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Outcomes of dietary management approaches in active ulcerative colitis: A systematic review.
Marsh, A, Rindfleish, S, Bennett, K, Croft, A, Chachay, V
Clinical nutrition (Edinburgh, Scotland). 2022;(2):298-306
Abstract
BACKGROUND & AIMS The dietary management of active ulcerative colitis (UC) is currently poorly understood. Due to the lack of clinical guidelines for this population, diet choice may be based on the personal judgement of the clinician, and without sound evidence. The aim of this systematic review was to appraise the current literature on the dietary management of individuals with active UC, in both inpatient and outpatient settings, to determine if clinical outcomes differ by diet prescription. METHOD PUBMED, CINAHL, EMBASE, Web of Science and SCOPUS were comprehensively searched during March and April 2020. Eligible trials recruited adults with active UC comparing different methods of dietary management, including enteral nutrition (EN), total parenteral nutrition (TPN), elimination diets and standard oral diets, in both the inpatient and outpatient settings. RESULTS 10 studies met inclusion criteria of this qualitative synthesis. No difference was found between EN, TPN and bowel rest in terms of disease activity measures when compared to a standard oral diet. The results of this study also showed promising potential for the use of elimination diets in the outpatient setting with four studies finding a significant difference in disease activity measures between the intervention diet and control. CONCLUSION There is no strong evidence to support the use of any specific dietary prescription to improve clinical outcomes for individuals with active UC. A number of low quality studies suggest benefit of following an elimination diet, however, additional high quality studies are required before any more specific recommendations can be made.
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Female reproductive health and inflammatory bowel disease: A practice-based review.
, , Armuzzi, A, Bortoli, A, Castiglione, F, Contaldo, A, Daperno, M, D'Incà, R, Labarile, N, Mazzuoli, S, Onali, S, et al
Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver. 2022;(1):19-29
Abstract
Inflammatory bowel diseases, namely ulcerative colitis and Crohn's disease, occur worldwide and affect people of all ages, with a high impact on their quality of life. Sex differences in incidence and prevalence have been reported, and there are also gender-specific issues that physicians should recognize. For women, there are multiple, important concerns regarding issues of body image and sexuality, menstruation, contraception, fertility, pregnancy, breastfeeding and menopause. This practice-based review focuses on the main themes that run through the life of women with inflammatory bowel diseases from puberty to menopause. Gastroenterologists who specialize in inflammatory bowel diseases and other physicians who see female patients with inflammatory bowel diseases should provide support for these problems and offer adequate therapy to ensure that their patients achieve the same overall well-being and health as do women without inflammatory bowel diseases.
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Efficacy and safety of adjuvant curcumin therapy in ulcerative colitis: A systematic review and meta-analysis.
Yin, J, Wei, L, Wang, N, Li, X, Miao, M
Journal of ethnopharmacology. 2022;:115041
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Curcumin, an active polyphenol extracted from Traditional Chinese medicine Curcuma longa (turmeric), has shown many health-related benefits and pharmacological effects. Adjuvant curcumin therapy for ulcerative colitis has become increasingly popular, but its efficacy and safety of which is still controversial. The purpose of this study is to evaluate the efficacy and safety of adjuvant curcumin therapy in ulcerative colitis. MATERIALS AND METHODS The Medline, EMBASE, the Cochrane Library, CNKI, VIP, WanFang, and SinoMed databases were searched from inception to June 2021, to identify all randomized controlled clinical trials with adjuvant curcumin therapy in ulcerative colitis. The primary outcomes were clinical and endoscopic remission, and subgroup analyses were also performed. RESULTS Six randomized trials with a total of 385 participants were included in this study. Qualified trials recommended that adjuvant curcumin therapy for ulcerative colitis was effective in inducing clinical remission (RR = 2.10, 95% CI 1.13 to 3.89), but not in clinical improvement (RR = 1.62, 95% CI 1.00 to 2.61), endoscopic remission (RR = 4.17, 95% CI 0.63 to 27.71) or endoscopic improvement (RR = 4.13, 95% CI 0.20 to 87.07). Included studies showed that appropriate dosage, formation, longer duration, and topical medication may have a greater potential advantage. No severe adverse effects had been reported. CONCLUSIONS Available evidence suggested that adjuvant curcumin therapy may be effective for clinical remission in ulcerative colitis patients without causing severe adverse effects. The appropriate methods of administration can achieve better curative effect, which requires further study to verify.
