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Background Heterogeneity in demographic and outcomes data with corresponding measurement instruments [MIs] creates barriers to data pooling and analysis. Several core outcome sets have been developed in inflammatory bowel disease [IBD] to homogenize outcomes data. A parallel Minimum Data Set [MDS] for baseline characteristics is lacking. We conducted a systematic review to develop the first MDS. Methods A systematic review was made of observational studies from three databases [2000–2021]. Titles and abstracts were screened, full-text articles were reviewed, and data were extracted by two reviewers. Baseline data were grouped into ten domains: demographics, clinical features, disease behaviour/complications, biomarkers, endoscopy, histology, radiology, healthcare utilization and patient-reported data. Frequency of baseline data and MIs within respective domains are reported. Results From 315 included studies [600 552 subjects], most originated from Europe [196; 62%] and North America [59; 19%], and were published between 2011 and 2021 [251; 80%]. The most frequent domains were demographics [311; 98.7%] and clinical [289; 91.7%]; 224 [71.1%] studies reported on the triad of sex [306; 97.1%], age [289; 91.7%], and disease phenotype [231; 73.3%]. Few included baseline data for radiology [19; 6%], healthcare utilization [19; 6%], and histology [17; 5.4%]. Ethnicity [19; 6%], race [17; 5.4%], and alcohol/drug consumption [6; 1.9%] were the least reported demographics. From 25 MIs for clinical disease activity, the Harvey–Bradshaw Index [ n  = 53] and Mayo score [ n  = 37] were most frequently used. Conclusions Substantial variability exists in baseline population data reporting. These findings will inform a future consensus for MDS in IBD to enhance data harmonization and credibility of real-world evidence. [ABSTRACT FROM AUTHOR]

Background and Aims Home self-injection of the human anti-tumour necrosis alpha [anti-TNFα] monoclonal adalimumab complicates prospective serial-sampling studies. Although a recent study examined adalimumab levels and immunogenicity in Crohn's disease [CD] patients, prospective real-world data from ulcerative colitis [UC] patients are lacking. Methods A three-monthly home-visit programme from induction was established prospectively for UC patients. Clinical scores were determined at each visit, and sera were obtained for assessment of drug and anti-adalimumab antibody levels. Calprotectin was measured using a smartphone-based app. This cohort was compared to a parallel prospective cohort of adalimumab-treated CD patients [POETIC1]. Results Fifty UC patients starting adalimumab [median follow-up 28 weeks] were compared to 98 adalimumab-treated CD patients [median follow-up 44 weeks]. Only 11/50 UC patients [22%] continued treatment to the end of the follow-up compared with 50/98 [51%] CD patients (odds ratio [OR] = 0.27, p  = 0.001). Loss of response was significantly more common in UC patients [OR = 3.2, p  = 0.001]. Seventeen patients [34%] in the UC cohort developed anti-adalimumab antibodies, 9/17 [52.9%] as early as week 2. There was no difference between patient cohorts in the overall development of anti-adalimumab antibodies [34% vs 30.6%, respectively, OR = 1.67, p  = 0.67], nor was there a difference in early immunogenicity [OR = 1.39, p  = 0.35]. There was no difference in low drug levels [<3 µg/mL] between the two cohorts [OR = 0.87, p  = 0.83]. Conclusions Loss of response to adalimumab therapy was significantly more common in the UC compared to the CD cohort and was driven by a higher rate of non-immunogenic, pharmacodynamic parameters. [ABSTRACT FROM AUTHOR]

