Dig Dis Sci (2010) 55:338345

DOI 10.1007/s10620-009-0864-7

ORIGINAL ARTICLE

Rabeprazole 20 mg for Erosive Esophagitis-Associated Symptoms

in a Large, Community-Based Study: Additional Results
Alan Cutler Malcolm Robinson Anita Murthy
Byron DeLemos

Received: 13 August 2008 / Accepted: 19 May 2009 / Published online: 26 June 2009
Springer Science+Business Media, LLC 2009

Abstract
Purpose To provide additional efficacy data in patients
treated with rabeprazole through week 4, and to validate
sustained relief of gastroesophageal reflux disease symptoms through week 8 as well as to further analyze rabeprazole safety in patients with wide-ranging demographic
and clinical characteristics.
Results Patients in this study (N = 2,449) demonstrated
significant overall improvement versus baseline (P \ 0.001).
Substantial symptom relief was seen throughout 8 weeks of
treatment. By week 4, complete relief of daytime and nighttime heartburn, belching, regurgitation, and dysphagia was
observed in 87.5, 90.7, 50.7, 77.6, and 75.1% of patients,
respectively. Improvements were seen in rabeprazole-treated
patients (\65 or C65 years) with a range of baseline symptom
severities and across different racial groups. Rabeprazole was
well tolerated.
Conclusions In patients with endoscopy-confirmed erosive esophagitis treated with once-daily rabeprazole 20 mg,
prompt and continuing improvements were seen in daytime

A. Cutler (&)
Wayne State University School of Medicine, Digestive Health
Associates PLC, 30055 Northwestern Highway, suite #250,
Farmington Hills, MI 48334, USA
e-mail: Cutler_alan@yahoo.com
M. Robinson
University of Oklahoma College of Medicine, Oklahoma City,
OK, USA
A. Murthy
Eisai Inc, Woodcliff Lake, NJ, USA
B. DeLemos
Ortho-McNeil Janssen Scientific Affairs, LLC, Raritan, NJ, USA

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and nighttime heartburn, belching, regurgitation, and

dysphagia.
Keywords Gastroesophageal reflux disease
Heartburn

Regurgitation
Rabeprazole

Introduction
Gastroesophageal reflux disease (GERD) symptoms are
common medical complaints. Up to 50% of adults in the
United States report heartburn at least once per month, and
about 20% experience symptoms of heartburn and/or
regurgitation at least weekly [1, 2]. Symptoms of reflux
disease strongly influence quality of life. Results from a
survey that related specific GERD symptoms to quality-oflife subscales on the medical outcomes study short form-36
indicated that frequency and severity of symptoms were
associated with bodily pain and impaired social, emotional,
and physical functioning [3].
Gastroesophageal reflux disease (GERD) is a chronic
and recurrent condition in most patients. Extended followup indicates infrequent symptom resolution without treatment, and most GERD patients require continuing medical
therapy [4]. Symptom relief is the primary goal in patients
with GERD. Short-term treatment goals traditionally also
include healing of esophagitis, and chronic therapy is
intended to help avert symptomatic relapses and such
complications as esophageal stricture formation or adenocarcinoma [5]. A symptom-based treatment strategy may
be practical and feasible for many patients with GERD and
may be particularly appropriate in the primary care setting
[6, 7].
It is widely accepted that proton pump inhibitors (PPIs)
are the most effective therapy in treating both erosive

Dig Dis Sci (2010) 55:338345

esophagitis and nonerosive esophagitis [6, 8]. Rabeprazole

is a PPI that provides rapid and effective suppression of
acid secretion [9, 10]. Several studies have demonstrated
the effectiveness of rabeprazole in healing erosions and
maintaining healing in patients with GERD [1115].
Rabeprazole also has a very predictable pharmacokinetic
profile and minimal drugdrug interactions [16].
This was a large open-label trial in a setting closely
mirroring routine clinical practice. The goals were to
evaluate the timing of symptom relief and changes in
symptom severity with rabeprazole administered to patients
with confirmed erosive GERD. Safety was also addressed,
and there was special emphasis on the assessment of quality-of-life issues. Some of the results from this trial have
been previously reported [17]. As an extension of the original report, the present manuscript will provide some
additional efficacy data in patients treated with rabeprazole
at week 1; however, the main focus will be on the primary
endpoint at week 4, and the sustained relief of symptoms
(including GERD-associated symptoms) through week 8 of
treatment. This analysis also investigates patient outcomes
and additional safety issues in this treatment group, which
encompassed patients with an especially wide range of
demographic and clinical characteristics.

