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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.

MEDICAL FRONTIERS Canadian Digestive Diseases Week (CDDW) 2009

Banff, Alberta / February 27-March 2, 2009

In the management of GERD, the symptom relief associated with PPIs is sufficient to permit agents within this class to be used for both diagnosis and treatment, but there is increasing evidence that the degree and persistence of symptom relief is overestimated by physicians. The importance of verifying symptom control is underscored by a study conducted with the PPI Acid Suppression Symptom (PASS) test which was able to identify substantial numbers of patients on PPIs who were not achieving adequate symptom control (Table 1). When used to direct patients to alternative strategies, the PASS test proved to be a highly effective step toward improving symptom suppression and outcome.

“The problem is that many GERD patients are simply not asked about their symptoms once they have been placed on a PPI,” stated Dr. David Armstrong, Associate Professor of Medicine, Division of Gastroenterology, McMaster University, Hamilton, Ontario. “The PASS test was developed as a rapid assessment of whether patients still have bothersome symptoms despite therapy. It can help physicians make better choices for their patients.”

The problem that the PASS test addresses is large and underappreciated. A survey conducted by the American Gastroenterological Association (AGA) revealed that 40% of GERD patients on a PPI have significant persistent symptoms. Other studies suggest that up to 50% of patients on a PPI take additional therapies, such as antacids, to control symptoms. While many GERD patients placed on a PPI may be satisfied with the relative initial reduction in symptoms, chronic residual acid regurgitation, chest pain or other GERD symptoms can be debilitating over time. Dr. Armstrong suggested that GERD patients should be regularly questioned about symptom control, with or without the PASS test, because of the availability of alternative treatment strategies if symptoms persist.

Table 1.

“The PASS test is a simple questionnaire. There are five yes-or-no questions and it takes just a minute or so to complete. It is the only validated test for evaluating GERD symptoms in patients who are on treatment,” explained Dr. Armstrong, who led a multicentre team that confirmed the reliability of the test in both English and French versions (Armstrong et al. Can J Gastroenterol 2005;19:350-8).

EncomPASS Study

New evidence that the PASS test is practical and effective in primary care management has been generated by a study called EncomPASS, which evaluated outcomes in 1564 Canadian primary care patients on acid-suppression therapy who failed the PASS test by answering “yes” to any question signalling persistent GERD complaints. Of these patients, 973 were switched to an alternative therapy (the PPI esomeprazole was given 40 mg o.d. in 96.4% of the cases) and 591 were followed on their current therapy. Of patients who remained on the therapy they were taking when initially evaluated with the PASS test, the majority were taking a PPI, including 25% on rabeprazole, 21% on pantoprazole, and 13% each on lansoprazole and omeprazole.

The primary outcome of the study was change from baseline in the Global Overall Symptom (GOS) score in which upper GI symptoms are evaluated on a 7-point Likert scale. The proportion of patients who scored 1, signifying no problem with symptoms, was 57.9% among those switched to a new PPI vs. 28.8% (P<0.0001) who had remained on their initial therapy. When the comparison was restricted to the patients who were being treated with PPIs, the proportion of patients with symptom resolution on GOS after the switch was 63.5% vs. 36.1%
e 1).

Figure 1.

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The Reflux Disease Questionnaire, a secondary outcome, generated similar results. The advantage for the switch to esomeprazole was significant for every domain measured, including heartburn (39.8% vs. 22.5%; P<0.0001), regurgitation (37.4% vs. 22.2%; P<0.0001) and dyspepsia (36.4% vs. 20.3%; P<0.0001).

“After four weeks of treatment, 35.5% of the patients who switched treatment did not answer ‘yes’ to any of the PASS test questions compared with 13.2% of the control patients [P<0.0001],” Dr. Armstrong reported. “The findings support PASS as a method to identify primary care patients with persistent GERD who can respond to a change in therapy that results in an increase in acid suppression.”

Addressing Sleep Disturbance Due to GERD

In another EncomPASS analysis, led by Dr. Richard Hunt, Professor of Medicine, McMaster University, the focus was on reflux-related sleep disturbance. Of those who failed the PASS test, approximately 60% reported sleep impairment due to GERD, which is one of the five impairments evaluated by PASS. After switching therapies, 25.3% continued to report sleep disturbance vs. 53.3% who were not switched (P<0.0001). Similar differences were observed when just those previously taking a PPI were switched. Again, almost all patients who switched received esomeprazole in a dose of 40 mg o.d.

“This is quite an effective tool for identifying patients who require more effective therapy,” Dr. Hunt told delegates. He indicated that sleep disturbance is one of the most common manifestations of inadequately controlled GERD. Several surveys have found that patients identify impaired sleep as one of th
es of diminished quality of life (QOL) due to GERD.

Figure 2.

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Measuring Quality of Life

Even though inadequately managed GERD poses a risk for serious complications, including Barrett’s esophagus, the more immediate goal of the PASS test is to identify patients who have a diminished QOL that is potentially reversible. In another analysis from EncomPASS, change in quality-adjusted life-years (QALYs) was compared among those who were and were not switched. Using the EuroQOL Five-Dimension Questionnaire (EQ-5D) to assess as a basis for calculation, there was a highly statistically significant 0.071 mean gain in QALY (P<0.0001) for those switched to esomeprazole. This was consistent with the change in GOS scores which were about twice as great in those who changed acid suppression therapy (-2.0 vs. -1.1; P<0.0001). According to the senior author of this analysis, Dr. Paul Moayyedi, Professor of Medicine, McMaster University, this is the first randomized trial to demonstrate that a change in acid suppression therapy leads to a significant improvement in QALY in the Canadian setting.

