Understanding the Clinical Implications of Individual Patient Characteristics and Treatment Choice on the Risk of Exacerbation in Asthma Patients with Moderate–Severe Symptoms

Abstract

Introduction The assessment of future risk has become an important feature in the management of patients with asthma. However, the contribution of patient-specific characteristics and treatment choices to the risk of exacerbation is poorly understood. Here we evaluated the effect of interindividual baseline differences on the risk of exacerbation and treatment performance in patients receiving regular maintenance doses of inhaled corticosteroids (ICS) or ICS/long-acting beta-agonists (LABA) combination therapy. Methods Exacerbations and changes to asthma symptoms 5-item Asthma Control Questionnaire (ACQ-5) were simulated over a 12-month period using a time-to-event and a longitudinal model developed from phase III/IV studies in patients with moderate–severe asthma ( N = 16,282). Simulations were implemented to explore treatment performance across different scenarios, including randomised designs and real-world settings. Treatment options included regular dosing with ICS monotherapy [fluticasone propionate (FP)] and combination therapy [fluticasone propionate/salmeterol (FP/SAL) or budesonide/formoterol (BUD/FOR)]. Exacerbation rate was analysed using the log-rank test. The cumulative incidence of events was summarised stratified by treatment. Results Being a woman, smoker, having higher baseline ACQ-5 and body mass index (BMI) and lower forced expiratory volume in the first second (FEV 1 ) are associated with increased exacerbation risk ( p < 0.01). This risk is bigger in winter because of the seasonal variation effect. Across the different scenarios, the use of FP/SAL resulted in a 10% lower annual incidence of exacerbations relative to FP or regular dosing BUD/FOR, independently of baseline characteristics. Similar differences in the annual incidence of exacerbations were also observed between treatments in obese patients (BMI ≥ 25–35 kg/m 2 ) ( p < 0.01) and in patients who do not achieve symptom control on FP monotherapy. Conclusions Individual baseline characteristics and treatment choices affect future risk. Achieving comparable levels of symptom control whilst on treatment does not imply comparable risk reduction, as shown by the lower exacerbation rates in FP/SAL vs. BUD/FOR-treated patients. These factors should be considered as a basis for personalised clinical management of patients with moderate–severe asthma. Supplementary Information The online version contains supplementary material available at 10.1007/s12325-023-02590-2.

Effect of Individual Patient Characteristics and Treatment Choices on Reliever Medication Use in Moderate-Severe Asthma: A Poisson Analysis of Randomised Clinical Trials

“…Moreover, baseline ACQ-5 was derived from ACT scores for patients included in studies ADA109055 and ADA109057. This was required because only ACT was recorded in these studies and ACQ-5 has been identified as a covariate affecting exacerbation risk and individual symptom trajectories during the course of treatment [ 5 , 20 ]. Conversion was performed considering the symptom category and percentiles of the scores of each scale.…”

The Saudi initiative for asthma – 2024 update: Guidelines for the diagnosis and management of asthma in adults and children

“… Recommended options: It is recommended to use a daily fixed-dose combination of low-dose ICS/LABA with an as-needed reliever for symptom relief (Evidence A). [ 87 128 129 130 ] Reliever therapy is recommended in the form of SABA (with or without ICS) whenever a maintenance fixed-dose combination of ICS/non-formoterol LABA or in the form of ICS/formoterol whenever a maintenance fixed-dose ICS/formoterol combination is prescribed. [ 131 132 ] Physicians should ensure the adherence of patients to this regimen[ 106 ] Alternative options: The addition of LTRA to a low-dose ICS is another option, especially in patients with concomitant rhinitis (Evidence A)[ 133 134 135 ] Continuation of ICS as a monotherapy by increasing the dose to the medium level is generally a less effective strategy (Evidence A).…”

“…Recommended options: It is recommended to use a daily fixed-dose combination of low-dose ICS/LABA with an as-needed reliever for symptom relief (Evidence A). [ 87 128 129 130 ] Reliever therapy is recommended in the form of SABA (with or without ICS) whenever a maintenance fixed-dose combination of ICS/non-formoterol LABA or in the form of ICS/formoterol whenever a maintenance fixed-dose ICS/formoterol combination is prescribed. [ 131 132 ] Physicians should ensure the adherence of patients to this regimen[ 106 ]…”