The therapeutic potential of antibiotics and probiotics in the treatment of pouchitis

Pouchitis is the most frequent long-term complication of pouch surgery for ulcerative colitis. There is consistent evidence on the implication of bacterial flora in the pathogenesis of pouchitis, and there is evidence for a therapeutic role of antibiotics and probiotics in therapy of this disease. Antibiotics, particularly ciprofloxacin and metronidazole, are the mainstay of treatment for acute pouchitis. In chronic refractory pouchitis, after having excluded other diagnoses (infections, Crohn's disease of the pouch, ischemia and irritable pouch), antibiotic combination therapy is the treatment of choice. The highly concentrated probiotic mixture VSL#3 has been shown to be effective in prevention of pouchitis onset and in maintaining antibiotic-induced remission

Poor prognostic factors of pharmacokinetic origin predict outcomes in inflammatory bowel disease patients treated with anti-tumor necrosis factor-α

IntroductionWe evaluated baseline Clearance of anti-tumor necrosis factors and human leukocyte antigen variant (HLA DQA1*05) in combination as poor prognostic factors (PPF) of pharmacokinetic (PK) origin impacting immune response (formation of antidrug antibodies) and disease control of inflammatory bowel disease (IBD) patients treated with infliximab or adalimumab.MethodsBaseline Clearance was estimated in IBD patients before starting treatment using weight and serum albumin concentrations. HLA DQA1*05 carrier status (rs2097432 A/G or G/G variant) was measured using real time polymerase chain reaction. The outcomes consisted of immune response, clinical and biochemical remission (C-reactive protein<3 mg/L in the absence of symptoms), and endoscopic remission (SES-CD<3). Statistical analysis consisted of logistic regression and nonlinear mixed effect models.Results and discussionIn 415 patients enrolled from 4 different cohorts (median age 27 [IQR: 15-43] years, 46% females), Clearance>0.326 L/day and HLA DQA1*05 carrier status were 2-fold more likely to have antidrug antibodies (OR=2.3, 95%CI: 1.7-3.4; p<0.001, and OR=1.9, 95%CI: 1.4-2.8; p<0.001, respectively). Overall, each incremental PPF of PK origin resulted in a 2-fold (OR=2.16, 95%CI: 1.7-2.7; p<0.01) higher likelihood of antidrug antibody formation. The presence of both PPF of PK origin resulted in higher rates of antidrug antibodies (p<0.01) and lower clinical and biochemical remission (p<0.01). Each incremental increase in PPF of PK origin associated with lower likelihood of endoscopic remission (OR=0.4, 95%CI: 0.2-0.7; p<0.001). Prior biologic experience heightened the negative impact of PPF of PK origin on clinical and biochemical remission (p<0.01). Implementation of proactive therapeutic drug monitoring reduced it, particularly during maintenance and in the presence of higher drug concentrations (p<0.001). We conclude that PPF of PK origin, including both higher Clearance and carriage of HLA DQA1*05, impact outcomes in patients with IBD

Prepouch Ileitis After Ileal Pouch-anal Anastomosis: Patterns of Presentation and Risk Factors for Failure of Treatment

Background and Aims There is a lack in the literature about prepouch ileitis (PI), in particular regarding risk factors associated with failure of the medical treatment. Aim of the study is to analyse the characteristics of PI patients and to compare those who required surgery with those who were successfully treated with conservative therapy. Methods All cases presenting a diagnosis of PI were included and analysed. Patients eventually requiring surgery were compared to those who were managed conservatively for symptoms of presentation, endoscopic characteristics and rate of response to medical treatment. A sub-analysis of outcomes based on the final histology was performed. Results The overall incidence of PI over 1286 patients was 4.4% (57), after a median of 6.8 years from pouch surgery. Symptoms included increased frequency (26.4%), outlet obstruction (21%), bleeding (15.8%). Afferent limb stenosis affected 49.1% of patients. The comparison showed that patients requiring surgery had a higher rate of Crohn’s disease and indeterminate colitis (42.1 vs 0% and 15.8 vs 2.6%, p<0.0001), outlet obstruction as main symptom (47.4 vs 7.9% p=0.0023) and afferent limb stenosis (73.7 vs 36.8%. p=0.008) at endoscopy. Rate of failure of medical treatment at 5 year was 8.2% in patients with ulcerative colitis and 75% in the presence of both indeterminate colitis and Crohn’s disease (p<0.0001). Conclusions Crohn’s disease, indeterminate colitis and stenosis with outlet obstruction are risk factors for failure of treatment after diagnosis of PI. Early aggressive therapy and surgery should be considered in these cases

