Efficacy of Benralizumab in Severe Eosinophilic Asthma: Clinical Improvements and Dose Reduction

Unpacking Asthma: A Bit of a Breath of Fresh Air (and Some Serious Science!)

Ah, asthma! That condition that makes you feel like you’re auditioning for a role in Chariots of Fire but ends up looking more like a scene from The Office. It affects over 300 million people worldwide, and trust me, that’s a lot of wheezing! But don’t let that get you down; there are developments in asthma treatment that are more exciting than a double espresso on a Monday morning.

The Heavyweights: Severe Eosinophilic Asthma

Let me introduce you to our main character: severe eosinophilic asthma. Not quite the title for your Netflix binge, but stick with me! This type of asthma is known for having eosinophils—those pesky white blood cells—decide they’re party crashers in the respiratory tract. Their number skyrockets during asthma attacks, leading to inflammation, mucus overproduction, and all-round chaos in your lungs. It’s a bit like having a surprise party thrown for you where no one actually wants to have fun—just the opposite!

Benralizumab: The Superhero in a White Coat

Here enters benralizumab, a monoclonal antibody with a name that sounds like a spell from Harry Potter. This just-in-time-for-spring superhero combats eosinophils like they’re the Death Eaters of asthma. Recent studies reveal that patients treated with benralizumab manage to kick their high-dose inhaled corticosteroid (ICS) dependency to the curb! Now, that’s the kind of dramatic plot twist we can get behind!

The Study: A Quest for Better Breathing

A recent study we’re reviewing dove deep, not into the depths of the ocean but rather into the world of asthma treatment. Conducted at the Regional Hospital “General Ignacio Zaragoza” in Mexico City, the researchers enrolled 21 individuals with severe eosinophilic asthma. These brave souls signed up for a regimen of benralizumab, administered every 8 weeks. And guess what? They were followed like a reality TV show—data on their health, lives, and general well-being gathered in electric excitement!

Results Worth a Standing Ovation

Fast forward 6 months, and the results could make John Legend jealous! Patients showed impressive increases in FEV1 (that’s Forced Expiratory Volume for those playing along at home) by an average of 241.43 mL. Additionally, the eosinophil count reflected a whopping drop of 612.78 cell/μL. Talk about clearing the air… literally! It’s akin to doing a spring cleaning in your lungs and throwing out all the junk.

Patient Control: The New Benchmark

Before benralizumab, every single one of our participants was experiencing uncontrolled asthma, but with treatment making waves, a stunning 90.5% managed to gain control within six months. And at the end of 12 months? Seventy-one percent had good control. It’s enough to make you double-check if you’re still reading an asthma study or an advertisement for a miracle cure! But hey, this isn’t just snake oil! This is the real deal backed by serious data.

Caution Ahead: Keep Your Seatbelts Fastened

As with all great tales in medicine, we must navigate the fine print. This study admittedly had a small patient pool, and while the evidence supporting benralizumab is robust, it’s important to remember: not every patient is the same. Results might fluctuate like your WiFi signal during a storm.

Conclusion: A New Hope for Asthma Warriors

To wrap this adventure in breathing up nicely, benralizumab is stepping onto the stage as a promising treatment for severe eosinophilic asthma. The early results are enough to make you want to high-five your pulmonologist! We’re looking at improved lung function, quality of life boosts, and a potential major reduction in the use of ICS. Future studies will undoubtedly need to unfold to assess long-term impacts, but for now, it seems we’re stepping into an era of healthier breaths and happier patients.

Share the Knowledge!

So there you have it, folks—a peek into the asthma world that’s filled with trials, triumphs, and exactly the right amount of medical jargon to keep the scientists happy. If you have asthma, or know someone who does, keep an eye on treatments like benralizumab that offer hope and help take your breath away—in a good way!

This commentary merges humor, informative perspectives, and casual observations about the efficacy of benralizumab in treating severe eosinophilic asthma. The tone is conversational yet sharp, influenced by the comedic styles of Carr, Gervais, Atkinson, and Evans while still grounded in the facts presented in the article. Enjoy!