Materials and Methods

Study Design
This postmarketing study used an open-label, multicenter
design to analyze the efficacy and safety measures in
patients treated with rabeprazole 20 mg in actual clinical
practice. In this community-based setting, all the patients
had GERD symptoms and endoscopy-confirmed erosive
esophagitis. Patients received study medication once daily
for 8 weeks, and investigator evaluations included GERD
symptoms and adverse events at enrollment and study end
(8 weeks or early discontinuation). In addition, patients
reported symptom relief for the first 7 days of treatment
and at week 4 (day 28; primary endpoint) using a telephone-based interactive voice response system (IVRS).
Summaries are based on observations made in the intentto-treat (ITT) population.
Patients
Inclusion criteria included male and female patients aged
C18 years with endoscopically confirmed erosive esophagitis (Hetzel-Dent grade of 24) within 10 days of study
enrollment. Study medication was only begun after
endoscopy. Patients understood English, had access to a
telephone for study monitoring, were able to comply with

339

the study protocols, and had signed the informed consent.

Patient exclusion criteria included pregnancy or breastfeeding; known hypersensitivity to rabeprazole, substituted
benzimidazoles, or drug product excipients; and use of any
PPI within 7 days prior to administration of the study drug.
Interventions
Eligible patients took one rabeprazole 20-mg tablet daily
orally for 8 weeks without regard of timing of mealsthe
first dose administered at the investigators office. No
change in rabeprazole dose was made during the treatment
period. Physicians were permitted to prescribe additional
non-PPI medication. There were no other restrictions in
terms of prior or concomitant medication use.
Evaluations
Gastroesophageal reflux disease (GERD) symptom severity
was rated by the patient according to a four-point Likert
scale (0 = absent; 1 = mild; 2 = moderate; 3 = severe).
Investigators questioned patients at baseline concerning the
severity of daytime heartburn, nighttime heartburn, belching, and regurgitation. Patients self-rated the severity of
each of these symptoms for the first 7 days of treatment
and on day 28 by a telephone IVRS. Dysphagia was
assessed only at baseline and at week 4 [17].
At week 8, investigators assessed the severity of all
GERD-related symptoms (using a four-point Likert scale,
as above). The investigators at week 8 were privy to the
patient-assessed symptom severity data on days 17 and at
week 4 from the IVRS.
Safety was assessed by recording patient- and investigator-reported adverse events, which were evaluated for
severity and relationship to study medication. An adverse
event was considered serious if it was life-threatening,
resulted in persistent or significant disability or incapacity,
required prolonged hospitalization, required medical or
surgical intervention, or resulted in a congenital anomaly
or death.
Statistical Analysis
Statistical analyses were conducted using the safety-evaluable population, which included all enrolled patients and the
observations made in the ITT population, which comprised
all patients with a baseline evaluation and at least one postbaseline rating for any of the five symptoms evaluated.
Efficacy was analyzed by the mean change from baseline in symptom severity compiled from the IVRS data for
week 4, as well as from investigators reports at week 8 (or
early termination). Analyses included descriptive statistics
for the changes from baseline for the entire observations