Oral versus combination mesalazine therapy in active ulcerative colitis: a double-blind double-dummy, randomized multicentre study

Background: Oral and topical mesalazine formulations are effective in active ulcerative colitis, but little is known on the efficacy of combined treatment. Aim: To compare the efficacy of oral mesalazine vs. combined oral and topical mesalazine in mildly to moderately active ulcerative colitis. Methods: Patients with mildly to moderately active ulcerative colitis (Clinical Activity Index, CAI 4-12) were identified at 15 participating centres. They were randomized to receive either mesalazine 4 g orally plus placebo enema, or mesalazine 2 g orally plus mesalazine 2 g rectally as a liquid enema for 6 weeks. The rate of clinical remission (CAI < 4) or clinical remission/improvement (reduction of CAI of 50% from baseline) at 6 weeks and time to clinical remission/improvement were primary end-points; the rate of endoscopic remission was a secondary end-point. Results: 67 patients were assigned to oral treatment and 63 to combined treatment. One patient in the oral group and 2 in the combined group discontinued the treatment due to adverse events. Following an intention-to-treat analysis, the rate of clinical remission was 82% for oral treatment and 87% for combined treatment (P=0.56); the mean time to remission 22.2 and 20.2 days, respectively (P=0.29); the rate of clinical remission/improvement and the rate of endoscopic remission were 85% and 91% (P=0.503) and 58% and 71% (P=0.21), respectively. Conclusions: In patients with mild active ulcerative colitis, mesalazine 4 g orally and 2 g orally plus 2 g enema are equally effective in inducing disease remission

IBD: IBD and spondyloarthritis: Joint management

Spondyloarthritis (SpA) is the most common extraintestinal manifestation of IBD. SpA symptoms are not always recognized in patients with IBD. Subsequently, patients with symptoms of SpA can be underdiagnosed with effective treatment delayed. Cooperation between gastroenterologists and rheumathologists is necessary and, ideally, an integrated management of these patients should be adopted

Genetic analysis in Italian families with inflammatory bowel disease supports linkage to the IBD1 locus--a GISC study.

Epidemiological studies suggest that inherited factors influence susceptibility to inflammatory bowel disease (IBD), and some candidate loci have been described. In order to verify whether the same loci are responsible for predisposition to IBD in our population, we carried out a linkage study in a series of 58 Italian families with Crohn’s disease (CD) and ulcerative colitis (UC). HLA-DQ alleles, motilin gene, and 34 microsatellites flanking the previously described loci on chromosomes 3, 6, 7, 12 and 16 were analysed by non-parametric linkage analysis in 16 and 23 families with CD and UC, respectively, and in 19 families where CD and UC coexisted. Non parametric analysis using GENEHUNTER yielded maximum NPL scores for marker D16S408 in all IBD families combined (2.71, P = 0.003), for marker D16S419 in CD (1.97, P = 0.026) and for marker D16S514 in UC families (2.44, P = 0.007). These markers map in the previously described IBD1 region. No significant linkage was found for markers of chromosomes 3, 6, 7 and 12. The present study performed in a Southern European population provides additional support for the conclusion that the IBD1 locus has a clear role in the genetic susceptibility to IBD

New insights into the brain involvement in patients with Crohn\u2019s disease: a voxel-based morphometry study

Background Crohn\u2019s disease (CD) is a chronic intestinal disorder characterized by overproduction of inflammatory cytokines and recurrent abdominal pain. Recently, brain morphological abnormalities in the pain matrix were found in patients with chronic pain disorders including irritable bowel syndrome. To investigate potential structural brain changes associated with CD, we used magnetic resonance imaging (MRI). Furthermore, we tested whether in patients gray matter (GM) volumes correlated with disease duration. Methods Eighteen CD patients in remission and 18 healthy controls underwent structural MRI. Voxel-based morphometry (VBM) is a fully automated technique allowing identification of regional differences in the amount of GM enabling an objective analysis of the whole brain between groups of subjects. VBM was used for comparisons and correlation analysis. Key Results With respect to controls, CD patients exhibited decreased GM volumes in portion of the frontal cortex and in the anterior midcingulate cortex. Disease duration was negatively correlated with GM volumes of several brain regions including neocortical and limbic areas. Conclusions & Inferences Crohn\u2019s disease is associated with brain morphological changes in cortical and subcortical structures involved in nociception, emotional, and cognitive processes. Our findings provide new insight into the brain involvement in chronic inflammatory bowel disorders