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(A) The Bristol Stool Form Scale (BSFS) is a useful tool to evaluate bowel habit. The BSFS has been shown to be a reliable surrogate marker for colonic transit. (B) IBS subtypes should be established according to stool consistency, using the BSFS. IBS subtyping is more accurate when patients have at least 4 days of abnormal bowel habits per month. Bowel habit subtypes should be based on BSFS for days with abnormal bowel habits. Reprinted from Gastroenterology, 150(6), Lacy BE, Mearin F, Chang L, et al, Bowel disorders, 1393, copyright (2016), with permission from Elsevier.⁸
Source publication
Irritable bowel syndrome (IBS) is a functional gastrointestinal (GI) disorder characterized by chronic abdominal pain associated with changes in bowel habits. It is the most common GI problem seen by gastroenterologists. IBS is a heterogenous disorder encompassing a spectrum of underlying mechanisms and clinical presentations. The pathophysiology o...
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Background:
Fibromyalgia and functional gastrointestinal disorders (FGID) including irritable bowel syndrome (IBS) are common conditions presenting in clinical settings and are more prevalent in women. While the relationship between IBS and fibromyalgia has been demonstrated, a review of the prevalence of the broader group of FGID in adults with fi...
Citations
... 37 In March 2017, the Food and Drug Administration (FDA) issued a warning regarding an increased risk of severe pancreatitis in patients receiving eluxadoline treatment without a gallbladder. 38 Additionally, a case of ischaemic colitis was reported, with colonoscopy and histological examination revealing colonic ischaemia involving the entire length of colon. 39 Our study found the risk of ischaemic colitis associated with eluxadoline to be ROR=19. ...
Objective
Drug-induced ischaemic colitis is a significant adverse event (AE) in clinical practice. This study aimed to recognise the top drugs associated with the risk of ischaemic colitis based on the FDA Adverse Event Reporting System (FAERS) database.
Design
A cross-sectional design.
Setting
All data retrieved from the FAERS database from the first quarter of 2004 to the fourth quarter of 2023.
Participants
A total of 5664 drug-induced ischaemic colitis AEs eligible for screening.
Primary and secondary outcome measures
The Medical Dictionary for Regulatory Activities was used to identify ischaemic colitis (code: 10009895) cases. Disproportionality analysis for drug-associated ischaemic colitis signals.
Results
Drug-induced ischaemic colitis AEs were more prevalent in females (60.12%) and individuals aged =65 years (34.25%). The common outcomes were hospitalisation (46.85%) and death (9.73%). Disproportionality analysis identified 91 ischaemic colitis signals and the top 30 drugs mainly involved in the gastrointestinal and nervous systems. The top five drugs with the highest reported OR, proportional reporting ratio, information component and the empirical Bayesian geometric mean, were alosetron, tegaserod, osmoprep, naratriptan and kayexalate. Additionally, 20 of the top 30 drugs did not have ischaemic colitis risk indicated in the package insert.
Conclusions
This study identified key drugs associated with ischaemic colitis, particularly alosetron, tegaserod, osmoprep, naratriptan and kayexalate. Notably, two-thirds of these drugs lacked ischaemic colitis warnings in their package inserts. These findings underscore the need for greater clinical vigilance, improved regulatory oversight and further research to clarify underlying mechanisms and support safer medication use.
... High-fat meals can slow gastric emptying and increase gut motility, triggering abdominal discomfort and diarrhea in some individuals (81). Similarly, alcohol and caffeine, known irritants of the gastrointestinal tract, can aggravate IBS symptoms by promoting bowel irregularities and increasing sensitivity in the gut (82). Furthermore, emerging research has also highlighted the potential role of gut microbiota in the dietary management of IBS. ...
