Low levels of adherence with proton pump inhibitor therapy contribute to therapeutic failure in gastroesophageal reflux disease

To assess adherence to proton pump inhibitor (PPI) treatment and associated variables in patients with gastroesophageal reflux disease (GERD). Cross‐sectional and prospective comprising 240 consecutive adult patients, diagnosed with GERD for whom continuous use of standard or double dose of omeprazole had been prescribed. Patients were ranked as ne‐GERD (162: 67.5%) or e‐GERD classified according to the Los Angeles classification as A (48:20.0%), B (21:8.6%), C (1:0.5%), D (1:0.5%), and Barrett's esophagus (7:2.9%). The Morisky questionnaire was applied to assess adherence to therapy and a GERD questionnaire to assess symptoms and their impact. Adherence was correlated with demographics, cotherapies, comorbidities, treatment duration, symptoms scores, endoscopic findings, and patient awareness of their disease. 126 patients (52.5%) exhibited high level of adherence and 114 (47.5%) low level. Youngers (P= 0.002) or married (O.R. 2.41, P= 0.03 vs. widowers) patients had lower levels of adherence; symptomatic patients exhibited lower adherence (P= 0.02). All other variables studied had no influence on adherence. Patients with GERD attending a tertiary referral hospital in São Paulo exhibited a high rate of low adherence to the prescribed PPI therapy that may play a role in the therapy failure. Age <60 years, marital status and being symptomatic were risk factors for low adherence.     

Determinants of Long-Term Outcome of Patients with Reflux-Related Ear, Nose, and Throat Symptoms

Gastroesophageal reflux disease (GERD) is present in up to 75% of patients with chronic refractory ear, nose, and throat (ENT) symptoms, and proton pump inhibitor (PPI) therapy induces symptom relief in the majority of these patients. It has been suggested that endoscopic findings and quantification of esophageal acid exposure may help to predict the long-term outcome of medical therapy, but prospective studies that confirm this hypothesis are lacking. The aim of the present study was to investigate the relationship of endoscopic findings and quantification of reflux with long-term outcome in patients with reflux-related ENT symptoms. One hundred six consecutive patients with chronic refractory unexplained ENT symptoms underwent upper GI endoscopy, 24-hr dual-channel esophageal pH and Bilitec (n = 35) monitoring, and esophageal manometry. Subsequently, all were treated with omeprazole, 20 mg b.i.d., and patients were followed at 2-week intervals until symptom relief. Four weeks later, omeprazole therapy was gradually decreased and the lowest effective omeprazole maintenance dose, if any, was determined. Eighty-one patients (49 men; mean age, 50) experienced a clear or excellent therapeutic response after, on average, 4 weeks of omeprazole, 20 mg b.i.d. In 36 patients (44%; group A), PPI treatment could be stopped completely, 27 patients (33%; group B) required a maintenance dose of omeprazole, 20 mg/day, and 18 patients (22%; group C) required maintenance with omeprazole, 40 mg/day. The prevalence of reflux esophagitis was significantly lower in group A patients, who also had significantly lower distal esophageal acid exposure, proximal esophageal acid exposure, and esophageal duodenogastroesophageal reflux exposure compared to groups B and C. Multivariate analysis identified the presence of esophagitis and pathological distal esophageal acid exposure as risk factors for the need of maintenance therapy. In patients with reflux-related ENT symptoms, initial findings on upper GI endoscopy and 24-hr pH-metry help to predict the need for maintenance therapy.     

Endoscopic grading of gastroesophageal flap valve helps predict proton pump inhibitor response in patients with gastroesophageal reflux disease

