Nutrition Assessment and Management in Celiac Disease.

Celiac disease (CeD) is the most common immune condition affecting the gastrointestinal tract; it is triggered by gluten and the only available treatment is a strict gluten-free diet (GFD). Therefore, for patients with CeD, adopting a GFD is not a lifestyle choice. The major problem is that a GFD is restrictive and, like all restrictive diets, it has the potential for adverse nutritional outcomes, especially if adopted for a long term. It is well known that GFD can be nutritionally inadequate and is frequently associated with vitamin and mineral deficiencies; it is also associated with excessive sugar and fat intake, particularly when gluten-free substitutes are consumed. Consequently, people with CeD are affected by higher rates of overweight and obesity and metabolic complications, such as fatty liver and cardiovascular disease. Therefore, assessment of nutritional status and diet quality at diagnosis and while on a long-term GFD is key in the management of CeD. This narrative review addresses nutritional considerations in CeD and management of common challenges associated with a GFD.

Vedolizumab and Ustekinumab Levels in Pregnant Women With Inflammatory Bowel Disease and Infants Exposed In Utero.

BACKGROUND & AIMS: Vedolizumab and ustekinumab pharmacokinetics in pregnancy and the infant after in utero exposure remain incompletely defined. We aim to define the antenatal stability of ustekinumab and vedolizumab levels and the time at which infant drug levels become undetectable. METHODS: This multicenter prospective observational cohort study recruited pregnant or preconception women with inflammatory bowel disease receiving vedolizumab or ustekinumab. Trough drug levels, clinical data, and biochemical data were documented preconception, during each trimester of pregnancy, and postpartum. Maternal and cord blood drug levels were measured at delivery and in infants until undetectable. Infant outcomes were assessed until 2 years of age. RESULTS: A total of 102 participants (vedolizumab, n = 58) were included. The majority of mothers were, and remained, in clinical and biochemical remission. Maternal vedolizumab levels decreased over the course of pregnancy in association with increasing weight, rather than increasing gestation. Maternal ustekinumab levels remained stable. The median time to drug becoming undetectable in the infant was shorter for vedolizumab (11 wk; range, 5-19 wk; n = 32) than ustekinumab (14 wk; range, 9-36 wk; n = 17) and correlated positively with infant delivery level. Thirty-two of 41 (88%) and 17 of 30 (67%) vedolizumab- and ustekinumab-exposed infants had undetectable drug levels by 15 weeks of age, respectively. Pregnancy and infant outcomes were favorable. Twenty infants with undetectable drug levels received the rotavirus vaccine, with no adverse reactions reported. CONCLUSIONS: Maternal vedolizumab levels decreased, whereas ustekinumab levels remained stable over the course of pregnancy. Most vedolizumab- and approximately half of ustekinumab-exposed infants had undetectable drug levels by 15 weeks of age. No concerning maternal or infant safety signals were identified.

Comparison of digitally-delivered gut-directed hypnotherapy program to an active control for irritable bowel syndrome.

OBJECTIVES: Gut-directed hypnotherapy (GDH) treats irritable bowel syndrome (IBS) but its accessibility is limited. This problem may be overcome by digital delivery. This study aimed to perform a randomised control trial comparing the efficacy of a digitally-delivered program with and without GDH in IBS. METHODS: Adults with IBS were randomized to a 42-session daily digital program with the GDH Program (Nerva) or without (Active Control). Questionnaires were completed to assess gastrointestinal symptoms via IBS-SSS, quality of life (IBS-QOL) and psychological symptoms (DASS-21) at regular intervals during the program and 6 months following conclusion on the intervention. The primary endpoint was the proportion of participants with ≥50-point decrease in IBS-SSS between the interventions at the end of the program. RESULTS: Of 240/244 randomized participants, 121 received GDH Program - median age 38 (range 20-65) years, 90% female, IBS-SSS 321 (IQR 273-367) - and 119 Active Control - 36 (21-65), 91% female, IBS-SSS 303 (255-360). At program completion, 81% met the primary endpoint with GDH Program versus 63% Active Control (p=0.002). IBS-SSS was median 208 (IQR 154-265) with GDH and 244 (190-308) with Control (p=0.004), 30% reduction in pain was reported by 71% compared with 35% (p<0.001), and IBS-QOL improved by 14 (6-25) compared with 7 (1-15), respectively (p<0.001). Psychological status improved similarly in both groups. CONCLUSIONS: A digitally-delivered GDH Program provided to patients with IBS was superior to the active control, with greater improvement in both gastrointestinal symptoms and quality of life and provides an equitable alternative to face-to-face behavioural strategies.

