A Linked Electronic Medical Record-Claims Analysis of the Clinical and Economic Outcomes of Patients Coded for Erosive Esophagitis in the United States.

INTRODUCTION: Erosive esophagitis (EE) is a severe form of gastroesophageal reflux disease commonly treated with proton pump inhibitors (PPIs). The aim of this retrospective, observational cohort study was to describe the characteristics and healthcare burden of patients with EE. METHODS: We identified adults in the USA with an EE diagnosis between January  1, 2016 and February 28, 2019 in a linked dataset containing electronic health records (EHR) from the Veradigm Network EHR and claims data from Komodo Health. Patients were required to have 1 year of baseline data and 3 years of follow-up data. Patients were stratified by the number of PPI lines of therapy (LOT) during the 4-year study period. We descriptively captured patient characteristics and treatment patterns, along with all-cause and EE-related healthcare utilization and costs. RESULTS: Among the 158,347 qualifying adults with EE, 71,958 (45.4%) had 1 PPI LOT, 14,985 (9.5%) had 2 LOTs, 15,129 (9.6%) had 3+ LOTs, and 56,275 (35.5%) did not fill a PPI prescription. Omeprazole and pantoprazole comprised more than 70% of any LOT, with patients commonly switching between the two. Mean (standard deviation) annualized all-cause and EE-related healthcare costs in the follow-up period were $16,853 ($70,507) and $523 ($3659), respectively. Both all-cause and EE-related healthcare costs increased with LOTs. CONCLUSIONS: Patients with EE are commonly treated with prescription PPIs; however, 19.0% of patients cycled through multiple PPIs. Higher PPI use was associated with a higher comorbidity burden and higher healthcare costs compared to 0 PPI use.

The appropriate use of proton-pump inhibitors.

The introduction of proton-pump inhibitors (PPIs) into clinical practice since about thirty years has greatly improved our therapeutic approach to acid-related diseases for their well recognized efficacy and safety. Accordingly, the role of surgery has been enormously reduced in this field. The main indications for PPI use are universally acknowledged by many scientific societies and are the following: treatment of gastroesophageal reflux disease in its various forms and complications, eradication of H. pylori infection in combination with two or more antibiotics, therapy of H. pylori-negative peptic ulcers, healing and prevention of NSAID-associated gastric ulcers, co-therapy with endoscopic procedures to control upper digestive bleeding and medical treatment of Zollinger-Ellison Syndrome. Despite the above well-defined indications, however, the use of PPIs continues to grow every year in both Western and Eastern countries and this phenomenon poses serious queries about the appropriate prescription of these drugs worldwide. In fact, the endless expansion of PPI market has created important problems for many regulatory authorities for two relevant features: the progressive and irreversible increase of the costs of therapy with this class of drugs and the greater potential harms for the patients. So, there is the need for a reappraisal of PPI correct indications for both general practitioners and various specialists in order to re-establish a correct use of these effective drugs in daily clinical practice, according to the best evidence-based guidelines.

A health insurance company-initiated multifaceted intervention for optimizing acid-suppressing drug prescriptions in primary care: a randomized controlled trial.

OBJECTIVE: To evaluate the effectiveness of a health insurance company-initiated intervention strategy aimed at optimizing acid-suppressing drug (ASD) prescriptions in primary care. METHODS: In a cluster randomized controlled trial design, 112 primary care physician (PCP) peer review groups (993 PCPs) in the central region of the Netherlands were randomized. The PCPs in the intervention group received an ASD prescription optimization protocol, a list of their patients taking ASDs frequently on a long-term basis, and financial compensation for additional consultations with these patients. The PCPs in the control group did not receive any of these interventions. Prescription data on 23 433 patients were extracted from the database of the regional health insurance company. The main outcome measures were the proportion of patients who reduced ASD consumption by more than 50% and changes in annual volume and costs of ASD prescriptions. Differences in ASD reduction and in volume were analyzed applying multilevel regression analyses. RESULTS: At baseline, 2.4% of the patients (n = 967 506) of the participating practices used ASDs frequently on a long-term basis (>180 daily defined doses [DDDs] annually). During the 6-month intervention, 14.1% of the patients in the intervention group reduced ASD consumption compared with 13.7% in the control group (adjusted relative risk, 1.04; 95% confidence interval [CI], 0.97-1.11). Changes in intervention and control group in mean volume of ASD prescription per patient were similar (beta = 0.33 for DDD; 95% CI -3.00 to 3.60). CONCLUSIONS: A health insurance company-initiated multifaceted intervention, including practical tools and financial incentives, did not alter ASD prescription practice in primary care. More tailored interventions, including patient-targeted initiatives, are required to optimize ASD prescription.