Background Idiopathic thrombocytopaenic purpura [ITP] is an acquired haematological disorder with an incidence of 1–6 per 100 00/year. ITP and inflammatory bowel disease [IBD] comorbidity has been reported in the literature, but insights regarding the course, outcome and optimal management are limited by its rarity. The current study aimed to evaluate the clinical presentation and outcome of ITP in patients with IBD. Methods This multicentre retrospective case series was performed as part of the ECCO Collaborative Network of Exceptionally Rare case reports [CONFER] project. Cases of patients with ITP and IBD were collected by participating investigators. Clinical data were recorded in a standardized collection form. Results This report includes 32 patients with concurrent ITP and IBD: ten were females, and the median age was 32.0 years (interquartile range [IQR] 20.5–39.5). Fourteen patients had a diagnosis of Crohn's disease [CD] and the other 18 ulcerative colitis [UC]. The diagnosis of IBD preceded the ITP in 26 patients (median time between diagnoses was 7.0 years [IQR, 1.5–9.5]). Among those patients, 17 were in clinical remission at ITP diagnosis. Thirteen patients were treated with mesalamine, four with oral corticosteroids, one with rectal corticosteroids, two with azathioprine and five with anti-tumour necrosis factor agents. The median platelet count was 35 000/microliter [IQR, 10 000–70 000]. Eight patients had rectal bleeding, 13 had skin purpura, three had epistaxis, six had mucosal petechiae and 13 were asymptomatic. Regarding ITP treatment, 19 were treated with corticosteroids, one with anti-RhD immunoglobulin, 12 with intravenous immunoglobulins [IVIGs], four with thrombopoietin, three with rituximab and six patients eventually required splenectomy. Ten patients needed no treatment directed to the ITP. Three patients required colectomy during long-term follow-up, due to IBD or cancer but not to massive bleeding as a complication of ITP. One of eight patients who presented with rectal bleeding required splenectomy, and none required urgent colectomy. Two patients died during the follow-up, one of them due to bleeding complications located in the upper gastrointestinal tract. Median follow-up time was 6.5 years [IQR, 3–10]. With long-term follow-up, all patients had platelet counts above 50 000/microliter, and 24 were in IBD clinical remission. Conclusion Most ITP cases in this series occurred after the IBD diagnosis and responded well to regular ITP treatment. The course of the ITP in the IBD patients followed an expected course, including response to medical therapy and low rates of splenectomy. [ABSTRACT FROM AUTHOR]

Background and Aims The utility of real-world data is dependent on the quality and homogeneity of reporting. We aimed to develop a core outcome set for real-world studies in adult patients with inflammatory bowel disease [IBD]. Methods Candidate outcomes and outcome measures were identified and categorised in a systematic review. An international panel including patients, dietitians, epidemiologists, gastroenterologists, nurses, pathologists, radiologists, and surgeons participated in a modified Delphi consensus process. A consensus meeting was held to ratify the final core outcome set. Results A total of 26 panellists from 13 countries participated in the consensus process. A total of 271 items [130 outcomes, 141 outcome measures] in nine study domains were included in the first-round survey. Panellists agreed that real-world studies on disease activity should report clinical, endoscopic, and biomarker disease activity. A disease-specific clinical index [Harvey–Bradshaw Index, Partial Mayo Score, Simple Clinical Colitis Activity Index] should be used, rather than physician global assessment. In ulcerative colitis [UC], either the UC Endoscopic Index of Severity or the Mayo Endoscopic Score can be used, but there was no consensus on an endoscopic index for Crohn's disease, nor was there consensus on the use of the presence of ulcers. There was consensus on using faecal calprotectin and C-reactive protein. There was no consensus on the use of histology in real-world studies. Conclusions A core outcome set for real-world studies in IBD has been developed based on international multidisciplinary consensus. Its adoption will facilitate synthesis in the generation of real-world evidence. [ABSTRACT FROM AUTHOR]

Background Heterogeneity exists in reported outcomes and outcome measurement instruments [OMI] from observational studies. A core outcome set [COS] for observational and real-world evidence [RWE] in inflammatory bowel disease [IBD] will facilitate pooling large datasets. This systematic review describes and classifies clinical and patient-reported outcomes, for COS development. Methods The systematic review of MEDLINE, EMBASE, and CINAHL databases identified observational studies published between 2000 and 2021 using the population exposure outcome [PEO] framework. Studies meeting eligibility criteria were included. After titles and abstracts screening, full-text articles were extracted by two independent reviewers. Primary and secondary outcomes with corresponding OMI were extracted and categorised in accordance with OMERACT Filter 2.1 framework. The frequency of outcomes and OMIs are described. Results From 5854 studies, 315 were included: 129 [41%] Crohn's disease [CD], 60 [19%] ulcerative colitis [UC], and 126 [40%] inflammatory bowel disease [IBD] studies with 600 552 participants. Totals of 1632 outcomes and 1929 OMI were extracted mainly from medical therapy [181; 72%], surgical [34; 11%], and endoscopic [6; 2%] studies. Clinical and medical therapy-related safety were frequent outcome domains recorded in 194 and 100 studies. Medical therapy-related adverse events [ n = 74] and need for surgery [ n = 71] were the commonest outcomes. The most frequently reported OMI were patient or event numbers [ n = 914], Harvey-Bradshaw Index [ n = 45], and Montreal classification [ n = 42]. Conclusions There is substantial variability in outcomes reporting and OMI types. Categorised outcomes and OMI from this review will inform a Delphi consensus on a COS for future RWE in IBD. Data collection standardisation may enhance the quality of RWE applied to decision-making. [ABSTRACT FROM AUTHOR]