People with Inflammatory Bowel Disease Prefer Cognitive Behavioral Therapy for Fatigue Management: A Conjoint Analysis.

BACKGROUND: Psychological interventions are a promising area for fatigue management in patients with inflammatory bowel disease (IBD). However, most interventions trialled to date have been pilots with limited direct input from patients about the type of intervention they want. Thus, this study aimed to explore patient preferences for a psychological IBD fatigue intervention. METHODS: An international online cross-sectional survey was conducted with adults with self-reported IBD. A conjoint analysis was employed to elicit, through a series of forced-choice scenarios, patient preferences for a fatigue intervention. For this study, the attributes manipulated across these forced-choice scenarios were type of intervention, modality of delivery, and duration of intervention. RESULTS: Overall, 834 people with IBD were included in analysis. Respondents ranked the type of psychological intervention as most important for overall preference (with cognitive-behavioral therapy (CBT) preferred over the other approaches), followed by modality of delivery, but placed very little importance on how long the intervention runs for. Patients with IBD appear to most strongly preference a short online CBT intervention for managing their IBD-related fatigue. CONCLUSION: This study helps provide therapists and program developers clear direction on patient preferences when it comes to developing new psychological programs that address fatigue in IBD.

Probiotics: are they beneficial?

There are wide-ranging probiotic choices in Australasia. We reviewed the efficacy of probiotics for the management of gastrointestinal (GI) conditions in adults and assessed relevance to clinical practice. The benefits of probiotics were inconsistent, with a strong consensus reached for only a few of the indications. As different species/strains and combinations differ in efficacy, results cannot be extrapolated from one to another. This review endorses specific probiotics for limited indications. Efficacy of most marketed probiotic formulations remains unstudied and unproven, warranting further research.

Pharmacist-Driven Therapeutic Infliximab Monitoring at the Point of Care Using Rapidly Assessed Drug Levels in Patients with Inflammatory Bowel Disease.

BACKGROUND: Therapeutic monitoring of infliximab is limited by the time lag between drug-level measurement and dose adjustment, along with the cost of dose escalation. Strategies for dose reduction in stable patients on maintenance infliximab at supratherapeutic levels are uncertain. This study determined the feasibility of a pharmacist-driven strategy for immediate dose adjustment using a sliding scale at the point of care in stable patients with inflammatory bowel disease on maintenance therapy. METHODS: Adult patients with stable disease undergoing maintenance therapy with infliximab infusions, 5 mg/kg every 8 weeks, were prospectively studied. Trough drug levels were assessed by a rapid assay (and later by ELISA) at all infusions for up to 12 months with immediate but quantitatively small dose adjustment according to a sliding scale targeting a therapeutic range of 3-7 mcg/mL. Disease activity was assessed both clinically and biochemically. RESULTS: The rapid assay and ELISA detected similar infliximab levels, and the strategy added approximately 30 minutes to the duration of infusion events. Only 20% of 48 patients (77% with Crohn disease) had baseline trough infliximab concentrations within the therapeutic range. This value increased 3-fold after 24 and 48 weeks of interventions. One in 2 patients had baseline supratherapeutic levels, and most were brought into the therapeutic range without a discernible impact on disease activity by 1 dose adjustment, but 2 or 3 adjustments were generally needed for 29% of patients with subtherapeutic levels. Overall, drug costs were reduced by 4%. CONCLUSIONS: Immediate dose adjustment after infliximab rapid assay performed by a pharmacist using a sliding scale is a feasible strategy. Supratherapeutic infliximab levels can be safely and quickly brought into the therapeutic range using small dose adjustments without affecting disease activity, offsetting (at least partly) costs associated with dose escalation.