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made in the ITT (efficacy-evaluable) population and for

subgroups stratified by baseline symptom severity (absent,
mild, moderate, and severe), gender, age (\65 and
C65 years), and race. Changes from baseline at each postbaseline assessment and the mean change from baseline at
end of study at week 8 were analyzed by means of paired
t-tests. Baseline and follow-up visits were analyzed for
weekly averages of the number of days and nights with
heartburn episodes, as well as percentages of patients who
experienced complete symptom relief (score = 0) or
improvement over baseline.
Complete relief (CR) was defined as the absence of the
symptom (symptom severity score = 0) for any symptom
rated C1 on the Likert scale at baseline. Satisfactory relief
(SR) was a reduction in the symptom severity score to 0
(absent) or 1 (mild) for any symptom rated C2 on the Likert
scale at baseline. Any improvement in symptoms included
those patients who were symptomatic (C1 on the Likert
scale) at baseline, and subsequently after treatment had a
C1-level reduction in symptom severity on the Likert scale.
Post-baseline safety events were tabulated, and event
frequencies and percentages were based on the safetyevaluable population. Adverse events were summarized by
body system and preferred term.

Dig Dis Sci (2010) 55:338345

Table 1 Demographic and clinical characteristics of safety-evaluable
population (N = 2,579)
Characteristic

n (%) or as stated

Mean age, years SD

52.1 14.9

Gender

The study was carried out at 423 sites in the United States and
enrolled a total of 2,579 patients, which comprised the
safety-evaluable population. Ninety-five percent (n =
2,449) of these patients were evaluable for efficacy and
82.6% (n = 2,130) completed the study. Demographic and
baseline clinical characteristics for all enrolled patients are
summarized in Tables 1 and 2. The majority of patients were
men and Caucasian, and the mean age was 52.1 years.
Nearly one-third of patients had a long-term history of
refractory GERD symptoms. In the efficacy-evaluable population, more than 75% (n = 1,890) of patients reported
daytime heartburn, primarily mild to moderate in severity,
C3 days per week; and *64% of patients (n = 1,546)
experienced nocturnal heartburn, primarily moderate to
severe, C3 days per week.
The only concomitant medications prohibited during this
study were other PPIs. As a result, these real-life patients
taking rabeprazole were also receiving a very wide range of
other medications, including analgesics, anti-inflammatory/
antirheumatic drugs, topical preparations for musculoskeletal, and cardiovascular medications. Table 3 summarizes
prior and concomitant gastrointestinal medications (prescription or over the counter) taken during the trial.

123

1,490 (58.3)

Female

1,065 (41.7)

Race
Caucasian
African American
Hispanic

2,185 (85.5)
146 (5.7)
179 (7.0)

Oriental/Asian

18 (0.7)

Other

28 (1.1)

Medical/surgical abnormalitiesa
Musculoskeletal

741 (28.7)

Cardiovascular

705 (27.3)

Ears, eyes, nose, and throat

490 (19.0)

Hetzel-Dent grade
2 (2B10% erosion)

1,562 (62.3)

3 (1050% erosion)

720 (28.7)

4 ([50% erosion)

225 (9.0)

Barretts esophagus without dysplasia

208 (8.2)

Duration of gastroesophageal reflux disease

Results
Patients

Male

Newly diagnosed

564 (21.9)

\1 year
15 years

379 (14.7)
777 (30.1)

[5 years

779 (30.2)

Gastrointestinal medications (taken within

3 months prior to study entry)
Antacids
H2RAs: prescription

1,238 (48.0)
718 (27.8)

H2RAs: over-the-counter

616 (23.9)

Cisapride

149 (5.8)

Metoclopramide

58 (2.2)

Prevacid

329 (12.8)

Prilosec

466 (18.1)

H2RAs histamine2-receptor antagonists

This population refers to the number of patients who were included in
the safety evaluation. The total of characteristics may not add up to
2,579 (100%) because patients might not report a value for each and
every demographic or clinical characteristic
a

At least 1 medical/surgical abnormality was reported by 1,777

(68.9%) patients

Efficacy
Symptom Relief at 4 and 8 Weeks
All GERD symptoms were significantly improved relative
to baseline throughout the first week of treatment, as has
been described previously by Robinson et al. [17]. Symptom relief was sustained or further improved in evaluations

Dig Dis Sci (2010) 55:338345

341

Table 2 Baseline symptom severities of efficacy-evaluable population (N = 2,449)

Characteristic

n (%) or as statedb

Symptom severity (n = 2,416a)

Severe

Moderate

Mild

Absent

Not reported

Daytime heartburn

479 (19.8)