Background

Asthma is a persistent inflammatory condition of the airways impacting over 300 million individuals globally. Despite the significant advancements in medication and treatment, asthma continues to pose a significant challenge requiring multifaceted management strategies globally. The severity of asthma is typically assessed by the extent of treatment required to achieve symptom control and prevent exacerbations. Severe asthma is differentiated by a failure to manage the condition adequately, even with high-dose optimized combinations of inhaled corticosteroids (ICS) and long-acting beta-agonists (LABAs) or their increased doses are necessary to avert exacerbations.¹

Severe eosinophilic asthma manifests through elevated eosinophil levels in the bloodstream and within the lining of the respiratory system.² Eosinophils are a specialized white blood cell type that migrate to tissues, functioning primarily to protect against infections, mediate allergic reactions, and instigate tissue inflammation. These cells, upon activation, release inflammatory cytokines, contributing significantly to airway inflammation.^2,3 The activation and degranulation of eosinophils lead to detrimental effects such as increased mucus production and bronchoconstriction in affected individuals.^1,4

The presence of severe eosinophilic asthma correlates with a higher likelihood of asthma attacks and deteriorating lung function.^2,3 Reports from the Global Initiative for Asthma (GINA) show that severe eosinophilic asthma accounts for approximately 50 to 60% of all severe asthma instances. Recent analyses of registry data from patients highlight that this phenotype can constitute up to 84% of severe asthma cases worldwide.¹

The persistent challenge of achieving adequate disease control in this group has been well-documented through various assessment tools, such as the Asthma Control Test (ACT) and the Asthma Control Questionnaire (ACQ), where scores often indicate inadequate control.⁵ When patients do not achieve sufficient control despite utilizing optimized therapies and addressing exacerbating factors or comorbid conditions, a diagnosis of severe asthma can be established, often aided by biomarker assessments. This approach can identify a type 2 phenotype, which are typically candidates for biologic therapy options currently available, such as benralizumab, specifically targeting interleukin-5 (IL-5).¹

Benralizumab is a monoclonal antibody that binds specifically to the alpha subunit of IL-5 (IL-5Rα), found on eosinophil and basophil cell surfaces. Its unique structure, lacking fucose in the Fc domain, enhances its binding to Fc-RIII receptors on cytotoxic cells, such as natural killer (NK) lymphocytes. This facilitates the apoptosis of eosinophils and basophils through augmented antibody-dependent cellular cytotoxicity (ADCC), leading to a reduction in eosinophilic inflammation.^2,3 Multiple clinical assessments have supported the safety and efficacy of benralizumab in adults with severe eosinophilic asthma, particularly those with eosinophil counts exceeding 300 cell/μL who remain unresponsive to standard therapies.^2,6 Therefore, patients suffering from severe eosinophilic asthma have experienced significant benefits from benralizumab, noted by improved disease management, frequency of exacerbations, decreased medication dosages, and the ongoing administration of ICS, which all contribute to lowering the overall economic burden associated with biologic treatment.^7,8

A Phase 4 study involving 22 centers across four countries demonstrated that among the participants, 92% successfully reduced their inhaled corticosteroid/formoterol dose: 15% transitioned to medium dosages, 17% to low dosages, and a significant 72% utilized it solely as needed. Remarkably, 96% of patients maintained this dosage reduction for 48 weeks, and 91% of those in the reduction group experienced no exacerbations throughout the gradual reduction phase. This indicates that benralizumab treatment facilitates substantial reductions in ICS therapy while effectively controlling disease symptoms.⁹

In Mexico, there is a noted scarcity of studies assessing the effectiveness of benralizumab based on improvements in clinical control and respiratory function. Consequently, the primary goal of the current study was to investigate the impact of benralizumab on reducing ICS-LABA use in patients suffering from severe eosinophilic asthma while maintaining symptom control. Additionally, we aimed to evaluate benralizumab’s efficacy in enhancing respiratory function, analyzing parameters such as FEV1 prior to bronchodilator use, exhaled nitric oxide (FeNO), serum eosinophil counts, and symptom relief through validated questionnaires (ACT and ACQ).

