PUBLICATIONS

2024

Hiramoto B, Muftah M, Flanagan R, Shah ED, Chan WW. Cost-Effectiveness Analysis of Current Treatment Options for Eosinophilic Esophagitis. The American journal of gastroenterology. Published online 2024. doi:10.14309/ajg.0000000000003104

BACKGROUND AND AIMS: The management strategies for eosinophilic esophagitis (EoE) include proton pump inhibitors (PPI), swallowed topical steroids (tCS), elimination diets, and the biologic agent dupilumab, although there remains little guidance on the selection of initial treament. We performed cost-effectiveness analyses to compare these approaches of first-line therapy.

METHODS: A Markov model was constructed from a payer perspective to evaluate the cost-effectiveness of first-line therapies for EoE, including PPI, tCS, and six-food elimination diet (SFED), with.crossover in treatments for primary and secondary non-response. The primary outcome was incremental cost-effectiveness ratio (ICER) at two- and five-year time horizons. Secondary analyses included modeling from a societal perspective that also accounted for patient-specific costs, as well as a separate simplified model comparing dupilumab to tCS and PPI.

RESULTS: In the base-case scenario (five-year time horizon), the average costs were SFED:$15,296.81, PPI:$16,153.77, and tCS:$20,975.33 as initial therapy, with SFED being the dominant strategy (more effective/less costly), while PPI offered the lowest cost on a two-year time horizon. From a societal perspective, PPI was the dominant initial strategy on both two- and five-year time horizons. Amongst pharmacologic therapies, PPI was the most cost-effective first-line option. Dupilumab was not cost-effective relative to tCS, unless the quarterly cost is reduced from $7,311 to $2,038.50 per price threshold analysis under permissive modeling conditions.

CONCLUSIONS: SFED was the most effective/least costly first-line therapy from payer perspective, while PPI was more cost-effective from societal perspective. PPI is also the most cost-effective pharmacologic strategy. Dupilumab requires substantial cost reductions to be considered cost-effective first-line pharmacotherapy.

Shah ED, Chan WW, Jodorkovsky D, et al. Optimizing the Management Algorithm for Heartburn in General Gastroenterology: Cost-Effectiveness and Cost-Minimization Analysis. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association. 2024;22(10):2011-2022.e5. doi:10.1016/j.cgh.2023.08.026

BACKGROUND AND AIMS: Heartburn is the most common symptom seen in gastroenterology practice. We aimed to optimize cost-effective evaluation and management of heartburn.

METHODS: We developed a decision analytic model from insurer and patient perspectives comparing 4 strategies for patients failing empiric proton pump inhibitors (PPIs): (1) PPI optimization without testing, (2) endoscopy with PPI optimization for all patients, (3) endoscopy with PPI discontinuation when erosive findings are absent, and (4) endoscopy/ambulatory reflux monitoring with PPI discontinuation as appropriate for phenotypic management. Health outcomes were respectively defined on systematic reviews of clinical trials. Cost outcomes were defined on Centers for Medicare and Medicaid Services databases and commercial multipliers for direct healthcare costs, and national observational studies evaluating healthcare utilization. The time horizon was 1 year. All testing was performed off PPI.

RESULTS: PPI optimization without testing cost $3784/y to insurers and $3128 to patients due to lower work productivity and suboptimal symptom relief. Endoscopy with PPI optimization lowered insurer costs by $1020/y and added 11 healthy days/y by identifying erosive reflux disease. Endoscopy with PPI discontinuation added 11 additional healthy days/y by identifying patients without erosive reflux disease that did not need PPI. By optimizing phenotype-guided treatment, endoscopy/ambulatory reflux monitoring with a trial of PPI discontinuation was the most effective of all strategies (gaining 22 healthy days/y) and saved $2183 to insurers and $2396 to patients.

CONCLUSIONS: Among patients with heartburn, endoscopy with ambulatory reflux monitoring (off PPI) optimizes cost-effective management by matching treatment to phenotype. When erosive findings are absent, trialing PPI discontinuation is more cost-effective than optimizing PPI.

Leung R, Yeung MLC, Li Y, Muftah M, Chan WW, Leung WK. TEMPORAL TREND OF INCIDENCE AND PREVALENCE OF EOSINOPHILIC ESOPHAGITIS IN ASIA: A SYSTEMATIC REVIEW AND META-ANALYSIS. The American journal of gastroenterology. Published online 2024. doi:10.14309/ajg.0000000000003096

OBJECTIVE: There are limited epidemiological studies on eosinophilic esophagitis (EoE) in Asia. We studied the temporal trend of EoE in Asia, the presenting symptoms and association with atopic diseases.

