Associations between diet habits and inflammatory bowel disease (IBD) have been widely described. Flavonoids are taken with vegetables, fruits, and green tea. Because of barrier-protective and ...anti-inflammatory effects, flavonoid consumption (FC) may influence the severity of IBD. The aim of this study was to reveal the role of FC in the course and severity of IBD.
A prospective cohort study including 204 IBD patients (Crohn’s disease n = 126, ulcerative colitis n = 78) was conducted between 2016 and 2021. FC was calculated using questionnaires. In addition to standard activity scores and different treatments, a “severity index” was related to individual FC. Differences between groups and odds ratios were analyzed.
Inverse correlation (r = −0.0549; P = .01) between FC and severity of IBD was found. Patients were assigned to 3 different severity index ranges: mild, moderate, and severe disease. FC of patients with severe disease (331 ± 330 mg/week) was less than FC of patients with mild (1404 ± 1086 mg/ week) disease (P < .001). The risk of IBD patients with low FC (1000 mg/week) experiencing overall severe disease was 17 times increased (P < .001) compared to patients with high FC (>1000 mg/week). Patients with UC and low FC had a 9.6-times higher risk for disease progression (P < .001).
Consumption of dietary flavonoids and the overall severity of IBD are inversely correlated. Patients with mild diseases consume higher amounts of flavonoids than patients with severe diseases. Low dietary flavonoids were related to a considerable risk of severe IBD.
Background and Aims: KRP203 is a potent oral agonist of the sphingosine-1-phosphate receptor subtype 1 that induces the sequestration of peripheral lymphocytes, thereby potentially reducing the ...number of activated lymphocytes circulating to the gastrointestinal tract. Methods: We conducted a multicentre, double-blind, placebo-controlled, parallel-group, proof-of-concept study to evaluate the efficacy, safety, and tolerability of KRP203 in patients with moderately active 5-aminosalicylate-refractory ulcerative colitis (UC). Patients were randomly assigned to receive 1.2 mg KRP203 or placebo daily for 8 weeks. Primary efficacy variable was clinical remission, defined as partial Mayo Score 0–1 and modified Baron Score 0–1 with rectal bleeding subscore 0. Results: KRP203 was safe and well tolerated overall. The most common adverse events (AEs) were gastrointestinal disorders and headache. Importantly, no KRP203-related cardiac AEs were reported. Total peripheral lymphocytes and selectively affected lymphocyte subtypes decreased, causing marked decreases in naive and central memory CD4+ and CD8+ T cells, and also in B cells. Clinical remission occurred in 2/14 (14%) patients under KRP203, compared with 0/8 (0%) under placebo. Conclusions: Overall, KRP203 was safe and well tolerated by patients with UC. Importantly, no cardiac AEs were reported. Although KRP203 did not meet the minimum clinically relevant threshold for efficacy, the results may suggest that KRP203 treatment is superior to placebo. However, in this small study population, the difference was insignificant. Based on these data, studies with an improved design and a larger population should be considered.
In 1977, 5-aminosalicylic acid (5-ASA) was discovered as a therapeutically active moiety of sulfasalazine (SASP) and was launched for topical and oral therapy of ulcerative colitis (UC) in 1984. As a ...first-step, delivery systems had to be developed to protect 5-ASA against absorption in the upper gastrointestinal tract, resulting in different and competing strategies (azo compounds, controlled release, and pH-dependent release). In a second step, at the beginning of the new century, coinciding with the expiration of patent protection for the first 5-ASA formulations, two component composite release mechanisms (pH-dependent and controlled release) were developed. Furthermore, the drug was formulated as granules instead of tablets, allowing higher unit strengths compared with tablets. Neither Salofalk Granu-Stix(®), nor MMX 5-ASA, nor Pentasa(®) granules have initially been developed for once-daily (OD) dosing. A review of the achievements of 20 years of 5-ASA development has demonstrated that 5-ASA has equal efficacy compared with SASP at best, that there are no measurable differences in efficacy between various 5-ASA preparations, and that in a group of patients tolerating SASP, adverse event profiles of SASP and 5-ASA did not differ significantly, with SASP being the far cheaper substance. Therefore, drug adherence came into focus as a new goal for improving UC therapy. Although adherence is a complex and multifactorial construct, a simple dosing schedule may contribute to higher drug adherence and better efficacy of treatment. Simultaneously, the US 5-ASA market, estimated to be worth US$1.4 billion, is expected to grow continuously. Naturally, this very competitive market is not only driven by scientific progress but also by commercial interests. Thus, patents for minor changes to the formulation may serve as protection against drug companies trying to launch generic versions. Randomized controlled trials performed on OD dosing in induction of remission have demonstrated that OD administration of 5-ASA is as effective as conventional dosing in mild to moderate active UC. The three 5-ASA products MMX, Salofalk(®), and Pentasa(®) employed in those studies so far have not shown differences in efficacy between OD and conventional dosing. No differences regarding safety outcomes have been detected between OD and conventional dosing, including incidence of adverse events, serious adverse events, or withdrawal from treatment due to an adverse event. Although the majority of patients prefer OD dosing to conventional dosing, it was not possible to detect differences in adherence between OD and multiple dose regimens in the clinical trial setting. Well-designed and controlled large-scale community-based studies are necessary to further investigate and prove the point of improved long-term adherence and treatment efficacy in OD dosing.
