DISCUSSION
Several published clinical trials demonstrate that OMZ is able to improve the clinical condition and QoL of many children with SPAA uncontrolled with conventional treatment.(12–14) It has also proved to be effective in real-life studies,(15–18) including ours,(21) which is used for the present report.
OMZ is recommended in guidelines as an add-on therapy in the last step of treatment, mainly due to its higher cost compared to other drugs.(1) In patients with good response to OMZ, the rest of treatments are usually tapered or even withdrawn, either on medical recommendation or, quite often, by the patients themselves when they consider they do not need it. The improved clinical status is also reflected in the reduction of health encounters and the improvement of control tests scores.
The use of OMZ causes a substantial increase in direct costs in the first year. Thus, the mean ICER to avoid an MSE (main objective of this report) was \euro2,107 euros (median \euro998). We have not data in children for comparison, but in two studies in adult patients in our country, the ICER varied from \euro1,488 to \euro1,712 euros per avoided MSE with the same criteria we used.(27,28) When these studies included indirect costs, not available in our patients, the figures decreased to \euro1,130 and \euro1,607 euros, reductions of 24% and 6% respectively. In two studies in adults, the figures per avoided exacerbation were \euro1,789 and \euro2,244 euros, including indirect costs.(29,30) Importantly, our ICER cost of \euro2,107 euros was progressively reduced to \euro657 euros (median \euro369) in year six of treatment.
In other studies, the ICER for improvement in asthma control tests was higher than that for avoided exacerbations.(27–29) This also happened in our case, where the ICER to achieve the MIDs ranged from \euro3,141 in year 1 to \euro2,321 in year 6 for the c-ACT, and from \euro2,059 in year 1 to \euro380 in year 6 for the ACQ5. Cost in the first year for c-ACT were higher (\euro3,555 to \euro4,569, even including indirect costs) in the studies of adults available for comparisons.(27–29)
There are studies evaluating the costs for Quality Adjusted Life Years (QALY), in adults and adolescents,(31,32) and only one in children.(33) The costs for studies in the USA show very high figures, from US$75,319 (34) to US$821,000 (35) per QALY, whereas in the study in children, in China, that cost was calculated also as high as US$211,217.(45) (33) The cost was much lower in Europe, \euro56,847 in Italy (36) and that a cost of \euro30,000 to \euro45,000 per QALY would be an affordable price in Spain.(37) We have no data about quality of life in our patients, so we can only speculate that at least the cost for QALY would decrease in successive years, given the reduction of costs in the variables we evaluated.
There are several limitations in our study. We collected data retrospectively and there were missing data for some variables, especially regarding health encounters. When calculating the sum of variables (health encounters and medication) patients with missing data could not be included, leading to a lower number for analyses. As this was a multi-center study, the asthma control tests were not performed uniformly, and the number of available patients was even lower.
In addition, it should be noted that in order to harmonize costs, considering the variability between researchers, centers and patients, budesonide and formoterol were used as the gold standard, obtaining an approximate cost when calculating the equivalence to budesonide and formoterol in cases in which another ICS and/or LABA were taken. There may also be different budesonide products with different prices, depending on the inhalation mechanism. Furthermore, the cost of spacer chambers, possible treatment adherence failures, and inflation were not considered.
The cost of personnel for administering OMZ was not included either, nor were expenses for transportation. Although at the time of our study the home administration of OMZ was not yet authorized, it is foreseeable that nowadays these costs would diminish. The number of adverse effects of OMZ were low and mainly mild, as shown in the previous publication.(21) We were not able to calculate costs associated to them, a common situation in other studies, and this can be another limitation of our report.
This is the first study in a pediatric population in Europe to estimate these costs. One strength of our report is that it was a real-life study, with a long duration, a large sample of patients, and actual data, not extrapolated from theoretical evaluations. We found decreasing costs for OMZ, due to increasing intervals between administrations, an approach not based on clinical studies, but common practice across different hospitals, with no previous agreement, based on clinical individual assessment by attending physicians. The improvement was found since year 1 and the costs further decreased along the following years. The decrease in costs may be also partly due to withdrawal of OMZ in non-responders.
Indirect costs could not be collected. As health encounters diminished 95-99% from the basal ones, all the associated expenses for transportation, missing school days, missing workdays of the family or expenses for caregivers would be saved, reducing ICER to a greater extent.