Asia-Pacific guidelines for managing functional dyspepsia overlapping with other gastrointestinal symptoms.

Contemporary systems for the diagnosis and management gastrointestinal symptoms not attributable to organic diseases (Functional GI Disorders, FGID, now renamed Disorders of Gut-Brain Interaction, DGBI) seek to categorize patients into narrowly defined symptom-based sub-classes to enable targeted treatment of patient cohorts with similar underlying putative pathophysiology. However, an overlap of symptom categories frequently occurs and has a negative impact on treatment outcomes. There is a lack of guidance on their management. An Asian Pacific Association of Gastroenterology (APAGE) working group was set up to develop clinical practice guidelines for management of patients with functional dyspepsia (FD) who have an overlap with another functional gastrointestinal disorder: FD with gastroesophageal reflux (FD-GERD), epigastric pain syndrome with irritable bowel syndrome (EPS-IBS), postprandial distress syndrome with IBS (PDS-IBS), and FD-Constipation. We identified putative pathophysiology to provide a basis for treatment recommendations. A management algorithm is presented to guide primary and secondary care clinicians.

Behavioral and Diet Therapies in Integrated Care for Patients With Irritable Bowel Syndrome.

Irritable bowel syndrome (IBS) is a common, symptom-based condition that has negative effects on quality of life and costs health care systems billions of dollars each year. Until recently, management of IBS has focused on over-the-counter and prescription medications that reduce symptoms in fewer than one-half of patients. Patients have increasingly sought natural solutions for their IBS symptoms. However, behavioral techniques and dietary modifications can be effective in treatment of IBS. Behavioral interventions include gastrointestinal-focused cognitive behavioral therapy and gut-directed hypnotherapy to modify interactions between the gut and the brain. In this pathway, benign sensations from the gut induce maladaptive cognitive or affective processes that amplify symptom perception. Symptoms occur in response to cognitive and affective factors that trigger fear of symptoms or lack of acceptance of disease, or from stressors in the external environment. Among the many dietary interventions used to treat patients with IBS, a diet low in fermentable oligosaccharides, disaccharides, monosaccharides, and polyols is the most commonly recommended by health care providers and has the most evidence for efficacy. Patient with IBS who choose to follow a diet low in fermentable oligosaccharides, disaccharides, monosaccharides, and polyols should be aware of its 3 phases: restriction, reintroduction, and personalization. Management of IBS should include an integrated care model in which behavioral interventions, dietary modification, and medications are considered as equal partners. This approach offers the greatest likelihood for success in management of patients with IBS.

Comparing Costs and Outcomes of Treatments for Irritable Bowel Syndrome With Diarrhea: Cost-Benefit Analysis.

BACKGROUND: Irritable bowel syndrome (IBS) is one of the most expensive gastroenterological conditions and is an ideal target for developing a value-based care model. We assessed the comparative cost-benefit of treatments for IBS with diarrhea (IBS-D), the most common IBS subtype from insurer and patient perspectives. METHODS: We constructed a decision analytic model assessing trade-offs among guideline-recommended and recently FDA-approved drugs, supplements, low FODMAP diet, cognitive behavioral therapy (CBT). Outcomes and costs were derived from systematic reviews of clinical trials and national databases. Health-gains were represented using quality-adjusted life years (QALY). RESULTS: From an insurer perspective, on-label prescription drugs (rifaximin, eluxadoline, alosetron) were significantly more expensive than off-label treatments, low FODMAP, or CBT. Insurer treatment preferences were driven by average wholesale prescription drug prices and were not affected by health gains in sensitivity analysis within standard willingness-to-pay ranges up to $150,000/QALY-gained. From a patient perspective, prescription drug therapies and neuromodulators appeared preferable due to a reduction in lost wages due to IBS with effective therapy, and also considering out-of-pocket costs of low FODMAP food and out-of-pocket costs to attend CBT appointments. Comparative health outcomes exerted influence on treatment preferences from a patient perspective in cost-benefit analysis depending on a patients' willingness-to-pay threshold for additional health-gains, but health outcomes were less important than out-of-pocket costs at lower willingness-to-pay thresholds. CONCLUSIONS: Costs are critical determinants of IBS treatment value to patients and insurers, but different costs drive patient and insurer treatment preferences. Divergent cost drivers appear to explain misalignment between patient and insurer IBS treatment preferences in practice.