Background Gastroenteropancreatic neuroendocrine neoplasms [GEP-NENs] have rarely been reported in association with inflammatory bowel diseases [IBDs]. Methods An ECCO COllaborative Network For Exceptionally Rare case reports project [ECCO-CONFER] collects cases of GEP-NENs diagnosed in patients with IBD. Results GEP-NEN was diagnosed in 100 IBD patients; 61% female, 55% Crohn's disease, median age 48 years (interquartile range [IQR] 38-59]). The most common location was the appendix [39%] followed by the colon [22%]. Comprehensive IBD-related data were available for 50 individuals with a median follow-up of 30 months [IQR 11-70] following NEN diagnosis. Median duration of IBD at NEN diagnosis was 84 months [IQR 10-151], and in 18% of cases NEN and IBD were diagnosed concomitantly. At diagnosis, 20/50 were stage-I [T1N0M0], and 28/50 were graded G1 [ki67 ≤2%]. Incidental diagnosis of NEN and concomitantly IBD diagnosis were associated with an earlier NEN stage [ p = 0.01 and p = 0.02, respectively]. Exposure to immunomodulatory or biologic therapy was not associated with advanced NEN stage or grade. Primary GEP-NEN were more frequently found in the segment affected by IBD [62% vs 38%]. At the last follow-up data, 47/50 patients were alive, and only two deaths were related to NEN. Conclusions In the largest case series to date, prognosis of patients with GEP-NEN and IBD seems favourable. Incidental NEN diagnosis correlates with an earlier NEN stage, and IBD-related therapies are probably independent of NEN stage and grade. The association of GEP-NEN location and the segment affected by IBD may suggest a possible role of inflammation in NEN tumorigenesis [ABSTRACT FROM AUTHOR]

Background We evaluated whether integration of novel diets for donors and patients, in addition to faecal transplantation [FT], could increase FT remission rate in refractory ulcerative colitis [UC]. Methods This was a blinded, randomised, controlled trial in adults with active UC, defined by a simple clinical colitis activity index [SCCAI] of ≥5 and ≤11 and endoscopic Mayo score 2–3, refractory to medication. Group 1 received free diet and single donor standard FT by colonoscopy on Day 1and rectal enemas on Days 2 and 14 without dietary conditioning of the donor. Group 2 received FT as above but with dietary pre-conditioning of the donor for 14 days and a UC Exclusion Diet [UCED] for the patients. Group 3 received the UCED alone. The primary endpoint was Week 8 clinical steroid-free remission, defined as SCCAI <3. Results Of 96 planned patients, 62 were enrolled. Remission Week 8 Group 1 was 2/17 [11.8%], Group 2 was 4/19 [21.1%], Group 3 was 6/15 [40%] [non-significant]. Endoscopic remission Group 1 was 2/17 [12%], Group 2 was 3/19 [16%], Group 3 was 4/15 [27%] [Group 1 vs 3 p  = 0.38]. Mucosal healing [Mayo 0] was achieved only in Group 3 [3/15, 20%] vs 0/36 FT patients [ p  = 0.022]. Exacerbation of disease occurred in 3/17 [17.6%] of Group 1, 4/19 [21.1%] of Group 2, and 1/15 [6.7%] of Group 3 [Group 2 vs 3, p  = 0.35]. Conclusions UCED alone appeared to achieve higher clinical remission and mucosal healing than single donor FT with or without diet. The study was stopped for futility by a safety monitoring board. [ABSTRACT FROM AUTHOR]

