Asthma is a chronic inflammatory airway disease characterized by reversible airflow obstruction, airway hyperresponsiveness, and variable respiratory symptoms such as wheezing, shortness of breath, and coughing. Despite advances in conventional treatment modalities, approximately 5–10% of asthma patients suffer from severe asthma, which remains poorly controlled even with high-dose inhaled corticosteroids and additional controller medications (1). This subset of patients often experiences frequent exacerbations, poor quality of life, and an increased burden of healthcare utilization.

Biologic therapies have revolutionized the management of severe asthma by targeting specific inflammatory pathways involved in its pathogenesis. These therapies primarily include monoclonal antibodies directed against immunoglobulin E (IgE), interleukin-5 (IL-5), IL-4 receptor alpha (IL-4Rα), and IL-13, which are crucial mediators in eosinophilic and allergic phenotypes of asthma (2,3). Traditionally administered via subcutaneous or intravenous routes, these biologics have demonstrated efficacy in reducing exacerbation frequency, improving lung function, and decreasing reliance on systemic corticosteroids (4).

Recent developments have introduced inhaled formulations of biologic agents, aimed at enhancing local delivery to the airways while minimizing systemic exposure and adverse effects. Inhaled biologics may offer several advantages, including faster onset of action, lower systemic immunogenicity, and improved patient compliance (5). However, head-to-head comparisons of different inhaled biologic agents in real-world settings are limited.

This study aims to compare the clinical efficacy and safety of two inhaled biologic therapies—an anti-IL-5 agent (Drug A) and an anti-IL-4R agent (Drug B)—in patients with severe asthma. By evaluating lung function, symptom control, exacerbation rates, and adverse events, this research seeks to provide evidence-based guidance for selecting optimal inhaled biologic therapy in severe asthma management.

Study Design and Setting

This was a prospective, randomized, double-blind, parallel-group clinical trial conducted over a period of six months at a tertiary care respiratory center. Written informed consent was obtained from all participants prior to enrollment.

Study Population

A total of 120 adult patients, aged between 18 and 65 years, diagnosed with severe persistent asthma as per Global Initiative for Asthma (GINA) guidelines, were enrolled. Inclusion criteria comprised individuals with a documented history of frequent exacerbations (≥2 per year), dependence on high-dose inhaled corticosteroids along with long-acting beta-agonists, and poor symptom control (Asthma Control Test – ACT; score <20). Patients with smoking history, other chronic pulmonary diseases, or recent respiratory infections were excluded.

Randomization and Intervention

Participants were randomly allocated into two equal groups (n=60 each) using a computer-generated randomization sequence.

• Group A received an inhaled anti-IL-5 biologic therapy (Drug A) administered via dry powder inhaler every two weeks.
• Group B received an inhaled anti-IL-4R therapy (Drug B) administered once every four weeks using a metered dose inhaler.

Both groups continued their standard background therapy for asthma as prescribed.

Outcome Measures

The primary outcome measures included:

1. Change in Asthma Control Test (ACT) scores from baseline to 24 weeks.
2. Improvement in forced expiratory volume in one second (FEV₁) measured by spirometry.
3. Frequency of asthma exacerbations, defined as episodes requiring systemic corticosteroids or emergency care.

Secondary outcomes included patient-reported quality of life using the Asthma Quality of Life Questionnaire (AQLQ) and the incidence of adverse events during the study period.

Follow-up and Data Collection

Patients were evaluated at baseline, 12 weeks, and 24 weeks. At each visit, spirometry was performed, ACT scores were recorded, and any adverse events or exacerbation episodes were documented. Compliance was assessed through patient diaries and device counters.

Statistical Analysis

Data were analyzed using SPSS version 25.0. Continuous variables were expressed as mean ± standard deviation and compared using the paired and unpaired t-tests. Categorical data were analyzed using the chi-square test. A p-value <0.05 was considered statistically significant.

A total of 120 patients were included in the final analysis, with 60 patients in each treatment group. Baseline characteristics were comparable between the two groups with no statistically significant differences in age, gender distribution, baseline ACT score, or FEV₁ (Table 1).

