Introduction
Although some factors associated with asthma symptom deterioration and risk of exacerbation have been identified, these are not yet fully characterised. We conducted a clinical modelling and simulation study to understand baseline factors affecting symptom control, reliever use and exacerbation risk in patients with moderate–severe asthma during follow-up on regularly dosed inhaled corticosteroid (ICS) monotherapy, or ICS/long-acting beta
2
-agonist (LABA) combination therapy.
Methods
Individual patient data from randomised clinical trials (undertaken between 2001 and 2019) were used to model the time course of symptoms (
n
= 7593), patterns of reliever medication use (
n
= 3768) and time-to-first exacerbation (
n
= 6763), considering patient-specific and extrinsic factors, including treatment. Model validation used standard graphical and statistical criteria. Change in symptom control scores (Asthma Control Questionnaire 5 [ACQ-5]), reduction in reliever use and annualised exacerbation rate were then simulated in patient cohorts with different baseline characteristics and treatment settings.
Results
Being a smoker, having higher baseline ACQ-5 and body mass index affected symptom control scores, reliever use and exacerbation risk (
p
< 0.01). In addition, low forced expiratory volume in 1 s percent predicted, female sex, season and previous exacerbations were found to contribute to a further increase in exacerbation risk (
p
< 0.01), whereas long asthma history was associated with more frequent reliever use (
p
< 0.01). These effects were independent from the underlying maintenance therapy. In different scenarios, fluticasone furoate (FF)/vilanterol was associated with greater reductions in reliever use and exacerbation rates compared with FF or fluticasone propionate (FP) alone or budesonide/formoterol, independently from other factors (
p
< 0.01).
Conclusions
This study provided further insight into the effects of individual baseline characteristics on treatment response and highlighted significant differences in the performance of ICS/LABA combination therapy on symptom control, reliever use and exacerbation risk. These factors should be incorporated into clinical practice as the basis for tailored management of patients with moderate–severe asthma.
Supplementary Information
The online version contains supplementary material available at 10.1007/s12325-024-02962-2.
