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Summary Background In a phase 2 study, mongersen, an oral antisense oligonucleotide targeting Smad7, was effective in inducing clinical remission in approximately 60% of patients with active Crohn's disease (CD). Aim In a post hoc analysis to evaluate those patient disease characteristics that may have influenced the efficacy and safety of mongersen therapy. Methods Patients with steroid‐dependent/resistant, active CD were randomised to mongersen 10, 40 or 160 mg/day or placebo for 2 weeks; patients were followed for 10 weeks. Clinical remission [Crohn's Disease Activity Index (CDAI) score 260. Additional patient baseline and disease characteristics were explored. Results Clinical remission and response rates were significantly higher in patients receiving mongersen 40 and 160 mg/day but not 10 mg/day vs. placebo and independent of disease duration and hsCRP. Patients with baseline CDAI ≤260 had significantly higher remission rates with 40 and 160 mg/day. In patients with baseline CDAI >260, remission rates were statistically greater with 160 mg/day and numerically better with 40 mg/day vs. placebo. Adverse event rates were similar across treatment groups. Mongersen was safe and well tolerated. Conclusions Patients with higher CDAI scores achieved clinical remission most frequently with the highest mongersen dose. Disease duration and baseline human serum C‐reactive protein did not appear to significantly impact efficacy of mongersen in this study (EudraCT Number: 2011‐002640‐27.)

Aliment Pharmacol Ther 2011; 34: 1088–1097 Summary Background Ulcerative colitis (UC) is characterised by impaired fatty-acid oxidation; l-carnitine has a key role in fatty-acid metabolism and short-chain fatty acids such as butyrate and propionate are important energy source for intestinal epithelial cells. Aim To evaluate efficacy and safety of colon-release propionyl-l-carnitine (PLC) in patients with mild-to-moderate UC receiving stable oral aminosalicylate or thiopurine therapy. Methods In a multicentre, phase II, double-blind, parallel-group trial, patients were randomised to receive PLC 1 g/day, PLC 2 g/day or placebo. Main inclusion criteria were as follows: age 18–75; disease activity index (DAI) score 3–10 inclusive, be under oral stable treatment with aminosalicylate or thiopurine. The primary endpoint was clinical/endoscopic response, defined as a decrease in DAI score ≥ 3 points or remission, defined as a DAI score ≤ 2 with no individual sub-score > 1. Results Of 121 patients who were randomised, 57 of 79 (72%) patients receiving PLC (combined 1 g and 2 g cohort) had a clinical/endoscopic response vs. 20 of 40 (50%) receiving placebo (P = 0.02). Specifically, in PLC 1 g/day group, 30 of 40 (75%) patients had clinical/endoscopic response (P = 0.02 vs. placebo) and 27 of 39 (69%) in the PLC 2 g/day group (P = 0.08 vs. placebo). Rates of remission were 22/40 (55%), 19/39 (49%), 14/40 (35%) in the PLC 1 g, PLC 2 g, and placebo groups, respectively. PLC had a similar safety profile to placebo; the most common adverse events were gastrointestinal. Conclusion Propionyl-l-carnitine 1 g/day should be investigated further as a co-treatment for mild-to-moderate ulcerative colitis (NCT-01026857).

Aliment Pharmacol Ther 2011; 34: 724–734 Summary Background Inflammatory bowel disease (IBD) frequently affects women during their reproductive years. Pregnancy outcome in women with IBD is well described, particularly in retrospective studies. Aim To evaluate the pregnancy outcome in patients with IBD in a prospective European multicentre case-control study. Methods Inflammatory bowel disease pregnant women from 12 European countries were enrolled between January 2003 and December 2006 and matched (1:1) to non-IBD pregnant controls by age at conception and number of previous pregnancies. Data on pregnancy and newborn outcome, disease activity and therapy were prospectively collected every third month using a standard questionnaire. Logistic regression analysis with odds ratio was used for statistical analyses. P value

