Full text of DOI:10.2165/00003495-200262080-00004

Drugs 2002; 62 (8): 1173-1184
0012-6667/02/0008-1173/$30.00/0
REVIEW ARTICLE
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Adis International Limited. All rights reserved.
Lansoprazole for Maintenance of
Remission of Erosive Oesophagitis
1
2
3
2
James W. Freston, Robert L. Jackson, Bidan Huang and E. David Ballard II
1
2
3
University of Connecticut Health Center, Farmington, Connecticut, USA
TAP Pharmaceutical Products, Inc., Lake Forest, Illinois, USA
Abbott Laboratories, Abbott Park, Illinois, USA
Contents
Abstract
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1173
1
2
. Rationale for Long-Term Maintenance Therapy of Healed Erosive Oesophagitis . . . . . . . . . . 1174
. Results with Lansoprazole . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1176
2.1 Long-Term Maintenance Therapy to Prevent Relapse of Erosive Oesophagitis . . . . . . . . 1176
2.2 Lesions Resistant to Healing with Histamine H2 Receptor Antagonist Treatment . . . . . . . . 1178
2.3 Effect of Baseline Oesophagitis Grade . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1178
2.4 Symptom Relief . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1180
2.5 Long-Term Safety . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1180
3. Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1181
Abstract
Gastro-oesophageal reflux disease, which is experienced daily by a significant
proportion of individuals, may result in serious sequelae such as erosive oeso-
phagitis. Short-term treatment with acid antisecretory therapy (a proton pump
inhibitor or a histamine H2 receptor antagonist) is highly effective in healing the
erosive oesophagitis lesion. However, numerous studies confirm that unless
maintenance therapy is initiated virtually all patients will experience oesophagitis
relapse within 1 year, as well as an increasing severity of oesophagitis and risk
for complications such as Barrett’s oesophagus and adenocarcinoma.
Studies evaluating the efficacy of proton pump inhibitor and H2 antagonist
maintenance therapy have found that only the proton pump inhibitors signifi-
cantly reduce the incidence of oesophagitis relapse. Pharmacoeconomic studies
have also confirmed that proton pump inhibitor maintenance therapy is cost ef-
fective, by virtue of the ability of these agents to reduce the incidence of relapse
as well as prolong the time to relapse and increase the number of weeks per year
that patients are without symptoms.
Lansoprazole, a member of the proton pump inhibitor class of agents, has been
extensively studied in the treatment of patients with a variety of acid-related
disorders. Among those with erosive oesophagitis, maintenance therapy with
lansoprazole 15 or 30mg once daily is highly effective in preventing relapse.
Studies have documented that lansoprazole 15 and 30mg once daily for six
months prevents oesophagitis relapse in up to 81 and 93% of patients, respec-
tively, with comparable percentages of patients remaining in remission after 1
year of treatment. These high rates of remission have also been observed in studies

1
174
Freston et al.
of patients with lesions that were difficult to heal at baseline (resistant to healing
with at least 3 months of H2 antagonist therapy). Moreover, lansoprazole pro-
duces high remission rates regardless of the grade of erosive oesophagitis before
acute healing. Among symptomatic patients with heartburn, lansoprazole pro-
vides rapid and effective relief of daytime and night-time heartburn and prevents
relapse of symptoms. Lansoprazole has a wide margin of safety and is well tol-
erated when administered as monotherapy in short- and long-term clinical trials.
Taken together these data suggest that proton pump inhibitor therapy repre-
sents the preferred and ideal long-term management strategy for the patient with
erosive oesophagitis. Lansoprazole is a well-established member of this class of
agents and, as such, has an extensive body of literature that supports its safety,
tolerability and clinical efficacy in preventing relapse in these patients.
Erosive oesophagitis is one of several severe
In addition, prospective as well as retrospective
analyses suggest that up to 23% of patients with
erosive oesophagitis progress to more severe
grades of the disease upon relapse.[
complications that may arise from the pathological
reflux of gastric or duodenal contents into the distal
oesophagus, a condition commonly known as gas-
tro-oesophageal reflux disease or GORD.[1,2] It is
estimated that 2% of the US population have ero-
sive oesophagitis, a disease characterised by a
chronic relapsing nature that produces significant
decrements in the quality of life of affected pa-
22-25]
Lansoprazole, a member of the proton pump in-
hibitor class of agents, has been extensively studied
in a wide variety of acid-related diseases. This ar-
ticle describes the rationale for long-term treatment
of oesophagitis and reviews the body of clinical
trials that confirm the high degree of efficacy and
benign safety profile of lansoprazole in preventing
relapse of erosive oesophagitis and providing con-
tinuous relief of symptoms during long-term ther-
apy. Alternative approaches to long-term medical
therapy, such as alternate-day and ‘on-demand’
therapy, have not been compared with continuous
maintenance therapy in clinical trials. They are
therefore not addressed in this review.
tients.[
3-6]
Short-term treatment with a proton pump inhib-
itor is highly effective in healing erosive oesophag-
itis, as confirmed by the results of two recently
[
7,8]
published clinical trials.