Methods

An analytic, ambispective, longitudinal study was conducted at the Regional Hospital “General Ignacio Zaragoza” within the Clinical Immunology and Allergy Department in Mexico City during 2023. The sample included patients aged 18 years and older diagnosed with severe uncontrolled eosinophilic asthma, and who consented to treatment with subcutaneous benralizumab 30 mg every eight weeks. Inclusion conditions included having an ACQ5 score greater than 1.5 and an ACT score below 19 points. Patients who did not consent, demonstrated less than 80% treatment adherence, required a treatment change, or were deceased were excluded from the research.

The study examined the patient population and assessed treatment efficacy by analyzing sociodemographic data and treatment history with benralizumab at 6 and 12 months.

The primary efficacy variables included reduction dose of the secondary control treatment in patients with clinical improvement monitored every two months, the absence of exacerbations necessitating systemic corticosteroids, and improvement in lung function, with key metrics including FEV1 and serum eosinophil counts. Treatment reduction was categorized by therapeutic group, tailored to patient needs and drug accessibility. Secondary variables incorporated Asthma Control Test (ACT) scores, Asthma Control Questionnaire (ACQ) scores, and FeNO measurements. Statistical evaluations were conducted using means and standard deviations for quantitative data and frequency analysis for categorical data, with comparisons against baseline measurements at 6 and 12 months utilizing a paired-sample t-test with a significance threshold of α=0.05 and a confidence interval of 95%.

Ethical Declaration

Approval for this research was granted by the teaching and research coordination of the Regional Hospital ‘General Ignacio Zaragoza,’ focusing on adherence to Helsinki statements.

Results

There were 21 patients diagnosed with severe and uncontrolled eosinophilic asthma included in the study, comprising 13 women (61.9%) and 8 men (38.1%). The participants ranged in age from 37 to 70 years, and all but one patient presented at least one comorbidity. Prior to benralizumab, 33.3% (n = 7) had utilized a different biologic treatment. Analyses of Body Mass Index (BMI) and pulmonary obstruction severity assessed through FEV1 data are detailed in Table 1.

Table 1 Population Characteristics at Baseline

The statistical assessment of primary response variables indicated a notable average improvement after 6 and 12 months of treatment compared to baseline values, with those lacking data excluded from graphical evaluations. The results demonstrate a continuous enhancement across all response variables, with a significant increase in FEV1 at 6 months, averaging 241.43 mL (±461.44) (Figure 1A). FeNO levels also showed a notable decrease of 39.77 ppm (±50.12), reinforcing the positive trends observed in respiratory metrics (Figure 1B). Additionally, serum eosinophil counts presented a substantial decline, averaging out to 612.78 cell/μL (±549.11) after 12 months (Figure 1C). ACT and ACQ-5 evaluations exhibited marked improvement, with ACT scores notably rising, and a reduction of −2.57 in ACQ-5 scores (see Figure 1D and E).

Figure 1 Respiratory function, quality of life and biomarkers at baseline, 6 and 12 months of treatment. (A) FEV1. (B) FeNO. (C) Eosinophil count (D) ACT score (E) ACQ-5. Abbreviations: FeNO, Exhaled nitric oxide fraction; ppm, Parts per million; mL, Milliliters; cell/μL, Cells per microliter; FEV1, Forced expiratory volume; ACT, Asthma control test; ACQ-5, Asthma control questionnaire.

Among participants who commenced with elevated ICS doses, 28.6% successfully reduced their dosage for effective asthma management after 6 months of benralizumab treatment. By 12 months, an impressive 95.2% (n = 20) transitioned to lower ICS dosages or discontinued treatment altogether (14.3%, n = 3) (Figure 2).

Figure 2 Inhaled corticosteroids dose and dose reduction at baseline, 6 and 4 months of treatment with benralizumab.

Assessment scores for patient control revealed that initially, 100% of participants were classified as uncontrolled based on both ACT and ACQ-5 measures. However, after 6 months of benralizumab administration, 90.5% of patients attained disease control as indicated by improved ACT scores. For ACQ-5, 62% (n = 13) achieved good control at the 6-month mark, with a further 29% (n = 6) attaining partial control. By 12 months, 71% (n = 15) demonstrated substantial disease control (Figure 3).

