Aliment Pharmacol Ther 2005; 21: 455–463.
Efficacy of esomeprazole 40 mg vs. lansoprazole 30 mg for healing
moderate to severe erosive oesophagitis
M. B. FENNERTY*, J. F. JOHA NSON , C. HWANG à & M . SOSTEKà
*Oregon Health & Science University, Portland, OR, USA;  Rockford Gastroenterology Associates, Ltd, Rockford, IL, USA;
àAstraZeneca LP, Wilmington, DE, USA
Accepted for publication 29 November 2004
SUMMARY
Background: Secondary analyses from previous studies
indicated that esomeprazole was more effective than
lansoprazole and omeprazole in healing moderate or
severe (Los Angeles grades C or D) erosive oesophagitis
(EE).
Aim: To compare prospectively healing rates with
esomeprazole vs. lansoprazole in patients with moderate
to severe EE.
Methods: In this multicentre, randomized, double-blind,
parallel-group trial, adult patients with endoscopically
confirmed moderate or severe EE received esomeprazole
40 mg (n ¼ 498) or lansoprazole 30 mg (n ¼ 501)
once daily for up to 8 weeks. The primary end point was
EE healing through week 8. Secondary assessments
INTRODUCTION
Erosive oesophagitis (EE), caused by gastro-oesophageal
reflux, is a common medical problem. Data from large
clinical trials indicate that the prevalence of moderate to
severe [Los Angeles (LA) Classification grades C and D]
EE at the time of screening is as high as 13–15% in
patients with frequent heartburn.1, 2 The severity of
oesophagitis is in large part affected by the duration of
oesophageal acid exposure, with greater acid exposure
being associated with more severe mucosal lesions.3
Correspondence to: Dr M. B. Fennerty, Division of Gastroenterology,
Oregon Health & Science University, Mail Code PV-310, 3181 SW Sam
Jackson Park Rd, Portland, OR 97239-3098, USA.
E-mail: fennerty@ohsu.edu

2005 Blackwell Publishing Ltd
doi: 10.1111/j.1365-2036.2005.02339.
included investigator-assessed resolution of symptoms
and safety and tolerability.
Results: Time to healing was significantly different
(P ¼ 0.007), favouring esomeprazole. Estimated healing
rates at week 8 were 82.4% with esomeprazole 40 mg
and 77.5% with lansoprazole 30 mg. Heartburn
resolved at week 4 in 72% and 64% of patients who
received esomeprazole and lansoprazole, respectively
(P ¼ 0.005). Control of other GERD symptoms was
similar between treatments. Both treatments were well
tolerated.
Conclusions: With 8 weeks’ treatment, esomeprazole
40 mg once daily heals moderate to severe EE faster
and in more patients, and resolves heartburn in more
patients after 4 weeks of treatment, than lansoprazole
30 mg once daily.
Currently, therapy for gastro-oesophageal reflux disease
(GERD) largely focuses on the pharmacological reduc-
tion of gastric acid secretion. This approach to therapy
for GERD has been effective in eliminating many of the
symptoms of GERD, such as heartburn and acid
regurgitation, and effectively heals the oesophageal
mucosa in the majority of patients. The goal of acid
suppression therapy in patients with EE is to achieve
sufficient acid control necessary to relieve GERD-related
symptoms and optimize oesophageal healing rates.
Oesophagitis healing rates have been correlated with
the amount of time that the intragastric pH level can be
maintained above a pH of 4.4
Proton pump inhibitors (PPIs) are widely recognized
as the most effective agents for treating GERD and
455
456 M. B. FENNERTY et al.
have been the mainstay of pharmacological GERD
management.5 These drugs produce greater inhibition
of intragastric acid secretion, more rapid symptom
control, and better healing of EE than H2-receptor
antagonists.5–7 Esomeprazole, the S-enantiomer of
omeprazole (a racemic mixture of R- and S-enantio-
mers) has increased bioavailability compared with the
R-enantiomer and omeprazole because of stereoselec-
tive differences in hepatic metabolism by cytochrome
P-450 isoenzymes 2C19 and 3A4.8 Treatment with
esomeprazole resulted in significantly greater inhibition
of intragastric acid secretion vs. other PPIs as well as
higher EE healing rates than other currently available
PPIs at doses approved for healing EE.1, 2, 9–11 In post-
hoc analyses, the differences in healing rates between
esomeprazole and other PPIs observed in these studies
were more pronounced in patients with moderate to
severe disease (LA grades C and D), which typically is
more difficult to heal with antisecretory therapy than
less severe states of disease (LA grades A and B) [data
on file, AstraZeneca LP (Wilmington, DE, USA),
reference codes, DA-NEX-17, DA-NEX-18, DA-NEX-
24, DA-NEX-25]. One of these previous analyses
showed that the observed healing rates after 8 weeks
of treatment in patients with moderate or severe EE
(LA grades C or D) were 86.6% with esomeprazole
40 mg and 73.9% (P ¼ 0.0013) with lansoprazole
30 mg (data on file, AstraZeneca LP, reference code,
DA-NEX-18 and Castell et al.9) No previous study has
used healing of moderate to severe EE as the primary
outcome measure. We hypothesized that, because of
the better antisecretory activity of esomeprazole 40 mg
compared with that of lansoprazole 30 mg and
because the results of the previously described post-
hoc analyses showed better healing in patients with
LA grades C and D EE using esomeprazole, healing of
moderate to severe EE would be more effective using
esomeprazole 40 mg vs. lansoprazole 30 mg when
evaluated as a primary end point of a randomized
clinical trial. Thus, the primary objective of this study
was to compare prospectively the healing rates
achieved with esomeprazole 40 mg vs. lansoprazole
30 mg over 8 weeks among patients with endoscopi-
cally determined moderate or severe EE (LA grades C
or D). Secondary objectives included healing at
4 weeks, comparison of the resolution of investigator-
evaluated GERD symptoms and patient-recorded heart-
burn symptoms, and evaluation of the safety and
tolerability of these therapies.