Supplementing Dietary Fibers With a Low FODMAP Diet in Irritable Bowel Syndrome: A Randomized Controlled Crossover Trial.

BACKGROUND & AIMS: Institution of a diet low in fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAPs) in patients with irritable bowel syndrome (IBS) may lead to inadequate fiber intake. This trial aimed to investigate the effects of supplementing specific fibers concomitantly with a low FODMAP diet on relevant clinical and physiological indices in symptomatic patients with IBS. METHODS: A double-blind crossover trial was conducted in which 26 patients with IBS were randomly assigned to 1 of 3 low FODMAP diets differing only in total fiber content: control, 23 g/d; sugarcane bagasse, 33 g/d; or fiber combination (sugarcane bagasse with resistant starch), 45 g/d. Each diet lasted 14 days with most food provided and ≥21 days' washout between. Endpoints were assessed during baseline and dietary interventions. RESULTS: From a median IBS Severity Scoring System total score at baseline of 305, all diets reduced median scores by >50 with no differences in rates of symptom response between the diets: control (57%), sugarcane bagasse (67%), fiber combination (48%) (P = .459). Stool output was ∼50% higher during the fiber-supplemented vs control diets (P < .001 for both). While there were no overall differences overall in stool characteristics, descriptors, and water content, or in gastrointestinal transit times, supplementation with sugarcane bagasse normalized both low stool water content and slow colonic transit from during the control diet. CONCLUSIONS: Concomitant supplementation of fibers during initiation of a low FODMAP diet did not alter symptomatic response in patients with IBS but augmented stool bulk and normalized low stool water content and slow transit. Resistant starch did not exert additional symptomatic benefits over sugarcane bagasse alone. (Australia and New Zealand Clinical Trial Registry; Number, ACTRN12619000691145).

The Role of Food in the Treatment of Bowel Disorders: Focus on Irritable Bowel Syndrome and Functional Constipation.

Irritable bowel syndrome (IBS) and functional constipation (FC) are among the most common disorders of gut-brain interaction, affecting millions of individuals worldwide. Most patients with disorders of gut-brain interaction perceive food as a trigger for their gastrointestinal symptoms, and specific dietary manipulations/advice have now been recognized as a cornerstone therapeutic option for IBS and FC. We discuss in detail the 2 most common dietary interventions used for the management of IBS-general dietary advice based on the National Institute for Health and Care Excellence guidelines and a diet low in fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAPs). We summarize the literature around the possible mechanisms of FODMAP-mediated IBS pathophysiology, the current 3-step, top-down approach of administering a low FODMAP diet (LFD) (restriction phase, followed by reintroduction and personalization), the efficacy data of its restriction and personalization phases, and possible biomarkers for response to an LFD. We also summarize the limitations and challenges of an LFD along with the alternative approach to administering an LFD (e.g., bottom-up). Finally, we discuss the available efficacy data for fiber, other dietary interventions (e.g., Mediterranean diet, gluten-free diet, and holistic dietary interventions), and functional foods (e.g., kiwifruit, rhubarb, aloe, and prunes) in the management of IBS and FC.

Therapeutic Potential of the 4 Strategies to SUlfide-REduction (4-SURE) Diet in Adults with Mild to Moderately Active Ulcerative Colitis: An Open-Label Feasibility Study.