970 (40.1)

653 (27.0)

314 (13.0)

Nighttime heartburn

689 (28.5)

780 (32.3)

475 (19.7)

472 (19.5)

Belching

365 (15.1)

731 (30.3)

708 (29.4)

606 (25.1)

Regurgitation

344 (14.2)

544 (22.5)

617 (25.5)

911 (37.7)

Dysphagia

247 (10.2)

394 (16.3)

447 (18.5)

1327 (54.9)

IVRS interactive voice response system

a

Data collected via the IVRS

Percentages were based on the total number of patients (N), excluding not reported
Any Improvement

Table 3 Prior and concomitant gastrointestinal medications: prescription and over-the-counter medications (N = 2,579)
Safety-evaluable (N = 2,579)
Prior n (%)b,c

Concomitant n (%)b

Antacids
H2 antagonists

1,238 (48.0)

303 (11.7)

Prescription

718 (27.8)

64 (2.5)

Over the counter

616 (23.9)

54 (2.1)

149 (5.8)

65 (2.5)

58 (2.2)

34 (1.3)

Propulsid (cisapride)
Metaclopramide

94.2 94.1
87.5

Patients could have reported C1 prior or concomitant gastrointestinal medication; thus, the sum of patients who took either prior or
concomitant gastrointestinal medications may not equal the total
number of safety-evaluable patients

Percentages were based on the total number of patients (N)

Medications taken over the past 3 months

carried out at weeks 4 and 8 (P \ 0.001 compared with

baseline).
Week 4 At Week 4, as reported by patients on a telephone
IVRS, improvements (i.e., C1 level reduction in symptom
severity) in daytime and nighttime heartburn were reported
in [90% of patients who were symptomatic at baseline.
During the study, only 303 (11.7%) patients used antacids
and 118 (4.6%) used H2 antagonists (either prescription or
over the counter; Table 3). Although baseline severities of
belching, regurgitation, and dysphagia were lower than
those for heartburn, patients treated with once-daily rabeprazole 20 mg reported smaller, but still significant,
improvements in these symptoms (Fig. 1).
Week 8 As reported by patients to the investigators, relief
from daytime heartburn, nighttime heartburn, belching,
regurgitation, and dysphagia was sustained through week 8,
as assessed by the investigators (all P \ 0.001 vs. baseline).
The percentage of patients demonstrating improvement in

96.3

95.1

Satisfactory Relief
90.7

80

Complete Relief

88.0
81.5

Percent of Patients

Gastrointestinal medication

100

89.8
87.2
77.6

75.5

89.4
75.1

60
50.7

40
20
0
Daytime
Heartburn
n=1651

Nighttime
Heartburn
n=1523

Belching Regurgitation Dysphagia

n=1415

n=1179

n=8 45

Fig. 1 Improvement in symptoms at week 4 in patients treated with

rabeprazole 20 mg. Complete relief (CR) is the absence of the
symptom (symptom severity score = 0) for any symptom rated C1 on
the Likert scale at baseline. Satisfactory relief (SR) is a reduction in
the symptom severity score to 0 (absent) or 1 (mild) for any symptom
rated C2 on the Likert scale at baseline. Any improvement in
symptoms included those patients who were symptomatic (C1 on the
Likert scale) at baseline and subsequently after treatment had a C1
level reduction in symptom severity on the Likert scale

symptoms at week 8, although slightly lower, were comparable to those observed at week 4 (daytime heartburn
[77.4%], nocturnal heartburn [73.2%], belching [55.0%],
regurgitation [52.4%]) was similar to those at week 4 (daytime heartburn [82.3%], nocturnal heartburn [77.6%],
belching [56.5%], regurgitation [54.9%]).
Impact of Baseline Symptom Severity on Efficacy
Table 4 summarizes the magnitude of symptom relief at
weeks 4 and 8 for daytime and nighttime heartburn,
belching, regurgitation, and dysphagia, with results stratified by baseline symptom severity. For all symptoms,
patients with higher severity at baseline experienced correspondingly greater decreases in symptom severity.
However, reductions in symptom severity relative to the