2005 Blackwell Publishing Ltd, Aliment Pharmacol Ther 21, 455–463
MATERIALS AND METHODS
Study design
The primary inclusion criteria for this randomized,
double-blind, double-dummy, parallel-group, multicen-
tre study (D9612L00046/Study 322), were LA grades C
or D EE confirmed by an oesophagogastroduodenoscopy
within 1 week before randomization and heartburn
(described as a burning feeling, rising from the stomach
or lower part of the chest up towards the neck) for ‡2 of
the 7 days before randomization. Qualified patients
received up to 8 weeks of oral therapy with esomepra-
zole 40 mg or lansoprazole 30 mg taken once daily in
the morning with a glass of water before breakfast.
Study medications were provided as single capsules.
To maintain double-blind conditions, patients were
instructed to take both an active treatment, a capsule
containing esomeprazole or lansoprazole, and a dummy
capsule that was identical to the comparator. Patients
were enrolled sequentially within each site using
predetermined, computer-generated randomization
schedules, using a block size of 4 and by-site allocation
that were concealed from both the patients and
investigators by using an opaque panel on the study
drug label assigned to that patient that could only be
broken by the investigator in case of medical emergency
and, if done, was documented. Endoscopy was repeated
after approximately 4 weeks of treatment, and patients
with no evidence of EE, based on the LA classification of
oesophagitis, were considered healed and were with-
drawn because they had achieved the end point of
healing. The patients who still had EE continued their
assigned treatment and returned after 4 more weeks
(8 weeks from study entry) for a repeat endoscopic
evaluation. Once again, the absence of EE based on the
LA classification was used as the determinant of
healing.
Patients also received 200-mg antacid tablets [Gelusil;
Warner-Lambert Consumer Healthcare (Parke-Davis),
Morris Plains, NJ, USA] and were instructed to take no
more than six tablets per day only for the relief of acute
intolerable heartburn symptoms. Patients returned all
unused study drugs at each visit and returned capsule
counts were used to assess treatment compliance.
Independent Ethics Committee or Institutional Review
Board approval was obtained before enrolment of any
patient into the study, which was performed in accord-
ance with the Declaration of Helsinki, Good Clinical
Practice, and applicable regulatory requirements. Signed
 ESOMEPRAZOLE VS. LANSOPRAZOLE IN EROSIVE OESOPHAGITIS
informed consent was obtained from all patients before
study entry.
Patients
Men and non-pregnant, non-lactating women between
the ages of 18 and 75 years were included. A negative
pregnancy test at study baseline and a medically
acceptable form of birth control were required for
women of childbearing potential. Patients were exclud-
ed if they experienced any bleeding disorder or signs of
gastrointestinal bleeding at the time of the baseline
endoscopy or within 3 days before randomization; had a
history of gastric or oesophageal surgery, except for
simple closure of perforated ulcer; or had current or
historical evidence (within 3 months) of Zollinger–
Ellison syndrome, primary oesophageal motility disor-
ders (achalasia, scleroderma and/or primary oesopha-
geal spasm), inflammatory bowel disease, pancreatitis,
malabsorption, generalized bleeding disorders resulting
from haemorrhagic diathesis, oesophageal stricture,
duodenal ulcer, gastric ulcer, evidence of upper gastro-
intestinal malignancy, endoscopic Barrett’s oesophagus
(>3 cm), significant dysplastic changes in the oesopha-
gus, or any other severe concomitant disease. Patients
who used a PPI within 28 days before the baseline visit
or daily histamine H2-receptor antagonists in doses
exceeding standard approved prescription-strength
doses within the last 3 months were excluded, as were
patients who had need for continuous concurrent
therapy with warfarin or other anticoagulants, prosta-
glandin analogues, antineoplastic agents, salicylates
(unless £165 mg daily for cardiovascular prophy-
laxis), steroids (oral or intravenous), pro-motility
drugs, sucralfate, non-steroidal anti-inflammatory
drugs, phenytoin, or tegaserod. Use of Helicobacter
pylori eradication therapy or a concomitant medication
that depends on the presence of gastric acid for optimal
absorption was not permitted. Compliance assessments
were based on returned drug counts. Patients were
considered compliant if they consumed >90% of the
study drug.
Efficacy measures
Endoscopic confirmation of the EE healing was the
primary efficacy assessment. An oesophagogastroduo-
denoscopy was performed at baseline, at week 4, and at
week 8 (if EE was not healed at the week-4 visit).

