We performed a multicenter study to determine whether transabdominal bowel wall ultrasonography, a noninvasive procedure that does not require radiation, can be used to monitor progression of Crohn's ...disease (CD).
We performed a 12-month prospective, noninterventional study at 47 sites in Germany, from December 2010 through September 2014. Our study included 234 adult patients with CD who experienced a flare, defined as Harvey-Bradshaw index score of ≥7. All patients received treatment intensification, most with tumor necrosis factor antagonists. Ultrasound parameters and clinical data were assessed at baseline and then after 3, 6, and 12 months. The primary endpoint was the change in ultrasound parameters within 12 months of study enrollment.
All patients included had bowel wall alterations either within the terminal ileum and/or segments of the colon. After 3 and 12 months, ultrasonographic examination showed significant improvements of nearly all ultrasound parameters, including reductions in bowel wall thickening or stratification, decreased fibrofatty proliferation, and increased signals in color Doppler ultrasound (P < .01 for all parameters at months 3 and 12). Median Harvey-Bradshaw index scores decreased from 10 at baseline to 2 after 12 months. Improvement in bowel wall thickness correlated with reduced levels of C-reactive protein after 3 months (P ≤ .001).
In a multicenter prospective study, we found that ultrasonographic examination can be used to monitor disease activity in patients with active CD. Bowel ultrasonography seems to be an ideal follow-up method to evaluate early transmural changes in disease activity, in response to medical treatment. German Clinical Trials Register: drks.de/DRKS00010805.
Lactic acid bacteria inhibits NFκB‐mediated transcriptional activation of IBD causing factors (IL‐23/IL‐17/CD40) by reducing histone acetylation while enhancing DNA methylation.
The pathophysiology ...of IBD is characterized by a complex interaction between genes and the environment. Genetic and environmental differences are attributed to the heterogeneity of the disease pathway and to the epigenetic modifications that lead to altered gene expression in the diseased tissues. The epigenetic machinery consists of short interfering RNA, histone modifications, and DNA methylation. We evaluated the effects of Bifidobacterium breve (DSMZ 20213) and LGG (ATCC 53103), as representatives of commensal probiotics on the expression of IL‐17 and IL‐23, which play an important role in IBD, and on the epigenetic machinery in a 3D coculture model composed of human intestinal HT‐29/B6 or T84 cells and PBMCs. The cells were treated with LPS in the presence or absence of bacteria for 48 h, and the expression of IL‐17, IL‐23, and CD40 at the mRNA and protein levels was assessed using TaqMan qRT‐PCR and ELISA, respectively. Western blotting was used to assess the expression of the MyD88, the degradation of IRAK‐1 and IκBα, the expression of the NF‐κB p50/p65 subunits, the p‐p38 MAPK and p‐MEK1, as well as histone modifications. NF‐κB activity was assessed by NF‐κB‐dependent luciferase reporter gene assays. The accumulation of Ac‐H4 and DNA methylation was quantitatively assessed using colorimetric assays. B. breve and LGG diminished the LPS‐induced expression of IL‐17, IL‐23, CD40, and histone acetylation, while slightly enhancing DNA methylation. These effects were paralleled by a decrease in the nuclear translocation of NF‐κB, as demonstrated by a decrease in the expression of MyD88, degradation of IRAK‐1 and IκBα expression of the nuclear NF‐κB p50/p65 subunits, p‐p38 MAPK and p‐MEK1, and NF‐κB‐dependent luciferase reporter gene activity in LPS‐stimulated cells. B. breve and LGG may exert their anti‐inflammatory effects in the gut by down‐regulating the expression of the IBD‐causing factors (IL‐23/IL‐17/CD40) associated with epigenetic processes involving the inhibition of histone acetylation and the optimal enhancement of DNA methylation, reflected in the limited access of NF‐κB to gene promoters and reduced NF‐κB‐mediated transcriptional activation. We describe a new regulatory mechanism in which commensal probiotics inhibit the NF‐κB‐mediated transcriptional activation of IBD‐causing factors (IL‐23/IL‐17/CD40), thereby simultaneously reducing histone acetylation and enhancing DNA methylation.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Real-world comparisons of biologic treatment outcomes for ulcerative colitis (UC) or Crohn's disease (CD) patients are limited. We sought to evaluate the real-world effectiveness of vedolizumab (VDZ) ...and anti-tumor necrosis factor alpha (anti-TNFα) in UC and CD patients in Germany.