Summary Background Approximately 20% of patients with ulcerative colitis have a chronic active disease often requiring several courses of systemic steroids in order to achieve remission, but followed by relapse of symptoms during steroid tapering or soon after their discontinuation. Although short term control of symptoms can be achieved with steroid treatment, this pattern of drug response, known as steroid-dependency, leads to important complications of the treatment, while a significant proportion of patients requires colectomy. Aim To review the studies currently available specifically evaluating the management of steroid-dependent ulcerative colitis. Results The clinical and biological mechanisms of steroid-dependency are not well understood compared with those determining steroid-refractoriness. Very few evidence-based data are available concerning the management of patients with steroid-dependent ulcerative colitis. The therapeutic role of aminosalicylates, thiopurines, methotrexate, infliximab, leukocyte apheresis and other drugs in the treatment of steroid-dependent ulcerative colitis are evaluated. Conclusions Outcomes of studies in steroid-refractory patients may not be applicable to steroid-dependency. Trials are needed to define the correct approaches and new strategies to ameliorate the therapy of steroid-dependent ulcerative colitis.

Summary Aim : To establish whether intestinal ultrasound, clinical or biochemical indices of activity can assess histological features of ileal stenosis in Crohn's disease. Methods : In 43 patients undergoing surgery for a single ileal stenosis, clinical and biochemical parameters, as well as intestinal ultrasound, were assessed prior to surgery. The echo pattern of thickened bowel segments at the site of stenosis was classified as hypoechoic, stratified or mixed (segments with/without stratification). During surgery, stenoses were identified, resected and then histologically examined using standardized criteria. Results : Clinical and biochemical indices of activity showed an overall weak positive correlation with histological inflammatory parameters and a negative correlation with fibrosis. The intestinal ultrasound echo pattern at the stenosis site was stratified in 25 patients, hypoechoic in 14 and mixed in four. Stenoses characterized by a stratified echo pattern showed a significantly higher degree of fibrosis, those characterized by hypoechoic echo pattern showed a higher degree of inflammation, while stenoses with a mixed echo pattern showed high degrees of both fibrosis and inflammation. Conclusion : Ultrasound and, to a lesser degree, clinical and laboratory indices discriminate between inflammatory and fibrotic ileal stenoses complicating Crohn's disease, thus allowing appropriate medical and/or surgical treatment to be defined.

Background : The efficacy of sulphasalazine and mesalazine in preventing relapse in patients with ulcerative colitis is well known. It is less clear how long such maintenance should be continued, and if the duration of disease remission is a factor that affects the risk of recurrence. Aim : To determine whether the duration of disease remission affects the relapse rate, by comparing the efficacy of a delayed-release mesalazine (Asacol, Bracco S.p.A., Milan, Italy) against placebo in patients with ulcerative colitis with short- and long-duration of disease remission. Methods : 112 patients (66 male, 46 female, mean age 35 years), with intermittent chronic ulcerative colitis in clinical, endoscopic and histological remission with sulphasalazine or mesalazine for at least 1 year, were included in the study. Assuming that a lower duration of remission might be associated with a higher relapse rate, the patients were stratified according to the length of their disease remission, prior to randomization into Group A (Asacol 26, placebo 35) in remission from 1 to 2 years, or Group B (Asacol 28, placebo 23) in remission for over 2 years, median 4 years. Patients were treated daily with oral Asacol 1.2 g vs. placebo, for a follow-up period of 1 year. Results : We employed an intention-to-treat analysis. In Group A, whilst no difference was found between the two treatments after 6 months, mesalazine was significantly more effective than placebo in preventing relapse at 12 months [Asacol 6/26 (23%), placebo 17/35 (49%), P = 0.035, 95% Cl: 48–2.3%]. In contrast, in Group B no statistically significant difference was observed between the two treatments, either at 6 or 12 months [Asacol 5/28 (18%), placebo 6/23 (26%), P = 0.35, 95% Cl: 31–14%] of follow-up. Patients in group B were older, and had the disease and remission duration for longer, than those in Group A. Conclusions : Mesalazine prophylaxis is necessary for the prevention of relapse by patients with ulcerative colitis in remission for less than 2 years, but this study casts doubt over whether continuous maintenance treatment is necessary in patients with prolonged clinical, endoscopic and histological remission, who are at very low risk of relapse.