2005 Blackwell Publishing Ltd, Aliment Pharmacol Ther 21, 455–463
457
Healing was defined as no mucosal breaks according to
the LA classification. It was assumed for this study that
patients healed at week 4 (but who did not continue in
the study) would have remained healed through week 8
(if they had continued therapy). The proportion of
patients healed by week 8 was estimated by the Kaplan–
Meier method. The observed healing rates at weeks 4
and 8 were also calculated.
Investigators evaluated GERD symptoms (heartburn,
acid regurgitation, dysphagia, and epigastric pain) for
the 7 days before the patient’s study visit on a four-
point scale from ‘none’ to ‘severe’ [incapacitating
symptom, with inability to perform normal activities
(including sleep)]. For each symptom, resolution was
defined as no symptoms (severity ¼ none) during the
7 days before the clinical visit.
During the first 4 weeks of the study, patients kept a
diary in which they assessed their heartburn symptoms
each morning by rating the most intense episode during
the previous 24 h using the same scale as that used by
the investigators to assess symptoms. Resolution of
heartburn was defined as no symptoms. Sustained
resolution of heartburn was defined as no symptoms
for 7 consecutive days. The first day of the 7 days was
used to calculate the days to sustained resolution. In
their diaries, patients also indicated whether or not they
had nocturnal heartburn (during sleeping hours). From
these diary data, the proportions of heartburn-free days
and heartburn-free nights were calculated for each
patient. Patients were asked to complete diary cards
only during the first 4 weeks because of the anticipated
discontinuation of many patients after the week-4 visit
due to healing of EE.
Safety
Adverse events spontaneously reported by the patient or
in response to an open question from the study
personnel or revealed by physical or laboratory obser-
vations were recorded. Investigators recorded the inten-
sity (mild, moderate, or severe) of adverse events and
whether or not there was a reasonable possibility that
the adverse event was caused by the study drug. Fasting
blood samples for serum chemistry and haematological
measurements were obtained by standardized tech-
niques at baseline and final visits and were analysed by
a central laboratory. An H. pylori serology test (FlexSure
HP; Beckman Coulter, Inc., Fullerton, CA, USA)
was performed at the site during the baseline visit.
458 M. B. FENNERTY et al.
A pregnancy test (dipstick in urine) was performed for
women of childbearing potential. Physical examinations
and vital signs were recorded and evaluated.
Statistical analysis
Efficacy analyses included all randomized patients who
took at least one dose of study medication and had LA
grade C or D EE (intention-to-treat analysis). The safety
evaluation included all patients who took at least one
dose of study medication.
All statistical tests were two-sided. A difference
between the two treatment groups was considered
statistically significant if P £ 0.05. The analysis was
performed using SAS software, version 8.2 (SAS
Institute Inc, Cary, NC, USA).
The primary efficacy variable was healing of EE by
week 8. The EE healing rate through 8 weeks was
estimated by the Kaplan–Meier method. The primary
analysis comparing the time-to-healing curves of eso-
meprazole 40 mg and lansoprazole 30 mg was per-
formed using a log-rank test, which considers both the
time of healing and the magnitude of difference between
treatment groups. In addition, observed healing rates
were calculated for weeks 4 and 8 separately. Healed
patients who discontinued from the study at week 4
were included in a cumulative week-8 healing rate, on
the basis of the assumption that they would remain
healed if treatment continued for another 4 weeks.
The secondary analysis comparing the observed heal-
ing rates between treatment groups was performed
using a Cochran–Mantel–Haenszel (CMH) test that was
stratified by baseline severity of EE. The proportions of
patients with resolution of GERD symptoms at week 4 as
recorded by investigators were compared between
treatment groups using a CMH test stratified by the

2005 Blackwell Publishing Ltd, Aliment Pharmacol Ther 21, 455–463
baseline severity of that symptom. Concurrence
between investigator-assessed resolution of GERD symp-
toms (resolved, not resolved) and EE healing status
(healed, not healed) was summarized. Time-to-event
curves for time to sustained resolution and time to first
resolution of heartburn from diary data were compared
between treatments using a log-rank test. Analysis of
variance (anova) was used to compare treatment groups
for the percentage of heartburn-free days and heart-
burn-free nights.
Because the planning of this study was based on the
subgroup results of a previous study,9 the results from
that study were used as a reference for the sample-size
calculation. An estimated 474 patients randomized to
each group were needed to detect a 10% difference in EE
healing rate (85% in the esomeprazole 40-mg group
and 75% in the lansoprazole 30-mg group), with a 5%
significance level, 95% power, and allowing up to 10%
withdrawals.
RESULTS
Patients
Of 4015 patients screened, 1001 patients were ran-
domized at 163 US centres (Figure 1). The first patient
enrolled in December 2002 and the last patient
completed the study in August 2003. One patient in
each group did not take any study medication, and
these patients were not included in the efficacy or safety
analyses. Overall, 94% of those randomized completed
the study (Figure 1). The most common reasons for
withdrawal were lost to follow-up in the esomeprazole
group and lost to follow-up and adverse events in the
lansoprazole group. Baseline demographic and clinical
characteristics were similar between groups (Table 1).
Figure 1. Patient disposition.
 ESOMEPRAZOLE VS. LANSOPRAZOLE IN EROSIVE OESOPHAGITIS 459

