Potential Value of Biomarker-Based Approaches for Evaluation and Management of Costly Functional Gastrointestinal Diseases

Abstract

Functional gastrointestinal disorders including irritable bowel syndrome (IBS) are costly diseases associated with significant direct and indirect costs. This treatise deals predominantly with IBS, and we apply the same principles to another example, functional dyspepsia. Strategies to control direct expenditure in IBS were proposed over 2 decades ago1Camilleri M. Williams D.E. Economic burden of irritable bowel syndrome. Proposed strategies to control expenditures.Pharmacoeconomics. 2000; 17: 331-338Crossref PubMed Scopus (97) Google Scholar and include the education of physicians that manage patients with IBS, education of the patients themselves, introduction of psychological treatments, and addressing psychosocial issues early in the management process, curtailing unnecessary investigations, and developing effective doctor–patient relationships.2Drossman D.A. Chang L. Deutsch J.K. et al.A review of the evidence and recommendations on communication skills and the patient-provider relationship: a Rome Foundation working team report.Gastroenterology. 2021; 161: 1670-1688.e7Abstract Full Text Full Text PDF PubMed Scopus (33) Google Scholar Since then, there has been significant documentation regarding the direct and indirect costs associated with IBS. A prior study evaluated the cost-effectiveness of tests for diarrhea-predominant IBS (IBS-D), but the biomarker tests pertained to investigations to exclude alternative diagnoses, rather than to focus on biomarkers related to the etiopathogenesis of the IBS.3Almario C.V. Noah B.D. Jusufagic A. et al.Cost effectiveness of biomarker tests for irritable bowel syndrome with diarrhea: a framework for payers.Clin Gastroenterol Hepatol. 2018; 16: 1434-1441.e21Abstract Full Text Full Text PDF PubMed Scopus (6) Google Scholar Since that report in 2018, there has been significant advance in the identification of biomarkers and potentially therapeutic reversal of the related mechanisms. The purpose of this review is to introduce the potential of biomarker-based approaches for the evaluation and management of IBS as an alternative to sequential therapeutic trials as proposed in recent guidelines. There are several lines of evidence that document the high cost associated with IBS. First, a study from the United Kingdom4Goodoory V.C. Ng C.E. Black C.J. et al.Direct healthcare costs of Rome IV or Rome III-defined irritable bowel syndrome in the United Kingdom.Aliment Pharmacol Ther. 2022; 56: 110-120Crossref PubMed Scopus (25) Google Scholar has documented direct healthcare costs of Rome IV– or Rome III–defined IBS. Thus, the mean annual direct cost of IBS per person among 752 patients with Rome IV IBS was £556.65 ± 1023.92, and for 995 patients with Rome III IBS, the mean annual direct cost was £474.16 ± 897.86. It was also estimated that the annual direct healthcare cost of IBS in the United Kingdom is £1.27 billion (Rome IV IBS) and £2.07 billion (Rome III IBS). In fact, among patients with Rome IV IBS, mean annual costs were higher in those with opiate use (£907.90 vs £470.58; P < .001), more severe symptoms (P < .001 for trend), shorter duration of IBS (1 year: £1227.14 vs >5 years: £501.60; P = .002), lower quality of life (P < .001 for trend), and higher depression, somatization, and gastrointestinal symptom-specific anxiety score. Second, also from the United Kingdom, symptom subgroups in individuals with IBS predicted disease impact and burden.5Black CJ, Ng CE, Goodoory VC, et al. Novel symptom subgroups in individuals with irritable bowel syndrome predict disease impact and burden. Clin Gastroenterol Hepatol. 2023 Feb 27 [E-pub ahead of print].Google Scholar In this analysis, 7 clusters of patients with IBS were identified based on the presence of diarrhea, constipation, gastrointestinal symptoms, and psychological burden. It was demonstrated that high psychological burden was associated with worse quality of life (both IBS specific and generic), as well as with reduced productivity, ability to work, ability to manage affairs at home, engage in social and private leisure activities, and maintain close relationships. Moreover, high psychological burden was associated with higher IBS-related healthcare costs during the prior year, particularly in patients who had a high degree of gastrointestinal symptoms as well as high psychological burden, which were associated with greater than the equivalent of US$1200 per person per year. Third, a study from the Netherlands6Bosman M, Weerts Z, Snijkers JTW, et al. The socioeconomic impact of irritable bowel syndrome: an analysis of direct and indirect health care costs. Clin Gastroenterol Hepatol. 2023 Jan 31 [E-pub ahead of print].Google Scholar documented the socioeconomic impact of IBS including an analysis of direct and indirect healthcare costs. The total quarterly mean cost per IBS patient was estimated to be $2444, with $1354 indirect costs and $909 direct costs. Factors associated with significantly higher costs were age, male sex, unemployment, increased depressive symptoms, reduced IBS quality of life, and IBS subtypes other than constipation-predominant IBS (IBS-C). Current guidelines for the management of IBS stress the importance of symptom-based diagnosis, as with the Rome criteria, followed by guideline-based treatment.7Lembo A. Sultan S. Chang L. et al.AGA Clinical Practice Guideline on the pharmacological management of irritable bowel syndrome with diarrhea.Gastroenterology. 2022; 163: 137-151Abstract Full Text Full Text PDF PubMed Scopus (24) Google Scholar,8Chang L. Sultan S. Lembo A. et al.AGA Clinical Practice Guideline on the pharmacological management of irritable bowel syndrome with constipation.Gastroenterology. 