Cost-effectiveness of GRAZAXsfor prevention of
grass pollen induced rhinoconjunctivitis in
G.W. Canonicaa, P.B. Poulsenb,?, U. Vestenbækc
aAllergy & Respiratory Diseases Clinic, DIMI, University of Genova, Pad.Maragliano, L.go R.Benzi 10, 16132 Genoa, Italy
bMUUSMANN Research & Consulting, Haderslevvej 36, DK-6000 Kolding, Denmark
cALK-Abello ´, Bøge Alle ´ 6-8, DK-2970 Hørsholm, Denmark
Received 14 September 2006; accepted 2 May 2007
Available online 3 July 2007
Grass pollen allergy;
Grass allergen tablet;
Background: Allergic rhinoconjunctivitis is a global health problem. Around 14 million
people in Spain, France, Italy, and Austria suffer from grass pollen induced allergic rhinitis.
Standard care only provides symptoms relief, while allergen specific immunotherapy (SIT)
treats the underlying cause of the disease. Grazaxsfrom ALK-Abello ´ is a new, tablet-
based, effective route of SIT for home treatment. The objective was to assess the cost-
effectiveness of Grazaxsin four Southern European countries.
Methods: A prospective pharmacoeconomic analyses was carried out alongside a multi-
national, clinical trial measuring the efficacy of Grazaxs. Pooled data on resource use and
health outcomes were collected. A societal perspective was adopted, and the analysis had a
nine-year time horizon. The primary outcome measure was quality adjusted life years (QALYs).
Results: Grazaxswas superior to standard care for all efficacy endpoints, including QALYs
gained, and resulted in significantly less use of rescue medication and fewer hours missed
from work. Grazaxswas cost-effective for all countries for an annual price in the range of
h1500–h1900. The result was improved by inclusion of future costs of asthma and exclusion
of Spanish trial centers which experienced an exceptionally low pollen season.
Conclusion: The analysis illustrates that allergen SIT with Grazaxsfor grass pollen
induced rhinoconjunctivitis is a cost-effective intervention in Southern Europe.
& 2007 Published by Elsevier Ltd.
Allergic rhinoconjunctivitis is a very common, global health
problem.1Numerous studies have shown a dramatic increase
in the disease prevalence in recent decades. While the
ARTICLE IN PRESS
0954-6111/$-see front matter & 2007 Published by Elsevier Ltd.
?Corresponding author. Tel.: +4570112210; fax: +4570112220.
E-mail address: email@example.com (P.B. Poulsen).
Respiratory Medicine (2007) 101, 1885–1894
prevalence of allergic rhinitis is believed to have been in the
order of 1% in the beginning of the 20th century,2an average
adult prevalence of allergic rhinitis between 17.8% and
26.0% was found in European countries in 2004 with
approximately 52% of these patients suffering from grass
pollen induced rhinitis.3This means that around 12% of the
adult population in Europe suffer from grass pollen induced
allergic rhinitis. For the Southern European countries—
Spain, Italy, France, and Austria, which are in focus in the
present study, this amount to nearly 14 million people.
When looking at the future prevalence of allergic rhinitis the
economic burden of the disease becomes even more
evident. A recent survey projects that one out of two
children will have allergic rhinitis in 2020.4
The increase in the occurrence of allergic rhinitis is
paralleled by similar increases in other allergic disorders
such as eczema and asthma, and several studies have shown
that asthma and allergic rhinitis often co-exist in the same
patients.1,5,6It has been estimated that asthma affects
approximately 38% of patients diagnosed with allergic
and among patients diagnosed with asthma,
60–78% have allergic rhinitis.8
The goal of symptomatic treatment is to reduce the
symptoms, both in severity and duration. The most
commonly used symptomatic medications in Europe are
antihistamines, corticosteroid nasal spray and eye drops.9As
symptomatic medication is solely used for the relief of
symptoms and has no long-lasting effect, allergic patients
may require life-long symptomatic medication.
As opposed to symptomatic medication allergen specific
immunotherapy (SIT) treats the underlying course of the
allergic disease and offers a long-lasting preventive effect.10
A large number of randomized controlled trials have
documented symptomatic relief as well as the beneficial
and long-lasting preventive effect of SIT.11–18In Spain and
Austria SIT has predominantly been delivered by subcuta-
neous injections, while in France (75%) and Italy (70%)
sublingual immunotherapy is the most widespread route of
administration (unpublished data). For optimal effect the
WHO recommends that SIT should be given over a period of
at least three years.10,19
Grazaxsfrom ALK-Abello ´ is a new, registered, tablet-
based SIT product against allergic rhinoconjunctivitis, for
home administration. Daily intake of Grazaxsshould start at
least eight weeks prior to the grass pollen season.