Table 1. Baseline demographic and clinical characteristics Healing rates

Esomeprazole Lansoprazole During 8 weeks of treatment, the time-to-healing
40 mg once 30 mg once curves were significantly different (P ¼ 0.007) favour-
daily (n ¼ 498) daily (n ¼ 501)
ing esomeprazole, which indicated that esomeprazole
Mean age in years (s.d.) 47.3 (13.2) 47.1 (12.9) healed EE faster and in more patients than lansoprazole.
Sex, n (%) The estimated healing rates were 82.4% with esomep-
Men 327 (65.7) 333 (66.5)
razole 40 mg once daily and 77.5% with lansoprazole
Women 171 (34.3) 168 (33.5)
Race, n (%)
30 mg once daily (Table 2). The secondary analysis
White 411 (82.5) 411 (82.0) showed that the observed healing rates for all patients
Black 20 (4.0) 27 (5.4) at 4 weeks were also significantly higher in the
Asian 3 (0.6) 2 (0.4) esomeprazole group than in the lansoprazole group
Other 64 (12.9) 61 (12.2) (55.8% vs. 47.5% respectively; P ¼ 0.005), but the
GERD history, n (%)
difference was not significant at 8 weeks (77.5% vs.
<1 year 38 (7.6) 27 (5.4)
1–5 years 204 (41.0) 203 (40.5) 73.3% respectively; P ¼ 0.099) (Table 2). Both in the
>5 years 256 (51.4) 271 (54.1) group of patients with grade C EE and the group with
H. pylori status by serology, n (%) grade D EE, at weeks 4 and 8, observed healing rates
Positive 54 (10.8) 34 (6.8) were higher in the esomeprazole group compared with
Negative 437 (87.8) 466 (93.0)
the lansoprazole group (Table 2).
Not evaluable/missing 7 (1.4) 1 (0.2)
Baseline LA grade, n (%)
C 390 (78.3) 403 (80.4) Control of symptoms
D 108 (21.7) 98 (19.6)
Investigator-recorded GERD symptoms at baseline Investigator assessments showed that a significantly
Heartburn, n (%) greater proportion of patients (P ¼ 0.005) had resolu-
None 2 (0.4) 4 (0.8)
tion of heartburn symptoms with esomeprazole than
Mild 40 (8.0) 40 (8.0)
Moderate 202 (40.6) 192 (38.3)
Table 2. Estimated life-table and observed EE percentage healing
Severe 254 (51.0) 265 (52.9)
rates after 4 or 8 weeks of treatment with once-daily esomepra-
Acid regurgitation, n (%)
zole 40 mg or lansoprazole 30 mg
None 40 (8.0) 39 (7.8)
Mild 91 (18.3) 93 (18.6) Esomeprazole Lansoprazole
Moderate 195 (39.2) 200 (39.9) 40 mg once 30 mg once
Severe 172 (34.5) 169 (33.7) Time daily (n ¼ 498) daily (n ¼ 501) P-value
Dysphagia, n (%)
None 294 (59.0) 295 (58.9) Week 4
Mild 105 (21.1) 97 (19.4) Estimated % 58.6 49.4 –
Moderate 62 (12.4) 71 (14.2) (95% CI) (54.1, 63.0) (44.9, 53.8)
Severe 37 (7.4) 38 (7.6) Observed %
Epigastric pain, n (%) (95% CI)
None 135 (27.1) 134 (26.7) C 60.3 50.6 –
Mild 99 (19.9) 117 (23.4) D 39.8 34.7 –
Moderate 177 (35.5) 150 (29.9) C and D 55.8 47.5 0.005*
Severe 87 (17.5) 100 (20.0) (51.5, 60.2) (43.1, 51.9)
Week 8
Estimated % 82.4 77.5 0.007 
(95% CI) (78.9, 85.9) (73.7, 81.2)
Observed %
Compliance with study medication was similar between
(95% CI)
groups [92% (458 of 498) and 90% (452 of 501) by C 80.3 74.9 –
esomeprazole and lansoprazole recipients respectively]. D 67.6 66.3 –
During the first 4 weeks of treatment, mean (standard C and D 77.5 73.3 0.099*
deviation [s.d.]) antacid tablets used were 0.52 (0.72) (73.8, 81.2) (69.4, 77.1)
per day in the esomeprazole group and 0.57 (0.77) per * Compared using a Cochran–Mantel–Haenszel test.
day in the lansoprazole group.   Comparison of the time-to-healing curves using a log-rank test.

2005 Blackwell Publishing Ltd, Aliment Pharmacol Ther 21, 455–463

460 M. B. FENNERTY et al.

Table 3. Percentage of patients with resolution of symptoms at days and nights were numerically higher with esomep-
week 4 as assessed by the investigator razole but were not significantly different between
Percentage of patients treatments (Table 4).