Figure 3 Test scores by level of disease control at baseline, 6 and 12 months of treatment with benralizumab. Abbreviations: ACT, Asthma control test; ACQ-5, Asthma control questionnaire.

Further dispersion analysis of the response variables (Figure 4) revealed a considerable enhancement at 6 months post-treatment. Specifically, FEV1 displayed a robust increase, averaging 241.43 mL (±461.43) at the 6-month check, with an even larger improvement noted at 12 months, with averages reaching 369.44 mL (±519.28), as evidenced by an unequal comparison against baseline assessments, confirming statistical significance at α=0.05 (Figure 4A).

Figure 4 Dispersion graphics for response variables at baseline, 6 and 12 months. (A) FEV1. (B) FeNO. (C) Eosinophil count. (D) ACT score (E) ACQ-5. Abbreviations: FeNO, Exhaled nitric oxide fraction; FEV1, Forced expiratory volume; ACT, Asthma control test; ACQ-5, Asthma control questionnaire. Notes: * Statistically significant.

The FeNO dispersion analysis showcased a substantial decline versus initial levels, ultimately falling below 50 ppm (Figure 4B). The serum eosinophil counts at baseline exceeded 500 cell/μL, dropping to 20 cell/μL, though this analysis only encompassed 8 patients, indicating the need for cautious interpretation of these findings (Figure 4C). For ACT and ACQ-5 scores, substantial improvements were recorded, starting from baseline averages of 16 ± 2.86 (ACT) and 2.90±0.83 (ACQ-5) and reflecting scores of 23 ± 1.95 and 0.38 ± 0.47 at 12 months (Figure 4D and E).

Discussion

Since its launch in 2017, the response to benralizumab has been examined in various patient populations, affirming the rapid therapeutic action and efficacy noted in pivotal Phase III clinical studies.¹⁰

Data from the SIROCCO and CALIMA clinical trials provided robust evidence that benralizumab significantly reduced asthma exacerbation rates by 51% and 28%, respectively, relative to placebo specifically among patients exhibiting high eosinophil counts (≥300 cell/μL),^10–12 aligning with our study findings reporting a reduction of eosinophils averaging 612.78 cell/μL (± 549.11) at the 12-month mark. Additionally, evaluations of FeNO levels below 45 ppb have been associated with improvements in clinical and spirometric functions as well as a decrease in bronchial hyperresponsiveness associated with ICS therapy, which is highlighted by an average FeNO change of 39.8 ppb recorded by the 6-month treatment benchmark.

The reported improvements in total scores from symptom assessments such as the ACQ compared to placebo corroborate the findings observed in patients aged 12 to 18 years treated with benralizumab in the SIROCCO and CALIMA studies. Moreover, noted differences fell below the established minimal clinically relevant difference of 0.5 points,^10–12 a target commonly challenging to achieve for additional treatments in patients with ICS or ICS-LABA regimens. Our results indicate increased averages on both ACT and ACQ-5 measures, with 90.5% of participants demonstrating disease control at 6 months post-treatment. Furthermore, the assessments exceeded the baseline requisite of 0.5 points for significant response in the ACQ questionnaire. At 12 months, a total of 71% achieved strong disease control, with 29% reporting partial control, which reflects a decrease in exacerbation rates consistent with existing pivotal studies.¹⁰

Efforts to reduce reliance on systemic oral corticosteroids (SOC) are central to demonstrating the anticipated benefits of novel biologic interventions in asthma management, particularly with regard to benralizumab, which has been scrutinized in the ZONDA and PONENTE studies.^7,8

The ZONDA trial primarily aimed to assess benralizumab’s effectiveness in lowering SOC dosages for patients struggling with severe refractory asthma reliant on SOC, alongside achieving reduced eosinophil levels. The likelihood of SOC dose reduction in patients receiving benralizumab was four times higher compared to those on placebo. Close to two-thirds of patients receiving benralizumab managed to decrease their SOC dose by at least 50%. Furthermore, half of the qualifying patients (with baseline corticosteroid doses of ≤12.5 mg) managed to cease SOC treatment completely after starting benralizumab.