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Management of acute severe ulcerative colitis in chile: Experience of a multidisciplinary team.
Pérez de Arce, E, Quera, R, Núñez, P, Simian, D, Ibáñez, P, Lubascher, J, Figueroa, C, Pizarro, G, Flores, L, Carrasco-Avino, G, et al
Gastroenterologia y hepatologia. 2022;(3):206-207
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Etrolizumab as induction and maintenance therapy for ulcerative colitis in patients previously treated with tumour necrosis factor inhibitors (HICKORY): a phase 3, randomised, controlled trial.
Peyrin-Biroulet, L, Hart, A, Bossuyt, P, Long, M, Allez, M, Juillerat, P, Armuzzi, A, Loftus, EV, Ostad-Saffari, E, Scalori, A, et al
The lancet. Gastroenterology & hepatology. 2022;(2):128-140
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Abstract
BACKGROUND Etrolizumab is a gut-targeted, anti-β7 integrin, monoclonal antibody. In an earlier phase 2 induction study, etrolizumab significantly improved clinical remission compared with placebo in patients with moderately to severely active ulcerative colitis. We aimed to evaluate the efficacy and safety of etrolizumab in patients with moderately to severely active ulcerative colitis who had been previously treated with anti-tumour necrosis factor (TNF) agents. METHODS HICKORY was a multicentre, phase 3, double-blind, placebo-controlled study in adult (18-80 years) patients with moderately to severely active ulcerative colitis (Mayo Clinic total score [MCS] of 6-12 with an endoscopic subscore of ≥2, a rectal bleeding subscore of ≥1, and a stool frequency subscore of ≥1) previously treated with TNF inhibitors. Patients were recruited from 184 treatment centres across 24 countries in North America, South America, Europe, Asia, Oceania, and the Middle East. Patients needed to have an established diagnosis of ulcerative colitis for at least 3 months, corroborated by both clinical and endoscopic evidence, and evidence of disease extending at least 20 cm from the anal verge. In cohort 1, patients received open-label etrolizumab 105 mg every 4 weeks for a 14-week induction period. In cohort 2, patients were randomly assigned (4:1) to receive subcutaneous etrolizumab 105 mg or placebo every 4 weeks for the 14-week induction phase. Patients in either cohort achieving clinical response to etrolizumab induction were eligible for the maintenance phase, in which they were randomly assigned (1:1) to receive subcutaneous etrolizumab 105 mg or placebo every 4 weeks through to week 66. Randomisation was stratified by baseline concomitant treatment with corticosteroids, concomitant treatment with immunosuppressants (induction randomisation only), baseline disease activity, week 14 MCS remission status (maintenance randomisation only), and induction cohort (maintenance randomisation only). All patients and study site personnel were masked to treatment assignment. Primary endpoints were remission (Mayo Clinic total score [MCS] ≤2, with individual subscores of ≤1 and a rectal bleeding subscore of 0) at week 14, and remission at week 66 among patients with a clinical response (MCS with ≥3-point decrease and ≥30% reduction from baseline, plus ≥1 point decrease in rectal bleeding subscore or absolute rectal bleeding score of 0 or 1) at week 14. Efficacy was analysed using a modified intent-to-treat population. Safety analyses included all patients who received at least one dose of study drug during the induction phase. This study is registered at ClinicalTrials.gov, NCT02100696. FINDINGS HICKORY was conducted from May 21, 2014, to April 16, 2020, during which time 1081 patients were screened, and 609 deemed eligible for inclusion. 130 patients were included in cohort 1. In cohort 2,479 patients were randomly assigned to the induction phase (etrolizumab n=384, placebo n=95). 