Abstract

Objective. Limited information is available on predictors of the response to proton pump inhibitor (PPI) treatment in patients with gastroesophageal reflux disease (GERD). Endoscopic grading of gastroesophageal flap valve (GEFV) is simple and reproducible, and can provide useful information on patients with suspected reflux undergoing an endoscopy. The aim of this study was to prospectively identify predictors, including endoscopic findings such as GEFV, for PPI treatment outcomes in patients with GERD. Material and methods. One hundred and fifty consecutive patients with GERD were enrolled. All patients were treated with pantoprazole 40 mg daily for 8 weeks. Treatment response was defined as greater than 50% reduction in symptom scores between the two symptom assessments (i.e., over 4 or 8 weeks). Univariate and multivariate logistic regression analyses between responders and non-responders were performed to identify variables predicting response to pantoprazole treatment. Results. Of the 150 consecutive patients considered for this study, 31 were excluded based on exclusion criteria and/or refusal to participate, leaving 119 eligible patients. After 4-week pantoprazole treatment, 70 of 119 (58.8%) patients were classified as responders. Patients with obesity and Helicobacter pylori infection demonstrated a higher response rate to 4-week pantoprazole treatment (odds ratio (OR) 5.28, p = 0.008; OR 3.76, p = 0.023, respectively). Patients with abnormal GEFV showed a lower response rate to 4-week treatment (OR 0.17, p = 0.016). After 8-week treatment, 86 of 119 (72.3%) patients were classified as responders. Abnormal GEFV and aspirin intake were associated with a lower response rate to 8-week treatment (OR 0.17, p = 0.021; OR 0.11, p = 0.020, respectively). Conclusions. Abnormal GEFV was a significant independent factor predicting poor response to both 4-week and 8-week pantoprazole treatment. Endoscopic grading of GEFV provides useful information for predicting the response to PPI treatment in patients with GERD.     

胃食管反流病抑酸疗效预测因素研究进展

质子泵抑制剂(PPI)是胃食管反流病(GERD)治疗首选药物,但调查显示48%～63%的患者抑酸治疗后仍有症状[1],且长期使用会出现诸多副反应。因此,预测哪些患者抑酸治疗有效,对于指导临床治疗、节省花费及减少药物副反应是非常必要的。     

Effect of pantoprazole in older patients with erosive esophagitis

Several studies suggest that older adults with gastroesophageal reflux disease (GERD) are more likely to develop complications, including erosive esophagitis, but it is unclear whether erosive esophagitis is more difficult to treat in older patients. The purpose of this study was to determine if adults > or = 65 years with erosive esophagitis are more difficult to treat than younger adults. The study was a post hoc analysis of two double-blind, randomized, multicenter trials of patients with erosive esophagitis. Patients received pantoprazole 40 mg once daily, nizatidine 150 mg twice daily or placebo. Patients were evaluated for endoscopic healing at 4 and 8 weeks. Patients recorded typical reflux symptoms using a daily diary to note presence or absence of symptoms. Results showed that 44, 13 and 11 patients > or = 65 years and 210, 69, and 71 patients < 65 received pantoprazole 40 mg daily, nizatidine 150 mg twice daily, or placebo, respectively. Eighty-six percent (86%[76%, 97% CI]) of older and 83% (78%, 88% CI) of younger pantoprazole-treated patients were healed at 8 weeks; 46% (19%, 73% CI) and 35% (24%, 46% CI) of nizatidine-treated and 27% (1%, 54% CI) and 34% (23%, 45% CI) of placebo-treated were healed at 8 weeks. Median time to persistent absence of GERD-related symptoms was similar for older and younger patients treated with pantoprazole. We conclude that older patients with erosive esophagitis do not appear to have more difficult-to-treat disease. Erosive esophagitis is effectively healed and GERD symptoms are controlled in older patients using pantoprazole 40 mg daily.     

Efficacy of Rabeprazole in the Treatment of Symptomatic Gastroesophageal Reflux Disease

The purpose of this study was to assess the rapidity of symptom relief and 4-week efficacy of rabeprazole 20 mg in patients with moderately severe nonerosive gastroesophageal reflux disease. Data were analyzed from 2 similarly designed, double-blind, placebo-controlled, multicenter, U.S. trials. After a 2-week placebo run-in period, patients (N = 261) were randomized to 4 weeks of rabeprazole 20 mg once daily or placebo. Patients kept symptom diaries and scored symptom severity. Median time to first 24-hour heartburn-free interval was 3.5 days for the rabeprazole group compared with 19.5 days for the placebo group (P ≤ .0002). Complete heartburn relief at week 4 was 32% with rabeprazole and 3.8% with placebo (P ≤ .001). Rabeprazole also significantly improved other GERD-associated symptoms (e.g., regurgitation, belching, early satiety) by week 4 compared with placebo (P ≤ .05). Rabeprazole provides fast and potent relief from heartburn and other symptoms of nonerosive gastroesophageal reflux disease. Supported by Eisai Inc., Teaneck, New Jersey, and Janssen Pharmaceutica Inc., Titusville, New Jersey.     

