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BACKGROUND: Endoscopic and histologic healing are emerging as new therapeutic goals in ulcerative colitis (UC), as these endpoints are associated with less relapse, hospitalization and colectomy. AIM: We investigated the association of serum infliximab trough concentrations during maintenance therapy with endoscopic or histologic healing in UC. METHODS: In this multi-center retrospective cohort study, we included consecutive patients with moderate-to-severe UC on infliximab maintenance therapy who had an endoscopic evaluation and underwent therapeutic drug monitoring within three months of the colonoscopy, between February 2008 and March 2016. Per event analysis was performed. Endoscopic healing was defined as Mayo endoscopic sub-score of ≤1. Histologic healing was defined as no or only focal mild active inflammation. RESULTS: Seventy colonoscopies from 56 patients were evaluated. Infliximab trough concentrations (median [interquartile range]) were significantly higher in patients with endoscopic (11.3 [7.6–14.5] vs. 6.3 [0–9.8] μg/mL, p

OBJECTIVE Low serum infliximab concentrations are associated with an increased risk of loss of response in inflammatory bowel disease (IBD). The objective of this study was to evaluate the test characteristics of C-reactive protein (CRP) in identifying low serum infliximab concentrations in patients with IBD. METHODS We measured serum infliximab concentrations and CRP levels in patients who experienced deteriorating symptoms while on infliximab (the reactive cohort). Receiver operating characteristic (ROC) curves were used to determine the CRP concentration threshold that identified an infliximab concentration

SummaryBackground Guidelines published by the international gastroenterology societies establish standards of care and seek to improve patient outcomes. Aim We examined inflammatory bowel disease guidelines (IBD) for quality of evidence, methods of grading evidence and conflicts of interest (COI). Methods All 182 guidelines published by the American College of Gastroenterology, American Gastroenterological Association, British Society of Gastroenterology, Canadian Association of Gastroenterology, Crohn's and Colitis Foundation of America and European Crohn's and Colitis Organisation as of 27 September 2012 were reviewed. Nineteen IBD guidelines were found. Results Eighty-nine per cent (n = 17/19) of the guidelines graded the levels of evidence using seven different systems. Of the 1070 recommendations reviewed, 23% (n = 249) cited level A evidence; 28% (n = 302) level B; 36% (n = 383) level C and 13% (n = 136) level D. The mean age of the guidelines was 4.2 years. In addition, 61% (n = 11/19) of the guidelines failed to comment on COI. All eight articles commenting on COI had conflicts with 81% (n = 92/113) of authors reported an average 11.7 COI. Lastly, there were variations in the recommendations between societies. Conclusions Nearly half the IBD guideline recommendations are based on expert opinion or no evidence. Majority of the guidelines fail to disclose any COI, and when commenting, all have numerous COI. Furthermore, the guidelines are not updated frequently and there is a lack of consensus between societal guidelines. This study highlights the critical need to centralize and redesign the guidelines development process.

SummaryBackground While the Crohn's disease activity index (CDAI) is the gold standard for defining clinical endpoints in Crohn's disease (Crohn's) clinical trials, its ability to distinguish symptoms due to inflammation from those that are non-inflammatory has been questioned. Aim To compare CDAI scores in patients with Crohn's and those with Irritable Bowel Syndrome (IBS). Methods This was a prospective, cross-sectional cohort study of 91 patients with either Crohn's (n = 44) or IBS (n = 47). Total CDAI and individual component scores were recorded and comparisons were made between Crohn's and IBS patients. Results Mean CDAI scores were higher in the IBS patients (183 vs. 157, P = 0.1). Sixty-two per cent (n = 29) of IBS patients had CDAI scores greater than 150. Mean CDAI haematocrit score (35.9 vs. 23.0, P = 0.02) and CRP level (6.8 vs. 2.0, P = 0.002) were higher in the Crohn's group. Analysis of CDAI sub-scores demonstrated that IBS patients had significantly higher pain (mean 1.7 vs. 0.8, P = 0.0007) and well-being scores (mean 1.2 vs. 0.8, P = 0.04) relative to patients with Crohn's. Specifically evaluating patients with CDAI greater than 150 (n = 51), IBS patients had higher pain sub-scores (mean 2.4 vs. 1.4, P = 0.002), whereas patients with Crohn's had higher CRP (mean 8.4 vs. 1.8, P = 0.001). Conclusions Our study demonstrates that the CDAI does not discriminate patients with symptoms due to active Crohn's from patients with IBS. Patients with IBS can have CDAI scores in the clinically meaningful range. Objective measures, such as CDAI haematocrit score and CRP, are more specific markers of inflammation.

