Lawrence M. Prescott, PhD

Close to 5,000 physicians, nurses, and other healthcare professionals gathered at the 66th Annual Scientific Meeting of the American College of Gastroenterology, held in Las Vegas, Nevada, on October 22–24, 2001, to hear the latest information on the prevention, detection, and treatment of a wide variety of gastrointestinal (GI) diseases. Gastroesophageal reflux disease (GERD) is one of the most prevalent of GI diseases in Western populations, with erosive esophagitis (EE) being a frequent complication of this disease. The symptoms of GERD, with or without EE, may result in a large burden on the working public, impairing employee productivity through decreased performance and increased absenteeism.

Following successful initial treatment of EE, at least 50% of patients relapse within six to twelve months after drug therapy is withdrawn. Most patients require long-term maintenance therapy following initial healing. Proton pump inhibitors (PPIs) are the most effective therapy, in terms of efficacy and cost, for both initial healing and maintenance of healing in GERD patients with EE. The need for the most efficacious treatment, both for acute disease and for maintenance therapy, therefore, is obvious.

One of the most innovative approaches presented at the meeting involved the use of evidence-based medicine to provide a systemic appraisal of research findings to facilitate clinical decision making. This analysis focuses on the number needed to treat (NNT); that is, the number of patients who would need to be treated with one regimen to avoid a treatment failure on a comparative regimen or with placebo.

Although the techniques of evidence-based medicine have been extensively used in cardiology and other medical specialties to help assess the clinical utility of alternate therapies, they have not been widely used in gastroenterology. Listed below are highlights of a study demonstrating the benefits of a new PPI, esomeprazole (Nexium®, AstraZeneca) compared to placebo, using the techniques of evidence-based analysis.

Esomeprazole vs. Placebo

Based on extensive clinical trial data, treatment with esomeprazole, the S-isomer of omeprazole, 40 mg or 20 mg once daily, was proven to be significantly more effective treatment for maintaining healing of erosive esophagitis for up to six months, compared to placebo, according to Dr. David A. Johnson, professor of medicine and chief of gastroenterology, Eastern Virginia School of Medicine, Norfolk, Virginia. Evidence-based medicine analysis indicated that two patients would need to be treated for six months with esomeprazole 40 mg or 20 mg instead of placebo to prevent one treatment failure (relapse of EE); that is, for every two patients treated with esomeprazole, one treatment failure is avoided.

To reach these conclusions, data from two maintenance trials with identical study protocols were pooled. A total of 693 Helicobacter pylori negative patients with endoscopically verified healed EE were treated once daily with esomeprazole 40 mg (n = 174), esomeprazole 20 mg (n = 180), esomeprazole 10 mg (n = 168), or placebo (n = 171) for up to six months. The proportion of patients whose esophageal healing was maintained according to endoscopy after six months was calculated by life-table estimates. The absolute risk reduction (ARR) and relative risk reduction (RRR) for treatment failure was calculated from the maintenance of healing at Month 6. The NNT was then calculated to determine the number of patients who needed to be treated with esomeprazole compared to placebo to avoid one treatment failure.

All doses of esomeprazole had a significantly higher maintenance of healing rate after six months than placebo (Eso40 = 90.5%; Eso20 = 85.7%; Eso10 = 55.7%; placebo = 29.1%). The magnitude of efficacy among patients treated with esomeprazole 10 mg suggested this is not a clinically viable dose.

Calculating the RRR, or the proportional reduction treatment failure rates between esomeprazole and placebo patients, was carried out as follows:

Esomeprazole 40 mg (E) — 90.5% patients maintained; 9.5% relapse

Placebo (P) — 29.1% patients maintained; 70.9% relapse

The risk of relapse is therefore reduced by 86.6% on esomeprazole compared with placebo. To calculate the AAA, or absolute arithmetical difference in treatment failures between esomeprazole and placebo, the following formula was used:

ARR=P–E=70.9%–9.5% = 61.4%

Or, for every 100 patients treated with esomeprazole, 61 treatment failures are prevented.

Finally, the NNT was calculated as follows:

NNT=1/ARR or 1/61.4% = 1.62 (2)

Or, for approximately every two patients treated with esomeprazole, one treatment failure is avoided.

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