232 patients were randomly assigned to the maintenance phase (etrolizumab to etrolizumab n=117, etrolizumab to placebo n=115). At week 14, 71 (18·5%) of 384 patients in the etrolizumab group and six (6·3%) of 95 patients in the placebo group achieved the primary induction endpoint of remission (p=0·0033). No significant difference between etrolizumab and placebo was observed for the primary maintenance endpoint of remission at week 66 among patients with a clinical response at week 14 (27 [24·1%] of 112 vs 23 [20·2%] of 114; p=0·50). Four patients in the etrolizumab group reported treatment-related adverse events leading to treatment discontinuation. The proportion of patients reporting at least adverse event was similar between treatment groups for induction (etrolizumab 253 [66%] of 384; placebo 63 [66%] of 95) and maintenance (etrolizumab to etrolizumab 98 [88%] of 112; etrolizumab to placebo 97 [85%] of 114). The most common adverse event in both groups was ulcerative colitis flare. Most adverse events were mild or moderate. During induction, the most common serious adverse event was ulcerative colitis flare (etrolizumab ten [3%] of 384; placebo: two [2%] of 95). During maintenance, the most common serious adverse event in the etrolizumab to etrolizumab group was appendicitis (two [2%] of 112) and the most common serious adverse events in the etrolizumab to placebo group were ulcerative colitis flare (two [2%] of 114) and anaemia (two [2%] of 114). INTERPRETATION HICKORY demonstrated that a significantly higher proportion of patients with moderately to severely active ulcerative colitis who had been previously treated with anti-TNF agent were able to achieve remission at week 14 when treated with etrolizumab compared with placebo; however, there was no significant difference between groups in remission at week 66 among patients with a clinical response at week 14. FUNDING F Hoffmann-La Roche.
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Assessment of Vedolizumab Disease-Drug-Drug Interaction Potential in Patients With Inflammatory Bowel Diseases.
Sun, W, Lirio, RA, Schneider, J, Aubrecht, J, Kadali, H, Baratta, M, Gulati, P, Suri, A, Lin, T, Vasudevan, R, et al
Clinical pharmacology in drug development. 2021;(7):734-747
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Abstract
Disease-drug-drug interactions (DDDIs) have been identified in some inflammatory diseases in which elevated proinflammatory cytokines can downregulate the expression of cytochrome P450 (CYP) enzymes, potentially increasing systemic exposure to drugs metabolized by CYPs. Following anti-inflammatory treatments, CYP expression may return to normal, resulting in reduced drug exposure and diminished clinical efficacy. Vedolizumab has a well-established positive benefit-risk profile in patients with ulcerative colitis (UC) or Crohn's disease (CD) and has no known systemic immunosuppressive activity. A stepwise assessment was conducted to evaluate the DDDI potential of vedolizumab to impact exposure to drugs metabolized by CYP3A through cytokine modulation. First, a review of published data revealed that patients with UC or CD have elevated cytokine concentrations relative to healthy subjects; however, these concentrations remained below those reported to impact CYP expression. Exposure to drugs metabolized via CYP3A also appeared comparable between patients and healthy subjects. Second, serum samples from patients with UC or CD who received vedolizumab for 52 weeks were analyzed and compared with healthy subjects. Cytokine concentrations and the 4β-hydroxycholesterol-to-cholesterol ratio, an endogenous CYP3A4 biomarker, were comparable between healthy subjects and patients both before and during vedolizumab treatment. Finally, a medical review of postmarketing DDDI cases related to vedolizumab from the past 6 years was conducted and did not show evidence of any true DDDIs. Our study demonstrated the lack of clinically meaningful effects of disease or vedolizumab treatment on the exposure to drugs metabolized via CYP3A through cytokine modulation in patients with UC or CD.
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Oral Sucrosomial Iron Is as Effective as Intravenous Ferric Carboxy-Maltose in Treating Anemia in Patients with Ulcerative Colitis.