Purinergic signaling and associated ectonucleotidases, such as CD39 and CD73, have been implicated in the pathogenesis of inflammatory bowel disease (IBD). CD39 is known to be a Treg memory cell marker, and here we determine the phenotype and function of CD73+CD4+ T lymphocytes in patients with IBD. We describe elevated levels of CD73+CD4+ T cells in the peripheral blood and intestinal lamina propria of patients with active IBD. The functional phenotype of these CD73+CD4+ T cells was further determined by gene expression, ecto-enzymatic activity, and suppressive assays. Increased numbers of CD73+CD4+ T cells in the periphery and lamina propria were noted during active inflammation, which returned to baseline levels following anti-TNF treatment. Peripheral CD73+CD4+ T cells predominantly expressed CD45RO, and were enriched with IL-17A+ cells. The CD73+CD4+ cell population expressed higher levels of RORC, IL-17A, and TNF, and lower levels of FOXP3 and/or CD25, than CD73−CD4+ T cells. Expression of CD73 by peripheral CD4+ T cells was increased by TNF, and decreased by an anti-TNF monoclonal antibody (infliximab). In vitro, these peripheral CD73+CD4+ T cells did not suppress proliferation of CD25− effector cells, and expressed higher levels of pro-inflammatory markers. We conclude that the CD73+CD4+ T-cell population in patients with active IBD are enriched with cells with a T-helper type 17 phenotype, and could be used to monitor disease activity during treatment.

Aliment Pharmacol Ther 2011; 34: 1318–1327 Summary Background Anti-tumour necrosis factor (TNF) antibodies are used to treat both psoriasis and inflammatory bowel disease. The seemingly paradoxical occurrence of psoriasis in patients treated with anti-TNF antibodies is increasingly recognised, but the distinct features associated with inflammatory bowel disease have been incompletely characterised. Aim To identify inflammatory bowel disease patients who developed psoriasis while receiving an anti-TNF antibody at two academic medical centres between 2000 and 2009 and review all published cases of this phenomenon in inflammatory bowel disease. Methods We identified retrospectively all cases of anti-TNF-induced psoriasis in inflammatory bowel disease patients attending two North American healthcare centres. We analysed these cases alongside the published reports of anti-TNF-induced psoriasis. Results We identified 30 subjects who developed a psoriatic rash while receiving anti-TNF therapy for inflammatory bowel disease. Forty-seven per cent (14/30) responded to topical therapy and 23% (7/30) ultimately discontinued the anti-TNF. The new data were combined with those from 120 published cases of anti-TNF-induced psoriasis in inflammatory bowel disease. Anti-TNF-induced psoriasis in inflammatory bowel disease was more common in women (70%). The most common distributions were palmoplantar (43%) and scalp (42%). Complete follow-up in 148 cases showed that 41% responded to topical therapy but 43% required definitive withdrawal of anti-TNF therapy due to the rash. A second anti-TNF was tried in 27 cases with recurrence or persistence of the rash in 14 (52%). Conclusions In this analysis, psoriasiform lesions related to anti-TNF therapy in inflammatory bowel disease occurred most commonly in women. Approximately 41% of those who developed psoriasis while on anti-TNFs responded to topical therapy and were able to continue the drug, while 52% of those treated with an alternate anti-TNF had recurrence of the rash.

Summary Background Little is known about long-term outcomes in patients who experience infusion reactions while receiving infliximab. Aim To investigate long-term outcomes in patients who experience infusion reactions while receiving infliximab. Methods Retrospective electronic chart review of long-term clinical outcomes. Results Clinical data on 287 patients who received infliximab infusions for Crohn’s disease were reviewed, of whom 51 developed at least one infusion reaction (18%). Ileo-colonic disease (OR 2.2, 95% CI 1.1–4.4) and episodic infliximab (OR 2.4, 95% CI 1.2–4.7) were associated with a higher risk of infusion reactions in univariate analysis, but concomitant azathioprine/mercaptopurine therapy at the initiation of infliximab was associated with a reduced risk (OR 0.4, 95% CI 0.2–0.8). Only the effect of concomitant immunomodulators persisted on multivariate analysis. Patients who experienced infusion reactions were less likely to be in remission at 1 year (OR 0.6, 95% CI 0.3–1.2), 2 years (OR 0.4, 95% CI 0.2–0.8, P = 0.01), or 5 years (OR 0.4, 95% CI 0.1–1.3) and more likely to require surgery (OR 2.2, 95% CI 1.1–4.1, P = 0.01) than those who did not experience such reactions. Conclusions Patients who experienced infusion reactions to infliximab had a high rate of discontinuation of therapy in this cohort. Concomitant immunomodulators and maintenance therapy reduced the risk of infusion reactions.