Background Hypogammaglobulinaemia is a disorder characterized by low serum immunoglobulin levels and a high prevalence of gastrointestinal manifestations. In some cases, clinical and endoscopic features are indistinguishable from those of inflammatory bowel disease [IBD]. Methods This was a multicentre case series performed as a part of the European Crohn's and Colitis Organisation [ECCO] Collaborative Network of Exceptionally Rare case reports [CONFER] project. Results This report includes 27 patients with primary hypogammaglobulinaemia and IBD-like features: 20 males and seven females, median age 45.6 years (interquartile range [IQR] 35.2–59). Crohn's disease-like features were noted in 23 patients, and four patients had ulcerative colitis-like features. The diagnosis of hypogammaglobulinaemia preceded a diagnosis of IBD-like features in 20 patients [median of 7 years prior, IQR 2.6–20.6 years], and followed the appearance of IBD-like features in seven cases [median of 1 year after, IQR 0.45–5.6 years]. Hypogammaglobulinaemia aetiologies were common variable immunodeficiency [66.6%], agammaglobulinaemia [7.4%], selective IgA-deficiency [11.1%], Good's syndrome [7.4%], IgG subclass deficiency with IgA deficiency [3.7%] and hyper-IgM [3.7%]. In addition to antibiotics and intravenous immunoglobulin [IVIG] for hypogammaglobulinaemia, 12 patients received IBD-related treatment including 5-aminosalicylate agents [two patients], corticosteroids [one patient], thiopurines [three patients], anti-tumour necrosis factor [four patients] and vedolizumab [two patients]. By the end of the follow-up (44.5 months [IQR 18–81]), 21/27 [77%] patients were in clinical remission. Conclusion This case series describes IBD-like features in patients with hypogammaglobulinaemia. The diagnosis of IBD-like features mainly occurred after that of hypogammaglobulinaemia, with successful recovery in the majority of cases after appropriate treatment. [ABSTRACT FROM AUTHOR]

Inflammatory bowel disease is a chronic disease with variable degrees of extent, severity, and activity. A proportion of patients will have disease that is refractory to licensed therapies, resulting in significant impairment in quality of life. The treatment of these patients involves a systematic approach by the entire multidisciplinary team, with particular consideration given to medical options including unlicensed therapies, surgical interventions, and dietetic and psychological support. The purpose of this review is to guide clinicians through this process and provide an accurate summary of the available evidence for different strategies. [ABSTRACT FROM AUTHOR]

Background Real life data regarding pharmacokinetics of vedolizumab in patients needing dose optimisation are scarce. We set to examine whether pre-optimisation vedolizumab levels associate with therapy outcomes and which mechanisms explain the associations. Methods A multicentre observational study assessed the outcome of dose increase in association with pre-escalation levels in vedolizumab-treated patients. SubsequentIy, α4β7 occupancy on peripheral blood [PB] and intestinal lamina propria [LP] tissues was investigated on various cellular subsets in patients undergoing lower endoscopy on infusion day. Cellular localisation of vedolizumab-bound α4β7 and effects on M1 and M2 macrophages were also explored. Results A total of 161 inflammatory bowel disease [IBD] patients were included. Among 129/161 patients intensified during maintenance [Week 14 onward], pre-intensification trough levels were comparable or higher among those subsequently attaining post-optimisation clinical, biomarker, and endoscopic remission, compared with non-remitting patients [ p  = 0.09, 0.25, 0.04, respectively]. Similar results were demonstrated for those dose-optimised during induction [Week 6, n  = 32]. In the immune sub-study [ n  = 43], free α4β7 receptors at trough were similarly low among patients with/without mucosal healing, on PB T cells [ p  = 0.15], LP T cells [ p  = 0.88], and on PB eosinophils [ p  = 0.08]. Integrin receptors on M1 and M2 macrophages were also saturated by low levels of vedolizumab and anti-inflammatory cytokine secretion was not increased. Co-localisation and dissociation experiments demonstrated membranal α4β7 receptors of two origins: non-internalised and newly generated α4β7, but re-binding was still complete at very low concentrations. Conclusions These results do not support pharmacokinetics as the mechanism responsible for loss of response to vedolizumab, nor do they support a need for higher drug concentration to enhance vedolizumab's immune effects. Higher pre-escalation levels may indicate less clearance [less severe disease] and higher likelihood of subsequent re-gained response, regardless of therapy escalation. [ABSTRACT FROM AUTHOR]

