Medical treatment of chronic inflammatory bowel diseases: clinical and pharmacokinetic aspects, with emphasis on 5-aminosalicylic acid delivering drugs

Contains fulltext : mmubn000001_118419005.pdf (publisher's version ) (Open Access)Promotores : J. van Tongeren en P. van Hees175 p

Phenotype of inflammatory bowel disease at diagnosis in the Netherlands: A population-based inception cohort study (the Delta Cohort)

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. Copyrigh

Benefit of earlier anti-TNF treatment on IBD disease complications?

Background: Anti-tumour necrosis factor [anti-TNF] treatment was demonstrated to have disease-modifying abilities in inflammatory bowel disease [IBD]. In this study, we aimed to determine the effect of anti-TNF treatment timing on IBD disease complications and mucosal healing [MH]. Methods: The following IBD-related complications were tested in relation to timing of anti-TNF therapy start in newly diagnosed IBD patients [n = 413]: Fistula formation, abscess formation, extra-intestinal manifestations [EIM], surgery, referral to academic centre, and MH. Results: A total of 85 patients [21%] received anti-TNF (66 Crohn's disease [CD], 16 ulcerative colitis [UC], 3 inflammatory bowel disease unclassified [IBDU]) of whom 57% [48 patients] were treated 16 months] regarding gender, age, smoking status, and familial IBD. More importantly, patients receiving anti-TNF early did not suffer less IBD-related complications during follow-up as compared with patients started on anti-TNF late, nor was more MH observed. Similar results were obtained when anti-TNF treated patient were stratified more stringently, ie 2 4 months [24 patients]. Cox regression analysis showed no beneficial correlations between anti-TNF timing and IBD-related complications. Anti-TNF treated patients achieving MH were 11 times less likely to develop EIMs compared with patients who did not achieved MH while on anti-TNF. Conclusions: This study was unable to confirm a benefit of earlier anti-TNF treatment on IBD disease complications. This could be explained by more aggressive treatment earlier in disease, resulting in fewer IBD complications. However, it seems more likely that inappropriate selection of patients for therapy leads to suboptimal treatment and subsequently suboptimal outcome

Urgent endoscopic retrograde cholangiopancreatography with sphincterotomy versus conservative treatment in predicted severe acute gallstone pancreatitis (APEC):a multicentre randomised controlled trial

Background It remains unclear whether urgent endoscopic retrograde cholangiopancreatography (ERCP) with biliary sphincterotomy improves the outcome of patients with gallstone pancreatitis without concomitant cholangitis. We did a randomised trial to compare urgent ERCP with sphincterotomy versus conservative treatment in patients with predicted severe acute gallstone pancreatitis.Methods In this multicentre, parallel-group, assessor-masked, randomised controlled superiority trial, patients with predicted severe (Acute Physiology and Chronic Health Evaluation II score >= 8, Imrie score >= 3, or C-reactive protein concentration >150 mg/L) gallstone pancreatitis without cholangitis were assessed for eligibility in 26 hospitals in the Netherlands. Patients were randomly assigned (1:1) by a web-based randomisation module with randomly varying block sizes to urgent ERCP with sphincterotomy (within 24 h after hospital presentation) or conservative treatment. The primary endpoint was a composite of mortality or major complications (new-onset persistent organ failure, cholangitis, bacteraemia, pneumonia, pancreatic necrosis, or pancreatic insufficiency) within 6 months of randomisation. Analysis was by intention to treat. This trial is registered with the ISRCTN registry, ISRCTN97372133.Findings Between Feb 28, 2013, and March 1, 2017, 232 patients were randomly assigned to urgent ERCP with sphincterotomy (n=118) or conservative treatment (n=114). One patient from each group was excluded from the final analysis because of cholangitis (urgent ERCP group) and chronic pancreatitis (conservative treatment group) at admission. The primary endpoint occurred in 45 (38%) of 117 patients in the urgent ERCP group and in 50 (44%) of 113 patients in the conservative treatment group (risk ratio [RR] 0.87, 95% CI 0.64-1.18; p=0.37). No relevant differences in the individual components of the primary endpoint were recorded between groups, apart from the occurrence of cholangitis (two [2%] of 117 in the urgent ERCP group vs 11 [10%] of 113 in the conservative treatment group; RR 0.18, 95% CI 0.04-0.78; p=0.010). Adverse events were reported in 87 (74%) of 118 patients in the urgent ERCP group versus 91 (80%) of 114 patients in the conservative treatment group.Interpretation In patients with predicted severe gallstone pancreatitis but without cholangitis, urgent ERCP with sphincterotomy did not reduce the composite endpoint of major complications or mortality, compared with conservative treatment. Our findings support a conservative strategy in patients with predicted severe acute gallstone pancreatitis with an ERCP indicated only in patients with cholangitis or persistent cholestasis