The improved clinical efficacy and resource utilization
patterns associated with the practice of SIT have cost
implications for the health care sector and the society in
general. For authorities to decide how to spend the
resources within the health care sector in an optimal way,
prospective cost-effectiveness analyses conducted alongside
clinical trials of a certain size are needed. Attempts have
been made to assess the cost implications for sublingual
immunotherapy,20–22but the present analysis is to our
knowledge the first study that analyses the cost-effective-
ness of sublingual immunotherapy prospectively and accord-
ing to guidelines for pharmacoeconomic evaluation.
The objective of the present study was therefore to assess
the cost-effectiveness of Grazaxscompared with sympto-
matic medication against grass pollen induced rhinocon-
junctivitis. This pharmacoeconomic analysis was carried out
for a group of four Southern European countries — Spain,
Italy, France, and Austria. These countries were chosen,
because of the perception of the burden of allergic rhinitis
was assumed to be uniform across the four countries, and
because of similarities in costs, treatment patterns and
health care systems.
The pharmacoeconomic analysis was designed as cost-
effectiveness and cost-utility analyses. Prospective data on
resource use and quality of life (QoL) was collected
alongside a clinical phase III trial which was part of the
largest clinical development programme that has been
undertaken for a SIT product, including more than 1700
patients.23–25The trial was conducted as a multinational
trial including eight countries (Austria, Denmark, Germany,
Italy, The Netherlands, Spain, Sweden, and United King-
dom). The trial included 634 patients where 316 patients
were randomized to the Grazaxsarm and 318 patients to
the placebo arm. The average age was 34 years (Table 1).26
Inclusion criteria in the trial were: 18–65 years old; at least
2-year clinical history of significant grass pollen induced
allergic rhinoconjunctivitis; specific IgE against Phleum
pratense CAP class 2; positive skin prick test against Phleum
pratense, wheal diameter 3mm; and FEV1 higher than 70%
of predicted value.26
Grazaxswas compared to standard care, i.e. sympto-
matic medication against grass pollen induced rhinocon-
junctivitis using the placebo alternative of the trial. This
ARTICLE IN PRESS
Demography of the patients in the clinical trial
Total number of subjects
Mean (standard deviation) 33.8 (9.6)34.5 (10.0)
Grass pollen allergy
Grass pollen allergy
Mean (standard deviation)
Source: Dahl et al.26
G.W. Canonica et al.1886
was possible as both study arms were allowed symptomatic
medication, which made it possible to model the placebo
arm as standard care. This has implications which are
discussed later in the discussion section. Following the
different national guidelines for pharmacoeconomic evalua-
tion in the countries considered, a societal perspective
focusing on both the direct health care costs and indirect
costs in the form of productivity losses due to allergic
rhinoconjunctivitis was adopted.27–30
Due to the relatively small number of patients from the
centers in Spain, Italy, and Austria, the data on resource use
and QoL from all 634 patients in the trial were analyzed in a
pooled manner.26,31However, country-specific unit costs
from each of the four countries considered were used.
Resource use, as well as unit costs (partly), was identified
before the randomization code of the trial was broken. The
resource use data collected included visits to the physician
and acute ward visits, symptomatic medication, asthma
medication, eventual hospitalization, and hours missed from
work due to allergic rhinitis. During the trial period, patients
were allowed to use clearly defined rescue medication
against rhinitis (i.e. loratadine and budesonide), and asthma
(i.e. salbutamol and fluticasone) dispensed according to
protocol criteria. This concomitant medication was con-
firmed by country-specific experts in allergy to be relevant
for patients in the four countries considered, although it was
more limited than in real practice.
Use of symptomatic medication was recorded by the
patients on a daily basis in diaries, whereas visits to
physicians and hours missed from work were recorded in
weekly diaries during the pollen season. Besides the
physician visits collected in the weekly diary, the literature
was searched to determine the annual number of physician
visits for a patient that has not undergone immunotherapy. A
recent European survey found this to be between 2.7 and 5.1
visits in the four Southern European countries considered.9
These literature-based visits were added to the analysis.