Numerous other com-
parative studies performed with lansoprazole 30mg
once daily for 8 weeks have confirmed erosive
oesophagitis healing rates of greater than 90%.[
9-12]
The effectiveness of proton pump inhibitors in
healing erosive oesophagitis lesions is underscored
by their ability to produce high rates of healing in
patients whose oesophagitis failed to heal follow-
ing a course of histamine H2 receptor antagonist
therapy. Studies have confirmed healing rates of
greater than 84% with lansoprazole 30 or 60mg
1
. Rationale for Long-Term
Maintenance Therapy of Healed
Erosive Oesophagitis
Among those with healed erosive oesophagitis
not given maintenance therapy, approximately
[
10,13,14]
once daily in these patients.
Proton pump
7
0% will experience relapse within 6 months and
[
17-21]
inhibitors are also highly effective in rapidly re-
lieving the symptoms associated with erosive oeso-
phagitis and improving the quality of life of pa-
tients.[
up to 90% will relapse within 1 year.
Al-
though the proton pump inhibitors and the H an-
2
tagonists are widely used and effective in the acute
healing of erosive oesophagitis, numerous studies
have confirmed that only the proton pump inhibi-
15,16]
Following acute erosive oesophagitis healing
and symptom relief, virtually all patients will ex-
perience oesophagitis relapse within 1 year unless
tors significantly reduce the incidence of oeso-
phagitis relapse.[
24-29]
Less than 30% of patients
[
17-21]
continuous maintenance therapy is initiated.
prescribed proton pump inhibitor maintenance
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Drugs 2002; 62 (8)

Lansoprazole in Remission of Erosive Oesophagitis
1175
therapy experience relapse of erosive oesophagitis
In contrast, among those
prescribed maintenance H2 antagonist therapy, be-
their chronicity were found to have a significant
effect on the risk of developing oesophageal ade-
nocarcinoma. More than three episodes of heart-
within 1 year.[
20,21,29-33]
tween 68 and 88% experience oesophagitis recur-
burn per week increased the risk of oesophageal
rence within 1 year.[
17,25]
These relapse rates seen
[43]
adenocarcinoma by more than 16-fold.
Simi-
with H2 antagonist therapy are only slightly lower
than those observed (up to 90%) in placebo-treated
patients.[
larly, those who experienced heartburn for more
than 20 years also had a greater than 16-fold in-
creased risk for oesophageal adenocarcinoma.
17,25]
[43]
Patients with erosive oesophagitis are also at
risk for the development of complications such as
stricture (4 to 20% prevalence), ulceration (2 to
Numerous studies have confirmed that proton
pump inhibitor therapy reduces the incidence, fre-
[15,44-46]
quency and severity of heartburn,
and stud-
7
% prevalence) and haemorrhage (<2% preva-
ies have found an association between treatment
with lansoprazole or omeprazole and the formation
[
23]
lence). Among patients with erosive oesophag-
itis with stricture, recurrence following dilatation
is common unless acid reflux is well controlled.
of ‘islands’ of squamous mucosa within the area of
[
34]
[47,48]
columnar epithelium.
Nevertheless, there is
Results from several studies suggest that maintain-
ing acid suppression with a proton pump inhibitor
prevents or delays the occurrence of erosive oeso-
no evidence that the long-term use of proton pump
inhibitors for erosive oesophagitis reduces the risk
of developing Barrett’s oesophagus or reduces the
rate of progression to dysplasia or adenocarci-
noma.
In addition to numerous clinical benefits, sev-
eral pharmacoeconomic evaluations have docu-
mented the cost effectiveness of proton pump in-
hibitor therapy in the maintenance of healed
erosive oesophagitis. The cost effectiveness of
these agents is primarily due to the reduction in
the number of relapses, prolonged time to relapse,
and more weeks per year without reflux symp-
toms in those treated with a proton pump inhibitor
[
23]
phagitis-related stricture
and reduces the fre-
quency of repeated dilatation in patients with oe-
sophageal stricture.[
35-40]
In a comparative study
with ranitidine 600mg twice daily, lansoprazole
0mg once daily prolonged the time to first repeat
dilatation and increased the probability of not re-
3
[
40]
quiring further dilatation.