BACKGROUND: Diet therapy may bridge the therapeutic gap in ulcerative colitis (UC). OBJECTIVES: The novel 4-SURE diet (4-strategies-to-SUlfide-REduction), designed to modulate colonic fermentation and influence production of excess hydrogen sulfide, was examined in a feasibility study for tolerability, clinical efficacy, and effects on microbial endpoints. METHODS: Adults aged ≥18 y old with mild to moderately active UC were advised to increase intake of fermentable fibers, restrict total and sulfur-containing proteins, and avoid specific food additives for 8 wk. The primary outcome was tolerability of diet [100-mm visual analogue scale (VAS) with 100-mm being intolerable]. Secondary exploratory outcomes were self-reported adherence (always adherent ≥76-100%), clinical and endoscopic response (reduction in partial Mayo ≥2 and Mayo endoscopic subscore ≥1), modulation of fecal characteristics including markers of protein and carbohydrate fermentation, and food-related quality of life (IBD-FRQoL-29). Primary analysis was by intention to treat, performed using paired t and Wilcoxon signed-rank statistical tests. RESULTS: Twenty-eight adults with UC [mean (range) age: 42 (22-72) y, 15 females, 3 proctitis, 14 left-sided, and 11 extensive] were studied. Prescribed dietary targets were achieved overall. The diet was well tolerated (VAS: 19 mm; 95% CI: 7, 31 mm) with 95% frequently or always adherent. Clinical response occurred in 13 of 28 (46%) and endoscopic improvement in 10 of 28 participants (36%). Two participants (7%) worsened. Fecal excretion of SCFAs increased by 69% (P < 0.0001), whereas the proportion of branched-chain fatty acids to SCFAs was suppressed by 27% (-1.34%; 95% CI: -2.28%, -0.40%; P = 0.007). The FRQoL improved by 10 points (95% CI: 4, 16; P < 0.001). CONCLUSIONS: The 4-SURE dietary strategy is considered tolerable and an acceptable diet by adults with mild to moderately active UC. The dietary teachings achieved the prescribed dietary and fecal targets. Given signals of therapeutic efficacy, further evaluation of this diet is warranted in a placebo-controlled trial. This trial was registered at https://www.anzctr.org.au (Australian New Zealand Clinical Trials Registry) as ACTRN12619000063112.

Hypermobile Ehlers-Danlos syndrome and disorders of the gastrointestinal tract: What the gastroenterologist needs to know.

BACKGROUND AND AIM: Hypermobile Ehlers-Danlos syndrome (hEDS) and the hypermobility spectrum disorders (HSD) can be challenging to diagnose and manage. Gastrointestinal symptoms and disorders of gut-brain interaction are common in this cohort and multifactorial in origin. The primary aim of this review is to arm the gastroenterologist with a clinically useful understanding of HSD/hEDS, by exploring the association of gastrointestinal disorders with HSD/hEDS, highlighting current pathophysiological understanding and providing a pragmatic approach to managing these patients. METHODS: Literature relevant to the gastrointestinal system and hypermobile Ehlers-Danlos syndrome was systematically searched, critically appraised, and summarized. RESULTS: Diagnosis is based upon clinical criteria and a genetic basis is yet to be defined. The prevalence of many gut symptoms, including abdominal pain (69% vs 27%, P < 0.0001), postprandial fullness (34% vs 16%, P = 0.01), constipation (73% vs 16%, P < 0.001), and diarrhea (47% vs 9%, P < 0.001) are significantly higher in HSD/hEDS compared with non-HSD/hEDS individuals. Disorders of gut-brain interaction are also common, particularly functional dyspepsia. The pathophysiology of gut symptoms is poorly understood but may involve effects of connective tissue laxity and its functional consequences, and the influence of autonomic dysfunction, medication and comorbid mental health disorders. Awareness is the key to early diagnosis. Management is limited in evidence-base but ideally should include an integrated multidisciplinary approach. CONCLUSIONS: HSD/hEDS is a multisystemic disorder in which gastrointestinal symptoms, particularly related to disorders of gut-brain interaction are common. Deficiencies in knowledge regarding the pathophysiological processes limit evidence-based interventions and remain important areas for future research.