Resource use only associated with the trial per se (protocol
driven costs) such as visits for monitoring purposes was not
included in the pharmacoeconomic analysis,32as these costs
would not occur in a real life setting, which the analysis
Unit costs represent the values assigned to the consumed
resources.32In each of the four countries, country-specific
unit costs were identified and used in the valuation of the
resource use data. These unit costs were official tariffs,
retail drug prices (pharmacy selling prices), average wage
rates from national statistics bureaus, etc. (Table 2). All unit
costs were in Euro (2005) were possible.
In accordance with the guidelines for pharmacoeconomic
analyses in the countries assessed, all future costs and
health effects were discounted at rates between 3% and 5%
depending on the country. Discounting is a method used to
adjust future costs and benefits to their present value, i.e.
ARTICLE IN PRESS
Unit costs applied from the four countries (2004–2005 prices, Euros)
General practitioner (per office visit)a
Allergy specialist (per office visit)b
Accident & emergency (per visit)c
Loratadine, 10mg (per tablet)d
Budesonide, 50mcg (per dose)e
Prednisone, 5mg (per tablet)f
Salbutamol, 200mcg (per dose)g
Fluticasone, 250mcg (per dose)h
Production loss (average salary/h)i
aFrance: Service-Public, http://www.service-public.fr/. Italy: Degli et al.34Spain: Lindgren et al.35Austria: Expert advice.
bFrance: Service-Public, http://www.service-public.fr/. Italy: Pinotti et al.36Spain: Sera-Batles et al.37Austria: Expert advice.
cFrance: Van Ganse et al.38Italy: ERMES, http://www.regione.emilia-romagna.it. Spain: Lindgren et al.35Austria: Expert advice.
dFrance: Clarityne, 15 tablets (L’Assurance Maladie, www.codage.ext.cnamts.fr). Italy: Fristamin, 7 tablets (Federfarma, https://
www.federfarma.it). Spain: Ratiopharm, 20 tablets (www.portalfarma.com/www.vademecom.medicom.es). Austria: Acris, 7 tablets
(Omni medical center, www.omc24.at).
eFrance: Budesonide Arrow, 20 doses (L’Assurance Maladie, www.codage.ext.cnamts.fr). Italy: Aircort Spray Nas, 200 doses
(Federfarma, https://www.federfarma.it). Spain: Aldo-Union, 200 doses (www.portalfarma.com/www.vademecom.medicom.es).
Austria: Pulmicort Topinasal, 120 doses (Omni medical center, www.omc24.at).
fFrance: Prednisone Arrow, 30 tablets (L’Assurance Maladie, www.codage.ext.cnamts.fr). Italy: Deltacortene, 10 tablets
(Federfarma, https://www.federfarma.it). Spain: Dacortin, 30 tablets (www.portalfarma.com/www.vademecom.medicom.es).
Austria: Galen, 20 tablets (Omni medical center, www.omc24.at).
gFrance: Ventodisk, 56 doses (L’Assurance Maladie, www.codage.ext.cnamts.fr). Italy: Ventolin Diskus inal, 60 doses (Federfarma,
https://www.federfarma.it). Spain: Aldo-Union, 200 doses (www.portalfarma.com/www.vademecom.medicom.es). Austria: Cyclo-
caps, 60 doses (Omni medical center, www.omc24.at).
hFrance: Flixotide Diskos, 15 doses (L’Assurance Maladie, www.codage.ext.cnamts.fr). Italy: Flixotide Diskus, 60 doses (Federfarma,
https://www.federfarma.it). Spain: Inalacor, 120 doses (www.portalfarma.com/www.vademecom.medicom.es). Austria: Artemur, 60
doses (Omni medical center, www.omc24.at).
iFrance, Italy and Spain: Eurostat, http://epp.eurostat.cec.eu, Austria: Statistik Austria.
Cost-effectiveness of Grazaxsin Southern Europe1887
the future resource use cost and benefit streams are
reduced or ‘discounted’ to reflect the fact that resources
spent or saved in the future should not weigh as heavily in
programme decisions as resources spent or saved today, due
to positive time preferences.32The term positive time
preference refers to the fact that individuals value one Euro
today more than one Euro received a year from now.