After 6 months of
continuous treatment, 77% of the lansoprazole-
treated patients reported no dysphagia compared
with 55% of the ranitidine-treated patients (p =
.0086).[
40]
0
Daily heartburn is experienced by approxi-
compare with a H2 antagonist or a prokinetic
mately one-third of patients with a previous diag-
agent.[
18,49-53]
These effects, in turn, reduce the
[
6]
nosis of erosive oesophagitis. While this symp-
tom may be trivialised, it has serious implications
in the risk for developing Barrett’s oesophagus (10
to 15% prevalence among those with erosive oeso-
phagitis) and its progression to adenocarcinoma,
two diseases that have substantially increased in
utilisation of healthcare resources such as physi-
cian office visits, repeat procedures and the need
for hospitalisation.[
18,49-53]
These data have resulted in most clinicians
recognising the need for continuous maintenance
treatment with a proton pump inhibitor in order to
prevent erosive oesophagitis relapse as well as
keeping patients symptom-free and at decreased
risk for complications. On the basis of their high
rate of clinical efficacy (i.e. low incidence of re-
lapse), effective and prompt control of patient
symptoms, and reduction in the occurrence of com-
plications, the proton pump inhibitor class of
[
41,42]
prevalence during the last decade,
as well as
[
6]
quality of life of patients. Among those with
heartburn studied by McDougall and colleagues,
9% of patients considered the symptom to be of
[
6]
4
moderate or major severity and 4% considered it
to be unbearable. Moreover, in a case-controlled
[
43]
study by Lagergren and colleagues,
the fre-
quency and intensity of heartburn symptoms and
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Drugs 2002; 62 (8)

1
176
Freston et al.
agents represents an ideal long-term maintenance
regimen.
Table I. Remission rates during long-term lansoprazole therapy of
erosive oesophagitis in patients enrolled in randomised, double-
blind, parallel group studies
Reference
Drug regimen (no. of
evaluable patients)
Remission
rate (%)
2
. Results with Lansoprazole
6
mo 12 mo
a
2
.1 Long-Term Maintenance Therapy to
Lansoprazole dosage versus placebo comparisons
b
Prevent Relapse of Erosive Oesophagitis
Hatlebakk et al.;
1
Lansoprazole 15mg (50)
Lansoprazole 30mg (53)
Lansoprazole 15mg (99)
Lansoprazole 30mg (85)
76
90b
72
85
87
89
79
90
24
997[
54]
The results of eight trials that studied lansop-
razole for healed erosive oesophagitis maintenance
therapy are summarised in table I.
ferences in study design, population charac-
teristics, and erosive oesophagitis grading scale of-
ten limit the ability to compare and contrast results
across studies, however, several consistencies are
apparent. Daily dosages of lansoprazole 15 or
Poynard et al.;
1
995[
55]
c
[
20,21,27,54-59]
Robinson;
1
Lansoprazole 15mg (59)
81
93
27
Dif-
996[
20]
c
Lansoprazole 30mg (56)
Placebo (55)
Lansoprazole dosage versus active treatment comparisonsa
Baldi et al.;
Lansoprazole 15mg (295)
Lansoprazole 30mg (309)
Omeprazole 20mg (302)
Lansoprazole 30mg (124)
83
95
93
73
86
87
90
91
65
15
66
79
31
[56]d
1996
3
0mg are associated with low rates of oesophagitis
Carling et al.;
1996[
57]d
relapse at the end of 6 months as well as at the end
Omeprazole 20mg (120)
of 1 year.[
20,21,27,54-59]
c
Hirschowitz et al.; Lansoprazole 15mg (100)
71
29
81
86
39
74
83
1999[
58]d,e
Robinson and colleagues[20] in a double-blind
Ranitidine 300mg (106)
c
Gough et al.;
Lansoprazole 15mg (86)
study of patients who had healed erosive oesophag-
itis after a course of antisecretory therapy (lans-
oprazole or ranitidine) were randomised to lans-
oprazole 15mg, lansoprazole 30mg or placebo,
each administered once daily. After 6 months, heal-
ing was maintained in 81% of those receiving
lansoprazole 15mg and 93% of those receiving
lansoprazole 30mg compared with only 27% of
1
996[
27]
c
Lansoprazole 30mg (75)
Ranitidine 600mg (74)
Lansoprazole 15mgc,f
Esomeprazole 20mgf
Lauritsen et al.;
2002[
59]d
Lansoprazole dosage versus placebo in patients not re-
a
sponding to H2 antagonist therapy
c
Sontag et al.;
1
Lansoprazole 15mg (50)
72
72
13
67
55
13
996[
21]
c
Lansoprazole 30mg (49)
[
20]
Placebo (47)
those receiving placebo.
months are similar to those found in an active treat-
ment comparator trial of lansoprazole and om-
These results after 6
a
Patients enrolled in maintenance trials demonstrated healing of
erosive oesophagitis in short-term treatment studies or in
non-blind lead-in phases.
