Asthma remission with benralizumab therapy in severe eosinophilic Indian asthmatics

Dear Editor, Severe eosinophilic asthma (SEA) represents a distinct and clinically important phenotype of asthma characterized by persistent type 2 airway inflammation driven by elevated eosinophil counts. Globally, asthma affects nearly 340 million individuals, of whom 3%–10% have severe disease. Approximately 45% of severe asthmatics exhibit the eosinophilic pheno-endotype.[1] This subgroup contributes disproportionately to asthma-related morbidity, healthcare utilization, and impaired quality of life. Patients with SEA frequently experience recurrent exacerbations, persistent airflow limitation, and inadequate symptom control despite optimal adherence to high-dose inhaled corticosteroids and additional controller therapies. These conventional treatment strategies often fail to address the underlying eosinophilic inflammation, underscoring the need for targeted and more effective interventions. In the last two decades, biologic agents have transformed the way we manage severe asthma. Omalizumab, a humanised anti IgE antibody, was the first approved biologic agent against severe atopic asthma. The introduction of biologic agents directed against interleukin-5 (IL-5) or its receptor—specifically mepolizumab, reslizumab, and benralizumab has significantly advanced the therapeutic armamentarium. IL-5 plays a central role in eosinophil differentiation, maturation, activation, and survival, making it a critical therapeutic target. Clinical trials have consistently demonstrated that anti–IL-5 therapies substantially reduce exacerbation rates, corticosteroid dependence, and hospitalizations, alongside improving lung function, asthma control, and health-related quality of life.[2-6] Despite inter individual variability in response, these biologics exemplify precision medicine in asthma care, offering sustained clinical benefits for appropriately selected patients. Ongoing research continues to refine long-term treatment strategies, evaluate safety and durability of response, and identify predictive biomarkers to further individualize therapy and optimize outcomes in this high-burden asthma phenotype. Severe asthma in India presents unique clinical and epidemiological challenges due to the country’s diverse environmental exposures, genetic heterogeneity, and variable access to healthcare. Factors such as high levels of air pollution, biomass fuel exposure, parasitic infections, and differing allergen profiles contribute to distinct asthma phenotypes that may not align with global classifications. Additionally, poor disease awareness, underdiagnosis, and inconsistent treatment adherence further complicate disease management. Despite these peculiarities, there is a significant paucity of robust, population-based data on severe asthma in the Indian context. Salvi and colleagues, in the AP-AIM study,[7] have observed the unique aspects of asthma treatment and control in India. A substantial majority (91%) of Indian asthmatics believed that their disease control was optimal, whereas none of them met the control criteria when evaluated by objective measures. Up to two unscheduled casualty visits a year was a routine norm for Indian patients, and they believed that this does not breach the definition of optimum control. Short courses of oral steroids (>10 times a year) were consumed by 85% of Indian asthmatics. There has been a paucity of data on the attitude of asthmatic patients toward therapy with monoclonal antibodies. The ARTWORK study looked at the acceptance and results of therapy with omalizumab in realworld South Indian settings. Improved asthma control and decreased frequency of exacerbation were noted in all patients during therapy that persisted during the 6month followup after cessation of therapy.[8] Data on the results of therapy with benralizumab in India is scarce.[9] Previous reviews have focused on the unique aspects of biologic use in Indian asthmatic patients.[10] This single-centre, prospective observational study was conducted to evaluate the real-world effectiveness of benralizumab in reducing the annual exacerbation rate in patients with SEA. This study aims to provide robust real-world data on the effectiveness of benralizumab in the Indian population, contributing to the growing body of evidence supporting precision biologic therapies in SEA and formulating individualized treatment strategies. The primary objective was to assess the impact of benralizumab on exacerbation frequency over a 12-month period. Secondary objectives included evaluating improvements in asthma control using the Asthma Control Test (ACT), reductions in maintenance oral corticosteroid (OCS) use, and identifying clinical predictors of asthma remission in patients receiving benralizumab therapy. Adult patients (aged ≥18 years) with a confirmed diagnosis of SEA—defined by an absolute eosinophil count (AEC) ≥300 cells/μL—who completed 12 months of benralizumab therapy with documented compliance were included. Exclusion criteria were patients with other chronic pulmonary conditions such as COPD, emphysema, or bronchiectasis, those with allergic bronchopulmonary aspergillosis, active malignancy, or immunodeficiency disorders. At baseline, comprehensive data were recorded, including demographic characteristics, comorbidities, personal habits, serum IgE levels, AEC, pulmonary function test results, annual exacerbation rates, and ACT scores. Patients were followed monthly for the first 3 months and subsequently at 2-month intervals. The primary and secondary outcome measures were assessed after 12 months of therapy and compared to corresponding parameters from the year prior to benralizumab initiation. Statistical analysis was performed using SPSS version 26 (IBM Corporation, Armonk, N.Y). The Wilcoxon signed-rank test was employed to compare pre- and post-treatment exacerbation rates and ACT scores, with a P < 0.05 considered statistically significant. Univariate analysis using the Chi-square test was conducted to identify independent clinical predictors of asthma remission. Ethical approval was obtained from the institutional ethics committee. The requirement for informed consent was waived off, as the study involved no deviation from standard clinical care. Table 1 provides the baseline characteristics of the study population.Table 1: Baseline characteristics of study subjectsA total of 25 patients with SEA who were initiated on benralizumab were followed up over a 12-month period to evaluate treatment outcomes. The results demonstrated significant and sustained improvements across all key clinical