Irritable bowel syndrome (IBS) is a multifaceted gastrointestinal disorder that transcends the gut, affecting the physical, psychological, and social well-being of millions worldwide. Despite its prevalence, IBS remains enigmatic, with no single biomarker or diagnostic test providing clarity. This review explores the intricate interplay of genetic, dietary, and psychological factors that contribute to IBS, revealing its profound impact on both individual lives and society at large. From debilitating gastrointestinal symptoms to comorbid anxiety and depression, the disorder imposes substantial personal and economic burdens. New research shows that the gut-brain axis is a key player in the pathophysiology of IBS, connecting microbial dysbiosis and changes caused by stress. New dietary approaches, like the low FODMAP diet, have shown promise in managing symptoms, but the fact that different patients react differently demonstrates how complicated this condition is. Pharmacological treatments offer limited relief, while psychological therapies, such as cognitive behavioral therapy, address the psychosomatic dimensions of IBS, fostering resilience and coping. This article advocates for a multidisciplinary approach to IBS management, integrating dietary guidance, stress reduction, pharmacotherapy, and psychological support to improve patient outcomes. It also emphasizes the need for future research to unravel IBS's molecular underpinnings and develop targeted therapies. By bridging gaps in understanding and care, this review aims to shed light on the hidden toll of IBS, inspiring innovation and compassion in its treatment.
... While µ-opioid receptor activation slows intestinal transit and reduces gastrointestinal secretion, δ-opioid receptor antagonism weakens these effects. Consequently, bowel function is normalized, producing an effect more similar to the natural physiological activity of the colon, unlike the effects of non-antagonized µ-opioid receptor agonists such as loperamide [32]. Eluxadoline alleviates overall IBS-D symptoms, though its therapeutic effect is more pronounced in reducing diarrhea than in alleviating other general complaints. ...
Irritable bowel syndrome (IBS) is a common and chronic bowel disease which, although it does not lead to severe and permanent complications, significantly deteriorates patients' quality of life. It constitutes a considerable psychological burden for them and also represents a significant socio-economic problem for the healthcare system. Although the cause of the disease is complex and still not fully understood, the update of the Rome criteria has led to significant progress in understanding the pathophysiology of the disease and researching alternative treatment methods. As a result, modern therapeutic approaches can be better tailored to the predominant symptoms and individual needs of the patient. This review compiles the latest research findings on the etiopathogenesis of the disease and discusses available therapeutic strategies, including options unavailable in Poland. This enables a better selection of effective therapy and achievement of satisfactory treatment outcomes through a more individualized approach, tailored to the patient's specific clinical profile.
... El síndrome del intestino irritable (SII) es un trastorno gastrointestinal funcional complejo que se caracteriza por dolor abdominal crónico asociado con la defecación o cambios en la frecuencia o forma de las heces. 1 El SII no es una entidad patológica única, sino un grupo heterogéneo de trastornos que abarcan un espectro de mecanismos fisiopatológicos y presentaciones clínicas. Según el patrón de hábito intestinal, el SII puede agruparse en uno de cuatro subtipos: SII con diarrea predominante (SII-D), SII con estreñimiento predominante (SII-E), SII con hábitos intestinales mixtos (SII-M) o SII no clasificado (SII-U). 1 SII es 1,5 a 2 veces más común en mujeres que en hombres y se diagnostica más comúnmente en personas menores de 50 años. ...
... Entre ellos se pueden mencionar el psyllium, la fibra, antiespasmódicos, el aceite de menta, antidiarreicos, probióticos, antagonista del 5HT3 (alosetrón), antidepresivos tricíclicos, inhibidores selectivos de recaptación de la serotonina/norepinefrina y rifaximina. 1,3 En este documento se plantea evaluar la eficacia y seguridad del uso de eluxadolina en adultos con síndrome del intestino irritable con diarrea. ...
... Mientras que la activación de los receptores opioides μ produce un retraso del tránsito gastrointestinal y una atenuación de la secreción gastrointestinal, el antagonismo del receptor opioide δ parece promover la actividad motora propulsiva del intestino. 1 Se comercializa en comprimidos por vía oral de 75 mg y 100 mg. La dosis recomendada en adultos es de 100 mg dos veces al día con alimentos; mientras que se corrige a 75 mg dos veces al día en personas que no tienen vesícula biliar, o que no pueden tolerar la dosis de 100 mg, o que están recibiendo inhibidores concomitantes de OATP1B, o que tienen insuficiencia hepática leve o moderada. ...