Background and Aims This study aimed to compare real-world clinical effectiveness and safety of vedolizumab, an α4β7-integrin inhibitor, and anti-tumour necrosis factor-α [anti-TNFα] agents in biologic-naïve ulcerative colitis [UC] and Crohn's disease [CD] patients. Methods This was a 24-month retrospective medical chart study in adult UC and CD patients treated with vedolizumab or anti-TNFα in Canada, Greece and the USA. Inverse probability weighting was used to account for differences between groups. Primary outcomes were cumulative rates of clinical effectiveness [clinical response, clinical remission, mucosal healing] and incidence rates of serious adverse events [SAEs] and serious infections [SIs]. Secondary outcomes included cumulative rates of treatment persistence [patients who did not discontinue index treatment during follow-up] and dose escalation and incidence rates of disease exacerbations and disease-related surgeries. Adjusted analyses were performed using inverse probability weighting. Results A total of 1095 patients [604 UC, 491 CD] were included. By 24 months, rates of clinical effectiveness were similar between groups, but incidence rates of SAEs (hazard ratio [HR] = 0.42 [0.28–0.62]) and SIs (HR = 0.40 [0.19–0.85]) were significantly lower in vedolizumab vs anti-TNFα patients. Rates of treatment persistence [ p < 0.01] by 24 months were higher in vedolizumab patients with UC. Incidence rates of disease exacerbations were lower in vedolizumab patients with UC (HR = 0.58 [0.45–0.76]). Other outcomes did not significantly differ between groups. Conclusion In this real-world setting, first-line biologic therapy in biologic-naïve patients with UC and CD demonstrated that vedolizumab and anti-TNFα treatments were equally effective at controlling disease symptoms, but vedolizumab has a more favourable safety profile. [ABSTRACT FROM AUTHOR]

Background and Aims Passable intestinal strictures are frequently detected on capsule endoscopy [CE]. Such strictures are a major component of inflammatory scores. Deep neural network technology for CE is emerging. However, the ability of deep neural networks to identify intestinal strictures on CE images of Crohn's disease [CD] patients has not yet been evaluated. Methods We tested a state-of-the-art deep learning network for detecting CE images of strictures. Images of normal mucosa, mucosal ulcers, and strictures of Crohn's disease patients were retrieved from our previously described CE image bank. Ulcers were classified as per degree of severity. We performed 10 cross-validation experiments. A clear patient-level separation was maintained between training and testing sets. Results Overall, the entire dataset included 27 892 CE images: 1942 stricture images, 14 266 normal mucosa images, and 11 684 ulcer images [mild: 7075, moderate: 2386, severe: 2223]. For classifying strictures versus non-strictures, the network exhibited an average accuracy of 93.5% [±6.7%]. The network achieved excellent differentiation between strictures and normal mucosa (area under the curve [AUC] 0.989), strictures and all ulcers [AUC 0.942], and between strictures and different grades of ulcers [for mild, moderate, and severe ulcers—AUCs 0.992, 0.975, and 0.889, respectively]. Conclusions Deep neural networks are highly accurate in the detection of strictures on CE images in Crohn's disease. The network can accurately separate strictures from ulcers across the severity range. The current accuracy for the detection of ulcers and strictures by deep neural networks may allow for automated detection and grading of Crohn's disease-related findings on CE. [ABSTRACT FROM AUTHOR]

This was a multicentre case series 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. The aim was to report on whether cutaneous lesions associated with inflammatory bowel disease [IBD] and refractory to standard medical therapy including anti-tumour necrosis factors [anti-TNFs], would respond to the newer biologic agents ustekinumab [UST] or vedolizumab [VDZ]. This report includes 28 patients with cutaneous lesions from 14 centres, all of whom had failed immunomodulator and anti-TNF therapy. Metastatic Crohn's disease [MCD] was diagnosed in 10 patients: UST led to remission in five cases and partial response in four cases, with a single report of VDZ inducing remission. All cases of MCD treated with UST responded after the first or second dose, and the median time for the five cases that attained remission was 5 months. Pyoderma gangrenosum [PG] was diagnosed in four cases: three of these attained remission with UST [median time to remission 4 months] and one case did not respond to VDZ. There were seven cases of erythema nodosum [EN]: UST led to remission in four cases and partial response in 1 case whilst VDZ had partial response in 2 cases and non-response in two cases. There were seven single cases of other inflammatory lesions. In summary, UST appears to be useful for different cutaneous lesions including MCD, PG, and EN, whereas VDZ does not appear to be useful for lesions that are independent of disease activity. [ABSTRACT FROM AUTHOR]