Duration of the analysis
A crucial point in the model used in this cost-effectiveness
analysis is the assumption on the sustained effect of SITwith
Grazaxs. Based on results from current SIT treatment it is
assumed that after three years of treatment with Grazaxs,
there will be an additional sustained effect for six additional
years. As a consequence the prospective data from the
clinical trial is extrapolated into a nine-year time horizon by
linear extrapolation as outlined in Fig. 1.
Several studies have documented a sustained effect of
injection SITup to seven years after the treatment has been
finalized.14,16–18,33This sustained effect has also been
documented for the sublingual route of administration.15
Based on the evidence above we have used a nine-year
time horizon in this analysis — assuming six years of
sustained effect after treatment with Grazaxsis finalized.
The assumption on six years of sustained effect has been
documented in studies where patients have been treated
with SIT containing the same active ingredient as works in
Grazaxs.14,33Any sustained effect past the six years which
is assumed in the model will further strengthen the overall
Impact of allergic asthma
As presented in the Introduction, patients with allergic
rhinitis often also experience symptoms of asthma.7,8This
has been shown both for children and adults.16,39An
additional benefit of SIT is that it reduces the risk of
developing allergic asthma later in life. This preventive
effect has previously been demonstrated for subcutaneous
immunotherapy in children.16,17
treated with SIT developed asthma within three years
compared with 44% of the patients treated with conven-
tional pharmacotherapy — standard care with antihista-
Only 24% of patients
Assuming that this evidence was transferable to tablet-
based immunotherapy, the future costs related to asthma
was included in the country-specific cost-effectiveness
analyses of Grazaxsas a sensitivity analysis. This was done
in each of the four Southern European countries by
identifying existing country-specific costs and cost of illness
studies, which had estimated the annual direct health care
costs of asthma as well as the annual production loss due to
asthma.37,38,41,42The cost figures for Austria due to asthma
were taken from a German study as no Austrian study was
present.42Based on this evidence the annual direct and
indirect health care costs per asthma patient were
calculated and included in the cost-effectiveness analysis.
The risk of developing asthma was then included in the cost-
effectiveness analysis by assigning weights to the risk
corresponding to the result from Mo ¨ller et al.16
Similar results have been demonstrated for
A common feature of resource use data is that they are
positively skewed, because costs are naturally bounded by
zero, i.e. patients with zero utilization, and because costs
have no logical upper bound, i.e. outlier patients with very
high costs.32This was also the case in the trial. Performing
statistical analyses such as t-tests standard assumptions of
normal distributions are not appropriate in these situations,
why a logarithmic transformation of log(Ri+1) was used to
make the distribution more normally distributed.43
Quality of life
Quality adjusted life years (QALYs) measure the patients’
health-related QoL on a scale from zero (dead) to one
(perfect health), and are a multi-attribute utility scale that
can generate a single numeric index of health related
QoL.44,45Validated, country-specific versions of the com-
monly used EuroQol-5D (EQ-5D) instrument was used to
measure QALYs in each of the countries participating in the
trial. EQ-5D describes the patients’ QoL using five dimen-
sions — mobility, self-care, usual activities, pain/discomfort
and anxiety/depression.32Each of these dimensions are
divided into three levels of severity indicating no problems,
ARTICLE IN PRESS
9 years of time horizon
Immunotherapy (3 years)
Outline of the pharmacoeconomic analysis.
G.W. Canonica et al.1888
some problems and extreme problems. In total, EQ-5D
covers 245 different health states, including unconscious-
ness and dead. QoL was assessed by the patients on a weekly
basis. To obtain QALYs the health profiles described by the
patients were assigned QoL weights based on public
preferences based on a random sample of approximately
3000 members of the adult population of the United
The patients who participated in the clinical trial filled in
the EQ-5D questionnaire in their weekly diary (Palm Pilot)
during the pollen season as well as one registration prior to
— and one registration after the pollen season. We assumed
constant QoL outside the pollen season and used the
patients’ earliest registration prior to the pollen season as
a baseline measurement before the pollen season while the
patients’ last registration after the pollen season was used
as baseline after the season. Using all the patient’s EQ-5D
registrations a patients’ QALY value was estimated as the
area under the QoL curve during the year (Fig. 2). The total
number of QALYs in each of the two groups was the sum of
gained QALYs for each patient. The differences between the
two treatment groups were then finally calculated as the
difference in the total number of QALYs between both
treatment groups during a full year.