[
56]
eprazole by Baldi and associates.
Healed ero-
b
c
Personal communication from investigator.
p < 0.001 lansoprazole vs ranitidine or placebo; esomeprazole
vs lansoprazole.
sive oesophagitis was maintained in 83% of those
treated with lansoprazole 15mg and 95% of those
treated with lansoprazole 30mg once daily, respec-
tively, compared with 93% of those treated with
omeprazole 20mg once daily.
d
e
f
Presented as an abstract.
Results of intent-to-treat population analysis.
A total of 1236 patients were randomised in the study.
Compared with H2 antagonist treatment, signif-
icantly higher percentages of patients treated with
lansoprazole remained in remission. After 6
ine 300mg twice daily, which is twice the approved
US Food and Drug Administration (FDA) dosage
for this indication, and found 6-month remission
rates of 81% with lansoprazole 15mg, 86% with
lansoprazole 30mg and 39% with ranitidine. The
reasons for the superiority of proton pump inhibi-
tors over H2 antagonists in maintaining remissions
may be due to more prolonged control of intragast-
months in the study by Hirshowitz et al.,[
58]
71%
of those treated with lansoprazole 15mg continued
to have healed erosive oesophagitis compared to
2
9% of those treated with ranitidine 150mg twice
[
27]
daily. Gough and colleagues
treated patients
with lansoprazole 15 or 30mg once daily or ranitid-
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Drugs 2002; 62 (8)

Lansoprazole in Remission of Erosive Oesophagitis
1177
ric pH above 4 by the proton pump inhibitors[60]
and the development of tolerance to H2 antago-
nists.[
month remission rate is identical to that observed
with lansoprazole 15mg in the abstract by Baldi
61,62]
[56]
and colleagues,
and comparable to that ob-
Given the chronic nature of erosive oesophag-
itis requiring long-term treatment as well as factors
that may increase the risk for relapse (i.e. decreas-
ing patient compliance with long-term therapy),
studies that follow patients for longer periods of
time (i.e. 1 year) may provide more accurate meas-
ures of maintenance therapy efficacy. Several stud-
ies have confirmed that the oesophagitis remission
rates observed with lansoprazole after 1 year of
therapy were comparable to those observed after 6
months.
served with lansoprazole 15mg in studies by Rob-
inson[ and Gough (81% remission rate noted
in both studies). Of note, as compared to the es-
omeprazole results in this study, higher 6-month
20]
[27]
remission rates have consistently been observed in
[20,27,56]
studies of lansoprazole 30mg (≥86%).
the study by Lauritson,
In
[59]
a 6-month remission
rate of 73% was observed with lansoprazole 15mg.
Like the findings of Hirschowitz and collea-
[58]
gues, clinical or patient population factors that
may have contributed to this observation are un-
known. Furthermore, this study only followed pa-
tients for 6 months in contrast to several lans-
oprazole trials that have confirmed high remission
In the trial by Robinson and colleagues,[20] 79
and 90% of patients treated with lansoprazole 15
or 30mg, respectively, remained in remission after
1
year of treatment compared with 24% of placebo-
[20,54-57]
rates after 12 months of treatment.
treated patients. This disparity in remission rates
favouring lansoprazole therapy was also observed
in comparative trials of ranitidine, even when
ranitidine was administered at 300mg twice daily.
Treatment with lansoprazole is significantly
more effective in preventing oesophagitis relapse
as well as reducing the number of recurrences dur-
ing maintenance therapy than placebo. In the study
[
27]
Gough and colleagues and Hirschowitz and as-
[20]
by Robinson and colleagues,
75% (41/55) of
sociates[
58]
reported 1-year remission rates in
placebo recipients experienced one or more recur-
rences of erosive oesophagitis during the 1-year
maintenance period compared with 20% (12/59) of
those treated with lansoprazole 15mg once daily
and 9% (5/56) of those receiving lansoprazole
ranitidine-treated patients of 31 and 15%, respec-
tively, compared with 66 and 65% with
lansoprazole 15mg and 79% with lansoprazole
3
0mg.