Esomeprazole Lansoprazole
40 mg once 30 mg once Safety
Symptom daily (n ¼ 478) daily (n ¼ 483) P-value*
Overall, adverse events were similar between groups and
Heartburn 72.0 63.6 0.005 mostly mild or moderate in severity. Adverse events
Acid regurgitation 79.5 76.2 0.203 were reported by 33.1% of patients in the esomeprazole
Dysphagia 93.1 93.8 0.614
group and 36.9% of those in the lansoprazole group; no
Epigastric pain 83.1 82.6 0.831
treatment-related serious adverse events were reported.
* From the Cochran–Mantel–Haenszel test. The most common adverse events (occurring in >2% of

with lansoprazole (Table 3). Resolution of the other Table 4. Mean (s.d.) percentage of heartburn-free days and
symptoms of GERD was not significantly different heartburn-free nights based on patients’ daily diaries
between treatments (Table 3). Among patients with
Esomeprazole Lansoprazole
resolution of a given symptom, 60–65% of those treated 40 mg once daily 30 mg once daily P-value*
with esomeprazole were also healed of EE, and the
corresponding range for those treated with lansoprazole Heartburn-free days
n  476 474
was 49–59%.
Mean (s.d.) % 74.6 (30.0) 72.7 (30.5) 0.303
As shown in Figure 2, the difference in sustained Heartburn-free nights
resolution of heartburn started to emerge after 1 week n  480 477
of treatment (54.2% for esomeprazole vs. 51.7% for Mean (s.d.) % 86.0 (21.5) 84.7 (21.8) 0.263
lansoprazole) and remained apparent throughout the
* From analysis of variance.
4-week diary period, although the difference was not   Includes only patients for whom results could be calculated from the
significant. The mean percentages of heartburn-free diary data.

Figure 2. Cumulative percentage of

patients reporting sustained resolution of
heartburn by study day.

2005 Blackwell Publishing Ltd, Aliment Pharmacol Ther 21, 455–463

 ESOMEPRAZOLE VS. LANSOPRAZOLE IN EROSIVE OESOPHAGITIS
patients) were Barrett’s oesophagus, gastritis, diarrhoea,
and headache, all of which were reported by <5% of
patients in each group. The most common adverse event
leading to study withdrawal was abdominal pain (two in
each group, one of which in each group was considered
related to treatment). There were no clinically significant
differences in the results of clinical laboratory tests or
vital signs either within or between treatments.
DISCUSSION
This study in patients with moderate to severe EE (LA
grades C or D) confirmed that esomeprazole 40 mg once
daily provided significantly faster healing and a higher
healing rate than lansoprazole 30 mg once daily when
taken for up to 8 weeks of treatment. Comparison of the
time-to-EE healing curves suggests that healing
occurred significantly earlier and in more patients with
esomeprazole than with lansoprazole. This finding was
supported by the analysis of the observed healing rates
for which esomeprazole 40 mg had higher healing rates
than lansoprazole 30 mg at both weeks 4 and 8. When
timing of the healing was not taken into account, the
difference in observed healing rates between treatment
groups at week 4 (8.3%) was greater and was
significant; however, the difference at week 8 (4.3%)
was not significant. Investigator assessments indicated
that esomeprazole resolved heartburn, the most com-
mon GERD symptom, in a significantly higher percent-
age of patients than did lansoprazole. The symptoms of
acid regurgitation, dysphagia, and epigastric pain were
resolved similarly with both treatments.
This study had a similar design and included patients
who were similar to the subgroup of patients with
moderate to severe EE in the study of Castell et al.9 In
that study,9 which included more than 5200 patients
with EE of all grades of severity, a significantly higher
healing rate was observed for up to 8 weeks of once-
daily treatment with esomeprazole 40 mg than with
lansoprazole 30 mg (92.6% vs. 88.8%; P ¼ 0.0001).
The greatest differences between treatments in EE
healing rates were for patients with moderate or severe
EE at baseline (differences of 17% for LA grade D, 11%
for grade C). In addition, a significantly higher percent-
age of patients in the esomeprazole group than in the
lansoprazole group had complete resolution of heart-
burn by week 4.9 The present study prospectively
confirms the significantly faster EE healing and greater
number of patients healed of EE with esomeprazole