2022; 163: 118-136Abstract Full Text Full Text PDF PubMed Scopus (25) Google Scholar Given the variation in the iterations of the Rome criteria, as well as multiple deficiencies documented elsewhere9Camilleri M. Irritable bowel syndrome: straightening the road from the Rome criteria.Neurogastroenterol Motil. 2020; 32e13957Crossref Scopus (20) Google Scholar that question the rationale for splitting the different syndromes identified by the criteria such as functional diarrhea and IBS-D, or functional constipation and IBS-C, there has been a plea for simpler identification of the classical symptoms of abdominal pain, bowel dysfunction, and bloating, and exclusion of alarm symptoms in identifying the clinical syndromes. An alternative approach to management is to apply the advances in the application of actionable biomarkers that identify the pathophysiologic mechanisms resulting in the generation of symptoms, followed by individualized therapy directed toward the mechanisms relevant to the individual patient (Figure 1).10Camilleri M. Boeckxstaens G. Irritable bowel syndrome: treatment based on pathophysiology and biomarkers.Gut. 2023; 72: 590-599Crossref PubMed Scopus (8) Google Scholar,11Camilleri M. Chedid V. Actionable biomarkers: the key to resolving disorders of gastrointestinal function.Gut. 2020; 69: 1730-1737Crossref PubMed Scopus (24) Google Scholar The guidance from the American Gastroenterological Association guidelines on the treatment of IBS7Lembo A. Sultan S. Chang L. et al.AGA Clinical Practice Guideline on the pharmacological management of irritable bowel syndrome with diarrhea.Gastroenterology. 2022; 163: 137-151Abstract Full Text Full Text PDF PubMed Scopus (24) Google Scholar,8Chang L. Sultan S. Lembo A. et al.AGA Clinical Practice Guideline on the pharmacological management of irritable bowel syndrome with constipation.Gastroenterology. 2022; 163: 118-136Abstract Full Text Full Text PDF PubMed Scopus (25) Google Scholar is essentially to pursue first the establishment of an optimal provider–patient relationship, education and reassurance, and lifestyle modifications including exercise, sleep, and stress reduction, as well as dietary modifications such as the introduction of fiber supplementation for patients who have constipation. After pursuing these general management strategies, patients with IBS-C are exposed to first- and second-line treatments directed at the constipation and abdominal pain, including osmotic laxatives and antispasmodics as first-line treatment for mild disease, and the introduction of secretagogues for moderate disease. In patients with IBS-D, the therapeutic approaches are treatment with loperamide and an empiric trial of and the same approach for the abdominal patients with severe disease, are particularly which also have an for moderate disease include the and the which has on different The treatment for is abdominal and psychological symptoms are is that there be focus on use of as well as such as therapy or A question that from such guidelines are these approaches for the and the by et Chang L. J.K. et and to irritable bowel syndrome: 2021; PubMed Scopus Google J.K. et costs and of treatments for irritable bowel syndrome with diarrhea: Gastroenterol Hepatol. 2022; Full Text Full Text PDF PubMed Scopus Google J.K. et and psychological treatments for irritable bowel syndrome with cost 2021; Google Scholar have several of the relevant for of IBS. First, from an with treatments for IBS and and is more than with In first IBS treatments for those patients who are to the was associated with a total of with an of in with IBS-D, and a total of and an of in IBS-C with Chang L. J.K. et and to irritable bowel syndrome: 2021; PubMed Scopus Google Scholar Second, from the of a analysis, and patient in and IBS-C have been J.K. et costs and of treatments for irritable bowel syndrome with diarrhea: Gastroenterol Hepatol. 2022; Full Text Full Text PDF PubMed Scopus Google J.K. et and psychological treatments for irritable bowel syndrome with cost 2021; Google Scholar to the cost of the patient and by the individual the cost of treatment for was estimated to be with costs of treatments such as and from to J.K. et costs and of treatments for irritable bowel syndrome with diarrhea: Gastroenterol Hepatol. 2022; Full Text Full Text PDF PubMed Scopus Google Scholar for IBS-C, the cost of treatment was estimated to be and the cost for treatments with and therapy from the patient from to J.K. et and psychological treatments for irritable bowel syndrome with cost 2021; Google Strategies in and Irritable Strategies in per irritable bowel J.K. et costs and of treatments for irritable bowel syndrome with diarrhea: Gastroenterol Hepatol. 2022; Full Text Full Text PDF PubMed Scopus Google irritable bowel J.K. et and psychological treatments for irritable bowel syndrome with cost 2021; Google and in a and In based on the direct and indirect costs of IBS as well as the of is that the sequential application of these pharmacological based on of the of and treatment based on symptoms of diarrhea or constipation significant It is relevant to that the biomarkers are predominantly to exclude diseases such as disease or A study demonstrated that these biomarkers to IBS Thus, among patients with Rome IBS who were the of and had such as or evaluated at a of for IBS S. et biomarkers to irritable bowel Gastroenterol Hepatol. 2022; PubMed Scopus Google Scholar the and investigations, that of and during the first to the of patients who were followed for at year. these also and the were IBS, bowel disease, and disease. 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