In the studies comparing lansoprazole with om-
3
0mg once daily (table II). Multiple relapses of
eprazole, the high 1-year remission rates observed
in the treatment groups were comparable: 73%
with lansoprazole 15mg, 86 to 90% with lans-
erosive oesophagitis were common among those
receiving placebo, with 45% (25/55) of placebo
oprazole 30mg, and 87 to 91% with omeprazole
0mg.[
56,57]
Although the reason for the low remis-
2
Table II. Frequency of recurrences: distribution of patients by
number of recurrences during the 1-year maintenance period and
by treatment group. Reproduced with permission[
sion rate data in the study by Hirschowitz and col-
leagues[ is unknown, it is noteworthy that the
therapeutic gain in those treated with lansoprazole
over those treated with ranitidine was 42% after 6
months and 50% after 1 year. These therapeutic
gains are comparable to those of the trial by Gough
and colleagues[27] in which the study populations
had higher remission rates.
20]
58]
Treatment group
no. pts)
Number of recurrences (% pts)a
(
0b
1
2
3
4
5
Placebo (55)
Lansoprazole
25.5 29.1
79.7 11.9
10.9
6.8
12.7
1.7
14.6
0
7.3
0
15mg (59)
Lansoprazole
30mg (56)
91.1 3.6
3.6
1.8
0
0
In a recent abstract presented by Lauritsen and
a 6-month remission rate of 83%
was reported with esomeprazole 20mg. This 6-
a
b
Numbers total slightly more than 100% because of rounding.
colleagues,[
59]
Patients who remained healed throughout the maintenance
period.
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Drugs 2002; 62 (8)

1
178
Freston et al.
recipients experiencing two or more relapses com-
pared with 8% (5/59) of those receiving lans-
oprazole 15mg and 5% (3/56) of those receiving
lansoprazole 30mg.[
patients with difficult to heal erosive oesophag-
itis.[ In a study of patients with healed erosive
oesophagitis that had been resistant to healing after
at least 3 months of H2 antagonist therapy, Sontag
and colleagues[ observed that at the end of 6
months a significantly (p < 0.001) greater percent-
age of patients treated with either lansoprazole 15
or 30mg remained in remission compared with
those receiving placebo, 72% in both lansoprazole
treatment groups versus 13% in the placebo treat-
ment group. This significantly higher 6-month re-
mission rate observed in those treated with
lansoprazole 15 and 30mg compared with placebo
persisted during the remainder of the study period
with 1-year remission rates of 67 and 55% versus
21]
20]
21]
The results of the majority of placebo- and
active-control treatment trials confirm that long-
term maintenance therapy with lansoprazole, at a
dosage of 15 or 30mg once daily, is highly effective
in sustaining erosive oesophagitis remission. Six-
month and 1-year remission rates among patients
treated with lansoprazole were generally 80% or
greater at both evaluation endpoints. Numeric dif-
ferences in remission rates that favoured the 30mg
dose of lansoprazole over the 15mg dose were ob-
served, however, these differences were not statis-
tically significant.[
20,27,54-56]
Oesophagitis remis-
[21]
13%, respectively.
sion rates observed with lansoprazole were
comparable to those found with omeprazole and
significantly higher than those with placebo or
ranitidine, even when the latter was used at dosages
that exceed those recommended by the US FDA.
The low remission rates observed with H2 antago-
nist maintenance therapy (<40% at 6 months and
The data observed in the maintenance trial by
Sontag and colleagues[
21]
support the use of
lansoprazole maintenance therapy even in patients
with difficult to heal erosive oesophagitis lesions.
The remission rates observed were comparable to
those observed in other studies involving patients
with lesions that were not previously resistant to
healing with H2 antagonist therapy.[
20,27,56-58]
<
31% at 1 year) were comparable to those found
with placebo. This suggests that both of these
maintenance strategies represent less than optimal
management of the patient with healed erosive
oesophagitis.
Overall, given the high remission rates observed
with lansoprazole in this trial[ and the low remis-
sion rates observed with H2 antagonist therapy in
other trials, these data suggest a clear preference
for proton pump inhibitor maintenance therapy, re-
gardless of the acute healing regimen of the pa-
tient.
21]
2
.2 Lesions Resistant to Healing with Histamine
H2 Receptor Antagonist Treatment
Approximately 50% of patients with erosive
oesophagitis treated with standard doses of H2 an-
2
.3 Effect of Baseline Oesophagitis Grade
tagonists fail to exhibit mucosal healing after 8
The results of studies that analysed the 6-month
and 1-year efficacy of lansoprazole in sustaining
oesophagitis remission by baseline grade of muco-
sal damage before healing are presented in figure
1 and figure 2. Lansoprazole maintenance therapy
at a dosage of 15 or 30mg once daily produced
6-month remission rates of 85 and 96%, respec-
tively, in patients with grade 2 erosive oesophagitis
weeks of treatment.[
14,63-65]
In studies of patients
with healed erosive reflux oesophagitis that had
been resistant to healing with a course of H2 antag-
onist therapy, results have confirmed that lan-
soprazole is highly effective in acute lesion heal-
ing. Three studies performed with lansoprazole
3
0mg once daily found healing rates of between 84
[
10,13,14]
[20]
and 96% after 8 weeks
and up to 100% after
at baseline before healing (figure 1). Remission
[
10]
1
2 weeks of treatment.