Bertani, L, Tricò, D, Zanzi, F, Baiano Svizzero, G, Coppini, F, de Bortoli, N, Bellini, M, Antonioli, L, Blandizzi, C, Marchi, S
Nutrients. 2021;(2)
Abstract
Anemia is a frequent complication of ulcerative colitis, and is frequently caused by iron deficiency. Oral iron supplementation displays high rates of gastrointestinal adverse effects. However, the formulation of sucrosomial iron (SI) has shown higher tolerability. We performed a prospective study to compare the effectiveness and tolerability of oral SI and intravenous ferric carboxy-maltose (FCM) in patients with ulcerative colitis in remission and mild-to-moderate anemia. Patients were randomized 1:1 to receive 60 mg/day for 8 weeks and then 30 mg/day for 4 weeks of oral SI or intravenous 1000 mg of FCM at baseline. Hemoglobin and serum levels of iron and ferritin were assessed after 4, 8, and 12 weeks from baseline. Hemoglobin and serum iron increased in both groups after 4 weeks of therapy, and remained stable during follow up, without significant treatment or treatment-by-time interactions (p = 0.25 and p = 0.46 for hemoglobin, respectively; p = 0.25 and p = 0.26 for iron, respectively). Serum ferritin did not increase over time during SI supplementation, while it increased in patients treated with FCM (treatment effect, p = 0.0004; treatment-by-time interaction effect, p = 0.0002). Overall, this study showed that SI and FCM displayed similar effectiveness and tolerability for treatment of mild-to-moderate anemia in patients with ulcerative colitis under remission.
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Interventions for treating iron deficiency anaemia in inflammatory bowel disease.
Gordon, M, Sinopoulou, V, Iheozor-Ejiofor, Z, Iqbal, T, Allen, P, Hoque, S, Engineer, J, Akobeng, AK
The Cochrane database of systematic reviews. 2021;(1):CD013529
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Abstract
BACKGROUND Inflammatory bowel disease affects approximately seven million people globally. Iron deficiency anaemia can occur as a common systemic manifestation, with a prevalence of up to 90%, which can significantly affect quality of life, both during periods of active disease or in remission. It is important that iron deficiency anaemia is treated effectively and not be assumed to be a normal finding of inflammatory bowel disease. The various routes of iron administration, doses and preparations present varying advantages and disadvantages, and a significant proportion of people experience adverse effects with current therapies. Currently, no consensus has been reached amongst physicians as to which treatment path is most beneficial. OBJECTIVES The primary objective was to evaluate the efficacy and safety of the interventions for the treatment of iron deficiency anaemia in people with inflammatory bowel disease. SEARCH METHODS We searched CENTRAL, MEDLINE, Embase, and two other databases on 21st November 2019. We also contacted experts in the field and searched references of trials for any additional trials. SELECTION CRITERIA Randomised controlled trials investigating the effectiveness and safety of iron administration interventions compared to other iron administration interventions or placebo in the treatment of iron deficiency anaemia in inflammatory bowel disease. We considered both adults and children, with studies reporting outcomes of clinical, endoscopic, histologic or surgical remission as defined by study authors. DATA COLLECTION AND ANALYSIS Two review authors independently conducted data extraction and 'Risk of bias' assessment of included studies. We expressed dichotomous and continuous outcomes as risk ratios and mean differences with 95% confidence intervals. We assessed the certainty of the evidence using the GRADE methodology. MAIN RESULTS We included 11 studies (1670 randomised participants) that met the inclusion criteria. The studies compared intravenous iron sucrose vs oral iron sulphate (2 studies); oral iron sulphate vs oral iron hydroxide polymaltose complex (1 study); oral iron fumarate vs intravenous iron sucrose (1 study); intravenous ferric carboxymaltose vs intravenous iron sucrose (1 study); erythropoietin injection + intravenous iron sucrose vs intravenous iron sucrose + injection placebo (1 study); oral ferric maltol vs oral