AIM:To detect high risk patients with a progressive disease course of ulcerative colitis(UC) requiring immunosuppressive therapy(IT).METHODS:A retrospective,multicenter analysis of 262 UC patients ...from eight German tertiary inflammatory bowel disease centres was performed.Patients were divided into two groups depending on the patients need to initiate immunosuppressive therapy in the disease course.A comparison between the two groups was made with regard to demographics,clinical and laboratory parameters obtained within three months after UC diagnosis and the response to first medical therapy.Using this data,a prognostic model was established to predict the individual patients probability of requiring an immunosuppressive therapy.RESULTS:In 104(39.7%) out of 262 patients,UC therapy required an immunosuppressive treatment.Patients in this group were significantly younger at time of diagnosis(HR = 0.981 ± 0.014 per year,P = 0.009),and required significantly more often a hospitalisation(HR = 2.5 ± 1.0,P < 0.001) and a systemic corticosteroid therapy at disease onset(HR = 2.4 ± 0.8,P < 0.001),respectively.Response to steroid treatment was significantly different between the two groups of patients(HR = 5.2 ± 3.9 to 50.8 ± 35.6 compared to no steroids,P = 0.016 to P < 0.001).Furthermore,in the IT group an extended disease(HR = 3.5 ± 2.4 to 6.1 ± 4.0 compared to proctitis,P = 0.007 to P = 0.001),anemia(HR = 2.2 ± 0.8,P < 0.001),thrombocytosis(HR = 1.9 ± 1.8,P = 0.009),elevated C-reactive protein(CRP)(HR = 2.1 ± 0.9,P < 0.001),and extraintestinal manifestations in the course of disease(HR = 2.6 ± 1.1,P = 0.004) were observed.Six simple clinical items were used to establish a prognostic model to predict the individual risk requiring an IT.This probability ranges from less than 2% up to 100% after 5 years.Using this,the necessity of an immunosuppressive therapy can be predicted in 60% of patients.Our model can determine the need for an immunosuppressive drug therapy or if a "watch and wait" approach is reasonable already early in the treatment course of UC.CONCLUSION:Using six simple clinical parameters,we can estimate the patients individual risk of developing a progressive disease course.
Background & Aims: ISIS-2302, an antisense oligonucleotide directed against intercellular adhesion molecule 1, was effective in steroid refractory Crohn's disease in a pilot trial. The aim of this ...study was to investigate safety and efficacy of ISIS-2302 in chronic active Crohn's disease (CACD).
Methods: A dose-interval, multicenter, placebo-controlled trial was conducted in 75 patients with steroid-refractory CACD (Crohn's Disease Activity Index CDAI, 200-400). The primary endpoint was steroidfree remission (CDAI <150) at week 14.
Results: Only 2 of 60 (3.3%) ISIS-2302-treated and no placebo patients reached the primary endpoint. Steroid-free remission at week 26 (secondary endpoint) was reached in 8 of 60 (13.3%) active treatment and 1 of 15 (6.7%) placebo patients. A greater proportion of ISIS-2302-treated than placebo patients achieved a steroid dose <10 mg/day at weeks 14 and 26 (48.3% vs. 33.3% and 55.0% vs. 40.0%, respectively, and a glucocorticoid dose of 0 mg prednisone equivalent at week 26 23.3% vs. 6.7%, respectively). Treatment with ISIS-2302 was safe. The most common side effects were injection site reactions in the active treatment group (23% in ISIS-2302-treated patients vs. none in placebo patients). No statistically significant differences in the frequency of side effects were detected between dose groups.
Conclusions: The trial did not prove clinical efficacy of ISIS-2302 based on the primary endpoint. Positive trends were observed in some of the secondary endpoints.
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