Overutilization of proton pump inhibitors: a review of cost-effectiveness and risk [corrected].

Proton pump inhibitors (PPIs) are superior to histamine-2 receptor antagonists for the treatment of gastroesophageal reflux disease (GERD) and erosive esophagitis. Antisecretory therapy (AST), however, accounts for significant cost expenditure in the United States including over-the-counter and prescription formulations. Moreover, emerging data illustrate the potential risks associated with long-term PPI therapy including variations in bioavailability of common medications, vitamin B12 deficiency, Clostridium difficile-associated diarrhea, community-acquired pneumonia, and hip fracture. For these reasons, it is imperative to use the lowest dose of drug necessary to achieve desired therapeutic goals. This may entail the use of step-down, step-off, or on-demand PPI therapy for the treatment of GERD. In addition, PPIs are the most commonly used medications for stress ulcer prophylaxis (SUP), despite little evidence to support their use. Compounding this problem is evidence that patients erroneously administered SUP are often discharged on long-term PPI therapy. Pharmacy-driven step-down orders, limitation of the use of PPIs for SUP in non-ICU settings, and meticulous chart review to ensure that hospitalized patients are not discharged home on a PPI without an appropriate indication are interventions that can ensure proper PPI utilization with minimal of risk and optimization of cost-effectiveness.

An urn model for odds-ratio-based response-adaptive phase III clinical trials for two or more treatments.

Adaptive data-dependent allocation designs are used in phase III clinical trials having two or more competing treatments with sequential entrance of patients, in order to allocate a larger number of patients to the better treatment. The odds ratio is a popular concept for biomedical practitioners; hence, odds-ratio-based adaptive designs could be very useful in practice. Rosenberger et al. (2001) introduced an odds-ratio-based two-treatment response-adaptive design; however, they did not study the properties in details. In this article, we describe these designs by means of urn models and provide limiting results for them. Some properties of the design are also studied numerically. We compare the performance of the proposed design with some possible competitors with respect to a few criteria. A real dataset is used to illustrate the applicability of the proposed design. Thus, we provide a base for using odds-ratio-based response-adaptive designs in practice. We extend our design for covariates and also for more than two treatments. In particular, we study the three-treatment design in this article.

Economic reflections on proton pump inhibitor therapy for non-erosive reflux disease.

Proton pump inhibitor (PPI) therapy for gastroesophageal reflux disease is a good example of the evolution of economic analysis. Initial studies were simple models constructed on spreadsheets and described the most cost-effective therapy in terms of cost per cure of esophagitis. This tells a third-party payer what is the most efficient approach to healing esophagitis (technical efficiency) but does not give any indication of whether treating esophagitis is good value for money in the first place or whether health care dollars would be better spent in treating other diseases (allocative efficiency). As economic analyses became more sophisticated, more complex models were constructed. Outcomes were expressed in terms of cost per quality-adjusted life year gained or the question was framed in terms of the probability a strategy would be cost effective depending on willingness to pay for a month free from symptoms. These approaches answer the question of whether treating gastroesophageal reflux disease is good value for money. Models have traditionally evaluated treatment of esophagitis, but this does not address the most efficient therapy of non-erosive reflux disease. This article describes a simplified model (for illustrative purposes only) and suggests that PPI therapy is a cost-effective approach for the treatment of esophagitis whether generic or proprietary PPI costs are applied. PPI therapy is also likely to be a cost-effective strategy for non-erosive reflux disease at generic but not at proprietary prices.

Effectiveness of proton pump inhibitors: beyond cost.

As a drug class, proton pump inhibitors are excellent pharmacologic agents for the treatment of gastroesophageal reflux disease. All 5 of the agents discussed here are exceptionally effective, so much so that cost has often superseded other outcome measures as a primary reason for the choice of agent. This article reviews other important outcome measures including control of intragastric pH, healing, symptom relief, improvement in quality of life, sleep, and increase in work productivity in an effort to "move beyond cost" in decision-making related to patient care.

An overview of the pharmacology, efficacy, safety and cost-effectiveness of lansoprazole.