Comparison of efficacy of pantoprazole alone versus pantoprazole plus mosapride in therapy of gastroesophageal reflux disease: a randomized trial

The present study aimed to compare the efficacy for the therapy of GERD of pantoprazole alone with a combination of pantoprazole and mosapride. The study was a prospective, randomized trial involving 68 patients suffering heartburn and/or regurgitation at least twice a week for 6 weeks. Sixty-one patients consented to be randomized to receive either pantoprazole 40 mg b.i.d. (n = 33, group A) or pantoprazole 40 mg b.i.d. plus mosapride 5 mg t.d.s. (n = 28, group B) for 8 weeks. Twenty-four-hour esophageal pH-metry and endoscopy were conducted at recruitment and endoscopy was repeated at 8 weeks in all the patients studied. There were no differences in symptomatic responses to therapy between the groups (69.7% vs 89.2%; P = 0.11). The mean symptom score after 8 weeks was significantly lower in group B (3.78 +/- 3.62 vs 1.67 +/- 2.09; P = 0.009). Nonerosive esophagitis was present in 29 patients. In patients with nonerosive GERD there was no significant difference in symptomatic response to either regimen (17/20 in group A and 7/9 in group B responded; P = 0.63). In erosive esophagitis, symptomatic responses occurred more frequently in group B, 18/19 (94.7%), than in group A, 6/13 (46.2%; P = 0.003). However endoscopic healing of esophagitis occurred equally with either regimen (6/11, 54.5% in group A; 12/17, 70.5% in group B; P = 0.44). In nonerosive GERD, the addition of mosapride offers no benefit over pantoprazole alone. A combination of pantoprazole and mosapride is more effective than pantoprazole alone in providing symptomatic relief to patients with erosive GERD.     

Acid Challenge to the Human Esophageal Mucosa: Effects on Epithelial Architecture in Health and Disease

The histological changes that occur in the squamous epithelium in response to acute acid challenge was examined in healthy controls and proton pump inhibitor-treated gastroesophageal reflux disease (GERD) patients and related to the state of untreated erosive GERD in a saline-controlled, randomized perfusion study. In the basal state a stepwise significant increase in the thickness of the basal cell layer, papillary length, and dilatation of intercellular spaces (DIS) was seen when the three groups were compared. Acid perfusion induced a slight increase in the height of the basal cell layer mainly in healthy volunteers; this layer appears to be reactive to acute acid challenge as well as to acid suppressive therapy. DIS increases promptly in response to acute acid exposure in the healthy epithelium but no changes were seen in the lengths of the papillae or regarding DIS in the GERD patients. A protective effect of luminal nitric oxide on DIS development is suggested.This paper has been published as part of the PhD thesis of Mogens Bove.     

A novel endoscopic submucosal dissection technique for proton pump inhibitor-refractory gastroesophageal reflux disease

Abstract

Objectives: Although drug treatment is the usual first-line therapy for gastroesophageal reflux disease (GERD), not all patients receive satisfactory relief from drug therapy, alone. We developed an endoscopic fundoplication technique using endoscopic submucosal dissection (ESD); the technique is referred to as ESD for GERD (ESD-G). This study investigated the safety and efficacy of this novel technique in patients with drug-refractory GERD. Patients and methods: ESD-G narrows the hiatal opening through ESD of the esophagogastric junction (EGJ) mucosa. For safety reasons, the range of mucosal resection was limited to half (1/2 or 1/4 +1/4) of the circumference of the EGJ lumen. ESD-G was performed on 13 patients with proton pump inhibitor (PPI)-refractory GERD. GERD symptoms, PPI dose, and 24-h esophageal pH monitoring results were compared before and 6 months after the procedure. Results. In 12 cases, symptoms significantly improved after ESD-G. Five patients demonstrated improved esophagitis, three were able to discontinue PPI therapy, and three were able to reduce their PPI dosage following surgery. The esophageal pH <4 holding time ratio was also decreased after ESD-G. Conclusions. ESD-G may be useful for PPI-refractory GERD patients.     

