate recurrence after ileocolonic resection for Crohn's disease (CD). The aim of the study was to evaluate the association between the presence and severity of anastomotic and ileal lesions at early postoperative ileocolonoscopy and long-term outcomes. The REMIND group conducted a prospective multicenter study. Patients operated for ileal or ileocolonic CD were included. An ileocolonoscopy was performed 6 months after surgery. An endoscopic score describing separately the anastomotic and ileal lesions was built. Clinical relapse was defined by the CD-related symptoms, confirmed by imaging, endoscopy or therapeutic intensification; CD-related complications; or subsequent surgery. Among 225 included patients, long-term follow-up was available in 193 (median follow-up: 3.82 years [interquartile range: 2.56-5.41]). Median clinical recurrence-free survival was 47.6 months. Clinical recurrence-free survival was significantly shorter in patients with ileal lesions at early postoperative endoscopy whatever their severity was (I(1) or I(2,3,4)) as compared to patients without ileal lesions (I(0)) (I(0) vs I(2,3,4): P = 0.0003; I(0) vs I(1): P = 0.0008 and I(1) vs I(2,3,4): P = 0.43). Patients with exclusively ileal lesions (A(0)I(1,2,3,4)) had poorer clinical long-term outcomes than patients with exclusively anastomotic lesions (A(1,2,3)I(0)) (P = 0.009). A score describing separately the anastomotic and ileal lesions might be more appropriate to define postoperative endoscopic recurrence. Our data suggest that patients with ileal lesions, including mild ones (I(1)), could beneficiate from treatment step-up to improve long-term outcomes.

Data on the natural history of elderly-onset inflammatory bowel disease (IBD) are scarce. Methods In a French population-based cohort we identified 841 IBD patients >60 years of age at diagnosis from 1988 to 2006, including 367 Crohn's disease (CD) and 472 ulcerative colitis (UC). Results Median age at diagnosis was similar for CD (70 years (IQR: 65–76)) and UC (69 years (64–74)). Median follow-up was 6 years (2–11) for both diseases. At diagnosis, in CD, pure colonic disease (65%) and inflammatory behaviour (78%) were the most frequent phenotype. At maximal follow-up digestive extension and complicated behaviour occurred in 8% and 9%, respectively. In UC, 29% of patients had proctitis, 45% left-sided and 26% extensive colitis without extension during follow-up in 84%. In CD cumulative probabilities of receiving corticosteroids (CSs), immunosuppressants (ISs) and anti tumor necrosis factor therapy were respectively 47%, 27% and 9% at 10 years. In UC cumulative probabilities of receiving CS and IS were 40% and 15%, respectively at 10 years. Cumulative probabilities of surgery at 1 year and 10 years were 18% and 32%, respectively in CD and 4% and 8%, respectively in UC. In CD complicated behaviour at diagnosis (HR: 2.6; 95% CI 1.5 to 4.6) was associated with an increased risk for surgery while CS was associated with a decreased risk (HR: 0.5; 0.3 to 0.8). In UC CS was associated with an increased risk (HR: 2.2; 1.1 to 4.6) for colectomy. Conclusions Clinical course is mild in elderly-onset IBD patients. This information would need to be taken into account by physicians when therapeutic strategies are established.

BackgroundEndoscopy is the gold standard for the treatment of postoperative gastric leaks (GL). Large fistulas are associated with high rate of treatment failure. The objective of this study was to assess the clinical efficacy of a combining technique using a covered stent (CS) crossing through pigtails (PDs) for large postsurgical GL leaks.MethodsAll consecutive patients with large (> 10 mm) postsurgical GL treated endoscopically with a combination of a CS and PDs were included in a single-center retrospective study. The primary endpoint was the rate of GL closure.ResultsA total of 29 patients were included. Twenty-five patients underwent sleeve gastrectomy. The fistula (median diameter 15 mm) was diagnosed 6 days (IQR 4–9) after surgery. Technical success was observed in all procedures. After a median follow-up of 10.7 months (IQR 3.8–20.7), GL closure was observed in 82.7% with a median time of 63 days (IQR 40–90). Surgical management was finally necessary in four patients after a median of 186 days (IQR 122–250). No complications related to combined endoscopic treatment were observed especially stent migration during the follow-up.ConclusionAn endoscopic strategy combining CS crossing through PDs appears to be effective, safe and well tolerated for the treatment of large GL.