2005 Blackwell Publishing Ltd, Aliment Pharmacol Ther 21, 455–463
461
40 mg than with lansoprazole 30 mg in a patient
population exclusively with moderate to severe EE.
However, the difference between treatment groups in
healing rates in this study was not as great as the
difference in the Castell study.9 A possible explanation is
the different populations that were studied.
In other randomized clinical trials, esomeprazole
40 mg once daily also demonstrated significantly higher
healing rates and more rapid symptom resolution than
omeprazole 20 mg once daily, irrespective of patients’
age, gender, race, or H. pylori status (although, by
design, most patients enrolled in these trials were
H. pylori-negative).1, 2 Moreover, esomeprazole was
the first PPI to show efficacy better than that of the
standard recommended dose of omeprazole for healing
reflux oesophagitis. By contrast, data from randomized
controlled trials have shown that lansoprazole 30 mg
once daily and omeprazole 20 mg once daily have
similar efficacy for the healing of EE.12–14
In the present study, the healing rates with both
esomeprazole and lansoprazole in patients with moder-
ate EE (grade C) were higher than in those with severe
EE (grade D). This observation is consistent with those of
previous studies of patients with EE using these and
other PPIs.9, 13–21
Studies that compare EE healing rates between different
PPIs can provide useful information for the practising
clinician to help guide therapeutic decisions. The differ-
ence in estimated healing rates between treatments at
week 8 observed in this study (5%) and the difference in
heartburn resolution rates at week 4 (8%) are potentially
clinically relevant differences because GERD and EE are
common disorders. But factors other than efficacy, such
as cost of treatment, often have to be also considered
when making treatment decisions for a disease. As no
formal cost analysis was performed as part of this study,
we can base our findings only on estimated differences in
healing rates that was the primary outcome of the study.
Further studies or analyses looking at cost-effectiveness
of the various PPIs for managing EE may aid manage-
ment decisions in these patients.
Patients with moderate or severe EE are often not
readily identified in clinical practice, because the
presence and severity of symptoms do not correspond
with disease severity as assessed during endoscopy, and
most patients who have symptoms typical of uncompli-
cated GERD do not undergo an endoscopy.5, 22, 23 In
addition, empirical treatment with a PPI in clinical
practice is common. Therefore, an ideal treatment
462 M. B. FENNERTY et al.
should provide a high degree of efficacy across all grades
of disease severity. The findings of this study and of the
previous trial9 show that esomeprazole heals more
consistently than lansoprazole across all grades of
disease. This demonstrated increased speed in healing
EE when using esomeprazole also suggests that this
agent may be a better choice when using a PPI as an
empirical therapeutic trial in patients with GERD.
CONCLUSIONS
Data from this study show that esomeprazole 40 mg
once daily heals EE faster and in more patients with
moderate to severe EE (LA grade C or D) than does
lansoprazole 30 mg once daily. Furthermore, esomep-
razole resolved heartburn, the most commonly reported
symptom of GERD, in a significantly higher proportion
of patients than lansoprazole at week 4. Both esomep-
razole 40 mg once daily and lansoprazole 30 mg once
daily are well tolerated. Therefore, these results suggest
that esomeprazole is a treatment of choice for patients
with moderate to severe EE if healing and heartburn
relief are the primary goals of therapy.
ACKNOWLEDGEMENTS
This study was supported by AstraZeneca LP, Wilming-
ton, DE. We gratefully acknowledge the study partici-
pants and study coordinators at the investigational sites,
Colleen Jensen for study management, Donna Curtis and
Mary Wiggin for editorial assistance (funded by
AstraZeneca LP), and the following study investigators:
D. Aarons, Lodi, CA; H. Allende, San Antonio, TX; I.
Alam, Austin, TX; M.S. Avila, Hialeah, FL; D.L. Avner,
Salt Lake City, UT; F. Avni, Lake Worth, FL; L. Bank,
Binghamton, NY; C. Barish, Raleigh, NC; I. Bassan,
Miami Beach, FL; J.G. Beckwith, Fort Worth, TX; S.
Behar, Hialeah, FL; M. Bennett, San Diego, CA; C.
Berggreen, Baton Rouge, LA; P. Berggreen, Phoenix, AZ;
M.F. Beshay, Mission Hills, CA; T. Bianchi, Tallassee, AL;
B.L. Bleau, Tacoma, WA; E. Bonapace, Great Neck, NY;
B. Borkar, Jeffersonville, IN; D. Brandon, San Diego, CA;
W.C. Bray, Winston-Salem, NC; J. Breiter, Manchester,
CT; A. Caos, Ocoee, FL; S. Castillo, Chicago, IL; T. Chami,
Zephyrhills, FL; R. Chasen, Laurel, MD; P. Chen, Corpus
Christi, TX; D. Chua, Oakbrook Terrace, IL; G. Ciambotti,
Hillsborough, NJ; N. Cirillo, Wilkesboro, NC; L. Cohen,
New York, NY; F. Cortese, Butte, MT; M. Davis,
Rochester, NY; S. Desautels, Salt Lake City, UT;