Functional esophageal disorders

Functional esophageal disorders represent processes accompanied by typical esophageal symptoms (heartburn, chest pain, dysphagia, globus) that are not explained by structural disorders, histopathology-based motor disturbances, or gastroesophageal reflux disease. Gastroesophageal reflux disease is the preferred diagnosis when reflux esophagitis or excessive esophageal acid exposure is present or when symptoms are closely related to acid reflux events or respond to antireflux therapy. A singular, well-defined pathogenetic mechanism is unavailable for any of these disorders; combinations of sensory and motor abnormalities involving both central and peripheral neural dysfunction have been invoked for some. Treatments remain empirical, although the efficacy of several interventions has been established in the case of functional chest pain. Management approaches that modulate central symptom perception or amplification often are required once local provoking factors (eg, noxious esophageal stimuli) have been eliminated. Future research directions include further determination of fundamental mechanisms responsible for symptoms, development of novel management strategies, and definition of the most cost-effective diagnostic and treatment approaches.     

The Value of Ambulatory 24 hr Esophageal pH Monitoring in Clinical Practice in Patients Who Were Referred with Persistent Gastroesophageal Reflux Disease (GERD)-Related Symptoms While on Standard Dose Anti-Reflux Medications

To determine the value of pH testing in clinical practice in gastroesophageal reflux disease patients who failed anti-reflux treatment. Patients resistant to standard dose proton pump inhibitor or an H₂-blocker underwent pH testing. Randomly selected patients from the proton pump inhibitor failure group underwent the modified acid perfusion test as compared to patients with non-erosive reflux disease. In the proton pump inhibitor failure group (n = 70), 63.8% had a normal pH test as compared to 29% in the H₂-blocker group (n = 31) (P = 0.007). Sensory intensity rating and acid perfusion sensitivity score were significantly higher in the non-erosive reflux disease control group than the proton pump inhibitor failure group (P < 0.05). Most patients who continued to be symptomatic on proton pump inhibitor once daily demonstrated a normal pH test and overall lack of increased chemoreceptor sensitivity to acid.     

Pantoprazole: a proton pump inhibitor with oral and intravenous formulations

Proton pump inhibitors (PPI) are a significant part of therapy for most acid-related diseases including gastroesophageal reflux disease, peptic ulcer disease and acute gastrointestinal bleeding. Pantoprazole is one of several available proton pump inhibitor agents and provides dose-dependent control of gastric acid secretion. Pantoprazole has indications in gastroesophageal reflux disease and peptic ulcer disease, along with indications as co-therapy in the eradication of Helicobacter pylori infection and in the control of the acid secretion associated with the Zollinger–Ellison syndrome, as well as in NSAID ulcer prevention. Pantoprazole is available in both oral and intravenous formulations. It is effective across all age groups, although only indicated in adults (and adolescents in Europe). It has been approved for use in over 100 countries and has been used for over 13 years. Pantoprazole has an excellent safety profile and a low potential for drug–drug interactions. While still widely prescribed, pantoprazole and the other branded proton pump inhibitors are under considerable market pressure from the less expensive but similarly effective generic and over-the-counter formulations of omeprazole.     