... Experimental therapies such as budesonide, activated charcoal, probiotics, neomycin, and others are partially effective; however, none of these drugs have been studied or approved for managing CRD, and sufficient data is lacking to support their use [6]. Newer medications for treating irritable bowel syndrome with diarrhea (e.g., eluxoladine, alosetron) have not been studied in oncology [21]. Furthermore, available drugs are primarily used for the treatment of CRD rather than its prophylaxis. ...
Purpose
The impact of cancer-related diarrhea (CRD) on changes in cancer therapy remains poorly characterized despite its prevalence.
Methods
We performed a longitudinal observational study using IQVIA PharMetrics Plus claims data. Patients included adults with CRD identified by diagnosis codes or pharmacy claims and compared their outcomes to matched (1:1) patients without CRD. Treatment parameters (discontinuation, persistence, augmentation, dose titration, adherence) were evaluated and stratified for the first cancer therapy (chemotherapy vs. targeted therapy vs. both). A multivariate Cox proportional hazards model was used to estimate the difference in risk of each treatment parameter between cohorts, adjusting for cancer type, therapy, and comorbidities.
Results
We identified 104,135 matched pairs of patients with solid (n = 94,411) or hematologic cancers (n = 9,724) receiving chemotherapy (n = 47,220), targeted therapy (n = 2,427), or both (n = 5,313). Patients with CRD discontinued therapy more frequently than those without CRD (chemotherapy [81.5% vs. 62.3%], targeted therapy [69.2% vs. 64.3%], both [96.0% vs. 85.5%], p < 0.0001). The overall proportion of discontinuation was higher (82.4% vs. 64.6%, p < 0.0001), including a higher risk of discontinuation (HR = 1.40, p < 0.001) for patients with CRD. The mean time to discontinuation (59.6 ± 54.1 vs. 68.3 ± 76.6 days), switch (72.0 ± 48.6 vs. 96.9 ± 84.0 days), persistence (95.1 ± 98.1 vs. 154.3 ± 142.7 days), and adherence (25.5% ± 37.2 vs. 47.9 ± 41%) were all lower (p < 0.0001) among patients with CRD.
Conclusion
Patients who develop CRD undergo significant and clinically impactful index treatment discontinuation, treatment switching, and have lower adherence and persistence of anticancer therapy compared to patients without CRD. Strategies to control CRD to optimize cancer therapy are urgently needed.
... It is an over-thecounter antidiarrheal agent that is commonly used in IBS-D. Unlike eluxadoline, loperamide has unopposed µ-opioid receptor agonism, lacking the attenuating effects of δopioid receptor antagonism [65]. ...
... Agonism of µand κ-opioid receptors slows down motility and decreases visceral pain sensation. Antagonism of δ-opioid receptors counterbalances the inhibitory effects of µ-receptor agonism on gut contractility by promoting motor activity, thereby the antagonism allows for colonic motility that is more physiologic [65]. ...
... Alosetron is a selective 5-HT 3 antagonist with a primary indication for women with severe, chronic IBS-D that has been refractory to other treatment options [85]. While the drug was initially withdrawn due to concerns of ischemic colitis and constipation, it has since been reintroduced in markets [65]. According to an analysis over nine years (2002)(2003)(2004)(2005)(2006)(2007)(2008)(2009)(2010)(2011), the incidence of ischemic colitis remained stable, and the incidence of constipation declined [86]. ...
Irritable bowel syndrome (IBS) is a disorder of the gut–brain axis with pronounced adverse effects on physical health, psychological health, and overall quality of life. Diagnostic strategies can vary, highlighting a need to synthesize best-practice guidelines. Particularly, the American College of Gastroenterology and the British Society of Gastroenterology both support a positive diagnostic strategy; evaluation with C-reactive protein, fecal calprotectin, and fecal lactoferrin; and evaluation with celiac disease serology. Both guidelines do not support routine colonoscopy, and both differ in recommendations for anorectal physiology testing. Given there is currently no curative treatment available, IBS management focuses on symptomatic relief, and challenges exist in achieving and maintaining this relief. Many treatments, both pharmacologic and nonpharmacologic, exist to alleviate the uncomfortable, painful symptoms of the disorder; however, stratifying the quality of evidence behind each option is critical for application to clinical management and for tailoring this management to each patient. Lifestyle adjustments, especially in relation to diet, can be effective first-line therapies and supplements to pharmacologic therapy. Pharmacologic treatment is broadly categorized in accordance with the subtypes of IBS, with indications for different populations and mechanisms that work to target components of IBS pathophysiology. The aim of this article is to comprehensively compare updated diagnostic guidelines, review standard treatments, and outline recent pharmacologic advancements.