2005 Blackwell Publishing Ltd, Aliment Pharmacol Ther 21, 455–463
A. Dhand, Ormond Beach, FL; J. Doyle, Spokane, WA;
D.W. Dozer, Milwaukee, WI; M. Draelos, High Point, NC;
S. Duckor, Orange, CA; M. Eisner, Zephyrhills, FL;
P. Eweje, Jacksonville, NC; D. Fenner, Johnson City,
TN; V. Fishbein, Hillsboro NJ; F. Fowler, Charlotte, NC;
S. Frank, Chattanooga, TN; S. Gaddam, Garden Grove,
CA; E. Gallup, Overland Park, KS; H. Giller, Clive, IA; D.
Goddard, Upland, CA; A.C. Goetsch, Huntsville, AL; J.
Goff, Arvada, CO; J. Goldstein, Willingboro, NJ; M.R.
Grossman, Oklahoma City, OK; A.D. Haidar, Picayune,
MS; G. Halow, El Paso, TX; M. Hamad, Cary, NC; R.
Hansen, Golden, CO; V. Hee, Vancouver, WA; E. Hirsh,
Atlanta, GA; R. Holmes, Winston-Salem, NC; W. Igna-
towicz, Brooklyn, NY; A.K. Jain, Slidell, LA; V.S. Jayanty,
Houston, TX; B.R. Johnson, San Diego, CA; J. Jolley, San
Rafael, CA; J. Jones Jr, Ruston, LA; S.R. Jones, Little
Rock, AR; S. Jones, Salt Lake City, UT; R. Kaplan,
Greensboro, NC; K. Karimi, Indianapolis, IN; S. Kero,
Spring Hill, FL; P. Kiyasu, Portland, OR; T. Klein,
Wichita, KS; E. Klorfein, West Palm Beach, FL; V. Kodali,
Fayetteville, NC; V. Kolli, El Paso, TX; J. Kopp, Anderson,
SC; G. Koval, Portland, OR; R. Krause, Chattanooga, TN;
S. Krumholz, West Palm Beach, FL; F. Kucer, Sellersville,
PA; F. Lanza, Houston, TX; J. Leavitt, Miami, FL; M.
LeVine, Marietta, GA; R. Lindenberg, Torrington, CT;
D. Lipkis, San Diego, CA; J.E. Lowe, South Ogden, UT; H.
Maimon, Dayton, OH; S. Malhorta, Alexandria, VA; R.
Marks, Alabaster, AL; J. Medoff, Greensboro, NC; T.
Mendolia, Elkin, NC; A. Mihas, Richmond, VA; P.
Milman, Lake Success, NY; P. Monroe, Richmond, VA;
D. Morin, Bristol, TN; S. Moussa, Tucson, AZ; R. Movva,
Moline, IL; G. Mula, Covington, LA; R. Murphy, Little
Rock, AR; P. Nichols, Lake Charles, LA; J. Novick, Tow-
son, MD; E. Ojo, Corsicana, TX; J. Orchard, Knoxville,
TN; N. Patel, Kettering, OH; R. Patel, Lancaster, CA; L.
Peters, High Point, NC; W. Powell, Newark, DE;
V. Pratha, San Diego, CA; N.M. Price, Nashville, TN;
S. Prohaska, Kansas City, MO; M.V. Provenza, Shreve-
port, LA; M. Raikhel, Torrance, CA; A. Reymunde,
Ponce, PR; M.D. Reynolds, Dallas, TX; D. Ricci, Port
Orange, FL; D. Riff, Anaheim, CA; M. Ringold, Chris-
tiansburg, VA; R.E. Ringrose, Guthrie, OK; M.M. Rodri-
guez, Bradenton, FL; M. Rosenberg, Los Angeles, CA; A.
Roth, Rancho Cucamonga, CA; S.D. Rubin, Merrick, NY;
L. Saco, Lakeland, FL; S. Safavi, Irving, TX; L.A. Salas,
Baltimore, MD; J. Salcedo, Washington, DC; J. Santoro,
Egg Harbor, NJ; S.L. Scheinert, St Petersburg, FL; M.
Schmalz, Milwaukee, WI; L. Schmidt, Tucson, AZ; C.
Schmitt, Chattanooga, TN; J. Schneier, Edmonds, WA;
 ESOMEPRAZOLE VS. LANSOPRAZOLE IN EROSIVE OESOPHAGITIS
D. Schumacher, Columbus, OH; H. Schwartz, Miami, FL;
M. Schwartz, Jupiter, FL; A. Shaffi, Colorado Springs, CO;
A. Shah, Prince Frederick, MD; U. Shah, Hollywood, MD;
B. Shivakumar, Davenport, IA; D. Sikes, Zephyrhills, FL;
D. Silvers, Metairie, LA; T. Simmons, Los Angeles, CA;
G.A. Spiegelman, Knoxville, TN; E. Spiotta Jr, Memphis,
TN; D. Stanton, Orange, CA; M. Stern, Decatur, GA; C.
Strout, Mt Pleasant, SC; M. Swaim, Jackson, TN; R.
Tamayo, Longwood, FL; R. Tobin, Seattle, WA; N. Trent,
Hanover, PA; J. Turse, Melbourne, FL; J. Van Valkenburg,
Medford, OR; R. Wade, Bountiful, UT; J. Wang, Jefferson
City, MO; M. Weiss, Clearwater, FL; J. Winder, Sylvania,
OH; B. Winston, Houston, TX; R. Wholman, Bellevue,
WA; S.J. Woods, Bridgeport, CT; L. Wruble, Memphis, TN.
AstraZeneca was the sponsor of this multicentre
clinical trial.
REFERENCES
1 Kahrilas PJ, Falk GW, Johnson DA, et al. for the Esomeprazole
Study Investigators. Esomeprazole improves healing and
symptom resolution as compared with omeprazole in reflux
oesophagitis patients: a randomized controlled trial. Aliment
Pharmacol Ther 2000; 14: 1249–58.
2 Richter JE, Kahrilas PJ, Johanson J, et al. for the Esomeprazole
Study Investigators. Efficacy and safety of esomeprazole
compared with omeprazole in GERD patients with erosive
esophagitis: a randomized controlled trial. Am J Gastroenterol
2001; 96: 656–65.
3 Holloway RH, Dent J, Narielvala F, Mackinnon AM. Relation
between oesophageal acid exposure and healing of
oesophagitis with omeprazole in patients with severe reflux
oesophagitis [see comments]. Gut 1996; 38: 649–54.
4 Bell NJV, Hunt RH. Role of gastric acid suppression in the
treatment of gastro-oesophageal reflux disease. Gut 1992; 33:
118–24.
5 DeVault KR, Castell DO, The Practice Parameters Committee
of the American College of Gastroenterology. Updated
guidelines for the diagnosis and treatment
gastroesophageal reflux disease. Am J Gastroenterol 1999;
94: 1434–42.
6 Dent J, Brun J, Fendrick AM, et al. on behalf of the Genval
Workshop Group. An evidence-based appraisal of reflux
disease management – the Genval Workshop report. Gut
1999; 44(Suppl. 2): S1–16.
7 Chiba N, De Gara CJ, Wilkinson JM, Hunt RH. Speed of healing
and symptom relief in grade II to IV gastroesophageal reflux
disease: a meta-analysis. Gastroenterology 1997; 112: 1798–
810.
8 Andersson T, Hassan-Alin M, Hasselgren G, Röhss K, Weidolf
L. Pharmacokinetic studies with esomeprazole, the (S)-isomer
of omeprazole. Clin Pharmacokinet 2001; 40: 411–26.
9 Castell DO, Kahrilas PJ, Richter JE, et al. Esomeprazole
(40 mg) compared with lansoprazole (30 mg) in the