Background and Aims Discontinuation of thiopurine analogues is common prior to live vaccines, during infection or when de-escalating therapy. Data regarding clearance of active metabolites and immune re-constitution is scant. We aimed to determine drug elimination and immune re-constitution following thiopurine cessation. Methods The elimination kinetics of 6-thioguanine nucleotides (6-TGN) were determined in nine inflammatory bowel disease [IBD] patients discontinuing thiopurines. Immune reconstitution was evaluated by toxic shock syndrome toxin 1 [TSST1] or anti-CD3 [OKT3]-induced CD4+ T-cell proliferation, following an initial exposure to TSST1 and 6-mercaptopurine [6MP], separately or combined. Results All patients discontinuing thiopurines displayed first-order elimination kinetics of 6-TGN, with a median elimination half-life of 6.8 days [interquartile range 5.9–8.4]. Resting CD4+ T-cells exposed to 6MP preserved their response to subsequent polyclonal or Vβ2+-preferential stimulation. By contrast, exposure of TSST1-activated CD4+ T-cells to 6MP inhibited their subsequent Vβ2+clonal response to further stimulation [ p = 0.008], whereas overall response to further non-Vβ2-selective stimulation with OKT3 was unaltered [ p = 0.9]. Conclusions Upon 6MP/azathioprine discontinuation, a 6-TGN elimination half-life of less than 10 days is expected in most patients. Immune reconstitution, however, may take longer for T-cell clones exposed to stimulation during thiopurine treatment. These findings may be useful when considering thiopurine cessation. [ABSTRACT FROM AUTHOR]

Background and Aims: Capsule endoscopy [CE] and magnetic resonance enterography [MRE] are prime modalities for evaluation of the small bowel in Crohn's disease [CD]. Detection of proximal small bowel [SB] inflammation in CD by MRE is challenging. Currently available quantitative MRE scores do not incorporate proximal SB data. The MRE global score [MEGS] was designed for quantitative evaluation of the entire digestive tract; its accuracy in the proximal SB has not previously been evaluated. This study compared the evaluation of the small bowel inflammation by MEGS and CE-derived quantitative score (the Lewis score[LS]). Methods: CD patients in stable clinical remission were prospectively recruited and underwent MRE and CE; faecal calprotectin [FC] levels were obtained. MEGS was calculated for each SB segment and the entire SB [SBMEGS]. SB inflammation on CE was quantified using LS. A cumulative Lewis score [C-LS] was calculated based on summation of three tertiles scores. Results: Fifty patients were included. There was a significant correlation of SBMEGS with LS and C-LS [r = 0.61 and 0.71, both p = 0.001]. The correlation with FC was stronger for MEGS than for LS or C-LS [r = 0.68 vs r = 0.46 vs r = 0.53, all p = 0.001]. The correlation between the proximal LS and MEGS was significant [r = 0.55, p = 0.001]; median MEGS was significantly different in patients, with LS values consistent with mucosal healing, mild and moderate-to-severe inflammation. Conclusions: MEGS provides accurate evaluation of the SB and strongly correlates with FC; the main advantage of MEGS is the accurate quantification of proximal SB inflammation unavailable for alternative MRE scores. [ABSTRACT FROM AUTHOR]

Background Vedolizumab [VDZ] is an anti-integrin monoclonal antibody effective in ulcerative colitis [UC] and Crohn's disease [CD]. Several real-world experience [RWE] studies with VDZ have been published to date. The aim of this systematic review was to summarise the available real-life experience with VDZ. Methods We performed a systematic review of the available RWE studies of VDZ in CD and UC. We performed a pooled analysis of the available efficacy and safety data for induction and maintenance treatment in adult cohorts. A narrative review of VDZ use in special clinical settings was also performed. Results Nine studies including 1565 [571 UC, 994 CD] adult patients were identified. In CD, clinical response and remission were achieved in 54% (95% confidence interval [CI] 41–66%) and 22% [95% CI 13–35%] by Week 6 and in 49% [95% CI 37–51%] and 32% [95% CI 23–42%] by Week 14; at Week 52, 45% [95% CI 28–64%] and 32% [95% CI 12–62] of the patients responded, and were in clinical remission, respectively. In UC, clinical response and remission were achieved in 43% [95% CI 37–49] and 25% [95% CI 12–45] by Week 6, respectively, and in 51% [95% CI 43–61%]and 30% [95% CI 24–36%] by Week 14/22, respectively; at week 52, clinical response and remission were achieved in 48% and 39% of the patients, respectively. Adverse effects were mostly minor and occurred in 30.6% of the patients; infections were reported in 3.4% of the patients. Conclusions VDZ is efficacious in CD and UC and has a favourable safety profile in RWE studies. [ABSTRACT FROM AUTHOR]