Diet as a therapeutic tool in chronic gastrointestinal disorders: Lessons from the FODMAP journey.

BACKGROUND AND AIM: Diet is a powerful tool in the management of gastrointestinal disorders, but developing diet therapies is fraught with challenge. This review discusses key lessons from the FODMAP diet journey. METHODS: Published literature and clinical experience were reviewed. RESULTS: Key to designing a varied, nutritionally adequate low-FODMAP diet was our accurate and comprehensive database of FODMAP composition, made universally accessible via our user-friendly, digital application. Our discovery that FODMAPs coexist with gluten in cereal products and subsequent gluten/fructan challenge studies in nonceliac gluten-sensitive populations highlighted issues of collinearity in the nutrient composition of food and confirmation bias in the interpretation of dietary studies. Despite numerous challenges in designing, funding, and executing dietary randomized controlled trials, efficacy of the low-FODMAP diet has been repeatedly demonstrated, and confirmed by real-world experience, giving this therapy credibility in the eyes of clinicians and researchers. Furthermore, real-world application of this diet saw the evolution of a safe and effective three-phased approach. Specialist dietitians must deliver this diet to optimize outcomes as they can target and tailor the therapy and to mitigate the key risks of compromising nutritional adequacy and precipitating disordered eating behaviors, skills outside the gastroenterologist's standard tool kit. While concurrent probiotics are ineffective, specific fiber supplements may improve short-term and long-term outcomes. CONCLUSIONS: The FODMAP diet is highly effective, but optimal outcomes are contingent on the involvement of a gastroenterological dietitian who can assess, educate, and monitor patients and manage risks associated with implementation of this restrictive diet.

Self-Worth Beliefs Predict Willingness to Engage in Psychotherapy for Fatigue in Inflammatory Bowel Disease.

BACKGROUND: Fatigue in inflammatory bowel disease (IBD) is poorly controlled, with few existing interventions. Psychotherapy interventions for IBD fatigue show promise; however, due to mixed findings in efficacy and attrition, current interventions need improvement. Some research shows beliefs about psychotherapy and stigma toward psychotherapy may impact engagement in psychotherapy interventions. AIMS: This study aimed to examine the effects of IBD activity, fatigue, mental health status, previous experience with psychotherapy, and stigma toward psychotherapy on willingness to use psychotherapy as a fatigue intervention. METHODS: An online cross-sectional survey was conducted, and linear regression models were used to examine willingness to engage in psychotherapy for fatigue. RESULTS: Overall, 834 participants completed the survey. Regression analysis examining demographics, mental health status, IBD activity, fatigue, pain, antidepressant use, psychotherapy experience, and self-worth intervention efficacy belief significantly explained 25% of variance in willingness to use psychotherapy for fatigue. Significant factors included antidepressant use (b = .21, p < .01), pain (b = - .05, p < .001), and self-worth intervention belief (b = - .27, p < .001), which uniquely explained 18% of variance in the outcome. CONCLUSIONS: Willingness to engage in psychotherapy for fatigue in IBD appears to be driven by expectations related to specific self-worth beliefs, rather than stigma, IBD activity, or any prior experience with psychotherapy. Clinicians should directly address these expectations with their patients.

Dietary fibres and IBS: translating functional characteristics to clinical value in the era of personalised medicine.

Clinical guidelines in the use of fibre supplementation for patients with IBS provide one-size-fits-all advice, which has limited value. This narrative review addresses data and concepts around the functional characteristics of fibre and subsequent physiological responses induced in patients with IBS with a view to exploring the application of such knowledge to the precision use of fibre supplements. The key findings are that first, individual fibres elicit highly distinct physiological responses that are associated with their functional characteristics rather than solubility. Second, the current evidence has focused on the use of fibres as a monotherapy for IBS symptoms overall without attempting to exploit these functional characteristics to elicit specific, symptom-targeted effects, or to use fibre types as adjunctive therapies. Personalisation of fibre therapies can therefore target several therapeutic goals. Proposed goals include achieving normalisation of bowel habit, modulation of gut microbiota function towards health and correction of microbial effects of other dietary therapies. To put into perspective, bulking fibres that are minimally fermented can offer utility in modulating indices of bowel habit; slowly fermented fibres may enhance the activities of the gut microbiota; and the combination of both fibres may potentially offer both benefits while optimising the activities of the microbiota throughout the different regions of the colon. In conclusion, understanding the GI responses to specific fibres, particularly in relation to the physiology of the individual, will be the future for personalising fibre therapy for enhancing the personalised management of patients with IBS.