2005 Blackwell Publishing Ltd, Aliment Pharmacol Ther 21, 455–463
463
treatment of erosive esophagitis. Am J Gastroenterol 2002;
97: 575–83.
10 Miner Jr P, Katz PO, Chen Y, Sostek M. Gastric acid control
with esomeprazole, lansoprazole, omeprazole, pantoprazole,
and rabeprazole: a five-way crossover study. Am J
Gastroenterol 2003; 98: 2616–20.
11 Röhss K, Lind T, Wilder-Smith C. Esomeprazole 40 mg
provides more effective intragastric acid control than
lansoprazole 30 mg, omeprazole 20 mg, pantoprazole
40 mg and rabeprazole 20 mg in patients with gastro-
oesophageal reflux symptoms. Eur J Clin Pharmacol 2004;
60: 531–9.
12 Castell DO, Richter JE, Robinson M, Sontag SJ, Haber MM, The
Lansoprazole Group. Efficacy and safety of lansoprazole in the
treatment of erosive reflux esophagitis. Am J Gastroenterol
1996; 91: 1749–57.
13 Hatlebakk JG, Berstad A, Carling L, et al. Lansoprazole versus
omeprazole in short-term treatment of reflux oesophagitis.
Results of a Scandinavian multicentre trial. Scand J
Gastroenterol 1993; 28: 224–8.
14 Mee AS, Rowley JL. Rapid symptom relief in reflux
oesophagitis: a comparison of lansoprazole and omeprazole.
Aliment Pharmacol Ther 1996; 10: 757–63.
15 Vcev A, Stimac D, Vceva A, et al. Pantoprazole versus
omeprazole in the treatment of reflux esophagitis. Acta Med
Croatica 1999; 53: 79–82.
16 Mossner J, Holscher AH, Herz R, Schneider A. A double-blind
study of pantoprazole and omeprazole in the treatment of
reflux oesophagitis: a multicentre trial. Aliment Pharmacol
Ther 1995; 9: 321–6.
17 Mulder CJ, Dekker W, Gerretsen M. Lansoprazole 30 mg versus
omeprazole 40 mg in the treatment of reflux oesophagitis grade
II, III and IVa (a Dutch multicentre trial). Dutch Study Group.
Eur J Gastroenterol Hepatol 1996; 8: 1101–6.
18 Sontag SJ, Hirschowitz BI, Holt S, et al. Two doses of
omeprazole versus placebo in symptomatic erosive
esophagitis: the US Multicenter Study. Gastroenterology
1992; 102: 109–18.
19 Robinson M, Sahba B, Avner D, Jhala N, Greski-Rose PA,
Jennings DE. A comparison of lansoprazole and ranitidine in the
treatment of erosive oesophagitis. Multicentre Investigational
Group. Aliment Pharmacol Ther 1995; 9: 25–31.
of
20 Bardhan KD, Hawkey CJ, Long RG, et al. Lansoprazole versus
ranitidine for the treatment of reflux oesophagitis. UK
Lansoprazole Clinical Research Group. Aliment Pharmacol
Ther 1995; 9: 145–51.
21 Wurzer H, Schutze K, Bethke T, Fischer R, Luhmann R, Rie-
senhuber C. Efficacy and safety of pantoprazole in patients
with gastroesophageal reflux disease using an intravenous-
oral regimen. Austrian Intravenous Pantoprazole Study
Group. Hepatogastroenterology 1999; 46: 1809–15.
22 Green J. Is there such an entity as mild oesophagitis? Eur J Clin
Res 1993; 4: 29–34.
23 Johansson KE, Ask P, Boeryd B, Fransson SG, Tibbling L.
Oesophagitis, signs of reflux, and gastric acid secretion in
patients with symptoms of gastro-oesophageal reflux disease.
Scand J Gastroenterol 1986; 21: 837–47.