Probability of asthma
exacerbations
A post-hoc analysis was carried
out to estimate the probability of an asthma exacerbation using a
database of a population-based study by Dennis et al that reported that
43% (95% CI, 36.3-49.2) of patients with current asthma symptoms
reported requiring an ED visit or hospitalization in the last year
(28). Patients with 5-59 years of
age with a physician diagnosed asthma or rhinitis were selected. The
frequency of nocturnal symptoms (i.e., <2 nights/month,
2/month, 1-3 times/week and every night) was used to classify patients
among different severity categories. A previous diagnosis of asthma or
rhinitis by a physician was established as a selection criterion for a
better approximation of patients that were undergoing pharmacological
treatment and thus reflect the baseline scenario of routine care with
ICS in Colombia.
Two logistic regression models (one for patients with asthma and other
for patients with asthma and rhinitis) were constructed using patient
demographics and categories of nocturnal symptoms frequency as
predictors and the history of an ED visit/hospitalization as outcome
(yes/no). Coefficients were converted to probabilities and the estimated
parameter for the “1-3 times/week” category in the nocturnal symptoms
variable (using the “<2/per month” as reference level) was
assumed to reflect the baseline probability of an exacerbation in
patients with moderate persistent asthma. The resulting probabilities
were converted to rates and re-expressed as 3-month probabilities for
inclusion in the model.
A 75.4% of reduction in the proportion of patients that reported
unscheduled medical visits over a 9-month period reported by El-qutob et
al. was used in the model to reflect the effect of SCIT+ICS in the
reduction in the probability of asthma exacerbations (29). This
parameter was applied to the estimated baseline probabilities of an
asthma exacerbation of 0.331 and 0.465 for AA and AA+AR patients,
respectively (Table 1).
Health care resource utilization and
costs
The considered costs were cost of medications, medical services
(outpatient visits and specialized care) and ambulatory services (i.e.,
laboratory/image procedures). Costs per year were calculated by
multiplying individual costs inputs with age-specific medication doses
and medical services frequency considered to be appropriate to achieve
disease control based in local and international clinical guidelines
(18,30,31) (Table 1). For GINA Step 3 and GINA Step 2 states the
recommended average daily dose of ICS (medium and low dose per day) for
patients between 6-11 and >=12 years in the GINA report
were used, respectively (5). The number of days with salbutamol use per
month was obtained from a study by Sánchez et al and were multiplied
with the daily dose of salbutamol used in the analysis (32). Frequency
of outpatient, specialized care, ED visits and hospitalizationsper year was obtained from a study by Florez et al (3).
The administration of nasal ICS in addition to loratadine was allowed
for patients with AA+AR according to the Allergic Rhinitis and its
Impact on Asthma (ARIA) guidelines (30). For the GINA Step 3 and GINA
Step 2 states, medium and low doses of nasal ICS were used,
respectively. Loratadine was withdrawn in the GINA Step 2 state and no
use of AR medications were allowed in the remission state. It was
assumed that the reduction of AR medications was positively associated
to the reduction of AA medications. Disaggregated cost inputs according
to age group, health state and type of exacerbation are displayed in the
Supplementary material 1.
A complementary scenario analysis was conducted by evaluating the use of
SCIT as add-on therapy with a low dose of ICS + long acting
β2 agonists (LABAs) (i.e., formoterol/budesonide or
salmeterol fluticasone) and salbutamol. This scenario was conducted to
account for other controller strategies recommended in the Step 3 of the
GINA report that are frequently used in the clinical practice. A similar
effectiveness between BDP and formoterol/budesonide or
salmeterol/fluticasone was assumed. LABA medications were discontinued
in the GINA Step 2 and AR medications were considered to be administered
under the same scheme adopted in the base-case scenario. Costs and HCRU
parameters were validated by clinical experts in the research staff.
Unit cost parameters for all medications were obtained from the Drug
Price Information System of the Colombian Ministry of Health and Social
Protection (SISMED). Costs for the SCIT and other medical services were
obtained from the Social Security Institute medical fee manual of
2001+30% as recommended by Colombian guidelines for economic
evaluations (33,34).
Utility values
Previous EuroQol-5D utility values reported by Szende et al. for
intermittent, mild, and moderate severity levels in Hungary were used
(35). Utilities were assigned to the asthma without medication, GINA
Step 2 and GINA Step 3 states in the model, respectively. Disutility
associated to exacerbations were obtained from a previous study by Lloyd
et al. that reported changes in baseline
EuroQol-5D utility values in
patients from the UK (36).