New therapeutic options for patients with Crohn's disease (CD) with perianal lesions failing anti-tumor necrosis factor (TNF) agents are needed. We aimed to assess the effectiveness of ustekinumab in perianal CD (pCD) and predictors of clinical success in a real-life multicenter cohort. We conducted a national multicenter retrospective cohort study in patients with either active or inactive pCD who received ustekinumab. In patients with active pCD at treatment initiation, the success of ustekinumab was defined by clinical success at 6 months assessed by the physician's judgment without additional medical or surgical treatment for pCD. Univariate and multivariable logistic regression analyses were performed to identify predictors of success. In patients with inactive pCD at ustekinumab initiation, the pCD recurrence-free survival was calculated using the Kaplan-Meier method. Two hundred seven patients were included, the mean age was 37.7 years, the mean duration of CD was 14.3 years, and the mean number of prior perianal surgeries was 2.8. Two hundred five (99%) patients had previously been exposed to at least 1 anti-TNF and 58 (28%) to vedolizumab. The median follow-up time was 48 weeks; 56/207 (27%) patients discontinued therapy after a median time of 43 weeks. In patients with active pCD, success was reached in 57/148 (38.5%) patients. Among patients with setons at initiation, 29/88 (33%) had a successful removal. The absence of optimization was associated with treatment success (P = 0.044, odds ratio 2.74; 95% confidence interval: 0.96-7.82). In multivariable analysis, the number of prior anti-TNF agents (≥3) was borderline significant (P = 0.056, odds ratio 0.4; 95% confidence interval: 0.15-1.08). In patients with inactive pCD at initiation, the probability of recurrence-free survival was 86.2% and 75.1% at weeks 26 and 52, respectively. Ustekinumab appears as a potential effective therapeutic option in perianal refractory CD. Further prospective studies are warranted.

We evaluated the impact of immunosuppressants (IS) and antitumor necrosis factor (TNF) introduction on long-term outcomes of ulcerative colitis (UC) in a large population-based pediatric-onset cohort. All patients included in the EPIMAD registry with a diagnosis of UC made before the age of 17 years between 1988 and 2011 were followed up retrospectively until 2013. Medication exposure and disease outcomes were compared between 3 diagnostic periods: 1988 to 1993 (period [P] 1; pre-IS era), 1994 to 2000 (P2; pre-anti-TNF era), and 2001 to 2011 (P3; anti-TNF era). A total of 337 patients (female, 57%) diagnosed with UC were followed up during a median duration of 7.2 years (interquartile range 3.8-13.0). The IS and anti-TNF exposure rates at 5 years increased over time from 7.8% (P1) to 63.8% (P3) and from 0% (P1) to 37.2% (P3), respectively. In parallel, the risk of colectomy at 5 years decreased significantly over time (P1, 17%; P2, 19%; and P3, 9%; P = 0.045, P -trend = 0.027) and between the pre-anti-TNF era (P1 + P2, 18%) and the anti-TNF era (P3, 9%) ( P = 0.013). The risk of disease extension at 5 years remained stable over time (P1, 36%, P2, 32%, and P3, 34%; P = 0.31, P -trend = 0.52) and between the pre-anti-TNF era (P1 + P2, 34%) and the anti-TNF era (P3, 34%) ( P = 0.92). The risk of flare-related hospitalization at 5 years significantly increased over time (P1, 16%; P2, 27%; P3, 42%; P = 0.0012, P -trend = 0.0006) and between the pre-anti-TNF era (P1 + P2, 23%) and the anti-TNF era (P3, 42%) ( P = 0.0004). In parallel with the increased use of IS and anti-TNF, an important decline in the risk of colectomy in pediatric-onset UC was observed at the population level.

A 67-year-old man with an 8-month history of dysphagia and regurgitation presented to the gastroenterology clinic. A barium swallow examination showed an outpouching esophageal lesion consistent with a Zenker’s diverticulum.