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.