The pollen counts in Spain were extremely low during the
trial. This corresponds with the fact that 2005 was the driest
year in Spain since 1947, which caused the pollen season this
year to be less severe in terms of pollination.46,47This had
an impact upon the QoL, why sensitivity analyses excluding
the Spanish patients from the analysis was carried out.
The comparison of the two treatment strategies for grass
pollen induced rhinitis was based on their relative cost-
effectiveness. This was defined as the incremental cost-
effectiveness ratio (ICER) of Grazaxsversus standard care.
ICER determines the cost-effectiveness of a drug in
comparison to a viable alternative.48It is calculated in the
This is the difference in costs between two alternatives,
divided by the difference in their effects. In this study, it is
the ratio of the additional cost associated with Grazaxs
treatment over standard care divided by the gain in QALYs
associated with this treatment.
For decision makers to decide which technologies to
support, they need to establish a monetary value for an
extra QALY. Some health care systems are beginning to state
thresholds for this value.48In the UK, the National Institute
for Health and Clinical Excellence (NICE) has stated their
threshold: a drug that can generate one QALY for less than
£20,000 (h29,200) compared to an alternative, is considered
cost-effective, while a drug that requires more than £30,000
(h43,800) to generate one QALY is not considered cost-
effective.49In between these limits, a drug is considered
cost-effective, but additional criteria are specified to justify
adoption. The relevance of these levels of cost-effective-
ness is underlined by the fact that they are inversely linked
to the adoption of new health technologies.48,50
The overall result of the trial was that Grazaxscompared
with standard care showed highly statistically significant
improvements for all efficacy endpoints in terms of a 30%
reduction in mean rhinoconjunctivitis symptom score and a
38% reduction in mean rhinoconjunctivitis medication score
With respect to the health-related QoL in the two
treatment groups compared, the EQ-5D data from the trial
showed that significantly more QALYs were gained on
average when treated with Grazaxscompared with sympto-
matic treatment in the standard care group. The mean QALY
value was 0.9626 in the Grazaxsgroup and 0.9459 in the
standard care group (P ¼ 0.017). Hence, patients treated
with Grazaxsgained on average 0.0167 additional QALYs per
season compared with patients treated with standard care.
When extrapolating the QALYs gained nine years into the
future, the use of grass allergen tablets compared with
standard care resulted in extra 0.134 discounted QALYs
during the nine-year period. This is equal to a gain of 49 days
in perfect health during the period of nine years, or 5.4 days
per season corresponding to around 10% extra days in
perfect health during the pollen season.
When omitting the Spanish patients from the analysis, the
mean QALY value in the Grazaxsgroup increased to 0.9686
(P ¼ 0.006). Extrapolated into a nine-year perspective the
discounted gain in QALYs was 0.156 equal to a gain of 57 days
in perfect health.
None of the patients in the two groups were admitted to the
hospital, why this resource use parameter was excluded
ARTICLE IN PRESS
Quality of life of one patient, before, during and after
the pollen season
01/01/200501/02/200501/03/200501/04/2005 01/05/2005 01/06/200501/07/200501/08/200501/09/200501/10/2005
17/5 - 12/7
(QALYs) from the clinical trial.
Example of estimation of quality-adjusted life-years
Cost-effectiveness of Grazaxsin Southern Europe1889
from the analysis. The resource use in the two treatment
groups compared is summarized in Table 3.
The number of standard visits assumed during a season in
the standard care group was based on evidence from a
recent European survey.9In the Grazaxsgroup one standard
visit was assumed. With respect to additional physician visits
during the pollen season for the average patient, Table 3
shows only a small and insignificant difference for the two
groups compared. However, both for physician visits and for
acute ward visits no difference was found between the two
groups. It should be noted, however, that many patients in
both groups had zero visits. Table 3 also shows that the
usage of symptomatic medication was significantly higher in
the standard care group compared with the Grazaxsgroup,
although there was no difference in asthma medication. No
patients had an intake of Prednisolon in the trial.
Finally, Table 3 reveals a highly significant difference in
terms of production loss in the two ways of treating
rhinoconjunctivitis. The total number of hours missed from
work (production loss) by the patients was 294h (SD 5.47) in
the Grazaxsgroup compared with 1029h (SD 12.81) in the
standard care group. The mean number of hours missed in
the Grazaxsgroup was 1.06h, while it was 3.74h in the
standard care group, indicating a production loss for the
standard care group that is more than three times higher
than for the Grazaxsgroup.