MATERIALS AND METHODS: Literature search on PubMed, Embase, MEDLINE, Scopus, and Web of Science was performed to retrieve studies published between 1980 and 2023 that reported the prevalence or incidence of EoE in Asia. We employed the random effects model to estimate the pooled incidence and prevalence. I2 index and Cochran Q test were used to assess heterogeneity. Subgroup analyses were conducted for study types, different regions, years of examination, and age groups. The proportion of atopic diseases amongst patients with EoE was described.

RESULTS: 25 studies from Asia were included. The pooled prevalence of EoE was 33.5 cases per 100,000 inhabitants in population-based studies and 11.0 cases per 1000 patients/visitors in hospital-based studies. The incidence rate among children was 12.3 cases per 1,000 patients/visitors, whereas for adults it was only 0.2 cases per 1,000 patients/visitors. Amongst population-based studies, there was an increase in prevalence from 19.8 per 100,000 in 2005-2009 to 73.0 per 100,000 in 2015-2019. Similar upward trend was observed in hospital-based studies conducted during the same time period. Patients with EoE commonly presented with dysphagia (36.3%) and nausea and vomiting (34.6%). History of atopy was reported in 57.2% of EoE patients in Asia.

CONCLUSION: The prevalence and incidence of EoE in Asia have been rising over the past decades. Due to the limited number of Asian studies and variations in subjects' sources, caution should be exercised when interpreting these results.

Gyawali P, Marchetti L, Rogers BD, et al. THE LYON SCORE: A NOVEL REFLUX SCORING SYSTEM BASED ON THE LYON CONSENSUS 2.0 THAT ASSOCIATES WITH TREATMENT OUTCOME FROM ANTI-REFLUX THERAPY. The American journal of gastroenterology. Published online 2024. doi:10.14309/ajg.0000000000003083

BACKGROUND: We explored if a score derived from parameters from esophageal testing could increase confidence in diagnosing conclusive gastroesophageal reflux disease and in predicting outcome.

METHODS: A prediction score was developed using metrics based on Lyon Consensus 2.0 thresholds extracted from endoscopy and pH-impedance monitoring. The Lyon score was the sum of weighted scores derived from a logistic regression model. The outcome was response to anti-reflux therapy, defined as 50% reduction in global symptoms on validated questionnaires. An existing database of endoscopy-negative patients with typical reflux symptoms undergoing esophageal testing from two centers (Europe and US) constituted the developmental cohort, while two separate cohorts (Europe and Asia) served as validation cohorts. Receiver operating characteristics (ROC) analysis determined performance of the Lyon score in predicting treatment response.

RESULTS: In 281 developmental cohort patients (median age 53 years, 57.7% female), the Lyon score demonstrated an AUC of 0.819 in predicting 50% symptom improvement (p<0.001) on ROC, with an optimal threshold of 6.25 (sensitivity 81.2%, specificity 73.4%). Of the individual components, only acid exposure time (AUC 0.799, p<0.001), mean nocturnal baseline impedance (AUC 0.785, p<0.001) and reflux episodes (AUC 0.764, p<0.001) approached the Lyon score performance. The Lyon score segregated treatment response in both the European (AUC 0.908, p<0.001) and Asian validation cohorts (AUC 0.637, p<0.001), and outperformed the DeMeester score in sensitivity for predicting outcome in the developmental and Asian validation cohorts.

CONCLUSION: The novel Lyon score segregates reflux phenotypes, and identifies likelihood of symptom response from antireflux therapy.

Hiramoto B, Flanagan R, Muftah M, Shah ED, Chan WW. Centrally Distributed Adiposity as a Modifiable Risk Factor for Fecal Incontinence: United States Population-based Analysis. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association. 2024;22(9):1908-1916.e1. doi:10.1016/j.cgh.2024.04.002

BACKGROUND AND AIMS: Fecal incontinence (FI) is highly prevalent with substantial impacts on quality of life and health care utilization. The impact of obesity on FI remains unclear, with differing conclusions using body mass index (BMI) as a risk factor. We aimed to determine the association between obesity and FI, and whether this relationship is dependent on the distribution of adiposity (waist circumference-to-height ratio [WHtR]).