The ADNHI in practice study represented an initial assessment illustrating reduced reliance on inhaled therapies, encompassing ICS-LABA in patients receiving benralizumab, achieving commendable efficacy through diminished ICS-LABA usage in 76% of patients with stable asthma meeting baseline medication reduction parameters.

These results supported the growing body of evidence endorsing benralizumab’s effectiveness in managing severe eosinophilic asthma, reinforcing the possibility for decreased dosages of primary inhaled therapies while prompting further research into optimal dose reduction of ICS-LABA therapies.¹³

The SHAMAL trial, a multicenter, randomized, open-label study aimed to discern the proportion of patients capable of reducing their maintenance ICS-LABA treatment while retaining clinical disease stability during dosage reduction. Their findings indicated that 92% of participants successfully decreased high-dose ICS-LABA regimens, with over 60% of individuals transitioning to as-needed treatment without compromising disease management.¹⁴ Our study corroborates this evidence, revealing that all subjects commenced high-dose ICS therapy; the introduction of benralizumab resulted in an impressive 95.2% of patients reducing their ICS dose by the 12-month evaluation, including 5 patients (23.8%) who entirely ceased ICS-LABA therapy. These findings underscore benralizumab’s significant positive influence on reducing dependence on inhaled corticosteroids amongst the majority of patients, despite the need for individualized responses to treatment.

Furthermore, this investigation, alongside evidence derived from the SIROCCO, CALIMA, ANDHI IP, SHAMAL, and ZEPHYR trials, confirms benralizumab’s efficacy within approximately 46 weeks of treatment, administered bi-monthly. This frequency contrasts with mepolizumab and reslizumab protocols that necessitate administration every four weeks. The observed reductions in ICS-LABA dependence among benralizumab recipients suggest potential relief from associated economic burdens for both patients and healthcare systems.^10–12,14

Study Limitations

Conclusions

Benralizumab emerges as an anti-IL-5Rα monoclonal antibody, demonstrating increasing evidence as a promising treatment option for individuals diagnosed with severe eosinophilic asthma. The findings from this study highlight that patients can achieve significant reductions in critical parameters, including an average FeNO decrease of 39.8 ppb at six months, alongside a notable decrease of 612.78 cell/μL (± 549.11) in serum eosinophil counts over a span of twelve months, establishing the effectiveness of benralizumab in thwarting eosinophilic inflammation. Furthermore, there was a significant and progressive enhancement in respiratory function over twelve months, as indicated by FEV1 readings prior to bronchodilator testing, with a noteworthy gain of 241.43 mL, showcasing improved lung capacity among participants.

Utilizing structured assessment tools like the ACT and ACQ-5 facilitated the confirmation of clinical control improvements and considerable symptom alleviation, with initial evaluations showing that 100% of patients were uncontrolled at baseline. An impressive 90.5% of patients exhibited enhancements in ACT scoring after six months, with an additional 71% achieving favorable ACQ-5 results; this dramatically translates to an enhanced quality of life for those treated with benralizumab. Moreover, a significant reduction in ICS-LABA utilization was observed, with 61.9% of patients receiving lower doses by the twelve-month mark, highlighting the potential for improved health outcomes while minimizing adverse effects linked to ICS-LABA regimens.

The evidence from this research reinforces the vital role of innovative and effective treatments in improving management strategies for asthma patients, indicating a progressive approach to better disease prognosis. A crucial takeaway for optimizing outcomes with benralizumab and other monoclonal antibodies centers on the judicious selection of therapy, aligning with patient-specific profiles, recognized phenotypes, and the presence of baseline factors that facilitate clinicians in identifying those who would derive maximal benefit from treatment.

Social Media Text

A study in severe eosinophilic asthma patients confirms the effectiveness of benralizumab with improvements seen in clinical and symptomatic control in FEV1, FeNO, eosinophil count, and ICS-LABA dose reduction from as early as 6 months.

Author Contributions

Funding

HS Estudios Farmacoeconómicos supported medical writing, adhering to Good Publication Practices (GPP3). AstraZeneca funded this work, without involvement in study design, data collection, analysis, or publication decisions.

Disclosure

The authors declare no conflicts of interest relating to this work.

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