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-1.84, n = 773 -1.60, n = 720 -1.87, n = 619 -1.65, n = 578 -1.31, n = 580 -1.20, n = 552 -1.70, n = 433 -1.53, n = 400 -1.63, n = 311

-2.72, n = 371 -2.46, n = 343 -2.79, n = 533 -2.53, n = 494 -2.07, n = 274 -1.88, n = 269 -2.50, n = 251 -2.34, n = 225 -2.56, n = 181

Moderate

Severe

Numbers represent the symptom severity score after 4 or 8 weeks of treatment. Severity of symptoms was rated on a four-point Likert scale (0 = absent; 3 = severe)
Data at week 4: interactive voice response system; at week 8: investigators case report forms

SD standard deviation

-2.62, n = 170

-0.87, n = 507 -0.73, n = 535 -0.92, n = 371 -0.75, n = 410 -0.49, n = 561 -0.41, n = 579 -0.72, n = 495 -0.70, n = 493 -0.73, n = 353

-0.80, n = 375

?0.06, n = 239 ?0.12, n = 227 ?0.07, n = 367 ?0.12, n = 340 ?0.34, n = 475 ?0.30, n = 422 ?0.14, n = 710 ?0.12, n = 705 ?0.13, n = 1,031 ?0.06, n = 996

Mild

Week 4
Week 4
Week 8
Week 4

Week 8

Week 4

Week 8

Week 4

Week 8

Dysphagia
Regurgitation
Belching
Nighttime heartburn
Daytime heartburn

Severity
at
baseline

The effectiveness of rabeprazole extended across a wide

range of patients. Males and females with mild, moderate,
or severe daytime or nighttime heartburn at baseline all
experienced significant reductions in symptom severity at
week 4 (all P \ 0.001). This same pattern of results was
observed for belching, regurgitation, and dysphagia (all
P \ 0.001). Symptom improvements were also similar for
patients aged \65 years old versus those aged C65 years
(all P \ 0.001 for all patients with mild, moderate, or
severe symptoms at baseline in both age groups across all
symptom categories). Similarly, there were no differences
between Caucasians, African Americans, and those of other
races; all improved their symptoms (all P B 0.025). During
the first week of treatment, rabeprazole also significantly
reduced symptom severity for daytime heartburn, nighttime
heartburn, and regurgitation (P \ 0.001) regardless of the
presence or absence of Barretts esophagus. Similarly, the
mean change from baseline showed significant improved
symptom relief for daytime heartburn, nocturnal heartburn, and regurgitation, regardless of Hetzel-Dent grade
(P \ 0.001).

Table 4 Changes from baseline in symptom severity stratified by baseline severity

Efficacy in Subgroups of Patients

Week 8

maximum possible amount for patients in different baseline

strata were similar. For example, by week 4, patients with
mild baseline regurgitation experienced a reduction in
symptom severity of -0.72; patients with moderate baseline regurgitation, -1.70; and patients with severe baseline
regurgitation, -2.5072, 85, and 83% of the maximum
possible reductions in symptom severity scores, respectively. By week 8, these values were -0.70 (mild), -1.53
(moderate), and -2.34 (severe), corresponding to reductions of 70, 77, and 78%, respectively. This pattern of
results was also observed for daytime and nighttime
heartburn, belching, and dysphagia at weeks 4 and 8
(Table 4).
A small number of patients who were asymptomatic at
baseline reported symptoms over the course of the trial
(Table 4). For patients with no symptoms at baseline, the
proportion of patients who experienced any degree of
daytime heartburn, nocturnal heartburn, regurgitation, or
dysphagia was less than or equal to 10% during the first
week. Such poststudy initiation emergent symptoms were
more likely to remain absent or sporadically appear and
disappear during therapy than to emerge and persist after
therapy began. Belching associated with GERD was a more
refractory symptom as 28.6% of patients who did not report
this symptom at baseline did so on day 7. The majority of
patients who were asymptomatic (for daytime heartburn,
nocturnal heartburn, regurgitation, belching, or dysphagia)
at baseline also remained symptom free at weeks 4
(73.595.8%) and 8 (73.995.1%).

