Mucosal healing has been associated with long-term response to therapy for Crohn disease (CD). However, little is known about the significance of terminal ileum (TI) transmural thickness in predicting clinical outcomes. In this retrospective observational cohort study, we examined the association of an index ultrasonographic assessment of TI thickness during the maintenance phase and the subsequent clinical outcome of CD in a cohort of patients treated with infliximab (IFX). Treatment failure was defined as treatment discontinuation because of lack of efficacy, a need for dose escalation, or surgery. Clinical response was defined as treatment continuation in the absence of any of the aforementioned failure criteria. Sixty patients with CD receiving IFX therapy were included in the study. The patients were followed for a median of 16 months (5-24 months) after an index intestinal ultrasound. Thirty-eight patients (63.3%) maintained response to the therapy and 22 patients (36.6%) failed the treatment, with a mean follow up of 10.5 months (6.5-17 months) vs 9.25 months (1-10.25 months), respectively. On univariate analysis, the only variables differing between treatment response and failure were a TI thickness of 2.8 vs 5 mm (P < 0.0001) and an IFX trough level of 6.6 vs 3.9 µg/mL (P = 0.008). On multivariable analysis, only a small bowel thickness of ≥4 mm was associated with the risk of treatment failure (odds ratio, 2.9; 95% CI, 1.49-5.55; P = 0.002). Our findings suggest that transmural thickness of ≥4 mm can predict subsequent treatment failure in patients with CD treated using IFX, indicating transmural thickness <4 mm as a potential novel valuable therapeutic target.

Background: Orofacial granulomatosis [OFG] is a rare syndrome that may be associated with Crohn’s disease [CD]. We aimed to characterise this relationship and the management options in the biologic era.Methods: This multicentre case series was supported by the European Crohn’s and Colitis Organisation [ECCO], and performed as part of the Collaborative Network of Exceptionally Rare case reports [CONFER] project. Clinical data were recorded in a standardised collection form.Results: This report includes 28 patients with OFG associated with CD: 14 males (mean age of 32 years, ±12.4 standard deviation [SD]) and 14 females [40.3 years, ±21.0 SD]. Non-oral upper gastrointestinal tract involvement was seen in six cases and perianal disease in 11. The diagnosis of OFG was made before CD diagnosis in two patients, concurrently in eight, and after CD diagnosis in 18. The distribution of OFG involved the lips in 16 cases and buccal mucosa in 18. Pain was present in 25 cases, with impaired swallowing or speaking in six. Remission was achieved in 23 patients, notably with the use of anti-tumour necrosis factors [TNFs] in nine patients, vedolizumab in one, ustekinumab in one, and thalidomide in two. A further five cases were resistant to therapies including anti-TNFs.Conclusions: OFG associated with CD may occur before, concurrently with, or after the diagnosis of CD. Perianal and upper gastrointestinal [UGI] disease are common associations and there is a significant symptom burden in many. Remission can be obtained with a variety of immunosuppressive treatments, including several biologics approved for CD.

Background: In Crohn's disease, higher adalimumab trough levels and negative anti‐adalimumab‐antibodies associate with better clinical and endoscopic outcomes. Intestinal ultrasound has become a relevant non‐invasive method to monitor treatment. However, data on the association between adalimumab levels and bowel wall thickness measured with ultrasound is limited.Objective: The purpose of this study was to examine the possible association between the sonographic transmural‐thickness and adalimumab trough levels.Methods: This prospective observational cohort study was conducted at Sheba Medical Center in 2014–2018. Crohn's disease patients on adalimumab maintenance therapy with intestinal ultrasound performed within <30 days of trough level measurement were included. Associations between terminal ileum and colonic thickness, adalimumab levels and therapy retention were assessed.Results: Fifty events of ultrasound with concomitant adalimumab trough level measurements in 44 Crohn's disease patients were included. Patients with trough level <3 μg/ml had significantly higher bowel wall thickness, both for terminal ileum (p = 0.04) and colon (p = 0.02). Thirty‐two patients continued adalimumab therapy over one year. The adalimumab retention rate was higher among those with terminal ileum thickness <4 mm (p = 0.03).Conclusion: Lower adalimumab trough levels were associated with higher bowel wall thickness indicating poorer therapy outcome. Transmural thickness measurement with ultrasound may be a useful target for guiding biologic therapy in Crohn's disease.

Background and Aims: Fecal calprotectin (FC) is known to be a sensitive biomarker of colonic inflammation but to a lesser degree of small bowel (SB) inflammation. Moreover, data on FC’s diagnostic levels in different SB segments are scarce. We aimed to examine FC’s diagnostic levels along the SB axis in CD. Methods: This was a post hoc aggregated analysis of 5 prospective studies of adult CD patients who underwent FC testing and SB video capsule endoscopy. Lewis score (LS) inflammation in different SB segments was tested for correlation with FC level after the exclusion of colonic disease. The diagnostic levels of FC for SB inflammatory topographical gradient were assessed using a receiver operating characteristic. Results: Two hundred and fourteen patients were included (age: 30 [24-43] year-old, males-57%). For a similar SB inflammatory activity (LS ≥ 135), FC levels incrementally increased from proximal to distal SB segments (63 [30-121] vs 190 [78-549], p = 0.005) and from distal SB segment to the colon (190 [78-549] vs 542 [185-1000], p = 0.010). The best FC cutoffs to identify isolated mild proximal/distal SB inflammation (LS ≥ 135) were 77 µg/g and 123 µg/g, respectively. A cutoff of 234 µg/g was best to detect more significant proximal inflammation (LS ≥ 350) when only mild distal SB inflammation was present. In sensitivity analyses, this proximal-to-distal FC gradient was maintained when LS ≥ 350 and LS ≥ 790 were used as the inflammatory reference values. Unlike FC, the magnitude of CRP elevation was unrelated to the topography of inflammation along the SB axis. Conclusions: FC may serve as a topographical biomarker of CD-activity, with its sensitivity to identify mucosal inflammation increases from proximal to distal SB segments.

Background: Multiple studies have described the effectiveness of ustekinumab (UST) and vedolizumab (VDZ) in patients with Crohn’s disease (CD) failing anti- Tumor necrosis factors (TNFs); however, the effectiveness of VDZ or UST as a third-class biologic has not yet been described. Aims and Methods: In this retrospective multicenter cohort study, we aimed to investigate the effectiveness of VDZ and UST as a third-class biologic in patients with CD. Results: Two-hundred and four patients were included; 156/204 (76%) patients received VDZ as a second- and UST as a third-class therapy (group A); the remaining 48/204 (24%) patients received UST as a second- and VDZ as a third-class therapy (group B). At week 16–22, 87/156 (55.5%) patients and 27/48 (56.2%) in groups A and B, respectively, responded to treatment (p = 0.9); 41/156 (26.2%) and 15/48 (31.2%) were in clinical remission (p = 0.5). At week 52; 89/103 (86%) patients and 25/29 (86.2%) of the patients with available data had responded to third-class treatment in groups A and B, respectively (p = 0.9); 31/103 (30%) and 47/29 (24.1%) were in clinical remission (p = 0.5). Conclusion: Third-class biological therapy was effective in more than half of the patients with CD. No differences in effectiveness were detected between the use of VDZ and UST as a third-class agent.