Lansoprazole is a proton pump inhibitor that reduces gastric acid secretion in a dose-dependent manner via inhibition of H+/K+-adenosine triphosphatase in gastric parietal cells. It also exhibits antibacterial activity against Helicobacter pylori in vitro. During almost 10 years of clinical use, lansoprazole has proved effective and well tolerated in a wide range of acid-related disorders, including gastro-oesophageal reflux disease (GORD), duodenal ulcers, gastric ulcers, non-steroidal anti-inflammatory drug-related ulcers, as well as non-ulcer dyspepsia and acid hypersecretion. It is also used, in combination with antibiotics, for H. pylori eradication. In the above indications, lansoprazole has generally proved to be superior to the histamine H2-receptor antagonists, and is at least as effective as the other currently available proton pump inhibitors. This review aims to evaluate the pharmacology, efficacy, safety and cost-effectiveness of lansoprazole in acid-related disorders, with particular emphasis on its use in GORD and H. pylori eradication regimens.

Choice of long-term strategy for the management of patients with severe esophagitis: a cost-utility analysis.

BACKGROUND & AIMS: Omeprazole has shown remarkable efficacy and safety in the treatment of patients with gastroesophageal reflux disease (GERD); similarly, laparoscopic techniques have allowed less morbidity in patients undergoing fundoplication procedures. Concerns about the long-term cost and safety of both strategies have prompted a debate of their role in long-term management of patients with severe erosive esophagitis. METHODS: A cost-utility analysis was performed to compare two strategies: laparoscopic Nissen fundoplication (LNF) vs. omeprazole. A two-stage Markov model was used to obtain cost and efficacy estimates; all estimates were discounted at 3% per year. The time horizon was 5 years. Sensitivity analyses were performed on all relevant variables. RESULTS: Both strategies were similarly effective (4.33 quality-adjusted life years per patient), with omeprazole less expensive than LNF ($6053 vs. $9482 per patient). At 10 years, LNF and omeprazole costs were similar. Efficacy estimates were extremely sensitive to changes in quality of life associated with postoperative symptoms and long-term use of medication. CONCLUSIONS: Medical therapy is the preferred treatment strategy for most patients with severe erosive esophagitis. Individuals with a long life expectancy are good candidates for LNF if postoperative morbidity is low and GERD symptoms remain abated for many years.

Fluconazole compared with endoscopy for human immunodeficiency virus-infected patients with esophageal symptoms.

BACKGROUND & AIMS: The best initial treatment of human immunodeficiency virus (HIV)-infected patients with esophageal symptoms is unknown. The outcome, including safety and cost-effectiveness, of fluconazole compared with endoscopy as a treatment strategy for HIV-infected patients with new-onset esophageal symptoms was evaluated. METHODS: During a 53-month period, 134 HIV-infected patients with esophageal symptoms were randomized prospectively to groups receiving either standard doses of fluconazole or endoscopy. RESULTS: Among the 68 patients in the fluconazole group, a complete symptomatic response was observed in 56 patients (82%), usually within 1 week. The most common endoscopic findings in the 66 patients in the endoscopy group included Candida esophagitis alone in 42 patients (64%) and ulcerative esophagitis in 10 patients (15%). Patients responding to empirical antifungal therapy or who had Candida esophagitis alone at endoscopy were less like to have severe symptoms (P = 0.027) or odynophagia as the only symptom (P < 0.001) but more frequently had odynophagia and dysphagia (P = 0.007) and thrush (P = 0.002). Empirical fluconazole was cost-effective, saving $738.16 per patient. CONCLUSIONS: Empirical oral antifungal therapy with fluconazole is highly efficacious, safe, and cost-effective for HIV-infected patients with new-onset esophageal symptoms.

Omeprazole or ranitidine plus metoclopramide for patients with severe erosive oesophagitis. A cost-effectiveness analysis.

The objective of this study was to evaluate the clinical and economic effects of 2 clinical strategies for treating severe (grade II and above) erosive oesophagitis or poorly responsive gastro-oesophageal reflux disease. A single-blind, randomised controlled trial of up to 8 weeks' duration was undertaken comparing omeprazole with ranitidine plus metoclopramide in patients with severe and symptomatic erosive oesophagitis (endoscopic grade II and above). Two cost-effectiveness ratios were calculated: cost per healed patient and cost per symptom-free day. The study perspective was that of the payer or insurer of medical care. Healing rates were significantly higher among omeprazole-treated patients than among those who received ranitidine/metoclopramide at 4 weeks (68.5% vs 30.4%; p < 0.01) and overall (81.5% vs 45.7%; p < 0.01). Overall, mean gastrointestinal-related direct medical costs per healed patient were lower for the omeprazole group ($US189.60) than for the ranitidine/metoclopramide group ($US319.28). The incremental cost of an additional cure with omeprazole compared with ranitidine/metoclopramide was $US24.05. The overall average cost per symptom-free day was lower in the omeprazole group ($US7.88) than in the ranitidine/metoclopramide group ($US10.81). The incremental cost to obtain an additional symptom-free day with omeprazole, compared with ranitidine/metoclopramide, was $US1.41. In conclusion, superior efficacy at comparable cost is achieved by omeprazole compared with ranitidine/metoclopramide in the treatment of patients with severe erosive oesophagitis.