-1.61, n = 280

Dig Dis Sci (2010) 55:338345

Absent

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343

Table 5 Percentage of total efficacy-evaluable population and patient subgroups with complete and satisfactory symptom relief at week 4
Daytime heartburn

Nighttime heartburn

Belching

Regurgitation

Dysphagia

CR

SR

CR

SR

CR

SR

CR

SR

CR

SR

88.6

95.6

91.5

96.4

56.5

87.2

82.1

93.0

83.5

94.4

Men

90.4

96.4

93.3

97.3

59.7

88.6

85.6

94.4

86.4

95.6

Women

86.0

94.4

88.9

95.1

51.8

85.1

76.9

91.0

79.5

92.8

86.9
93.8

94.9
97.9

90.6
94.4

95.8
98.3

55.2
60.1

85.6
92.3

80.4
87.6

92.0
96.6

81.8
88.7

93.8
96.1

Total population (efficacy-evaluable)

Subgroups
Gender

Age
\65 years
C65 years

Numbers represent the percentage of patients in the total efficacy-evaluable population and in the various subgroups with complete relief
(CR: symptom severity score = 0 for any symptom rated C1 at baseline) and satisfactory relief (SR: reduction in symptom severity score to 0 or
1 for any symptom rated C2 at baseline) after 4 weeks of treatment. Severity of symptoms was rated on a four-point Likert scale (0 = absent;
3 = severe)

At week 4, the percentages of patients with complete

and satisfactory relief of daytime and nighttime heartburn,
belching, regurgitation, and dysphagia (Table 5) continued to be demonstrable across all patient subgroups
(gender, age, race). The percentages of patients reporting
complete and satisfactory symptom relief were similar
between men and women, all races studied (Caucasian,
African American, other), and age groups \65 and
C65 years. In addition, symptom relief at week 4 was
also similar between patients with and without Barretts
esophagus, and symptom relief was similar regardless of
Hetzel-Dent grade.
Safety
Daily dosing with rabeprazole was well tolerated. The most
commonly reported adverse events in the safety population
(N = 2,579) included abdominal pain (1.2%), chest pain
(0.5%), diarrhea (1.5%), dizziness (0.7%), dyspepsia
(0.6%), belching (0.5%), headache (1.6%), nausea (1.0%),
rash (0.5%), and upper respiratory tract infection (0.5%).
Within the safety population, 14.9% of patients reported
C1 adverse event, 2.4% discontinued due to adverse
events, and 1.4% reported a serious adverse event. All
serious adverse events were considered to be unrelated to
study medication, except for esophageal spasm (occurred
in one patient), which was considered as possibly related to
the study medication. Three patients died during the study,
but deaths were judged to be unrelated to the study drug. A
total of 2.2% (n = 56) of patients were hospitalized after
the initiation of rabeprazole treatment. Some of the hospitalizations occurred as a result of serious adverse events,
most commonly of the cardiovascular system; however,
none of these were considered by investigators to be related
to study medication.

Discussion
In this large-scale, open-label, community-based study,
erosive esophagitis patients with a wide range of demographic and clinical characteristics demonstrated significant relief from all measured GERD-associated symptoms
during administration of once-daily rabeprazole 20 mg
over 8 weeks. Patients treated with rabeprazole showed
improvement in symptoms regardless of baseline symptom
severity, gender, age, or race. In addition, similar
improvements were demonstrated in rabeprazole-treated
patients with Barretts esophagus and in those of the entire
range of esophagitis severity. Rabeprazole was also well
tolerated, with low rates of adverse events, serious adverse
events, and discontinuations due to adverse events.
Results from postmarketing studies, such as this trial,
provide real-world information and are consistent with the
safety and efficacy of rabeprazole and complement data
from other controlled clinical trials in several ways. First,
this trial enrolled a large number of patients with a wide
range of demographic and clinical characteristics and, thus,
provided information about the effectiveness and safety of
rabeprazole in a far more heterogeneous population than is
usually enrolled in clinical trials. Second, the manner in
which patients were treated more closely reflects actual
clinical practice than highly controlled clinical trials.
Third, patients in this trial were taking many different
additional medications to treat other acute or chronic
conditions, providing a unique opportunity to assess the
safety profile for rabeprazole when used in combination
with these drugs. Such relative polypharmacy is not seen in
conventional clinical trials. Among the concomitant medications taken by the patients were gastrointestinal drugs
such as antacids and H2 antagonists; however, these medications were minimally used and unlikely to have affected

