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2009

2000

Szucs et al13
(Switzerland)

Gerson et al7
(USA)

* O
pen-label, randomized, multicenter study comparing the
2 long-term management options with esomeprazole 20
mg-continuous daily or on-demand treatment during 26
weeks-in endoscopically uninvestigated patients seeking
primary care in Switzerland for symptoms suggestive of
GERD who demonstrated complete relief of symptoms after
an initial treatment of 4 weeks with esomeprazole 40 mg.
* Patients found to meet all the inclusion criteria and
none of the exclusion criteria at the end of the initial
treatment course were randomized in equal proportions
to continuous treatment with esomeprazole 20 mg 4
times a day or on-demand treatment with esomeprazole
20 mg. For the randomization, a centrally compiled,
computer-generated list was used, which was based on
a block size of 4. Each site received a kit consisting of a
list of randomization numbers and sealed randomization
envelopes for 4 patients. The investigator was
instructed to consecutively allocate the lowest available
randomization number, but open the randomization
envelopes containing the information on the allocated
treatment group only at randomization. It had been
planned that each site would recruit 4 patients (or an
exact multiple of 4). Each patient in the continuous
treatment arm was instructed to take 1 tablet once daily.
* In the on-demand arm, the patient was instructed to take
one tablet daily if needed for the relief of heartburn and to
stop when the heartburn is adequately controlled. The study
drugs were packed in bottles, and every patient received in
total 2 bottles of 100 tablets esomeprazole 20 mg free of
charge. The distribution schedule of the study drugs from
general practitioner to patient was at the discretion of the
general practitioner, ie, the treating physician decided when
to distribute study drugs and whether to distribute them all
at once or at several occasions. Compliance was determined
by counting the tablets returned by the patient.
* On-demand PPI Arm: Empirical treatment with an 8-week
course of PPI therapy administered on demand when GERD
symptoms reoccur. Patients in this group require at most
three 8-week courses (24 weeks) of medication per year.
Patients failing on-demand therapy (recurrence of symptoms
earlier than 2 months without medication) receive
continuous PPI therapy, and endoscopy is performed only if
symptoms recur on daily PPI therapy.

Methodology

* T
he researchers had done a decision analysis on ondemand PPI strategy in which the empirical treatment
with an 8-week course of PPI therapy administered on
demand when GERD symptoms recur. Patients in this
group require at most three 8-week courses (24 weeks)
of medication per year. Patients failing on-demand therapy
(recurrence of symptoms earlier than 2 months without
medication) receive continuous PPI therapy, and endoscopy
is performed only if symptoms recur on daily PPI therapy.
* On-demand PPI strategy is the most cost-effective
approach with discounted incremental cost-effectiveness
ratio of US$20 934 per QALY gained by patient with
mild to severe GERD symptoms and $379 223 per QALY
gained for patient with mild GERD symptoms. On-demand
PPI was dominant with an incremental cost-effectiveness
ratio of $2197/QALY gained.

* T
he patients in the on-demand group experienced slightly
more frequently GERD symptoms than those in the
continuous group. At the end of the 6-month maintenance
phase, 94% of the patients in the on-demand group and
were classified as "satisfied" (score = 1-4) with their
treatment, whereas 74% of the patients were reported to
be "very satisfied" (score = 1-2), Wilcoxon rank sum test
(score = 1-7): P < .056.
* The difference of the adjusted mean direct medical costs
between the treatment groups was CHF 88.72 (95% CI:
CHF 41.34-153.95) in favor of the on-demand treatment
strategy (Wilcoxon rank sum test: P < .0001). The mean
number of clinic visits to the investigator for any reason
required per patient was 0.52 (SD = 0.663) for those in
the on-demand group.
* Adjusted direct nonmedical costs and the productivity
loss were similar in both treatment groups during the
6-month maintenance phase. Hence, health care payers will
obtain net savings by implementing the use of on-demand
esomeprazole.
* These results confirm that the maintenance therapy
through 6 months with respect to patients' satisfaction
and symptom control, defined no need for change of
therapy, can be performed with a continuous, as well as
by an on-demand schedule using esomeprazole 20 mg
daily. The treatment with continuous esomeprazole was
more efficient than the on-demand therapy with regard to
remission of heartburn.
* The adjusted direct medical costs of a 6-month on-demand
treatment with esomeprazole 20 mg in patients with GERD
were significantly lower compared with a continuous
treatment with esomeprazole 20 mg once a day.

Outcome

* O
n-demand
PPI strategy
is the most
cost-effective
approach

* T
he data clearly
demonstrate
that on-demand
esomeprazole
20 mg therapy
is associated
with significantly
better
effectiveness
and lower costs
than a strategy
consisting of
intermittent
4-week
treatment
courses of
omeprazole 20
mg once daily.

Conclusion

* A
n analysis of lifetime costs-not
known how long patient can
expect symptomatic relief.
* Only few of the prior studies used
QALYs as a utility measurement,
and obtained their estimates
through a modified Delphi
process.
* Prior models did not allow
patients to switch from H2RAs to
PPIs without endoscopy, often did
not include the option of Nissen
fundoplication, or sent patients
without response to PPI for a
Nissen without consideration of
promotility therapy.
* None of the models included
patients with nonerosive disease.

* T
he endpoint used in this primary
care study (symptoms of any
severity on at least 2 days during
the previous week) may not
correspond to a definition of
relapse in clinical practice.

Limitation

Note. PPI = proton pump inhibitor; GERD = gastroesophageal reflux disease; CHF = congestive heart failure; CI = confidence interval; QALYs = quality-adjusted life in years; H2RAs = histamine 2 receptor antagonists.

Year

Author

Table 7. (continued)

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