The Future of Asthma Treatment: The Impact of Monoclonal Antibodies

Asthma remains a significant global health concern, affecting an estimated 262 million people worldwide as of 2019 and causing approximately 455,000 deaths annually (World Health Organization (WHO)). The prevalence and impact of asthma vary significantly across different regions and are influenced by factors such as air quality, healthcare access, and socioeconomic conditions.

For instance, asthma prevalence in different continents has been reported with varying rates: 3.44% in Asia, 3.67% in Africa, 4.90% in South America, 5.69% in Europe, 8.29% in North America, and 8.33% in Oceania. These differences are also reflected in the disparities observed within countries based on their air quality and healthcare quality indices. Countries with better air quality and healthcare systems tend to report higher asthma prevalence, likely due to better diagnosis and reporting practices (AJMC).

In India, asthma affects a considerable portion of the population, with urbanisation and air pollution cited as significant contributors to the rising prevalence. The challenge in India, as in many lower-middle-income countries, is the under-diagnosis and under-treatment of the disease, which exacerbates the health burden on the population (World Health Organization (WHO)) (AJMC).

A case history -
A 38-year-old male with a long-standing history of asthma, was managed on high-dose inhaled corticosteroids and long-acting beta agonists, remained severely symptomatic despite adhering strictly to his medication regimen and avoiding known triggers. He experienced frequent exacerbations that required systemic steroids and multiple hospital admissions each year, significantly impacting his quality of life. A thorough evaluation was undertaken to explore the cause of his poorly controlled asthma. This included ruling out differential diagnoses such as chronic obstructive pulmonary disease (COPD), allergic bronchopulmonary aspergillosis (ABPA), and vocal cord dysfunction, which can mimic or exacerbate asthma symptoms. Comprehensive testing included spirometry, chest imaging, blood tests for eosinophils, and IgE levels, as well as assessments for occupational hazards and gastroesophageal reflux disease.

With other potential diagnoses excluded and the identification of high eosinophilic activity in his blood, the patient was considered a suitable candidate for monoclonal antibody therapy. He was started on mepolizumab, a monoclonal antibody that targets IL-5, which plays a crucial role in eosinophil maturation and survival. Within months of initiating this treatment, there was a notable decrease in the frequency and severity of his exacerbations. His reliance on oral corticosteroids decreased, and follow-up visits showed significant improvement in his lung function tests and overall quality of life. This case highlights the importance of precise patient profiling and the impactful role of targeted therapies like monoclonal antibodies in transforming the management of severe asthma.

Here's a summary of the main types of monoclonal antibodies used in asthma, categorised by their mechanism of action, indications, usage frequency, and duration of therapy:

Omalizumab:
At the forefront of monoclonal antibody therapy for asthma is Omalizumab. Its mechanism involves binding to immunoglobulin E (IgE), thwarting its attachment to mast cells and basophils. By doing so, Omalizumab effectively dampens allergic responses, making it a valuable asset in the management of severe allergic asthma unresponsive to high-dose inhaled corticosteroids. Typically administered via subcutaneous injection every 2 to 4 weeks, Omalizumab offers long-term relief, with treatment duration tailored to individual clinical responses and ongoing needs.

Mepolizumab:
Targeting interleukin-5 (IL-5), Mepolizumab takes aim at eosinophils, pivotal players in eosinophilic asthma. By reducing eosinophil production and survival, Mepolizumab presents a compelling option for severe eosinophilic asthma cases. Administered subcutaneously every 4 weeks, its efficacy and tolerance are periodically evaluated, guiding treatment continuation

Reslizumab:
Similar to Mepolizumab, Reslizumab also targets IL-5 to diminish eosinophil counts. Primarily indicated for adults with severe eosinophilic asthma, Reslizumab stands out for its intravenous infusion every 4 weeks, offering a long-term treatment strategy contingent upon ongoing clinical assessments.

Benralizumab:
Distinguished by its unique mechanism, Benralizumab binds to the IL-5 receptor α on eosinophils and basophils, inducing apoptosis or programmed cell death. This makes it a potent option for severe eosinophilic asthma cases. Initially administered every 4 weeks for the first three doses, then spaced to every 8 weeks, Benralizumab's effectiveness is regularly monitored to ensure optimal patient outcomes.

Dupilumab:
Inhibiting the signaling of both interleukins 4 and 13 (IL-4 and IL-13), Dupilumab offers a broad approach to asthma management. Its utility extends to moderate-to-severe eosinophilic or steroid-dependent asthma cases. Administered every 2 weeks via subcutaneous injection, Dupilumab's ongoing use is contingent upon patient response and clinical necessity.

Assessment of therapy -
The success of therapy with monoclonal antibodies in asthma treatment is assessed through a combination of clinical evaluation and specific measurable outcomes. Here are the key parameters used to determine the efficacy of these therapies:

Reduction in exacerbation rate stands as a primary measure, showcasing a significant decrease in both frequency and severity of asthma exacerbations, particularly crucial for severe asthma patients with a history of frequent hospital visits. Improvement in lung function, evaluated through objective measures like spirometry, specifically focusing on parameters such as Forced Expiratory Volume in 1 second (FEV1), reflects the treatment's effectiveness in enhancing pulmonary capabilities. Symptom control, evidenced by reduced wheezing, coughing, and shortness of breath, is tracked through patient symptom diaries and validated questionnaires like the Asthma Control Test (ACT) or Asthma Control Questionnaire (ACQ). Enhancements in quality of life, assessed using tools such as the Asthma Quality of Life Questionnaire (AQLQ), mirror the broader impacts of treatment on daily activities, emotional well-being, and overall health status. Successful outcomes also include a reduction in oral corticosteroid use for patients previously dependent on these drugs, known for their significant side effects with long-term use. Decreased healthcare utilization, demonstrated by fewer emergency room visits, hospitalizations, and unscheduled doctor visits, further underscores the efficacy of monoclonal antibody therapy. Monitoring specific biomarkers such as eosinophil counts in blood and fractional exhaled nitric oxide (FeNO) provides objective data on immunological changes throughout the treatment course. Additionally, ensuring safety and tolerability of the treatment through vigilant monitoring for adverse effects is imperative, as a successful therapy must not only be effective but also safe for long-term use.

Call for Action For patients experiencing severe asthma, monoclonal antibody therapy offers a promising alternative to traditional treatments. If you or someone you know is struggling with asthma management, consider discussing monoclonal antibody therapy with your Pulmonologist to explore this advanced treatment option.

By - Dr. Pavan Yadav, Lead Consultant - Interventional Pulmonology & Lung Transplantation, Aster RV Hospital