... (FDA) has not given it special approval for IBS. [73] The synthesized peripheral μ-opioid receptor agonist loperamide has a limited bioavailability, is not absorbable, and cannot cross the blood-brain barrier. As a result, loperamide limits its effects inside the GI tract and does not have the range of negative effects seen with central opioids. ...
Rifaximin, a broad‐spectrum antibiotic, boasts a unique chemical composition and pharmacokinetic profile, rendering it highly effective in treating irritable bowel syndrome (IBS). Its minimal systemic absorption confines its impact to the gastrointestinal (GI) tract, where it yields significant therapeutic benefits. This review examines rifaximin's physico‐chemical attributes and its role in managing IBS symptoms. Its molecular structure facilitates intestinal lumen retention postoral administration, minimizing systemic exposure and adverse effects. This targeted action is crucial in addressing the gut microbiota's role in IBS pathophysiology. By modifying microbial populations and their metabolite production, rifaximin mitigates symptoms like bloating, irregular bowel habits, and abdominal pain associated with IBS. It achieves this by reducing pathogenic bacteria and altering bacterial metabolism, enhancing mucosal and immune function. Clinical trials affirm rifaximin's superiority over placebo and conventional therapies in alleviating overall IBS symptoms and addressing small intestine bacterial overgrowth (SIBO). Despite its promising efficacy and sustained symptom relief, further research is essential to optimize long‐term effectiveness and dosing regimens. Rifaximin stands as a vital treatment option for IBS due to its distinctive properties and clinical utility; yet, ongoing investigation is imperative for maximizing its therapeutic benefits.
... Experimental therapies such as budesonide, activated charcoal, probiotics, neomycin, and others are partially effective; however, none of these drugs have been studied or approved for managing CRD, and su cient data is lacking to support their use [6]. Newer medications for treating irritable bowel syndrome with diarrhea (e.g., eluxoladine, alosetron) have not been studied in oncology [21]. Furthermore, available drugs are primarily used for the treatment of CRD rather than its prophylaxis. ...
Purpose
The impact of cancer-related diarrhea (CRD) on changes in cancer therapy remains poorly characterized despite its prevalence.
Methods
We performed a longitudinal observational study using IQVIA PharMetrics Plus claims data. Patients included adults with CRD identified by diagnosis codes or pharmacy claims and compared their outcomes to matched (1:1) patients without CRD. Treatment parameters (discontinuation, persistence, augmentation, dose titration, adherence) were evaluated and stratified for the first cancer therapy (chemotherapy vs. targeted therapy vs. both). A multivariate Cox proportional hazards model was used to estimate the difference in risk of each treatment parameter between cohorts, adjusting for cancer type, therapy, and comorbidities.
Results
We identified 104,135 matched pairs of patients with solid (n = 94,411) or hematologic cancers (n = 9,724) receiving chemotherapy (n = 47,220), targeted therapy (n = 2,427), or both (n = 5,313). Patients with CRD discontinued therapy more frequently than those without CRD (chemotherapy [81.5% vs. 62.3%], targeted therapy [69.2% vs. 64.3%], both [96.0% vs. 85.5%], p < 0.0001). The overall proportion of discontinuation was higher (82.4% vs. 64.6%, p < 0.0001), including a higher risk of discontinuation (HR = 1.40, p < 0.001) for patients with CRD. The mean time to discontinuation (59.6 ± 54.1 vs. 68.3 ± 76.6 days), switch (72.0 ± 48.6 vs. 96.9 ± 84.0 days), persistence (95.1 ± 98.1 vs. 154.3 ± 142.7 days), and adherence (25.5%±37.2 vs. 47.9 ± 41%) were all lower (p < 0.0001) among patients with CRD.
Conclusion
Patients who develop CRD undergo significant and clinically impactful index treatment discontinuation, treatment switching, and have lower adherence and persistence of anticancer therapy compared to patients without CRD. Strategies to control CRD to optimize cancer therapy are urgently needed.