The cost-effectiveness result for Grazaxscompared with
standard care for a time horizon of nine years in terms of
cost per QALY gained was investigated in each of the four
Southern European countries for a range of annual costs of
immunotherapy with Grazaxsfrom h900 to h2,900. The
cost-effectiveness analyses applied country-specific unit
costs and discount rates to the resource use and outcome
data from the trial explained above.
The cost per QALY gained was similar in each of the four
countries (Fig. 3). The highest cost per QALY gained was
found in Spain, while France had the lowest costs per QALY
gained. Part of this was due to differences in discount rates
applied, as the discount rate in Spain is 6% as opposed to 3%
in France. A higher discount rate favors the standard care
group, as the cost of the higher use of symptomatic
medication in the future is reduced with the discount rate.
Furthermore, differences in unit costs and treatment costs
were an explanation.
Using h1200 as an example for an annual cost of Grazaxs
the total costs were between h3862 and h4192 in the
Grazaxsalternative and between h1078 and h2335 in the
standard care alternative. Grazaxsaccounted for between
83% and 91% of the total costs depending on country. The
second highest contributor to the costs was production losts
ARTICLE IN PRESS
Resource use of the average patient in Grazaxsand the standard care groups during the pollen season
Resource use itemGrazaxs
Share with zero
Extra physician visit
Acute ward visits
Work hours missedf
2781.06h 5.4787 2753.74h12.81 77
aSD ¼ standard deviation.
bOne standard visit assumed for the Grazaxsgroup, because the intake of the first tablet in the season should be made at a visit at
the GP or allergy specialist.
cEFA.9Different number of visits for each of the countries according to source.
dLoratadine: P ¼ 0.0001 (t-test, log-transformed log(Ri+1)).
eBudesonide: P ¼ 0.0001 (t-test, log-transformed log(Ri+1)).
fWork hours lost: Po0.0001 (t-test, log-transformed log(Ri+1)).
G.W. Canonica et al.1890
or visits to the allergy specialist. In terms of cost-
effectiveness the cost per QALY gained was h13,870 in
France, h20,690 in Italy, h20,955 in Austria and h21,659 in
Spain — all below the NICE cost-effectiveness threshold.
Fig. 3 furthermore shows that the annual cost of Grazaxs
could be in the range from h1500 to h1900, depending on
country, and still be below the official threshold value of
£20,000 (h29,200) marked with the horizontal full line in
Fig. 3. For the higher NICE cost-effectiveness threshold of
£30,000 (h43,800) — marked with the horizontal dotted line
in Fig. 3 — indicating that a technology is potentially
cost-effective, the annual cost of grass allergen tablets
could be in the range of h2100–h2550, depending on the
When including the future costs of allergic asthma, as
described above, the overall cost-effectiveness result of
Grazaxsis improved even further, which was due to the
contribution from the health care costs and production lost
caused by allergic asthma. This is illustrated in Fig. 4, where
the ICER curves have moved in the direction to the right
compared with Fig. 3. In the four countries the health care
costs per patient due to asthma accounted for between 4%
and 26% of the total health care costs in the Grazaxs
alternative and between 54% and 242% of the total health
care costs in the standard care alternative (France: 24% and
115%, Italy: 20% and 242%, Spain: 26% and 207%, Austria:
4% and 54%).
With the inclusion of future asthma costs, Spain no longer
had the highest cost per QALY, but was now the country with
the second lowest cost per QALY, following France with the
lowest cost. Austria had the highest cost per QALY gained.
Comparing with the threshold value at £20,000 (h29,200 —
full horizontal line in Fig. 4) Fig. 4 illustrates that the annual
cost of Grazaxscan be in the range from h1650 to h2400
depending on the country and still be a cost-effective
The study found that allergen SIT with Grazaxsfrom ALK-
Abello ´ was superior to symptomatic treatment resulting in
improvements for all clinical efficacy endpoints.23,24,26
Prospective data collected alongside the trial26,31was
used in the present pharmacoeconomic analysis carried out
in four Southern European countries (Spain, Italy, France,
and Austria) to assess the cost-effectiveness of Grazaxs.
