Thursday, July 3, 2008

Evaluating and Optimizing Treatment Response

Return to Medscape coverage of: Digestive Disease Week 2003  |  Posters and Abstracts: Clinical Applications of Proton-pump Inhibitors

Evaluating and Optimizing Treatment Response


Emma Hitt, PhD   

Evaluation of Treatment Response

An appropriate scale evaluating gastroesophageal reflux disease (GERD) symptom response to treatment has not been established. Monnikes and colleagues[1] developed a self-administered questionnaire called ReQuest (Reflux Questionnaire). The test consisted of questions in 7 dimensions: (1) general well-being, (2) acid complaints, (3) upper abdominal/stomach complaints, (4) lower abdominal/digestive complaints, (5) nausea, (6) sleep disturbances, and (7) other complaints. Each of the dimensions was tested by a leading question about frequency and intensity. A long version of the test comprised 67 symptom descriptions assigned to each of the 7 dimensions. ReQuest was validated in a clinical trial of 349 patients with erosive esophagitis (Los Angeles [LA] Grade A-D) receiving pantoprazole. On the basis of factor analyses, the long version of the test was reduced to a 60-item scale. The study authors concluded that the test was highly reproducible, valid, and responsive.

Another study evaluated the reliability and validity of a questionnaire on upper gastrointestinal symptoms. Kuo and colleagues[2] tested the questionnaire in patients on chronic acid suppression identified from pharmacy billing. They modified 7 questions taken from previously validated questionnaires about upper gastrointestinal symptom frequency. Questions collected information on heartburn, supine heartburn, use of antacids, stomach pain, bloating, pain after eating, and nausea or vomiting. The first 3 symptom domains involved GERD, and the third through seventh symptom domains involved dyspepsia. Validity was tested via correlation with standard quality-of-life questions. A total of 812 patients (53% of eligible patients) completed the questionnaire. The internal consistency reliability was reasonable, and the Pearson correlation coefficients between the symptom questions and the quality-of-life questions were modest to moderate (P < .0001 for all). The strongest correlations were with heartburn and dyspepsia symptoms and interference of normal activities. The study authors concluded that this test is convenient and has psychometric characteristics comparable to other upper gastrointestinal disease-specific questionnaires.

Quality of Life

Compared with the general population, GERD patients experience impaired health-related quality of life (HRQOL). But what is the effect of proton-pump inhibitors (PPIs) in ameliorating this health indicator?

A study by Calleja and colleagues[3] demonstrated that pantoprazole rapidly relieved symptoms in patients with GERD and resulted in a sustained improvement of HRQOL, which correlated with heartburn relief. These investigators conducted a 12-month multicenter study in 656 moderate-to-severe GERD patients taking once-daily pantoprazole 40 mg. They assessed HRQOL at baseline and at weeks 8, 24, and 48. Symptom relief occurred in an average of 2.0 days for heartburn, 2.1 days for regurgitation, 2.2 days for dysphagia, and 2.1 days for chest pain. Both the SF-12 scale, used to measure general well-being, and the GERD-HRQOL scale indicated significant improvement at the end of the study compared with baseline. For both scales, the improvement was greater in the first month of treatment. No serious adverse events were reported.

On-Demand Therapy

On-demand-treatment of GERD, also known as symptom-driven treatment, may offer an alternative option to continuous therapy in patients with mild-to-moderate disease. This strategy appears to reduce symptoms, improve quality of life, and to be cost-effective. One analysis has found that an on-demand strategy may be suitable for approximately 60% of newly diagnosed patients with GERD for the long-term management of symptomatic disease of mild or moderate severity.[4] Two studies presented during this year's Digestive Disease Week meeting further evaluated an on-demand strategy with PPIs.

Kaspari and colleagues[5] conducted a trial of 536 patients with endoscopically confirmed GERD stage 0 or I (Savary/Miller modified by Siewert). For symptom relief, patients were initially treated for 4 weeks with once-daily pantoprazole 20 mg. In a subsequent 6-month (long-term) phase, if symptoms relapsed, patients who were initially symptom-free took either pantoprazole 20 mg on-demand (n = 175) or placebo (n = 182). Antacids were available as rescue medication. The 4 weeks of continuous treatment with once-daily pantoprazole 20 mg provided complete relief of GERD symptoms in 86% of patients. In the subsequent comparison trial, GERD symptom score remained significantly lower among patients taking pantoprazole on demand as compared with those taking placebo (P = .007). These patients also used significantly fewer antacids (P </= .0001).

In another study evaluating on-demand therapy, Arguello and colleagues[6] found that symptom-driven treatment with rabeprazole was effective and improved HRQOL in patients with mild GERD. The study authors evaluated symptomatic patients with GERD (heartburn more than 2 days per week). Of the patients evaluated, 19 had esophagitis LA Grade A, 19 had esophagitis LA Grade B, and 17 had normal endoscopy but an abnormal 24-hour ambulatory esophageal pH recording. All patients received a maximum dose of once-daily rabeprazole 20 mg over a period of 8 or 4 weeks, depending on the presence or absence of esophagitis (acute phase), respectively. The 51 patients who responded to the acute-phase treatment entered an on-demand maintenance phase in which they received rabeprazole 20 mg on demand when heartburn was present. During on-demand treatment, 51%, 53%, and 41% patients had no symptoms when examined at 1, 3, and 6 months, respectively. The remaining patients had occasional heartburn (defined as once per week). Esophagitis relapsed in 3 patients who were symptomatic during on-demand treatment. An average of 0.36, 0.33, and 0.26 tablets per day (rate of drug consumption) were consumed at 1, 3, and 6 months, respectively. Patient satisfaction and HRQOL increased after acute therapy and were maintained or improved by the end of the study.


Monnikes H, Bardhan KD, Stanghellini V, et al. Request: Development and psychometric validation of a new evaluative symptom-scale in gastroesophageal reflux disease (GERD). Gastroenterology. 2003;124:A-535. [Poster #T1624] Kuo B, Ferris T. Reliability and validity of a modified questionnaire of upper GI symptoms utilized in a disease management program of patients on chronic acid suppression. Gastroenterology. 2003;124:A-505. [Poster #T1295] Calleja JL, Martin J, Banos F, et al. Rapid relief of symptoms and sustained improvement in health related quality of life (HRQOL) in moderate-severe gastroesophageal reflux disease (GERD) patients treated with pantoprazole. Gastroenterology. 2003;124:A-231. [Poster #S1612] Bardhan KD. Intermittent and on-demand use of proton pump inhibitors in the management of symptomatic gastroesophageal reflux disease. Am J Gastroenterol. 2003;98:S40-S48. Kaspari S, Kupcinskas L, Fischer R, et al. On-demand therapy with pantoprazole 20 mg as effective long-term management of patients suffering from mild GERD. Gastroenterology. 2003;124:A-538. [Poster #T1640] Arguello L, Pons V, Ponce M, et al. On demand therapy with rabeprazole in patients with mild gastroesophageal reflux disease (GERD): evaluation of effectiveness and patient-centered measures. Gastroenterology. 2003;124: A-227. [Poster #S1588]

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