Contrasting Clinician and Insurer Perspectives to Managing Irritable Bowel Syndrome: Multilevel Modeling Analysis.

INTRODUCTION: Insurance coverage is an important determinant of treatment choice in irritable bowel syndrome (IBS), often taking precedence over desired mechanisms of action or patient goals/values. We aimed to determine whether routine and algorithmic coverage restrictions are cost-effective from a commercial insurer perspective. METHODS: A multilevel microsimulation tracking costs and outcomes among 10 million hypothetical moderate-to-severe patients with IBS was developed to model all possible algorithms including common global IBS treatments (neuromodulators; low fermentable oligo-, di-, and mono-saccharides, and polyols; and cognitive behavioral therapy) and prescription drugs treating diarrhea-predominant IBS (IBS-D) or constipation-predominant IBS (IBS-C) over 1 year. RESULTS: Routinely using global IBS treatments (central neuromodulator; low fermentable oligo-, di-, and mono-saccharides, and polyols; and cognitive behavioral therapy) before US Food and Drug Administration-approved drug therapies resulted in per-patient cost savings of $9,034.59 for IBS-D and $2,972.83 for IBS-C over 1 year to insurers, compared with patients starting with on-label drug therapy. Health outcomes were similar, regardless of treatment sequence. Costs varied less than $200 per year, regardless of the global IBS treatment order. The most cost-saving and cost-effective IBS-D algorithm was rifaximin, then eluxadoline, followed by alosetron. The most cost-saving and cost-effective IBS-C algorithm was linaclotide, followed by either plecanatide or lubiprostone. In no scenario were prescription drugs routinely more cost-effective than global IBS treatments, despite a stronger level of evidence with prescription drugs. These findings were driven by higher prescription drug prices as compared to lower costs with global IBS treatments. DISCUSSION: From an insurer perspective, routine and algorithmic prescription drug coverage restrictions requiring failure of low-cost behavioral, dietary, and off-label treatments appear cost-effective. Efforts to address insurance coverage and drug pricing are needed so that healthcare providers can optimally care for patients with this common, heterogenous disorder.

Screening dietary fibres for fermentation characteristics and metabolic profiles using a rapid in vitro approach: implications for irritable bowel syndrome.

The therapeutic value of specific fibres is partly dependent on their fermentation characteristics. Some fibres are rapidly degraded with the generation of gases that induce symptoms in patients with irritable bowel syndrome (IBS), while more slowly or non-fermentable fibres may be more suitable. More work is needed to profile a comprehensive range of fibres to determine suitability for IBS. Using a rapid in vitro fermentation model, gas production and metabolite profiles of a range of established and novel fibres were compared. Fibre substrates (n 15) were added to faecal slurries from three healthy donors for 4 h with gas production measured using real-time headspace sampling. Concentrations of SCFA and ammonia were analysed using GC and enzymatic assay, respectively. Gas production followed three patterns: rapid (≥60 ml/g over 4 h) for fructans, carrot fibre and maize-derived xylo-oligosaccharide (XOS); mild (30-60 ml/g) for partially hydrolysed guar gum, almond shell-derived XOS and one type of high-amylose resistant starch 2 (RS2) and minimal (no differences with blank controls) for methylcellulose, another high-amylose RS2, acetylated or butyrylated RS2, RS4, acacia gum and sugarcane bagasse. Gas production correlated positively with total SCFA (r 0·80, P < 0·001) and negatively with ammonia concentrations (r -0·68, P < 0·001). Proportions of specific SCFA varied: fermentation of carrot fibre, XOS and acetylated RS2 favoured acetate, while fructans favoured butyrate. Gas production and metabolite profiles differed between fibre types and within fibre classes over a physiologically relevant 4-h time course. Several fibres resisted rapid fermentation and may be candidates for clinical trials in IBS patients.