METHODS: This was a population-based analysis of the National Health and Nutrition Examination Survey, including participants who responded to the bowel health survey in 2005 to 2010. FI was defined by the accidental bowel leakage of solid stool, liquid, or mucus at least once in the past month. Stepwise multivariable logistic regression models were constructed to assess risk factors for FI.

RESULTS: A total of 7606 participants were included, with an overall FI prevalence of 9.2%. When stratified by quartiles of body measurements, FI was increasingly prevalent from the 1st to the 4th quartile for both WHtR (range, 5.3%-12.5%) and BMI (range, 7.1%-10.5%). WHtR was associated with FI and was a stronger predictor than BMI in all quartiles of body measurement. On multivariable analysis, WHtR remained a significant predictor of FI comparing the 4th with the 1st quartile of body measurements (odds ratio [OR], 1.77; 95% confidence interval [CI], 1.11-2.80; P = .017), whereas BMI was not. A WHtR cutoff of >0.592 optimized the Youden index in prediction of FI in the overall sample.

CONCLUSION: WHtR was independently associated with increased odds of FI in this nationally representative sample of United States adults, whereas BMI was not consistently correlated. This suggests bowel continence may depend more on how body mass is distributed.

Krause AJ, Carlson DA, Chan WW, et al. High Diagnostic Yield of Abnormal Endoscopic Findings in the Evaluation of Laryngopharyngeal Reflux. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association. 2024;22(8):1741-1743.e1. doi:10.1016/j.cgh.2024.01.012

Esophagogastroduodenoscopy (EGD) is recommended in patients with typical gastroesophageal reflux disease (GERD) symptoms (heartburn, regurgitation, chest pain) in the setting of proton pump inhibitor (PPI) nonresponse. EGD evaluates for erosive disease, assesses antireflux barrier integrity, excludes non-GERD conditions, and, in the absence of erosive findings, is followed by reflux testing.1,2 The diagnostic utility of EGD is less clear in the evaluation for laryngopharyngeal reflux (LPR), and the current reference standard is ambulatory reflux monitoring.1,3,4 This study of patients referred for evaluation of chronic laryngeal symptoms had the following aims: (1) to characterize endoscopic findings, (2) to discern whether findings differed between patients with or without concomitant esophageal reflux symptoms, and (3) to measure the association between endoscopic findings and objective GERD on ambulatory reflux monitoring.

Lo WK, Muftah M, Goldberg HJ, Sharma N, Chan WW. Concurrent abnormal non-acid reflux is associated with additional chronic rejection risk in lung transplant patients with increased acid exposure. Diseases of the esophagus : official journal of the International Society for Diseases of the Esophagus. 2024;37(7). doi:10.1093/dote/doae020

Acid reflux has been associated with allograft injury and rejection in lung transplant patients; however, the pathogenic role of non-acid reflux remains debated. We aimed to evaluate the impact of concurrent abnormal non-acid reflux with acid reflux on chronic rejection in lung transplant patients with acid reflux. This was a retrospective cohort study of lung transplant recipients who underwent pre-transplant combined impedance-pH study off acid suppression. Only subjects with acid exposure >4% were included. Non-acid reflux (pH > 4) episodes >27 was considered abnormal per prior normative studies. Chronic rejection was defined as chronic lung allograft dysfunction (CLAD) per International Society for Heart and Lung Transplantation criteria. Time-to-event analyses were performed using Cox proportional hazards and Kaplan-Maier methods, with censoring at death, anti-reflux surgery, or last follow-up. In total, 68 subjects (28 abnormal/40 normal non-acid reflux) met inclusion criteria for the study. Baseline demographic/clinical characteristics were similar between groups. Among this cohort of patients with increased acid exposure, subjects with concurrent abnormal non-acid reflux had significantly higher risk of CLAD than those without on Kaplan-Meier analysis (log-ranked P = 0.0269). On Cox multivariable regression analysis controlling for body mass index, age at transplantation, and proton pump inhibitor use, concurrent abnormal non-acid reflux remained independently predictive of increased CLAD risk (hazard ratio 2.31, confidence interval: 1.03-5.19, P = 0.04). Presence of concurrent abnormal non-acid reflux in lung transplant subjects with increased acid exposure is associated with additional risk of chronic rejection. Non-acid reflux may also contribute to pathogenicity in lung allograft injury/rejection, supporting a potential role for impedance-based testing in this population.