“Proton-pump inhibitor-first” strategy versus “step-up” strategy for the acute treatment of reflux esophagitis: a cost-effectiveness analysis in Japan

Background Gastroesophageal reflux disease (GERD) is a common condition, and acid-suppressing agents are the mainstays of treatment. For the acute medical management of GERD, two different strategies can be proposed: either the most effective therapy, i.e., proton-pump inhibitors (PPIs), can be given first, or histamine H₂-receptor antagonists (H₂RAs) can be attempted first (the “step-up” approach). Methods A clinical decision analysis comparing the PPI-first strategy and the H₂RA-first “step-up” strategy for the acute treatment of reflux esophagitis in Japan was performed, using a Markov chain approach. Results The PPI-first strategy was consistently superior to the step-up strategy with regard to clinical outcomes for the patient and with regard to cost-effectiveness (direct cost per patient to achieve clinical success). This superiority was robust within the plausible range of probabilities according to the sensitivity analyses. Conclusions The PPI-first strategy is superior to the H₂RA-first “step-up” strategy with regard to both efficacy and cost-effectiveness and therefore, the PPI-first strategy is the preferred therapeutic approach for the acute medical treatment of reflux esophagitis.     

Survey of findings in patients having persistent heartburn on proton pump inhibitor therapy

In patients with refractory heartburn while on proton pump inhibitor (PPI) therapy, changing drugs or increasing treatment to a twice a day (b.i.d.) dose has become a common practice. This study aims to study patients with persistent heartburn while on PPI therapy and to determine if persistent symptom indicates the need for more aggressive or different therapy. A retrospective review of impedance‐pH tracings on PPI therapy (q.d. or b.i.d.) for patients with persistent heartburn was performed. DeMeester score, impedance, and symptom sensitive index (SSI) were used as indices. Statistical analyses were performed using chi‐squared test with Yates correction and paired t‐test. One hundred consecutive patients, (female 50%, male 50%, mean age 54 [range 16–83] years) were studied on q.d. (n = 45) or b.i.d. PPI (n = 55). Only 20% of the patients had abnormal DeMeester score; 41% had an abnormal impedance score and 56% had abnormal SSI; 29% had all indices normal. There was no difference between patients taking q.d. versus b.i.d. PPI for abnormal DeMeester score (22 vs. 18%), impedance (38 vs. 44%) and SSI (53 vs. 58%); P = 0.80, 0.69, and 0.77, respectively. In 56 patients with positive SSI, symptoms were due to acid reflux in 8 (14%) patients, nonacid reflux in 31 (55%) patients, and combined acid and nonacid reflux in 17 (30%) patients. Patients with persistent heartburn on PPI therapy show a variety of disorders: (i) acid reflux (20%); (ii) nonacid reflux (26%); (iii) positive SSI (56%); (iv) all normal indices (29%). These studies indicate that persistent heartburn on PPI therapy is a complex problem that may not respond to simply increasing acid inhibition.     

Comparison of patients of chronic laryngitis with and without troublesome reflux symptoms

Background and Aim: Little is known about the difference between patients of chronic laryngitis with and without troublesome reflux symptoms. The aim of this study was to compare the clinical characteristics and response to acid suppression between patients of chronic laryngitis with and without troublesome reflux symptoms. Methods: Consecutive patients with chronic laryngitis were enrolled. The frequency and severity of reflux and laryngeal symptoms were scored. All the patients underwent laryngoscopy, esophagogastroduodenoscopy and 24‐h multichannel intraluminal impedance and pH monitoring before receiving rabeprazole 10 mg b.i.d. for 3 months. Mild typical reflux symptoms (heartburn or regurgitation) occurring ≥ 2 days/week or moderate/severe symptoms occurring ≥ 1 day/week were defined as troublesome reflux symptoms. Results: Compared to patients without troublesome reflux symptoms, those with troublesome reflux symptoms were older and had more episodes of acid and liquid gastroesophageal reflux (GER) and acid and weakly acidic laryngopharyngeal reflux (LPR). They also had higher percentages of both bolus exposure time and acid exposure time of GER and LPR. Patients with troublesome reflux symptoms responded to acid suppression more often at 12 weeks (67.3% vs 20.9%, P < 0.001) and more rapidly (40.8% vs 14.0%, 3 weeks after the start of acid suppression; P = 0.004) compared to those without. Conclusion: Difference in reflux profile of GER and LPR between patients with and without troublesome reflux symptoms could partly explain the discrepancy of response to acid suppression among patients with chronic laryngitis. Acid suppression therapy may provide limited therapeutic benefits to patients of chronic laryngitis without troublesome reflux symptoms.