Background Robust and sensitive therapeutic targets are key in effective management of Inflammatory Bowel Disease1. Mesenteric hyperaemia is a recognized sign of active disease and in cross-sectional image is described as the comb sign. Although it is subjectively described, no automated quantitative MRI-based measures have been developed. We aim to develop an automated methodology using contrast-less time of flight (TOF) Magnetic resonance angiography (MRA). Methods A MATLAB algorithm was developed to track the vessels on a 3D maximum intensity projection of a TOF MRA data set and calculate an arborization Index which is the number of branching points in the intrabdominal vessels (figure 1). 2D TOF scans were acquired in the transverse plane between the top of the hip joint and L4 vertebra using a 3T Ingenia Wide bore scanner (Philips, The Netherlands). The primary outcome was a comparison of the arborization index between Crohn’s disease (CD) and healthy volunteers (HV) groups. A planned sub-analysis was undertaken across CD and HV matched for BMI to investigate the effect of visceral fat on the arborization index. Repeated measures were undertaken to evaluate the variability of the quantification method. No contrast agents were used for the TOF MRA scans. Biological variations within each group and test-retest repeatability were assessed using the coefficient of variation (CV). Statistical analysis with unpaired, two-tailed t-tests were conducted and differences were considered significant when the p-value ≤0.05. All absolute values are presented as mean ±standard deviation (SD). Results In this prospective pilot study, 7 CD patients (C-Reactive Protein=5.2±6.1 mg/L, Faecal Calprotectin 611±981μg/g, BMI=23±3 kg/m2) and 15 HVs (BMI=29±7 kg/m2) were recruited. Patients showed a significantly higher arborization index when compared to HVs (mean arborization in HV=94±21 and CD=139±26; p-value=0.002). The difference in arborization index persisted in a sub-analysis of 7 HVs (BMI=24±2 kg/m2) and 7 CD patients (mean arborization in matched HVs=101±22 vs mean index in CD=139±26; p=0.01) (Figure 2). The CV was 23% for HVs and 18% for CD indicating biological variation. Test-retest variability calculated from multiple TOF scans of the same subjects gave a mean CV of 6±5% for both groups combined. Conclusion Our preliminary data suggest that the arborization index may be a useful measure of hypervascularity and hence intestinal inflammation in Inflammatory Bowel Disease. Further validation to standard disease activity measures is needed across larger cohorts to better investigate the utility of this potential biomarker as a non-invasive measure of disease activity and its reversibility to IBD therapies. Reference 1.Turner,D.,et al.Gastro.2021;160(5):1570–1583.

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Background Infliximab is a monoclonal antibody that binds and neutralizes tumour necrosis factor-alpha, which is present in high levels in the blood serum, mucosa and stool of patients with Crohn’s disease (CD). We sought to determine the effectiveness and safety of infliximab in inducing remission in patients with CD. Methods On 31 August 2021, we searched CENTRAL, CINAHL, ClinicalTrials.gov, Embase, MEDLINE, and WHO ICTRP with no language, date, publication status, or document type limitations. We included randomized controlled trials (RCTs) in which infliximab was compared to placebo or another active comparator in adult (18 and over) patients with active CD. The review authors independently conducted data extraction and ‘Risk of bias’ assessment of the included studies. We expressed dichotomous and continuous outcomes as risk ratios and mean differences with 95% confidence intervals. We assessed the certainty of the evidence using GRADE methodology. The primary outcome was the proportion of patients who achieved clinical remission. Results We included 9 RCTs (1130 participants). Three studies compared multiple arms with different infliximab doses (between 5mg and 20mg/kg) to placebo. Two studies each with three arms compared azathioprine and placebo, infliximab and placebo, or infliximab and azathioprine combined. One study compared infliximab with biosimilar CT-P13. One study compared infliximab and azathioprine with steroids and azathioprine and only infliximab if no response. The final study compared a single dose (5mg/kg) of infliximab to placebo. In all trials that didn’t require a purine analogue to be given to both study groups, they allowed such concomitant use in both groups. There is evidence that infliximab combined with azathioprine is superior to azathioprine combined with placebo in inducing clinical remission for CD (RR 1.97, 95% CI 1.60–2.42, moderate certainty evidence downgraded due to risk of bias, NNT = 3). Sensitivity analysis considering a fixed effects model and then removing a study where most received azathioprine in both groups instead of all, had no impact on the result, which remained significant. There is evidence that there may be no difference in withdrawals from adverse events between infliximab combined with azathioprine and azathioprine combined with placebo when inducing clinical remission for CD (RR 0.74, 95% CI 0.29–1.86, low certainty evidence downgraded due to serious imprecision). The evidence is uncertain for all other comparisons and outcomes due to imprecision from small sample sizes. Conclusion There is evidence that infliximab with azathioprine is probably better than azathioprine, however the remaining data is based on limited total patient numbers and offers limited scope for meta-analysis.