“The QALYs gained with a change in acid suppression therapy to esomeprazole was highly statistically significant [P<0.0001], translating to a cost per QALY of $6,552 (CAN) for the change in therapy,” reported Dr. Moayyedi, who said the analysis was undertaken from the healthcare payer perspective. He indicated that was well within the range of currently accepted levels of cost efficacy.

Simplicity and Utility of PASS

The EncomPASS study program was conducted to demonstrate that the PASS test is a useful and simple clinical tool for patient management. It was not explicitly conducted to demonstrate the greater efficacy of esomeprazole over alternative PPIs, but the expectation that patients inadequately managed with alternative PPIs would improve on esomeprazole was anticipated both by previously published data and by the tight relationship between acid suppression and symptom control. Just as the advantage of PPIs over H2-receptor antagonists for treatment of GERD has been linked specifically to their greater acid suppression, significant differences in 24-hour acid control as measured by the percentage of time with a gastric pH>4 favour esomeprazole over alternative PPIs in standard dosages.

“We selected esomeprazole for the study because it does provide greater suppression of acid [than alternative PPIs in standard dosages],” explained Dr. Hunt, who was involved in some of the seminal work on PPIs that correlated degree of acid control with degree of treatment efficacy. Referring to the improvements in sleep specifically, Dr. Hunt confirmed that once patients are identified as being inadequately controlled on their GERD therapy with the PASS test, “significant improvement in sleep disturbance can be achieved within four weeks of switching to esomeprazole.”

The improvement in symptoms with a switch to esomeprazole is also predicted by the large multicentre studies that previously compared PPIs for healing of esophagitis. In a series of double-blind, randomized trials, the advantage of esomeprazole was highly statistically significant and consistent over every PPI to which it was compared (omeprazole, lansoprazole and pantoprazole). In the only large, double-blind studies to compare PPIs for preventing recurrence of esophagitis, esomeprazole was more effective than either lansoprazole or pantoprazole.

The PASS test itself is immediately applicable to clinical practice, according to Dr. Armstrong. It can be produced on a single page. Patients are eligible if they are taking a prescription medication for a list of symptoms outlined in the test itself. These include stomach pain or discomfort, heartburn, acid regurgitation, excess belching, increased abdominal bloating, nausea, or early satiety. For those who are eligible, the five questions require a simple “yes” or “no.” They include a question about stomach symptoms, a question about whether supplementary medications are required for symptom control, and three questions about impaired activities of daily living including sleep. A “yes” to any question signals a positive test.

“We wanted something very simple,” Dr. Armstrong told the audience. He expressed concern that more cumbersome tests might not be used, particularly by primary care physicians with significant time constraints. However, based on the EncomPASS study results, the test is not only simple but also effective in identifying patients with persistent symptoms and channelling them to more effective strategies. The PASS test can also be used serially to evaluate whether the first adjustment in therapy was sufficient, providing a basis for further escalation of treatment to control symptoms such as twice-daily PPI therapy or an increase in the PPI dose.

Patients Encouraged to Discuss Symptoms

Epidemiologic surveys indicate that a substantial proportion of patients with GERD sufficient to impair QOL do not present their complaints to a physician, choosing instead to self-medicate with over-the-counter (OTC) medications or to simply suffer episodes of GERD without therapy. In patients who do consult a physician, PPIs are the standard of care, but there appears to be an expectation by both physicians and patients that there is no further step if symptoms are not fully controlled. In the survey by the AGA that revealed persistent symptoms (>2 episodes of GERD per week) in a substantial percentage of patients on PPIs, 40% had not spoken to their physician about persistent symptoms. Physicians also frequently failed to ask patients questions relevant to symptom control, such as whether supplementary OTC drugs were being taken.

“Patients who are prescribed a PPI should be asked specific questions about symptom control on subsequent office visits,” maintained Dr. Armstrong. However, he suggested that the validated PASS test might be the most efficient and reliable approach. In the initial studies conducted during its development, the PASS test was associated with good content validity and test-retest reliability. In particular, a standardized but rapid evaluation reduces the risk that patients who could benefit from a relatively simple modification of therapy are being missed.

There is an enormous amount of data that links GERD to significantly impaired QOL, but the PASS test has emerged at a time of growing appreciation that a significant percentage of patients on a PPI continues to experience symptoms that generate persistent discomfort and impair sleep and other activities of daily living. Documenting inadequate relief is an important and necessary aspect of patient management. Based on the EncomPASS study, there is a reasonable expectation for improved control from a change in a PPI or an intensification of therapy.

Summary

Patients with GERD should be routinely evaluated for adequacy of symptom control even after PPI therapy has been initiated. TheEncomPASS clinical study evaluating the PASS test has demonstrated that patients who continue to experience symptoms are readily identified and can benefit from appropriate treatment modification. In this study, the switch from the current PPI program to esomeprazole, which has demonstrated greater 24-hour acid control than alternative PPIs, nearly doubled the proportion of patients who became asymptomatic. The study suggests that a simple screening method is effective and that PPI therapy can be modified to reduce symptom burden.