Patients treated with Grazaxs
symptomatic medication against rhinoconjunctivitis and
they missed significantly fewer hours from work than the
patients treated with standard care alone. The QALY data
collected alongside the trial also showed significant differ-
ences between the two groups in favor of Grazaxs, implying
that treatment with Grazaxsresults in an improved QoL for
The present pharmacoeconomic analysis illustrates that
SIT with Grazaxsis a cost-effective intervention in the
Southern European countries for a wide range of annual
costs of Grazaxscompared with symptomatic treatment
(standard care). The cost-effectiveness results for each of
the four countries differed only slightly with the cost per
QALY being highest in Spain and lowest in France. These
slightly different cost-effectiveness results were due to
differences in the country-specific unit costs and discount
An annual cost of Grazaxsbelow h1500 considering a
societal perspective or h1400 only focussing on direct health
care costs provides cost-effectiveness for all countries even
when the strictest level of the NICE cost-effectiveness
threshold is applied (Fig. 5).
The cost-effectiveness result was further improved when
the duration of sustained effect was prolonged past the six
years of sustained effect in the present analysis. The exact
duration of sustained effect is still under investigation.
used significantly less
ARTICLE IN PRESS
QALY threshold €29,200
(NICE: £ 20,000)
€43,800 (NICE: £30,000)
Annual cost of Grazax (Euro)
ICER - Cost per QALY gained (Euro)
QALY threshold €29,200 (NICE: £ 20,000)QALY Threshold €43,800 (NICE: £30,000)
Incremental cost-effectiveness ratios (ICER) for Grazaxs(cost per QALY gained).
Cost-effectiveness of Grazaxsin Southern Europe1891
In the present analysis, the placebo arm of the trial was
used as a proxy for standard care. This was possible as
patients in the placebo arm used symptomatic medication,
which was described by the clinical trial protocol. The
concomitant medication allowed was confirmed by experts
in allergy from each of the four countries to be relevant and
important for patients suffering from allergic rhinitis in the
four countries allowing it to substitute for ‘real life’
standard care. If the patients had been treated with
prophylactic medication this could have resulted in an
increase in the use of symptomatic medication. Assuming
that symptomatic medication has a positive influence on QoL
this could underestimate QoL in the standard care arm of
the analysis. On the other hand, the placebo effect has not
been addressed. Assuming that there is an effect of placebo
this could overestimate QoL in the standard care arm as this
effect would not be present in ‘real life’ standard care.
On the basis of this analysis it can be concluded that SIT
with Grazaxsis a cost-effective treatment of grass pollen
induced rhinoconjunctivitis in Southern European countries
such as Spain, Italy, France, and Austria for a range of
annual prices. This is supported by a previous study by
Donahue et al.51who found immunotherapy to be a less cost
intensive strategy compared with standard pharmacother-
apy over a ten year time horizon. SIT with Grazaxsought
therefore to be seen as an important part of the optimal
treatment for allergic rhinoconjunctivitis
Conflict of interest statement
The three co-authors have the following potential conflict of
interest regarding the manuscript ‘Cost-effectiveness of
ARTICLE IN PRESS
Annual cost of Grazax® (Euro)
ICER - Cost per QALY gained (Euro)
QALY threshold €29,200 (NICE: £ 20,000)QALY Threshold €43,800 (NICE: £30,000)
ICER ratios when the future costs of asthma are included (cost per QALY gained).
ItalySpain Austria France
Price of Grazax (Euro)
Only direct costs included
Direct costs + production costs + asthma costs
Direct costs + production costs included
Annual costs of Grazax below QALY threshold of h 29,200 (NICE,19Euro).
G.W. Canonica et al. 1892
Grazaxsfor prevention of grass pollen induced rhinocon-
junctivitis in Southern Europe’:
Canonica GWReports having received honoraria for
educational presentations, and/or funding
for research, and/or travel expenses,
and/or for service in advisory boards from:
Menarini, Alk Abello, Almirall, Altana,
Astra Zeneca, Boeringher Ingelheim, Chiesi
Farmaceutici, Gentili, GSK, Lofarma, MSD,
Novartis, Pfizer, Schering Plough,
Stallergenes, UCB Pharma, Uriach Valeas.
Have worked on this study as a consultant
payed by a research grant by ALK-Abello ´.
MUUSMANN Research & Consulting,
however, works in accordance with
guidelines for pharmacoeconomic
Is employed by ALK-Abello ´, who has funded
the present study and has marketed
The analysis was funded by ALK-Abello ´.
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