Proton pump inhibitor therapy is highly effec-
tive in maintaining oesophagitis remission, even in
rates observed in those with more severe disease at
baseline (grade 3 or 4 erosive oesophagitis) were
77 and 90% at 6 months in those receiving
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Drugs 2002; 62 (8)

Lansoprazole in Remission of Erosive Oesophagitis
1179
Lansoprazole 15mg-Grade 2
Lansoprazole 15mg-Grade 3 or 4
Lansoprazole 30mg-Grade 2
Lansoprazole 30mg-Grade 3 or 4
Placebo-Grade 2
In patients with erosive oesophagitis resistant to
healing after at least 3 months of H2 antagonist
therapy, the 6-month and 1-year remission rates in
those receiving lansoprazole 15 or 30mg once
daily were generally higher among those with
grade 2 disease at baseline compared with those
with grade 3 or 4 disease (figure 2).[21] Among
those with grade 2 disease, 6-month remission
rates of 85 and 68% were observed with lans-
oprazole 15 and 30mg once daily, respectively.
Six-month remission rates of 58 and 77% were ob-
served in patients with grade 3 or 4 disease receiv-
ing lansoprazole 15 and 30mg once daily, respec-
tively. After 1 year, healing was maintained in over
Placebo-Grade 3 or 4
1
00
9
8
7
6
5
4
3
2
1
0
0
0
0
0
0
0
0
0
0
8
0% of those with grade 2 disease receiving
0
1
2
3
4
5
6
7
8
9
10 11 12
lansoprazole 15mg. Among placebo recipients,
healing was maintained in only 21% of those with
grade 2 disease at baseline after 6 months and 1
year. Of note, all of the placebo recipients with
grade 3 or 4 erosive oesophagitis at baseline re-
lapsed within 1 month.
Duration of maintenance therapy (mo)
Fig. 1. Patients enrolled in maintenance trials demonstrating
healing of erosive oesophagitis in short-term treatment studies
or in non-blind lead-in phases were randomised to maintenance
therapy with lansoprazole 15mg, lansoprazole 30mg or pla-
cebo. The figure shows the proportion of patients who remained
healed (no erosions seen on endoscopy) during the 1-year
maintenance period, by treatment group and baseline oeso-
phagitis grade 2 versus 3 or 4 before healing. Significantly
higher percentages of those treated with lansoprazole re-
mained healed throughout the one-year maintenance treatment
period, even when remission rates were stratified by baseline
oesophagitis grade. Percentages were calculated by life-table
methods.[
The clinical interpretation of the lower remis-
sion rates observed with lansoprazole in patients
with grades 3 or 4 erosive oesophagitis at baseline
compared with those with grade 2 is limited by the
small number of patients with these more severe
forms of erosive oesophagitis who were enrolled
in these trials – a reflection of low overall preva-
lence of grade 3 and 4 disease (approximately 25
and 7%, respectively) among those with erosive
oesophagitis.[15] At least 50% of patients receiving
placebo experienced oesophagitis relapse within 1
month of initiation of maintenance therapy, re-
gardless of oesophagitis grade at baseline or his-
tory with H2 antagonists. The clinical importance
of the prompt initiation of effective remission
maintenance therapy is underscored by the results
of Sontag and colleagues.[21] All the patients with
healed grade 3 or 4 erosive oesophagitis at baseline
who had been resistant to healing with at least 3
months of H2 antagonist therapy and had been ad-
ministered placebo maintenance therapy experi-
enced relapse within 1 month.
20]
lansoprazole 15 and 30mg once daily, respectively.
These rates are just slightly lower than those ob-
served in patients with grade 2 disease at base-
line.[ Remission rates by grade of oesophagitis
at baseline observed after 1 year of lansoprazole
treatment were similar to those noted at 6 months.
Placebo-treated patients with grade 2 disease at
baseline were found to have remission rates that
were significantly lower than those observed with
lansoprazole: only 33 and 27% of placebo recipi-
ents with grade 2 disease remained in remission at
20]
6
months and 1 year, respectively. Among placebo
recipients with more severe disease (grade 3 or 4)
only 26 and 23% remained in remission at 6
months and 1 year, respectively.