A retrospective chart review (15 sites) investigated UC and CD patients who were biologic-treatment naïve (biologic-naïve) or had received no more than one prior anti-TNFα before initiating treatment with VDZ or anti-TNFα between 15 July 2014 and 20 October 2015. Kaplan-Meier analyses assessed time to first chart-documented clinical remission (CR) and symptom resolution (UC: rectal bleeding RB, stool frequency SF; CD: abdominal pain AP, liquid stools LS) and outcome duration.
A total of 133 UC (76 VDZ; 57 anti-TNFα) and 174 CD (69 VDZ; 105 anti-TNFα) patients were included. By Week 26, estimated cumulative rates of patients achieving CR or symptom resolution with VDZ vs anti-TNFα treatment were for UC: CR, 53.7% vs 31.7%; RB, 66.8% vs 55.8%; and SF, 59.8% vs 50.7%, respectively; and for CD: CR, 14.4% vs 32.8%; AP, 62.5% vs 56.0%; and LS, 29.9% vs 50.3%, respectively. Outcomes were sustained similarly between treatments, except RB (VDZ vs anti-TNFα: median 38.1 vs 15.1 weeks, P = 0.03). Treatment-related adverse events occurred in 5.3% vs 7.0% (UC) and 8.7% vs 19.0% (CD) of VDZ vs anti-TNFα patients, respectively.
Although there were differences in CR, symptom resolution, and safety profiles, real-world data support both VDZ and anti-TNFα as effective treatment options in UC and CD.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The aim of the study was to evaluate, if the strategy to stop anti-TNF treatment after determination of low trough serum levels and exclusion of inflammation is associated with lower relapse rates.
...Since 2013 we followed an exit strategy in patients treated with anti-TNF treatment for inflammatory bowel disease based on trough serum levels. The relapse rates were observed prospectively, data analysis was performed in a retrospective manner of the collected clinical data.
Forty patients were enrolled, who stopped anti-TNF therapy. 13 Patients followed the clinical algorithm, 27 patients were used as control group (13 patients with ulcerative colitis and 14 patients with Crohn's disease). 19 patients received Infliximab, 21 Adalimumab. The median follow-up time after discontinuation was 19 months (IQR 18). Relapses were observed in 22/40 patients (55%). Among the 13 patients with a targeted discontinuation of therapy based on the algorithm, three relapses were observed (23%), compared to 19/27 (70%) from the non-algorithm group (OR: 7.9; 95%-CI: 1.7–36.5). Relapse-free-survival after anti-TNF discontinuation was significantly higher in patients treated by the algorithm compared to the non-algorithm group (p = 0.032).
An exit strategy based on trough serum levels significantly reduces the relapse rate.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Prospective evaluation of intestinal ultrasound (IUS) for disease monitoring of patients with ulcerative colitis (UC) in routine medical practice.
TRansabdominal Ultrasonography of the bowel in ...Subjects with IBD To monitor disease activity with UC (TRUST&UC) was a prospective, observational study at 42 German inflammatory bowel disease-specialised centres representing different care levels. Patients with a diagnosis of a proctosigmoiditis, left-sided colitis or pancolitis currently in clinical relapse (defined as Short Clinical Colitis Activity Index ≥5) were enrolled consecutively. Disease activity and vascularisation within the affected bowel wall areas were assessed by duplex/Colour Doppler ultrasonography.