... 9 Eluxadoline is a mixed μ-opioid and κ-opioid receptor agonist and δ-opioid receptor antagonist approved for the treatment of diarrhea-predominant irritable bowel syndrome (IBS-D). 10,11 Following oral administration, eluxadoline is poorly absorbed, with an estimated systemic availability of approximately 1%. 12 It has gastrointestinal transit-inhibiting activity, 13 and the safety and effectiveness of eluxadoline to treat the symptoms of IBS-D have been demonstrated in 2 large, randomized, phase 3 clinical studies. [14][15][16] Eluxadoline is generally well tolerated, with incidences of nausea, constipation, and abdominal pain being the most common adverse events. ...
Eluxadoline is approved for the treatment of diarrhea‐predominant irritable bowel syndrome in the United States. The impact of renal impairment on the pharmacokinetic (PK) parameters of eluxadoline is currently unknown. This phase 1, open‐label, parallel‐group study evaluated the PK and safety profile of eluxadoline in 8 participants with renal impairment and 8 matched healthy controls. Of the participants with renal impairment, 2 had severe renal impairment (estimated glomerular filtration rate [eGFR] <30 mL/min/1.73 m²) and 6 had end‐stage renal disease while not yet on dialysis (eGFR <15 mL/min/1.73 m²). The primary objective was to assess plasma and urine PKs, and plasma protein binding of eluxadoline. In participants with renal impairment, mean plasma concentrations of eluxadoline were consistently higher compared with matched healthy controls: 1.4‐fold higher for mean maximum plasma concentration (Cmax) and 2.2‐fold higher for mean area under the plasma concentration‐time curve from time 0 to time t. The median time to Cmax was 2.5 hours in both groups. Although eluxadoline is a locally acting drug with low oral bioavailability, because of the increased systemic exposure in participants with renal impairment as a cautionary measure the lower approved dose of 75 mg twice daily is recommended for individuals with severe renal impairment and end‐stage renal disease while not yet on dialysis. Eluxadoline 100 mg single dose was well tolerated in participants with renal impairment and matched healthy controls.
... For example, the efficacy of eluxadoline could be described in terms of the number of patients that would need to be treated 3 months to avoid one episode of abdominal pain or diarrhoea, in this case between 8 and 33 patients over 3 months. 26 Metrics such as this, however, do not account for adverse events. Using the incremental QALY estimate that integrates gains and losses into a single measure (for eluxadoline, 0.015), it is possible to calculate that 67 patients would need to be treated over their lifetime horizons to gain the equivalent of 1 year in perfect health. ...
Objectives
To evaluate the incremental value of new drugs across disease areas receiving favourable coverage decisions by the UK’s National Institute for Health and Care Excellence (NICE) over the past decade.
Design, setting, and participants
This cross-sectional study assessed favourable appraisal decisions of drugs between 1 January 2010 and 31 December 2020. Estimates of incremental benefit were extracted from NICE’s evidence review groups reports.
Primary outcome measure
Incremental benefit of novel drugs relative to the best alternative therapeutic option, expressed in quality-adjusted life-years (QALYs).
Results
184 appraisals of 129 drugs provided QALYs. The median incremental value was 0.27 QALY (IQR: 0.07–0.73). Benefits varied across drug-indication pairs (range: −0.49 to 5.22 QALY). The highest median benefits were found in haematology (0.70, IQR: 0.55–1.22) and oncology (0.46, IQR: 0.20–0.88), the lowest in ophthalmology (0.09, IQR: 0.04–0.22) and endocrinology (0.02, IQR: 0.01–0.06). Eight appraisals (4.3%) found contributions of more than two QALYs, but one in four (50/184) drug-indication pairs provided less than the equivalent of 1 month in perfect health compared to existing treatments.
Conclusions
In our review period, the median incremental value of novel drugs approved for use within the English National Health System, relative to the best alternative therapeutic option, was equivalent to 3–4 months of life in perfect health, but data were heterogeneous. Objective evaluations of therapeutic value helps patients and physicians to develop reasonable expectations of drugs and delivers insights into disease areas where medicinal therapeutic progress has had the most and least impact.
