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Contains fulltext : 220068.pdf (Publisher’s version ) (Closed access), BACKGROUND: Ustekinumab is effective in Crohn's disease. However, a substantial proportion of patients will not respond or lose response to ustekinumab. The current evidence to support the effectiveness of dose-optimisation for ustekinumab nonresponse is limited. AIM: To assess the effectiveness of dose escalation of ustekinumab. METHODS: This was a multicentre retrospective cohort study. We included active Crohn's disease patients who received a standard-dose intravenous induction and at least one subcutaneous ustekinumab 90 mg dose. All enrolled patients received dose escalation by either shortening the interval between the doses to every 4 or 6 weeks, intravenous reinduction or a combination of strategies. The primary outcome of the study was clinical response at week 16 after dose escalation. RESULTS: A total of 142 patients (22 centres/14 countries) were included. The patients were dose-escalated after a median treatment duration of 30 weeks. At week 16 from escalation, 73/142 (51.4%) responded to treatment, including 55/142 (38.7%) in clinical remission. Corticosteroid-free remission was achieved in 6/34 (17.6%) patients on corticosteroids at the time of escalation; 118/142 (83%) continued treatment beyond week 16. Follow-up data beyond week 16 were available for 74/118 (62.7%) patients. On the last follow-up, 51/98 (52%) patients with available data responded to treatment, including 41/98 (42%) in clinical remission. CONCLUSIONS: Intensification of ustekinumab maintenance dosage was effective in over 50% of the patients. This strategy should be considered in patients who are nonresponsive to every 8 weeks ustekinumab maintenance dosing.

Thiopurines (TP) represent an important therapeutic tool for the treatment of inflammatory bowel diseases (IBD) in the current situation of rising incidence and health care costs. The results of multiple clinical studies aimed at finding correlations between levels of TP metabolites and response of IBD patients to the treatment are, however, often controversial due to variability in analytical and sample preparation procedures among these studies. In this work, therefore, an updated analytical and sample preparation procedure for therapeutic drug monitoring (TDM) of TP metabolites in blood samples obtained from patients with IBD was proposed to establish a unified protocol. An advanced analytical method based on ion-exchange liquid chromatography hyphenated with tandem mass s

Objective Antitumour necrosis factor (TNF) during pregnancy in patients with IBD is related to high fetal anti-TNF levels. We evaluated maternal and child safety on discontinuing anti-TNF in the second trimester of pregnancy. Design Two groups of women with IBD were prospectively followed-up during pregnancy: women in sustained remission stopped anti-TNF before week 25 (stop group) and the remaining group continued anti-TNF beyond week 30 (continue group). Maternal, birth and 1-year child outcomes were compared with children of non-IBD women. Results Overall, 106 patients with 83 completed pregnancies were included. Relapse rate after week 22 did not differ between the stop (n=51) and continue (n=32) groups (5 (9.8%) versus 5 (15.6%), p=0.14). There was no difference in allergic reactions (p=1.00) or loss of response (p=1.00) postpartum between the two groups. Birth outcomes were comparable. Infants from both groups had lower birth weight (p=0.001), shorter gestational term (p=0.0001), were more often delivered via caesarean section (p=0.0001) and were less often breastfed (p=0.0001) compared with infants from non-IBD controls. Growth, infection rate, allergies, eczema and adverse reactions to vaccines were comparable across the stop and the continue groups as well as the children of anti-TNF-exposed and non-IBD women at 1 year. Conclusions To limit anti-TNF exposure in utero, anti-TNF can be stopped safely in the second trimester in women with IBD in sustained remission. In patients not in sustained remission, anti-TNF may be continued without clear additional risks to the fetus. We observed excellent 1-year child outcomes compared with children from non-IBD controls.

Introduction: Women with inflammatory bowel disease [IBD] have a higher risk of undergoing gastrointestinal [GI] endoscopy during pregnancy than healthy women. Data on endoscopic procedures during pregnancy in IBD women are limited. The aim of this study was to investigate the safety of lower GI endoscopy during pregnancy in IBD women. Methods: All consecutive IBD women who underwent endoscopy during pregnancy [cases] from 2008-2014 were prospectively included. Cases were matched 1:1 on age, IBD medication, and disease activity with pregnant IBD patients without endoscopy during pregnancy [controls]. Maternal and neonatal outcomes were compared between the

Background: To describe the clinical characteristics of inflammatory bowel disease (IBD) at diagnosis in Netherlands at the population level in the era of biologics. Methods: All patients with newly diagnosed IBD (diagnosis made between January 1, 2006 and January 1, 2007) followed in 9 general hospitals in the southwest of the Netherlands were included in this population-based inception cohort study. Results: A total of 413 patients were enrolled, of which 201 Crohn's disease (CD) (48.7%), 188 ulcerative colitis (UC) (45.5%), and 24 IBD unclassified (5.8%), with a median age of 38 years (range, 14-95). Seventy-eight patients with CD (38.8%) had ileocolonic disease and 73 patients (36.3%) had pure colonic disease. In 8 patients (4.0%), the upper gastrointestinal tract was involved. Nineteen patients with CD (9.5%) had perianal disease. Thirty-nine patients with CD (19.4%) had stricturing phenotype. Of the patients with UC and IBDU, 39 (18.4%) suffered from pancolitis and 61 (29%) from proctitis. Severe endoscopic lesions at diagnosis were seen in 119 patients (28.8%, 68 CD, 49 UC, and 2 IBDU), whereas 98 patients (23.7%) had severe histological disease activity. Thirteen patients (3.1%, 10 CD and 3 UC) had extraintestinal manifestations at diagnosis. Twenty-three patients (5.6%, 20 CD and 3 UC) had fistula at diagnosis. Conclusions: In this cohort, 31% of the patients with CD had complicated disease at diagnosis, 39% had ileocolonic disease, 9.5% had perianal disease, and in 4% the upper gastrointestinal tract was involved. Most patients with UC suffered from left-sided colitis (51%). Severe endoscopic lesions were reported in 34% of the patients with CD and 26% of the patients with UC. Three percent of the patients with IBD had extraintestinal manifestations. Copyright

No one would argue that men and women differ. The differences between the sexes are obvious and affect every aspect of life. The biological grounds for these differences are determined by the complementary yet distinct roles of the two sexes in the process of procreation. The success of human reproduction is related to the very efficient selection process for the proper genetic material that will, after 40 weeks of intense physical investme

Background: Adalimumab is an effective treatment in patients with Crohn's disease; as it is a humanized anti-tumour necrosis factor monoclonal antibody, immunogenicity is thought not to be of any significance. Aim: To assess whether antibodies to adalimumab (ATAs) affect adalimumab treatment outcome in patients with Crohn's disease previously treated with infliximab. Methods: A retrospective study was pe