Comparison of SB2-Infliximab With Originator-Infliximab in the Measurement of Serum Concentrations: A Short Communication.

BACKGROUND: The optimal use of infliximab depends on the measurement of trough levels with subsequent appropriate dose adjustment. With the introduction of biosimilars, it is important to demonstrate that the biosimilar behaves similarly in the assay used as the originator-infliximab, for which the assays were developed. In this study, the authors aimed to compare the concentrations of SB2-infliximab (Renflexis) with that of originator-infliximab (Remicade) when added to serum from healthy subjects and those with inflammatory bowel disease when measured by commonly used commercial assays. METHODS: Sera from 2 healthy controls, 2 patients with ulcerative colitis (1 with quiescent disease and 1 with active disease), and 2 patients with Crohn disease (1 with quiescent disease and 1 with active disease) were spiked with SB2-infliximab or originator-infliximab at 0-20 mcg/mL. Concentrations were measured using 3 commonly used assay kits (Lisa-Tracker, Shikari Q-Inflix, Promonitor IFX) and one rapid test (Quantum Blue). The results were compared using Bland-Altman techniques. RESULTS: Close agreement was observed between measured concentrations for all assays, irrespective of the origin of the serum. Limits of agreement varied between at worst -0.302 and 0.465 mcg/mL, with the mean difference between the molecules being at worst 0.04 mcg/mL (95% confidence intervals, -0.011 to 0.093). CONCLUSIONS: The originator and SB-2 biosimilar-infliximab behaved similarly in several currently used assays in their concentrations in biological fluids. Clinicians can be confident that therapeutic drug monitoring using platforms designed and developed for the originator-infliximab can be applied to SB-2-infliximab.

Thiopurines and their optimization during infliximab induction and maintenance: A retrospective study in Crohn's disease.

BACKGROUND AND AIM: Combining therapy with a thiopurine is favored when commencing infliximab in Crohn's disease; however, the optimal 6-thioguanine nucleotide (TGN) level and how long to continue thiopurines after induction are uncertain. We aimed to compare outcomes after induction and during maintenance in combination therapy versus infliximab monotherapy in Crohn's and to examine whether TGN levels were associated with outcomes. METHODS: Crohn's patients induced with infliximab with or without concomitant thiopurines were retrospectively identified. Response to induction and clinical outcomes in subsequent 6-month maintenance semesters were analyzed. A TGN level ≥235 pmol/8 × 108 red blood cells was considered therapeutic. RESULTS: In 89 patients, response to induction was higher in combination therapy than monotherapy (74 vs 47%, P = 0.04). This benefit was only seen in patients with a therapeutic TGN (odds ratio 3.72, confidence interval 1.07-13.0, P = 0.04). Combination therapy during induction yielded a three times longer time to subsequent need for treatment escalation or treatment failure compared with monotherapy (29 vs 9 months, P = 0.01), with both therapeutic and subtherapeutic TGNs independent predictors on multivariate analysis. Among 370 semesters, there was no difference in outcomes between combination therapy and monotherapy (P = 0.42), nor when combination semesters were stratified by therapeutic versus subtherapeutic TGN (P = 0.56). In semester 1 only, a significantly higher remission rate was observed with therapeutic compared with subtherapeutic TGN (76% vs 33%, P = 0.02). CONCLUSIONS: Combination therapy dosed with an optimized thiopurine was superior to infliximab monotherapy for induction of response, durability of response, and clinical outcomes in the first 6 months following induction. Thereafter, combination therapy yielded no clinical advantage, supporting consideration of thiopurine withdrawal on a case-by-case basis.