©
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Drugs 2002; 62 (8)

1
180
Freston et al.
than placebo recipients (figure 3).[20] During the
first 6 months of treatment over 80% of patients
receiving lansoprazole 15 or 30mg once daily re-
mained asymptomatic compared with approxi-
mately 50% of those receiving placebo. After 12
months of treatment, 72% of those receiving
lansoprazole 15mg and 67% of those receiving
lansoprazole 30mg remained asymptomatic com-
pared with 35% of placebo recipients. Lans-
oprazole was significantly more effective com-
pared with placebo in controlling symptoms of
daytime and night-time heartburn (p < 0.001).
Sontag and colleagues[ observed a more dis-
parate difference in heartburn relief between
lansoprazole and placebo in the study of patients
with erosive oesophagitis lesions that were resis-
tant to healing with H2 antagonist therapy. After 6
months, 81 and 76% of those receiving lans-
oprazole 30 or 15mg, respectively, were asymp-
tomatic compared with 21% of those receiving pla-
cebo. At the end of the 1-year study period, all
placebo recipients were symptomatic or withdrew
from the study, whereas 66 and 64% of those
treated with lansoprazole 30 or 15mg once daily,
respectively, remained asymptomatic.
Lansoprazole 15mg-Grade 2
Lansoprazole 15mg-Grade 3 or 4
Lansoprazole 30mg-Grade 2
Lansoprazole 30mg-Grade 3 or 4
Placebo-Grade 2
1
00
Placebo-Grade 3 or 4
9
8
7
6
5
4
3
2
1
0
0
0
0
0
0
0
0
0
0
21]
0
1
2
3
4
5
6
7
8
9
10 11 12
Duration of maintenance therapy (mo)
Fig. 2. Patients who demonstrated erosive oesophagitis healing
and who had lesions that had been resistant to healing after at
least 3 months of H2 antagonist therapy were randomised to
treatment with lansoprazole 15mg, lansoprazole 30mg or pla-
cebo. The figure shows the proportion of patients who remained
healed (no erosions seen on endoscopy) during the 1-year
maintenance period, by treatment group and by baseline oeso-
phagitis grade 2 versus grade 3 or 4 before healing. Significantly
higher percentages of those receiving lansoprazole remained
healed throughout the 1-year maintenance treatment period,
even when remission rates were stratified by baseline oeso-
phagitis grade. All patients with grade 3 or 4 and 39% of those
with grade 2 erosive oesophagitis at baseline randomised to
placebo experienced relapse within 1 month. Percentages were
2.5 Long-Term Safety
[
21]
calculated by life-table methods.
Lansoprazole has been shown to have a wide
margin of safety and was well tolerated when used
as monotherapy in short- and long-term clinical tri-
als for a variety of indications. During long-term
treatment the most commonly reported adverse
event was diarrhoea, which was reported by be-
2
.4 Symptom Relief
Heartburn severity and chronicity are strongly
associated with an increased risk for adeno-
carcinoma (16-fold greater risk).
nificantly increased our appreciation of the need
to control this symptom in patients with gastro-
oesophageal reflux disease and erosive oesophag-
itis. Numerous clinical studies have confirmed that
treatment with lansoprazole produces rapid and ef-
[
43]
This has sig-
tween 1.9 and 5.0% of patients in these stud-
ies.[
20,21,27,54,56]
Other commonly reported adverse
[
21]
events in the studies by Sontag and colleagues
and Gough and associates
[27]
were headache, ab-
dominal pain, dizziness and vomiting. All other
events were reported by <1% of lansoprazole re-
cipients. In long-term trials, no significant differ-
ences in the incidence or severity of adverse events
were noted with lansoprazole 15 or 30mg once
[
15,44-46]
fect relief of heartburn.
A double-blind, randomised study of lansop-
razole 15 and 30mg once daily found that greater
percentages of patients with erosive oesophagitis
were asymptomatic (no moderate or severe day-
time or night-time heartburn) significantly longer
daily, and omeprazole 20mg once daily, ranitidine
300mg twice daily or placebo.[
20,21,27,56,57]
In a re-
cent review of 702 patients enrolled in lansoprazole
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Drugs 2002; 62 (8)

Lansoprazole in Remission of Erosive Oesophagitis
1181
Placebo
return to baseline levels within 1 month of treat-
ment discontinuation.