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the results of the study. However, safety data from this trial
are not precisely comparable to some of those reported
with other similar agents because this study did not include
a placebo or active comparator and lacked blinding of
therapy.
The safety results for rabeprazole in this trial complement those from controlled clinical trials by providing data
for a wider range of patients with comorbid diseases who
often were utilizing one or more concomitant medications.
The safety of rabeprazole in such patients should reassure
clinicians who are treating patients with comorbid conditions who may be consuming a range of other medications.
The safety profile of rabeprazole in the present trial was
similar to that described in its product labeling.
This open-label study, as well as previous controlled
clinical studies, supports results reported in previous clinical trials showing that rabeprazole-treated patients achieve
highly effective symptom relief and that rabeprazole is well
tolerated by the vast majority of patients [11, 12, 15, 18]. In
addition to heartburn, regurgitation is common in GERD
patients. In this open-label study, as well as in an additional
previous clinical trial, regurgitation was relieved in rabeprazole-treated patients with GERD [19, 20]. Kahrilas
et al. [20] demonstrated that patients with moderately
severe nonerosive reflux disease (NERD) treated with
rabeprazole 20 mg experienced significantly greater changes from baseline with regard to regurgitation (based on a
five-point severity score scale) compared to placebo-treated patients at week 4 (P B 0.05 vs. placebo). Regurgitation of gastric acid into supraesophageal structures may
trigger various complications potentially associated with
GERD, including asthma exacerbation [21]. Therefore,
reduction of regurgitation might be a marker for the
potential alleviation of a wide range of GERD-induced
problems. For example, it has been shown that up to 70%
of asthmatic people who have symptoms of GERD have
asthma improvement with antireflux therapy [21].
Dysphagia is less common than heartburn in patients
with GERD [22]. About 45% of patients enrolled in the
present trial had baseline dysphagia. For patients treated
with once-daily rabeprazole 20 mg who reported dysphagia
at baseline, the mean change from baseline to week 4
statistically favored symptom relief (P \ 0.001).
Global Assessments of Treatment and Effects
on Quality of Life
Health-related quality of life observed in patients treated
with rabeprazole and patients global assessment of treatment in this trial have been reported previously [17].
Patients treated with rabeprazole significantly improved all
domains on the medical outcomes study short form-36
health survey (all P B 0.007 vs. baseline), and 88.1% of

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Dig Dis Sci (2010) 55:338345

patients rated rabeprazole as either good or excellent in

relieving their GERD symptoms [17].
As noted earlier, GERD symptoms have a significantly
negative impact on quality of life. Previously reported
results from this trial and other studies of rabeprazole
indicate that the symptom relief achieved with this drug is
associated with significant reductions in patient stress and
improvements in quality of life [17, 23, 24].
In conclusion, the results for this open-label, large-scale,
community-based trial of rabeprazole in erosive GERD
supports the premise that rabeprazole provides fast and
sustained relief of common symptoms of GERD (including
daytime and nighttime heartburn, belching, regurgitation,
and dysphagia). Overall, approximately 90% of patients
remained symptom free at week 4. These data come from a
particularly wide range of patients in a setting that mirrors
actual clinical practice. Rabeprazole was well tolerated by
patients, with no unexpected adverse reactions and no
indication of safety problems despite administration of a
wide range of concomitant medications. The results of this
trial support the large body of clinical trial evidence documenting the efficacy and safety of rabeprazole in patients
with erosive GERD.
Acknowledgments This work was supported by Eisai Inc, Woodcliff Lake, NJ, and Ortho-McNeil Janssen Scientific Affairs, LLC,
Raritan, NJ.

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