The association of infliximab [IFX] trough levels with clinical and endoscopic outcomes in inflammatory bowel disease is well established. However, there is scarce data regarding the association of perianal fistula response with IFX. The aim of this study was to establish whether early induction infliximab levels and anti-infliximab antibodies [ATIs] are associated with perianal fistula response. Methods: Consecutive CD patients with perianal fistulae that were treated with IFX between 2008 and 2016 were included in the study. Response was defined as cessation or significant improvement of fistula drainage. Patients with unavailable IFX level or ATI measurements and/or missing clinical follow-up at Week 14 were excluded. Results: A total of 36 patients with perianal fistulae were included; 25/36 [69.4%] responded to treatment by Week 14. The median induction IFX levels at Weeks 2, 6 and 14 in the responders group at Week 14 were higher compared with those of the non-responders group [20/5.6 µg/mL, P = 0.0001; 13.3/2.55 µg/mL P = 0.0001; 4.1/0.14 µg/mL, P = 0.01]. On multivariate analysis, IFX leve at Weeks 2 and 6 were significantly associated with fistula response at Weeks 14 and 30. IFX drug levels of 9.25 µg/mL at Week 2 and 7.25 µg/mL at Week 6 were the best predictors of fistula response. Conclusion: High IFX trough levels during induction are associated with favorable fistula response to anti-TNF treatment. If validated in a larger prospective study, our findings may help guide anti-TNF treatment in patients with perianal CD, and suggest serum level–guided treatment escalation in non-responders or prompt changing of biologic treatment in non-responders. [ABSTRACT FROM AUTHOR]

Introduction and Aims: As inflammatory bowel diseases [IBD] affect female patients almost exclusively during their reproductive age, issues related to fertility, fecundity, pregnancy, delivery, and lactation are of utmost importance. Lack of education and misconceptions regarding the effect of disease and/or treatment on reproductive outcome may lead to voluntary childlessness and/or development of unwanted cervical pathologies which may impact tremendously on patients' welfare and quality of life. The aims of this study were to assess the perspectives of IBD patients on fertility, pregnancy and its outcomes, and lactation, as well as their awareness of human papillomavirus [HPV]-related pathologies and screening for cervical cancer. Methods: This prospective study was performed across nine different Mediterranean IBD centres between 2014 and 2015 and included consecutive female IBD patients between the ages of 16 and 50 years. All patients responded to a questionnaire based on ECCO guidelines. Results: A total of 348 IBD female patients with a mean age of 37.4 (standard deviation [SD] ± 2.1) years were recruited; 50% had a diagnosis of ulcerative colitis, 49.4% had Crohn`s disease, and 0.6% patients had a diagnosis of indeterminate colitis [IC]. A significant proportion of patients [ > 60%] were afraid that IBD may lead to a complicated pregnancy and that the disease itself and/or its medications can cause fetal harm. Patients had similar concerns that IBD can be transmitted to their offspring as well as with regard to breastfeeding. Counselling from health care professionals with regard to fertility, pregnancy, and lactation was associated positively with the highest number of pregnancies and inversely with the lowest number of patients who considered voluntary childlessness [p < 0.0001]. Patients with a higher level of education were more likely to get pregnant [p = 0.004]. There was a low uptake of the HPV vaccine. However, there was a reasonably good uptake of cervical cancer screening. Conclusion: Our study demonstrates that women with IBD have misperceptions about fertility, pregnancy, and health maintenance. We also show that education by physicians has a positive influence. We thus conclude that improved multidisciplinary approaches should be used to educate and implement European guidelines for women with IBD. [ABSTRACT FROM AUTHOR]

