DISCUSSION
To our knowledge, this is the
first study that evaluates the cost-effectiveness of HDM SCIT+ICS for
patients with moderate persistent AA using medication step down and
reduction of exacerbations as measures of clinical effectiveness. This
analysis suggests that treatment
with SCIT+ICS is a non-dominant but cost-effective therapy over ICS
alone in pediatric and adult patients with AA with or without AR. The
probabilistic sensitivity analysis confirmed the robustness of our
model. Despite our observation of a reduction in costs per cycle after
SCIT discontinuation, the magnitude of costs accumulated through the
first three years led to a higher total cost associated to SCIT at the
end of the time horizon. We consider that these results are driven by
the substantial low cost of the IC defined in the case scenario (i.e.,
BDP) and thus, the resulting cost reduction did not compensate the
initial additional costs associated to the SCIT. However, the resulting
ICERs fell below the willingness to pay threshold per QALY of one to
three GDP per capita of Colombia, making SCIT cost-effective in all
scenarios defined.
Although our study was conducted using some parameters from the
Colombian context, we consider that our results provide relevant inputs
for the decision-making process in different contexts, especially in
those where a significant pressure on health budgets exists. We
developed a novel Markov model based on a guideline accepted in the
clinical practice worldwide. Furthermore, Markov models are suitable for
modelling chronic diseases like asthma that are characterized by varying
symptomatic episodes of different severity over time (27). This aspect
constitutes one of the major strengths of our study, as this may allow
clinicians to obtain evidence regarding the economic implications of the
SCIT as add-on therapy to the commonly used pharmacological treatments
in the current practice and may base their decisions considering not
only a clinical dimension (38).
A relevant aspect in our study was the inclusion of parameters from
studies conducted in real-world settings. The efficacy of SCIT with HDM
extracts in the reduction of symptoms and medications has been reported
in previous experimental studies but its effectiveness in real-world
settings is scarce (11,21,22). A previous observational study by Jutel
et al. in Germany reported a 10.8% reduction in prescription of AA
medications and a 59.7% reduction of AR medications among pediatric
patients who received SCIT (39). Although the parameter for measuring
the impact of SCIT in our study was the proportion of patients achieving
reduction/discontinuation of medication usage, our results coincide in
the fact of a positive performance of SCIT in reducing the most
important factor that determines the cost of illness.
In a similar way, a previous population-based retrospective cohort study
by Schmitt et al. evaluated the protective effect of AIT in asthma
progression using the GINA treatment steps as a subrogate of disease
severity in a real-world setting. Authors suggest that exposure to AIT
is associated with a decreased risk of asthma progression from GINA Step
1 to Step 3 (HR 0.87 95% CI 0.80‐0.95) and from GINA Step 3 to GINA
Step 4 (HR 0.66 95% CI 0.60‐0.74) (40). Although authors adopted a
different definition of clinical effectiveness than that used in our
study, their results highlight the protective effect of the SCIT in a
real-world setting. In addition, our studies coincide with the use of a
GINA-based conceptual framework for the simplification of the course of
asthma.
We were able to obtain the probability of medication-step down and
discontinuation of medications in patients with moderate persistent
asthma that received SCIT from a real-world study in Colombia by Sánchez
et al (23). In addition, we estimated the baseline probability of an
asthma exacerbation using data form a population-based study by Dennis
et al. that included a sample of 5,978 individuals in six cities in
Colombia, and related the effect of the SCIT in this parameter using an
observational study from El-Qutob et al. (28,29).
Our study addresses limitations previously identified economic
evaluations of AIT. As stated by Asaria et al and Ehteshami-Afshar et
al., the evaluation of possible differences in the cost-effectiveness of
AIT across subgroups of patients remains one of the broader gaps in the
literature. Population-based treatment decisions may potentially led to
a loss of efficiency, as an intervention that is found to be
cost-effective in a general population of patients may not be equally
cost-effective among subgroups (or vice versa) (10,12). Our results
indicate that the SCIT with either ICS or ICS+LABA would reach the
highest cost-effectiveness in patients with AA+AR. We consider that
these results were mainly driven due to the higher baseline probability
of an asthma exacerbation compared to patients with AA only (0.465 vs
0.331) (28).
According to the latest guidelines on AIT for HDM mite-driven allergic
asthma by the European Academy of Allergy and Clinical Immunology
(EAACI), the reduction in asthma exacerbations and medications are
considered relevant co-primary outcomes in the assessment of the
efficacy of AIT (19). A previous study by Bruggenjurgen et al.,
evaluated the cost-effectiveness of HDM SCIT+ICS in the German setting
through Markov models under the societal perspective (41). The study
evaluated the strategies across different populations, but no attempt to
reflect the clinical efficacy of SCIT either through a reduction of
asthma medications or exacerbations was made. This aspect makes
difficult to compare our estimated QALYs gains with those reported by
the authors. In addition, relevant inputs in the model were retrieved
only through consultation of experts and no detailed description of
methods was conducted. Thus, it was defined as a low quality study by a
previous systematic review (10).
A previous study by Reinhold et al. evaluated the economic implications
of HDM SCIT+ICS in children with AA by a retrospective analysis of a
clinical trial (65 patients). After three years, SCIT+ICS was found to
be more expensive compared to ICS alone (7). Although authors considered
medication step-down, they were unable to account for the effect of the
SCIT in asthma exacerbations, neither were able to translate the
clinical efficacy of the strategies through QALYs. Their estimations may
thus underestimate the effect of the intervention in costs and QALYs.
This study has limitations and our results should be interpreted with
caution. Firstly, utility estimations attributed to health states in the
model were obtained from a survey conducted in Hungary, and they reflect
the preferences for specific health states in that population (35).
Utility parameters were associated with the greater uncertainty in our
model as evidenced in the deterministic sensitivity analysis and this
would have influenced the estimated QALYs gains. Nevertheless, the
parameters used were retrieved from a population of patients across
different GINA-defined disease categories using the EuroQol-5D
instrument, one of the recommended health utility measures for the
expression of clinical effectiveness in utility measures (42).
Secondly, given the limitations of information regarding the
effectiveness of the alternatives under evaluation in the reduction of
exacerbations and medication dosage in Colombia, we relied on important
assumptions regarding the effectiveness of SCIT and ICS. In the base
case scenario we assumed that the BDP would be the main IC administered
in this study, as it is the only IC covered by the Colombian health care
system and has the highest market share (24). We consider that this
assumption had an important influence in the estimated costs of the
controller treatment in our model. As BDP has a considerably lower cost
compared to other controller treatments, we potentially underestimated
the costs of ICS in the base case scenario. However, we assessed this
limitation in a complementary analysis using ICS+LABA as the controller
treatment, where the SCIT also resulted cost-effective. Moreover, we
could not take into account potential limitations and confounding
variables in all the observational studies used as the main source of
effectiveness parameters of the evaluated strategies. Nevertheless, we
included the effectiveness parameters in the deterministic sensitivity
analysis and results indicate that even under both conservative and
optimistic values, the SCIT+ICS resulted cost-effective. These
limitations could be minimized if there were more high-quality studies
that reported the frequency of the selected measures of effectiveness
for both treatment schemes in Colombia.