placebo (1 study); oral ferric maltol vs intravenous ferric carboxymaltose (1 study); intravenous ferric carboxymaltose vs oral iron sulphate (1 study); intravenous iron isomaltoside vs oral iron sulphate (1 study); erythropoietin injection vs oral placebo (1 study). All studies compared participants with CD and UC together, as well as considering a range of disease activity states. The primary outcome of number of responders, when defined, was stated to be an increase in haemoglobin of 20 g/L in all but two studies in which an increase in 10g/L was used. In one study comparing intravenous ferric carboxymaltose and intravenous iron sucrose, moderate-certainty evidence was found that intravenous ferric carboxymaltose was probably superior to intravenous iron sucrose, although there were responders in both groups (150/244 versus 118/239, RR 1.25, 95% CI 1.06 to 1.46, number needed to treat for an additional beneficial outcome (NNTB) = 9). In one study comparing oral ferric maltol to placebo, there was low-certainty evidence of superiority of the iron (36/64 versus 0/64, RR 73.00, 95% CI 4.58 to 1164.36). There were no other direct comparisons that found any difference in the primary outcomes, although certainty was low and very low for all outcomes, due to imprecision from sparse data and risk of bias varying between moderate and high risk. The reporting of secondary outcomes was inconsistent. The most common was the occurrence of serious adverse events or those requiring withdrawal of therapy. In no comparisons was there a difference seen between any of the intervention agents being studied, although the certainty was very low for all comparisons made, due to risk of bias and significant imprecision due to the low numbers of events. Time to remission, histological and biochemical outcomes were sparsely reported in the studies. None of the other secondary outcomes were reported in any of the studies. An analysis of all intravenous iron preparations to all oral iron preparations showed that intravenous administration may lead to more responders (368/554 versus 205/373, RR 1.17, 95% CI 1.05 to 1.31, NNTB = 11, low-certainty due to risk of bias and inconsistency). Withdrawals due to adverse events may be greater in oral iron preparations vs intravenous (15/554 versus 31/373, RR 0.39, 95% CI 0.20 to 0.74, low-certainty due to risk of bias, inconsistency and imprecision). AUTHORS' CONCLUSIONS Intravenous ferric carboxymaltose probably leads to more people having resolution of IDA (iron deficiency anaemia) than intravenous iron sucrose. Oral ferric maltol may lead to more people having resolution of IDA than placebo. We are unable to draw conclusions on which of the other treatments is most effective in IDA with IBD (inflammatory bowel disease) due to low numbers of studies in each comparison area and clinical heterogeneity within the studies. Therefore, there are no other conclusions regarding the treatments that can be made and certainty of all findings are low or very low. Overall, intravenous iron delivery probably leads to greater response in patients compared with oral iron, with a NNTB (number needed to treat) of 11. Whilst no serious adverse events were specifically elicited with any of the treatments studied, the numbers of reported events were low and the certainty of these findings very low for all comparisons, so no conclusions can be drawn. There may be more withdrawals due to such events when oral is compared with intravenous iron delivery. Other outcomes were poorly reported and once again no conclusions can be made as to the impact of IDA on any of these outcomes. Given the widespread use of many of these treatments in practice and the only guideline that exists recommending the use of intravenous iron in favour of oral iron, research to investigate this key issue is clearly needed. Considering the current ongoing trials identified in this review, these are more focussed on the impact in specific patient groups (young people) or on other symptoms (such as fatigue). Therefore, there is a need for studies to be performed to fill this evidence gap.
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Characterization of Creatine Kinase Levels in Tofacitinib-Treated Patients with Ulcerative Colitis: Results from Clinical Trials.