Background and aims: The classification of Crohn's disease (CD) is usually determined at initial diagnosis and is frequently based on ileocolonoscopic and cross-sectional imaging data. Advanced endoscopic and imaging techniques such as small-bowel video capsule endoscopy (VCE) and magnetic resonance enterography (MRE) may provide additional data regarding disease extent and phenotype. Our aim was to examine whether VCE or MRE performed after the initial diagnosis may alter the original disease classification. Methods: Consecutive patients with known small-bowel CD in clinical remission or mild disease were prospectively recruited and underwent MRE and VCE (if small-bowel patency was confirmed by a patency capsule (PC). Montreal classifications before and after evaluation were compared. Results: Seventy-nine patients underwent MRE and VCE was performed in 56. Previously unrecognized disease locations were detected with VCE and MRE in 51 and 25%, respectively (p < 0.01) and by both modalities combined in 44 patients (55%). Twenty-two patients (27%) were reclassified as having an advanced phenotype (B2/B3). MRE and VCE reclassified the phenotype in 26 and 11% of cases, respectively (p < 0.05). Overall, both modalities combined altered the original Montreal classification in 49/76 patients (64%). Conclusion: VCE and MRE may lead to reclassification of the original phenotype in a significant percentage of CD patients in remission. VCE was more sensitive for detection of previously unrecognized locations, while MRE was superior for detection of phenotype shift. The described changes in the disease classification may have an important impact on both clinical management and long-term prognosis in these patients. [ABSTRACT FROM AUTHOR]

Background and aims: Primary sclerosing cholangitis (PSC) is a rare chronic progressive cholestatic disorder. We assessed its characteristics and natural history in Israel and compared its outcome with respect to coexisting inflammatory bowel disease (IBD). Methods: Data on characteristics, course and outcome were retrospectively retrieved on patients diagnosed with PSC from five large Israeli medical centers between 1988 and 2012. Patients with isolated PSC were compared with those with coexisting IBD to identify predictors of outcome. Results: Of 141 patients (56% males) with confirmed PSC. 98 (69.5%} had coexisting IBD. The average age at presentation was 38.8±15.4 years and duration of follow-up was 7.93±6.26 years. The crude estimated point prevalence was 4 cases per 106 persons. Demographics and clinical characteristics were similar among all patients except for symptoms at diagnosis (which were more prevalent among PSC-IBD patients) and utilization of multiple diagnostic modalities (which was more prevalent among isolated-PSC patients). More than one-third of the entire cohort had cirrhosis. A total of 15 patients (10.6%) died and 19 patients (13.5%) developed malignancy during follow-up. Nine patients (6.3%) underwent liver transplantation. Mean survival for the entire cohort was 26.3+1.4 years and mean transplant-free survival was 23.5±1.6 years. Cox proportional-hazard regression for transplantation or death revealed two independent risk factors: cirrhosis and malignancy [hazard ratio 4.25 (p = 0.004) and 2.58 (p = 0.046), respectively]. Conclusions: Survival rate of PSC patients in Israel is longer than reported rates worldwide and is independent of coexisting IBD. [ABSTRACT FROM AUTHOR]

Background and aims Combination therapy with infliximab and azathioprine has been shown to be superior to either treatment alone in Crohn's disease (CD). However, the benefit of combining adalimumab with an immunomodulator remains controversial. The aim of this study was to compare the efficacy of adalimumab monotherapy with combination therapy for induction and maintenance of response and remission in CD using a meta-analysis of the current literature. Methods We performed a systematic literature search using Medline, Embase, Cochrane and several other databases. Prospective randomized controlled trials, retrospective cohort and case-controlled studies were included. The primary outcomes included induction of response and remission (up to week 12), maintenance of clinical response and remission (1 year) and the need for dose escalation. Several subgroup and sensitivity analyses were performed. Results Eighteen out of 2743 retrieved studies were included. A meta-analysis of 7 studies assessing induction of remission (n = 1984) showed that ADA monotherapy was inferior to combination therapy [OR = 0.78 (0.64–0.96), p = 0.02]. A meta-analysis of 4 studies revealed that combination therapy was not statistically different from ADA for maintenance of remission [OR = 1.08 (0.79–1.48), p = 0.48]. Combination therapy was also not different from ADA monotherapy in terms of requirement for dose escalation [OR = 1.13 (0.69–1.85), p = 0.62]. Conclusions Combination therapy with ADA and immunomodulator was mildly superior to ADA monotherapy for induction of remission in CD. The rate of remission at 1 year and the need for dose escalation were similar in both groups. These findings should be interpreted with caution in view of possible confounders and should be further validated by randomized controlled trials. [ABSTRACT FROM AUTHOR]