parameters. The mean ACT score showed a marked rise from 9.28 ± 3.4 at baseline to 16.88 ± 2.8 at the end of one year (P < 0.05), indicating a substantial enhancement in disease control. In parallel, the mean annual exacerbation rate declined from 5.76 ± 1.05 before initiation of benralizumab to 2.22 ± 1.08 at 12 months of therapy (P < 0.05), representing an approximate 62% reduction in exacerbations. This improvement was accompanied by a remarkable fall in hospitalizations, with the mean annual hospitalization rate decreasing from 2.72 ± 0.84 at baseline to 0.60 ± 0.48 following 1 year of treatment, suggesting that benralizumab effectively reduced severe exacerbations necessitating inpatient care and significantly alleviated the overall healthcare burden associated with uncontrolled asthma. A particularly striking finding was the sharp decline in maintenance OCS requirement following the initiation of therapy. At baseline, most patients required OCSs to maintain disease control, reflecting the severe and steroid-dependent nature of their asthma. Early and progressive reduction in systemic steroid use was observed soon after commencement of therapy, becoming apparent by the end of the second month. By the fourth month of treatment, nearly half of the study subjects were successfully weaned off maintenance OCSs and by 12 months, only 7 of the 25 patients (28%) remained on OCS therapy. The findings are summarised in Figures 1 and 2. This finding highlights the potent steroid-sparing effect of benralizumab, which not only facilitates improved asthma control but also minimizes the systemic side effects associated with chronic corticosteroid exposure. The early reduction in corticosteroid dependence reflects the rapid onset of clinical benefit that follows benralizumab’s near-complete eosinophil depletion, translating into better control of airway inflammation and reduced exacerbation frequency.Figure 1: Asthma outcomes prior to and after benralizumab therapy. Mean exacerbation rate and hospitalisation rate are annual valuesFigure 2: Number of study subjects who require maintenance systemic steroids as different time framesWe defined asthma remission based on the expert consensus framework[11] criteria, 2020. To identify baseline factors predictive of asthma remission with benralizumab, univariate analysis was performed. The analysis revealed that a total serum IgE value exceeding 600 IU/mL, an AEC above 500 cells/μL, and an asthma duration of less than three years were significantly associated with asthma remission (P < 0.05) [Table 2]. These associations suggest that patients with higher baseline type-2 inflammatory activity and shorter disease duration derive greater benefit from benralizumab therapy, emphasizing the importance of early biologic intervention in eligible individuals. Overall, benralizumab produced consistent and clinically meaningful improvements in asthma control, exacerbation prevention, hospitalization rates, and corticosteroid-sparing outcomes in this real-world Indian cohort.Table 2: Univariate analysis to identify the predictors of asthma remission with benralizumabAssessing the response to biologic therapy in SEA requires a comprehensive evaluation integrating clinical, functional, and biomarker-based parameters, supported by evidence from landmark trials.[12] Clinically, improvement in symptom control, reflected by validated tools such as the ACT or Asthma Control Questionnaire, along with reductions in exacerbation frequency, systemic corticosteroid use, and enhancement in health-related quality of life, are key indicators of therapeutic success. Objective measures, particularly an increase in pre-bronchodilator FEV1, further substantiate treatment efficacy. The Biologics Asthma Response Score[13] is a recently developed tool that grades response as good, moderate, or insufficient based on reductions in exacerbation rate. Benralizumab’s unique mechanism (IL-5Rα antagonism and eosinophil depletion) enables normalization of blood and sputum eosinophilia, even where prior anti–IL-5 therapeutic agents have failed. Pivotal trials, including SIROCCO and CALIMA,[2,3] have demonstrated that benralizumab achieves a ≥ 50% reduction in annual exacerbation rates in 70%–80% of patients, with up to 60% attaining complete exacerbation remission after 12 months of therapy. Additionally, mean improvements in pre-bronchodilator FEV1 of 200–340 ml and ACT score gains of 5–8 points were observed. These findings are further reinforced by real-world studies[14] reporting 60%–75% of patients achieving clinically meaningful responses, characterized by improved control, reduced corticosteroid dependence, and enhanced quality of life. Furthermore, the ORBE II and BPAP post-hoc analyses showed that nearly half of previously corticosteroid-dependent patients became OCS-free after 2 years of therapy and that 76% remained on benralizumab at 2 years, with 19% of patients being exacerbation-free, demonstrating durable clinical benefit even in treatment-experienced populations Thus, a multidimensional assessment combining clinical, functional, and biological endpoints, contextualized by robust trial evidence, provides the most reliable framework for evaluating and interpreting response to benralizumab in SEA. These results underpin the consistent, rapid, and sustained efficacy of benralizumab observed across multiple cohorts and subgroups, and position it as a valuable option for SEA—achieving clinical response rates up to 70%, marked reduction in exacerbations, and functional restoration in most patients. Finally, various slightly differing definitions of asthma remission have been employed in literature.[11,15-18] Most definitions incorporate one or more of the following criteria that must be satisfied - substantial reduction in asthma symptoms, absence of exacerbations, no need for systemic corticosteroids and stable lung function. However, subtle differences do exist in these criteria in individual definitions. Many of them do not address practical aspects that are of paramount importance to clinicians and patients, such as need of specific medications and quality-of-life outcomes. We employed the expert consensus framework criteria because of its global nature, employment of objective criteria and clinical relevance. To conclude, benralizumab provides excellent clinical outcomes in Indian patients with SEA including sizeable benefit in exacerbation rates, need for hospitalisation and asthma control. Early feasibility to wean systemic steroids is notable. The findings align with the results of multicentre landmark trials. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.