Panaccione, R, Isaacs, JD, Chen, LA, Wang, W, Marren, A, Kwok, K, Wang, L, Chan, G, Su, C
Digestive diseases and sciences. 2021;(8):2732-2743
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Abstract
BACKGROUND Tofacitinib is an oral, small-molecule JAK inhibitor for the treatment of ulcerative colitis (UC). Creatine kinase (CK) levels and CK-related adverse events (AEs) in tofacitinib-treated patients with UC were evaluated. METHODS Data were analyzed for three UC cohorts: Induction (phase 2 and 3 induction studies); Maintenance (phase 3 maintenance study); Overall [patients who received tofacitinib 5 or 10 mg twice daily (b.d.) in phase 2, phase 3, or open-label, long-term extension studies; data at November 2017]. Clinical trial data for tofacitinib-treated patients with rheumatoid arthritis, psoriasis, and psoriatic arthritis are presented for contextualization. RESULTS Week 8 mean change from baseline CK with tofacitinib 10 mg b.d. induction therapy was 91.1 U/L (95% CI, 48.1-134.1) versus 19.2 U/L (8.5-29.9) with placebo. Among patients completing induction with 10 mg b.d. and re-randomized to 52 weeks of maintenance therapy, mean increases from induction baseline to the end of maintenance were 35.9 (8.1-63.7), 90.3 (51.9-128.7), and 115.6 U/L (91.6-139.7), with placebo, 5 and 10 mg b.d., respectively. The incidence rate (unique patients with events per 100 patient-years) for AEs of CK elevation in the tofacitinib-treated UC Overall cohort was 6.6 versus 2.2, 6.5, and 3.7 for tofacitinib-treated patients with rheumatoid arthritis, psoriasis, and psoriatic arthritis, respectively. No serious AEs of CK elevation or AEs of myopathy occurred in UC studies. CONCLUSIONS In patients with UC, CK elevations with tofacitinib appeared reversible and not associated with clinically significant AEs. UC findings were consistent with tofacitinib use in other inflammatory diseases. TRIAL REGISTRATION NCT00787202; NCT01465763; NCT01458951; NCT01458574; NCT01470612; NCT01262118; NCT01484561; NCT00147498; NCT00413660; NCT00550446; NCT00603512; NCT00687193; NCT01059864; NCT01164579; NCT00976599; NCT01359150; NCT02147587; NCT00960440; NCT00847613; NCT00814307; NCT00856544; NCT00853385; NCT01039688; NCT02187055; NCT00413699; NCT00661661; NCT01710046; NCT00678210; NCT01276639; NCT01309737; NCT01241591; NCT01186744; NCT01163253; NCT01877668; NCT01882439; NCT01976364.
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Effects of fiber intake on intestinal pH, transit, and predicted oral mesalamine delivery in patients with ulcerative colitis.
Yao, CK, Burgell, RE, Taylor, KM, Ward, MG, Friedman, AB, Barrett, JS, Muir, JG, Gibson, PR
Journal of gastroenterology and hepatology. 2021;(6):1580-1589
Abstract
BACKGROUND AND AIM Limited data are available on the effects of fermentable fiber in altering intestinal pH and transit to predict efficacy-based delivery profiles of pH-dependent mesalamine coatings in ulcerative colitis (UC). This study aimed to examine regional pH and transit after acute changes in fermentable fiber intake in quiescent UC patients and their effects on drug release systems. METHODS In a randomized, double-blind study, 18 patients with quiescent UC and 10 healthy controls were supplied meals high (13 g) or low (≤ 2 g) in fermentable fiber and subsequently ingested a wireless pH-motility capsule. After a ≥ 3-day washout, they crossed over to the other diet. Measurements of intestinal pH and transit were used to predict drug release for the various pH-dependent coatings. RESULTS Increasing fermentable fiber intake lowered overall (median 6.2 [6.1-6.7] vs low: 6.9 [range or interquartile range: 6.4-7.4]; P = 0.01) and distal pH (7.8 [7.3-8.1] vs 8.2 [8.0-8.5]; P = 0.04) in controls. In UC patients, only cecal pH was decreased (high: 5.1 [4.8-5.5] vs low: 5.5 [5.3-5.7]; P < 0.01). Colonic transit in the UC cohort varied widely after a low-fiber intake but tended to normalize after the high fermentable fiber intake. Hypothetical coating dissolution profiles were heterogeneous in UC patients, with a multi-matrix delayed release system having the highest likelihood of patients (20-40%) with incomplete dissolution, and predominant small intestinal dissolution predicted for Eudragit L (94% patients) and S (44-69%). CONCLUSIONS Patients with quiescent UC have abnormalities in intestinal pH and transit in response to acute changes in fermentable fiber intake. These have potentially detrimental effects on predicted luminal release patterns of pH-dependent 5-aminosalicylic acid release systems.