At baseline, 88.5% (n=224) of the patients had an increased bowel wall thickness (BWT) in the descending or sigmoid colon. Even within the first 2 weeks of the study, the percentage of patients with an increased BWT in the sigmoid or descending colon decreased significantly (sigmoid colon 89.3%-38.6%; descending colon 83.0%-42.9%; p<0.001 each) and remained low at week 6 and 12 (sigmoid colon 35.4% and 32.0%; descending colon 43.4% and 37.6%; p<0.001 each). Normalisation of BWT and clinical response after 12 weeks of treatment showed a high correlation (90.5% of patients with normalised BWT had symptomatic response vs 9.5% without symptomatic response; p<0.001).
IUS may be preferred in general practice in a point-of-care setting for monitoring the disease course and for assessing short-term treatment response. Our findings give rise to the assumption that monitoring BWT alone has the potential to predict the therapeutic response, which has to be verified in future studies.
AIMS:The goal of the study was to compare persistence with vedolizumab versus adalimumab, golimumab, and infliximab in biologics-naïve patients with inflammatory bowel disease treated in ...gastroenterological practices and outpatient clinics in Germany.
METHODS:Patients aged 18 or older who had initiated a biological therapy (vedolizumab, infliximab, adalimumab, or golimumab) were included in the present study. Prescriptions between July 2014 and March 2017 of the respective biological drug emerging from gastroenterological practices or outpatient clinics in Germany were retrieved from the longitudinal prescription (LRx) database. Patients treated with vedolizumab were matched with patients treated with infliximab, adalimumab, or golimumab on the basis of age, gender, medication before biologic therapy, and index year. The primary outcome variable of the study was the rate of persistence with vedolizumab compared with antitumor necrosis factor biologics (infliximab, adalimumab, and golimumab) within 3 years of the first prescription in outpatient settings.
RESULTS:Kaplan-Meier analysis was performed in 15,984 patients naïve to biologics revealing the statistically lower risk of discontinuation for vedolizumab compared with adalimumab, golimumab, or infliximab. In matched-pairs analyses, within 3 years after the first prescription, 39.5% of 2076 patients were persistent to vedolizumab compared with 33.5% of matched patients persistent to adalimumab (P<0.001). 37.6% of 716 patients were persistent to vedolizumab compared with 24.7% of matched patients persistent to golimumab (P<0.001). 35.7% of 2055 patients were persistent to vedolizumab compared with 30.2% of matched patients persistent to infliximab (P=0.119). Vedolizumab was associated with a significantly lower risk of therapy discontinuation compared with adalimumab hazard ratio (HR)=0.86; 95% confidence interval (CI), 0.81-0.93 and golimumab (HR=0.60; 95% CI, 0.54-0.67), respectively; the vedolizumab risk of therapy discontinuation was numerically lower than infliximab but statistical significance was not achieved (HR=0.93; 95% CI, 0.85-1.02).
CONCLUSION:In biologics-naïve IBD patients treated in outpatient settings in Germany, matched-pair analyses showed that vedolizumab was associated with significantly improved drug persistence compared with adalimumab or golimumab, whereas numerical improvement was shown in comparison with infliximab.
ObjectivePostprandial (pp) lipid metabolism is associated with insulin resistance and type 2 diabetes. In young men, pp triglycerides (TGs) are more strongly associated with traits of metabolic ...syndrome (MS) than fasting TGs. We established a cohort of middle-aged men selected for traits of MS and pp lipid metabolism to determine if fasting TGs or pp TGs are more closely related to MS.Research design and methodsA total of 1558 men were characterized for MS. A total of 755 men underwent an oral metabolic tolerance test consisting of a standardized high-fat meal and an oral glucose tolerance test. Blood samples were drawn in the fasting state and hourly until 9 h to determine pp TGs and free fatty acids. Glucose and insulin were analyzed until 5 h pp.ResultsIn the overall cohort, 329 subjects (21.1%) had a complete MS based on the Adult Treatment Panel III criteria, and 650 subjects (41.7%) had a complete MS based on the International Diabetes Federation criteria. The association of pp TGs with MS parameters was not stronger than the association of fasting TGs with them. Pp TGs were independently associated with β-cell function.ConclusionsPp TGs did not show a higher correlation with MS traits than fasting TGs. This finding is probably due to the high incidence of overweight subjects in this middle-aged cohort.
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