Lansoprazole 15 mg/day
Lansoprazole 30 mg/day
[67]
100
9
8
7
6
5
4
3
2
1
0
0
0
0
0
0
0
0
0
0
3. Conclusion
Gastro-oesophageal reflux disease is a chronic
relapsing condition that often results in serious se-
quelae such as erosive oesophagitis. Because re-
flux of gastric acid is essential for the development
of oesophagitis, and its associated symptoms and
complications, the use of effective acid inhibitory
therapy represents the most rational strategy for
acute healing and symptom relief as well as for
maintaining the healed oesophageal mucosa. Pa-
tients with poorly managed erosive oesophagitis
have an increased risk for complications and a sub-
stantially diminished quality of life.[
Proton pump inhibitors represent a significant
breakthrough in the acute treatment and chronic
maintenance of healed erosive oesophagitis, and
are considered the “gold standard” for the manage-
ment of patients with these conditions.
together, clinical data strongly suggest that main-
tenance therapy with a proton pump inhibitor pre-
vents oesophagitis relapse in greater percentages
of patients than placebo as well as H2 antagonist
therapy, even in patients who do not respond to
initial H2 antagonist therapy for acute healing. Re-
sults suggest that proton pump inhibitor therapy
also reduces the risk of oesophagitis-related com-
plications such as stricture and need for repeat di-
latation. Moreover, emerging data suggest that
more aggressive gastric acid control may reduce
the risk of Barrett’s oesophagus and adenocarci-
noma, which are a growing burden. However, this
hypothesis remains to be tested.
Maintenance therapy with a proton pump inhib-
itor is cost effective in patients with healed erosive
oesophagitis based on the prevention of oesophag-
itis relapse, the reduction in patient symptoms, and
improvement in quality of life. Patients who expe-
rience erosive oesophagitis relapse impart an in-
creased load on the healthcare system through their
need for additional office visits, upper gastrointes-
tinal endoscopies and hospitalisation. The preven-
tion of oesophagitis relapse in these individuals, in
0
1
2
3
4
5
6
7
8
9
10 11 12
Duration of maintenance therapy (mo)
Fig. 3. Patients enrolled in maintenance trials demonstrating
healing of erosive oesophagitis in short-term treatment studies
or in non-blind lead-in phases were randomised to maintenance
therapy with lansoprazole 15mg, lansoprazole 30mg or pla-
cebo. The figure shows the proportion of patients who remained
asymptomatic during the 1-year maintenance period.
Lansoprazole was significantly superior to placebo in controlling
symptoms of daytime and night-time heartburn (p < 0.001). At 12
months, 72% of patients receiving lansoprazole 15mg and 67%
of those receiving lansoprazole 30mg were asymptomatic com-
pared with 35% of those receiving placebo. Percentages were
calculated by life-table methods; patient data were considered
to be censored at the time of the first erosive recurrence. An
asymptomatic state was defined as no moderate or severe day-
6,17]
[68]
Taken
[
20]
time or night-time heartburn. Reproduced with permission.
long-term comparator trials, diarrhoea was the
only event considered treatment-related and re-
ported by over 2% of patients in any treatment
group with 3.2% of lansoprazole recipients and
2
.0% of placebo recipients reporting this adverse
event.[ The percentage of patients discontinuing
a long-term clinical trial because of an adverse
event was also similar between placebo-treated
66]
(
8%, 16/201) and lansoprazole-treated (6%, 19/315)
patients.[66]
The effects of long-term administration of
lansoprazole on serum gastrin levels are not gen-
erally considered clinically significant or result in
a need to change drug therapy.[66,67] Long-term
treatment with a proton pump inhibitor may result
in an increase in median serum gastrin levels; how-
ever, these levels generally remain within the nor-
mal range throughout the course of treatment and
©
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Drugs 2002; 62 (8)

1
182
Freston et al.
turn, results in reductions in the utilisation of these
healthcare resources.
Acknowledgements
Dr Freston is a consultant for the following pharmaceu-
tical companies: Johnson and Johnson-Merck; TAP Pharma-
ceutical Products; Inc.; AstraZeneca; and Pfizer.
Lansoprazole is a well-established member of
the proton pump inhibitor class of agents and, as
such, has an extensive body of literature supporting
its clinical efficacy and patient tolerability, as well
as safety with short- and long-term use in patients
with a variety of acid-related disorders. Among
those with erosive oesophagitis, lansoprazole sig-
nificantly alters the natural course of the disease,
freeing patients from the inevitable relapse that oc-
curs in untreated patients and those prescribed H2
antagonists. A number of clinical trials performed
in different patient populations have confirmed
that up to 93 and 81% of those receiving lans-
oprazole 30 or 15mg, respectively, continue to
have healed oesophageal mucosa after 6 months,
with comparable percentages after 1 year (up to
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E-mail: freston@nso.uchc.edu
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