Background Recurrence of Crohn's disease is common after intestinal resection. A number of agents have been studied in controlled trials with the goal of reducing the risk of endoscopic or clinical recurrence of Crohn's disease following surgery. Objectives To undertake a systematic review of the use of medical therapies for the prevention of post-operative recurrence of Crohn's disease Search methods MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials (CENTRAL) were searched to identify relevant studies. References from selected papers and abstracts from Digestive Disease Week were also searched. Selection criteria Randomised controlled trials that compared medical therapy to placebo or other medical agents for the prevention of recurrence of intestinal Crohn's disease were selected for inclusion. Data collection and analysis Two authors reviewed all abstracts containing search terms, and those meeting inclusion criteria were selected for full data abstraction. Dichotomous data were summarised using relative risk and 95% confidence intervals. A fixed-effects model was used, and sensitivity analysis performed. Main results Twenty-three studies were identified for inclusion. Probiotics were not superior to placebo for any outcome measured. The use of nitroimidazole antibiotics appeared to reduce the risk of clinical (RR 0.23; 95%CI 0.09 to 0.57, NNT=4) and endoscopic (RR 0.44; 95%CI 0.26 to 0.74, NNT = 4) recurrence relative to placebo. However, these agents were associated with higher risk of serious adverse events (RR 2.39, 95% CI 1.5 to 3.7). Mesalamine therapy was associated with a significantly reduced risk of clinical recurrence (RR 0.76; 95% CI 0.62 to 0.94, NNT = 12), and severe endoscopic recurrence (RR 0.50; 95% CI 0.29 to 0.84, NNT = 8) when compared to placebo. Azathioprine/6MP was also associated with a significantly reduced risk of clinical recurrence (RR 0.59; 95% CI 0.38 to 0.92, NNT = 7), and severe endoscopic recurrence (RR 0.64; 95% CI 0.44 to 0.92, NNT = 4), when compared to placebo. Neither agent had a higher risk than placebo of serious adverse events. When compared to azathioprine/6MP, mesalamine was associated with a higher risk of any endoscopic recurrence (RR 1.45, 95% CI 1.03 to 2.06), but a lower risk of serious adverse events (RR 0.51; 95% CI 0.30 to 0.89). There was no significant difference between mesalamine and azathioprine/6MP for any other outcome. Authors' conclusions There are insufficient randomised controlled trials of infliximab, budesonide, tenovil and interleukin-10 to draw conclusions. Nitro-imidazole antibiotics, mesalamine and immunosuppressive therapy with azathioprine/6-MP or infliximab all appear to be superior to placebo for the prevention of post-operative recurrence of Crohn's disease. The cost, toxicity and tolerability of these approaches require careful consideration to determine the optimal approach for post-operative prophylaxis.

contrast, more objective measures, such as C-reactive protein (CRP) and haematocrit score, were, as one would predict, higher in Crohn’s patients. It is important to note that one half of all Crohn’s patients in this study appeared to be ‘active’ so one must be cautious in interpreting the application of their findings to Crohn’s patients in true remission. So where does this leave us? First and foremost, CDAI was never designed as a diagnostic tool for Crohn’s disease; to suggest otherwise is to erect a straw man. Its value lies in assessing the patient’s symptomatic response to treatment (we are, after all, treating patients, not blood tests or radiological images alone), but seems incapable, when expressed as a total score, of differentiating IBS from IBD; again no surprise. We contend that ‘IBStype symptoms’ in IBD should be regarded as representing IBD activity until proven otherwise. 6 In most instances, the differentiation is obvious; when uncertainty persists, sensitive biomarkers such as faecal calprotectin may be helpful.