Assessment of sucralfate coating by sequential scintigraphic imaging in radiation-induced esophageal lesions.

The value of mucosal protection with sucralfate in cases of gastric ulceration is well documented. Although sucralfate is advocated as treatment of esophageal lesions, we found it to be of limited value in the management of radiation-induced esophagitis; in a pilot study of 10 cases, minor relief of symptoms, with analgetics still required, was noted in 4 patients, and no improvement was seen at endoscopy after 6 weeks of treatment in any patient. To see if this might be the result of inadequate mucosal coating, we administered sucralfate labeled with technetium 99m to 26 patients with endoscopically proven esophagitis secondary to irradiation for esophageal carcinoma. The degree of coating was evaluated according to persistence of the radionuclide in the affected esophageal segment. Scans were performed at regular intervals for 120 minutes after administration of 150 MBq 99mTc-sucralfate. Although scans were positive for radioactivity in 24 of 26 (92%) patients, only 8 (31%) of these represented selective binding of sucralfate to tissue. In the other 16 cases, scans were positive for sucralfate and albumin, indicating nonspecific retention most likely caused by concomitant esophageal stenosis. Residual radioactivity was observed for 30 minutes or more in 11 (42%) patients, but scans were positive for radioactivity after 1 to 2 hours in only 4 (15%). The duration and intensity of tracer accumulation were similar in both acute lesions an chronic radiation damage. These findings suggest that the inability of sucralfate to alleviate irradiation-induced odynophagia may be related to insufficient duration of adherence of this compound to damaged esophageal mucosa.

Medical management of esophageal reflux.

Gastroesophageal reflux of varying severity is a common disorder for which medical attention is sought at all levels, from pharmacists to specialist physicians and surgeons. This brief overview represents my current understanding of reflux, its effects on the esophagus and my personal approach to treatment of these disorders. Of necessity, because the literature is so extensive (a Medline search on reflux from 1966 to 1993 yielded over 1500 papers.), I have relied in places on the extensive review by Marks and Richter [1]. My paper emphasizes the evaluation and treatment of patients with symptomatic reflux, esophagitis and its complications. It describes why it is important to grade the disorders so that the treatment used is appropriate to the severity of the disease. The more severe the disease, the more specific the diagnostic information needed and the more exacting the treatment. Various treatments and outcomes of therapy are discussed, and a role for surgery is defined. The essence of effective medical treatment of esophagitis is to reduce acidity of the refluxate to a level outside the optimum proteolytic pH range of pepsin, i.e. greater than pH 3.5.

Omeprazole versus H2-receptor antagonists in treating patients with peptic stricture and esophagitis.

BACKGROUND/AIMS: Although dysphagia in patients with peptic stricture is attributed to a decreased luminal diameter, coexistent esophagitis may be an equally important cause. The goals of this study were to determine whether medical healing of esophagitis in patients with stricture improves dysphagia and decreases dilatation need and to compare the efficacy and cost-effectiveness of omeprazole versus H2-receptor antagonists (H2RA). METHODS: Thirty-four dysphagic patients with peptic stricture and erosive esophagitis were dilated and randomized to omeprazole 20 mg every day versus H2RA (ranitidine 150 mg twice daily or famotidine 20 mg twice daily). Patients received further dilatations only if dysphagia frequency was greater than or equal to once per week. At 3 and 6 months, patients were assessed for esophagitis healing, dysphagia relief, and bougienage requirements. Cost-effectiveness of omeprazole and H2RA was determined. RESULTS: Patients with healed esophagitis at 3 and 6 months were more likely to dysphagia-free and to require fewer dilatations than patients with persistent esophagitis. At 6 months, omeprazole produced a significantly (P < 0.01) higher rate of esophagitis healing, dysphagia relief, and fewer dilatations compared with H2RA. Omeprazole was also 40%-50% more cost-effective. CONCLUSIONS: Esophagitis healing improves dysphagia and decreases dilatation need in patients with peptic stricture. Omeprazole heals esophagitis and relieves dysphagia more efficaciously than H2RA while decreasing costs to patients.