METHODS
We performed the ANCHORS (Asthma iN CHlidren: Omalizumab in Real-life in
Spain) study, a retrospective, observational, multicenter study, in real
life conditions, designed to evaluate the use OMZ in children with SPAA.
Demographic and clinical results of the ANCHORS study have been
published elsewhere.(21) Briefly, it included 484 patients aged
<18 years with SPAA from 25 Pediatric Allergy and Pulmonology
units in Spain, who had been started on OMZ between 2006 and 2018
because of uncontrolled symptoms despite treatment with ICS+LABA and
sometimes chronic oral corticosteroids (OCS). Some patients received OMZ
as an off-label indication because they did not fulfil the accepted
criteria either of age or of levels of serum total IgE, but were judged
as lacking other alternatives of treatment.
The primary outcome of the ANCHORS study was the evolution of the annual
number of moderate-to-severe exacerbations (MSE), defined as those
requiring systemic corticosteroids, emergency visits, and/or
hospitalizations, compared to baseline;(21) A secondary outcome was the
improvement in asthma control assessed by the validated Childhood Asthma
Control Test (c-ACT) or the Asthma Control Questionnaire (ACQ5). Other
clinical data, available in the previous publication, were not used for
the present report.
The aim of this report was to assess cost-effectiveness of the use of
OMZ measuring the costs from the perspective of the National Health
System. We calculated the ICER (formula displayed in the figure 1) to
avoid an MSE and for significant improvements in results of asthma
control tests. The c-ACT values range from 0 to 25, with higher scores
associated to better asthma control; conversely, the ACQ5, ranging from
0 to 6, shows better control with lower values. The cut-off points to
consider asthma as well controlled are above 20 points in c-ACT, and
below 1 point in ACQ5. We evaluated the cost for the clinical Minimally
Important Difference (MID) in the control tests, estimated as 3 points
for c-ACT and 0.5 points for ACQ5.(22,23)
We collected the number of asthma-related healthcare encounters:
unscheduled visits to primary care pediatricians and to specialists,
emergency room visits, ward hospitalizations and Pediatric Intensive
Care Unit (PICU) admissions. The official cost of each of these
encounters differed across centers, so the mean values were used for all
of them.
The use of medication was also recorded. It included montelukast,
prolonged OCS, bursts of rescue OCS, ICS alone, and ICS+LABA. The daily
doses of montelukast were calculated according to age (4 mg for children
<6 years, 5 mg for those 6-14 years, 10 mg for those
>14 years). The dose of chronic OCS was estimated as 1
mg/kg/day of prednisone for children >6 years and 1
mg/kg/day of prednisolone for those younger. The dose of bursts of OCS
was calculated, as per guidelines, at 2 mg/kg/day of prednisone or
prednisolone (according to the same age) for three days plus 1 mg/kg/day
for three more days. We used the mean weight of boys and girls for age
according to the reference by the Faustino Orbegozo Foundation.(24) The
actual doses of ICS or ICS+LABA received by each patient were
transformed to equivalent doses of budesonide or budesonide+formoterol,
used for a harmonized calculation of costs. We used the laboratory sale
price (LSP) for drugs, obtained from the Spanish General Council of
Official Associations of Pharmacists website.(25) Other drugs, as
theophylline, azithromycine or ipratropium bromide, were not included in
the analysis due to the limited impact on costs, because of the small
number of patients using these drugs, as well as their low price.
The dose of OMZ was that recommended by the manufacturer. Its cost was
calculated considering the number of 150 or 75 mg syringes needed by
each patient and the frequency of administration. A reduction of 7.5%
was applied according to Royal Decree-Law 8/2010.(26)
The unit cost of each health encounter and drug is shown in Table 1. The
cost for each patient was calculated multiplying the number of units of
used health encounters and drugs by their corresponding cost. We
calculated cost in euros of 2018, regardless of the year when it
occurred.
Data were retrospectively collected reviewing the electronic medical
records of the hospitals and primary care centers. The basal data were
those of the year before initiating OMZ treatment; thereafter data were
referred to each complete year. The time horizon was the duration of
follow-up since the start of treatment in each patient until closure of
database.
Results are shown as means and 95% confidence intervals, and medians
and interquartile range. As variables had a non-normal distribution, for
paired samples, Wilcoxon sign-ranked test for two and Friedman test for
three or more groups were used. SPSS 15.0 software program (Chicago,
Ill, USA) was used for calculations.
The study was approved by a Central Ethics Committee (Hospital
Universitari i Politècnic La Fe, Valencia-Spain), which granted a waiver
for informed consent.