Over the 24-week treatment period, both groups demonstrated significant improvement in asthma control and lung function; however, Group A (inhaled anti-IL-5) showed superior clinical outcomes compared to Group B (inhaled anti-IL-4R).

Asthma Control Test (ACT) Scores

Group A showed a marked improvement in ACT scores from a baseline mean of 12.5 ± 1.8 to 21.8 ± 2.3 at week 24. Group B showed a rise from 13.0 ± 1.6 to 19.4 ± 2.1 during the same period. The between-group difference at week 24 was statistically significant (p = 0.03) (Table 2).

Lung Function (FEV₁ % Predicted)

Group A demonstrated an increase in FEV₁ from 58.2% ± 6.5 at baseline to 76.4% ± 5.7 at 24 weeks, while Group B improved from 59.0% ± 5.8 to 71.0% ± 6.2 (p = 0.04 between groups at week 24) (Table 2).

Exacerbation Frequency

Group A experienced a 65% reduction in annualized exacerbation rate, while Group B showed a 50% reduction. The difference in reduction rate was statistically significant (p = 0.02) (Table 3).

Adverse Events

Adverse events were mild and self-limiting in both groups. Group A reported adverse events in 6 patients (10%), whereas Group B had 9 cases (15%). No serious adverse events or therapy discontinuations were noted (Table 4).

Table 1. Baseline Characteristics of Study Participants

Table 2. Comparison of ACT Score and FEV₁ at Baseline and Week 24

Table 3. Reduction in Exacerbation Frequency Over 24 Weeks

Table 4. Adverse Events During Study Period

This study compared the efficacy and safety of two inhaled biologic therapies—an anti-IL-5 agent and an anti-IL-4R agent—in patients with severe persistent asthma. The results demonstrated that both treatments led to significant improvements in asthma control, lung function, and a reduction in exacerbation frequency over a 24-week period. However, patients receiving the inhaled anti-IL-5 therapy (Group A) showed greater clinical benefit compared to those treated with anti-IL-4R (Group B).

The observed improvement in ACT scores in both groups aligns with previous findings that biologic therapies improve symptom perception and overall asthma control (1,2). The greater improvement in Group A supports the growing evidence favoring anti-IL-5 therapies in eosinophilic asthma phenotypes (3,4). IL-5 plays a central role in eosinophil survival and recruitment, and targeting this pathway has been shown to reduce eosinophilic inflammation effectively (5).

Enhancement in FEV₁ observed in this study corroborates findings from earlier trials of inhaled biologics, which reported significant increases in lung function following therapy (6,7). Group A's superior FEV₁ improvement is consistent with literature indicating that anti-IL-5 agents are particularly effective in improving airflow in patients with high baseline eosinophil counts (8,9). Although anti-IL-4R agents target broader inflammatory pathways, including IL-4 and IL-13, their effects may be more gradual and less pronounced in certain phenotypes (10).

The reduction in exacerbation frequency in both groups mirrors the outcomes of previous studies showing the utility of biologics in lowering the risk of severe asthma attacks (11,12). A 65% reduction in Group A compared to 50% in Group B is clinically meaningful and highlights the potential of inhaled anti-IL-5 biologics in minimizing disease burden.

Safety profiles in both groups were acceptable, with only mild adverse events reported. This finding supports existing literature suggesting that inhaled biologic delivery reduces systemic exposure and lowers the incidence of adverse reactions compared to parenteral administration (13,14). Additionally, patient adherence and satisfaction may be higher with inhaled therapies due to convenience and ease of use, as shown in recent patient-reported outcomes research (15).

Limitations: Limitations of the study include its relatively short duration (24 weeks) and the absence of long-term follow-up for sustained efficacy and safety. Biomarker assessments, such as blood eosinophil counts or FeNO levels, were not incorporated, which may have further stratified response patterns among patients. Moreover, the study did not evaluate cost-effectiveness, which is a critical factor in biologic therapy utilization.

The findings of this study reinforce the role of inhaled biologic agents as effective treatment options for severe asthma, with inhaled anti-IL-5 therapy showing superior outcomes in symptom control, lung function, and exacerbation reduction. These results support the tailored use of biologics based on individual inflammatory phenotypes and highlight the potential of inhaled routes for biologic delivery in respiratory care.

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