Reports

This report is based on medical evidence presented at sanctioned medical congress, from peer reviewed literature or opinion provided by a qualified healthcare practitioner. The consumption of the information contained within this report is intended for qualified Canadian healthcare practitioners only.

14th United European Gastroenterology Week

Berlin, Germany / October 21-25, 2006

Heartburn Control Alone Insufficient

In patients who present with heartburn, whether or not endoscopy has been performed, a diagnosis of gastroesophageal reflux disease (GERD) typically prompts a course of acid suppression therapy. Proton pump inhibitors (PPIs) are highly effective for controlling heartburn, but its presence should not blind clinicians to the presence of other complaints produced by GERD. In the past, only modest attention has been given to such co-existing complaints as sleep disturbances or nausea, but new tools for objectively and reproducibly measuring a broad array of related complaints provide a systematic approach to determining how well therapies can restore quality of life (QOL). This is an essential step toward more effective management.

“GERD is typically associated with heartburn and acid regurgitation while the broad spectrum of gastrointestinal (GI) symptoms experienced by GERD patients is often neglected,” observed Dr. Juan Malagelada, Hospital General Vall d’Hebron, Barcelona, Spain. This is an important clinical oversight because “further GI symptoms have a major impact on a patient’s health-related QOL.”

These remarks were based on objective data generated from studies of GERD symptoms using the ReQuest and GERDyzer methodologies. Both have been validated for capturing a far broader set of symptoms than commonly evaluated in GERD patients. The goal of both methodologies is to track symptoms as part of an effort to provide a global improvement in QOL. Dr. Malagelada emphasized that relief of heartburn is often only one step toward recovery from the perspective of the patient, the key arbiter of clinical benefit.

Data Assessment

In this most recent assessment of the ReQuest and GERDyzer methodology, data were analyzed from 578 patients treated with the PPI pantoprazole and 452 patients treated with the PPI esomeprazole in a series of clinical trials carried out over a two-year period. Both agents were administered in a 40-mg dose once daily. Covariance was analyzed for the GERDyzer test, a short self-assessment questionnaire with 10 dimensions of QOL, and the ReQuest test, a more detailed evaluation that generates data on 67 different symptoms in multiple dimensions. The covariance analysis included such GI complaints as acid-related discomfort, upper abdominal complaints and nausea. Results demonstrated a significant influence of all ReQuest dimensions on the GERDyzer sum score, reinforcing the important role of symptoms beyond acid complaints in defining the burden of GERD.

In further analyses from the same data pool, relative effects on different measures of clinical relief of GERD, such as speed of symptom control and effect on nighttime symptomatology, were compared. Using data gathered with ReQuest and GERDyzer methodology, symptoms in a three-day, pre-treatment baseline period were compared to change over the course of therapy. In the study on speed of pain relief, the baseline data provided confirmation for the impact of acid-related symptoms on patient well-being.

“Both frequency and intensity of acid episodes [during the baseline period] were associated with a highly significant impairment in QOL [P<0.0001],” reported Dr. Gerald Holtman, Royal Adelaide Hospital, Australia. Moreover, “the mean GERDyzer sum score increased with the number of acid episodes. Therefore, the health-related QOL of GERD patients decreased with the number of acid episodes.”

Measurable Acid Episode Intensity

After the first day of therapy, the mean number of acid episodes decreased by 1.3 in the pantoprazole group and 1.1 in the esomeprazole group (P=0.0491), while the mean intensity of acid episodes decreased by 1.4 and 1.1, respectively (P=0.0035). According to Dr. Holtman, relief of both frequency and intensity of acid episodes is critical to measures of the impact on QOL as previously documented with the GERDyzer method of analysis. The faster onset of action of pantoprazole relative to esomeprazole is consistent with previous analyses of the pharmacokinetics of these two PPIs. However, the main contribution of this study is to show that the opportunity to gauge outcome even on the first day of therapy is improved by observing sum scores of QOL rather than the impact of a single symptom.

In the sleep analysis, the effect of therapy was compared after four weeks of treatment. Using the GERDyzer methodology, patients were specifically asked about quality of sleep. At baseline, only 10.3% of patients were reporting “good sleep.” After four weeks of treatment, 80.4% of those receiving pantoprazole vs. 65.3% of those receiving esomeprazole (P<0.0001) reported “good sleep.” Again, there have been previous reports of a high degree of efficacy of pantoprazole for restoring sleep quality. However, the significance of this study is that sleep quality is one of a wide variety of outcomes that is important to measure in order to determine whether therapy is moving a patient toward complete remission rather than relieving only the chief complaint.

“GERD symptoms can appear at any time, but the impact of nighttime symptoms on QOL is underestimated. Nighttime symptoms disturbing the sleep quality and affecting the ability to function the next day were associated with daytime sleepiness and reduced productivity at the workplace,” observed Dr. Kenneth R. De Vault, Mayo Clinic, Jacksonville, Florida. Senior author of the sleep analysis, he noted that the ReQuest and GERDyzer methodologies are highly sensitive tools for use in clinical studies and that the studies of sleep are only one dimension of the array of outcomes that are important to measure.

Distinguishing Between GI Diseases

One of the key concepts raised by more comprehensive assessments of GERD symptoms is that the boundaries between upper GI diseases may be more blurred than previously appreciated. It has been well established that a high proportion of patients who do not have esophagitis on endoscopy often have symptoms that overlap with those of other functional diseases, such as non-ulcer dyspepsia and irritable bowel syndrome (IBS). In patients treated empirically for GERD, the concept of shared symptoms is again critical to strategies aimed at complete remission.

“Data from the large ReQuest database provide an opportunity to further understand the relationship among GI disorders. Findings from more than 6000 patients show that more than 60% of patients with GERD experience lower abdominal or digestive symptoms, which may be a part of the spectrum of GERD,” reported Dr. Jan Tack, Catholic University of Leuven, Belgium. He suggested that previous efforts to draw boundaries between GERD and upper GI diseases might not be in the best interest of the patient when the goal is symptom control, regardless of how the disease is classified.

A similar point was made by Dr. Ronnie Fass, University of Arizona, Tucson, who was assessing the relationship between GERD with esophagitis vs. non-erosive reflux disease (NERD). While he noted that there has been a debate about whether NERD is a milder form of esophagitis or a different disease, the distinction may not be particularly important to a patient who wants sufficient symptom relief to restore an acceptable QOL.

“Our knowledge of GERD has progressed significantly over the past few decades. It is now well established that GERD is a complex condition with a heterogeneous symptom pattern consisting of a spectrum of esophageal and extra-esophageal symptoms,” Dr. Fass stated. “Traditionally, outcomes have been measured by endoscopy or relief of heartburn for these conditions, but recent data suggest that the complete remission concept is useful in providing an overall picture of treatment success.”

Summary

In the treatment of GERD and other acid-related diseases of the upper GI tract, there has been an important movement away from control of key definitive symptoms, such as heartburn, to a more comprehensive approach that includes other concomitant symptoms that adversely influence QOL. New tools for evaluating upper GI symptoms, such as ReQuest and GERDyzer, are facilitating efforts to achieve complete symptom remission. While relief of heartburn is important, benefit to patients is best assessed by a change of symptomatology that leads to an improvement in QOL.