Biological targeted therapy for severe asthma

Author: Su Xinming, Chief Physician/Professor, The First Affiliated Hospital of China Medical University

Reviewer: Zhou Xin, Chief Physician/Professor, First People's Hospital, Shanghai Jiao Tong University School of Medicine

What is severe asthma

Everyone is familiar with asthma. It is a chronic inflammatory disease of the airways, and its clinical manifestations include recurrent wheezing and shortness of breath, with or without chest tightness or cough. As for the concept of "severe asthma", many friends may have doubts: the symptoms are more severe when the disease occurs, and some laboratory indicators are particularly high when going to the hospital for examination. Is it severe asthma? In fact, severe asthma has a clear definition. The asthma remission treatment plan currently commonly used in asthma guidelines at home and abroad divides patients into 5 levels based on symptoms and disease control, and recommends medication according to the level. Among them, severe asthma patients refer to patients whose asthma symptoms cannot be controlled or still have acute exacerbations even after receiving the maximum dose of standardized drug treatment (the 4th or 5th step), and removing other related factors (such as irregular medication, etc.), or whose asthma symptoms deteriorate again when the drug is reduced.

Figure 1 Copyright image, no permission to reprint

In my country, patients with severe asthma cover a wide population, and their conditions are often complex and protracted, which imposes a heavy disease burden on patients' families and society.

Fortunately, thanks to the progress of science and technology, a new treatment method has been developed in recent years for patients with severe asthma who have stubborn conditions - targeted therapy with biological agents. Biological agents for the treatment of asthma can be divided into anti-immunoglobulin E antibodies, anti-interleukin 5, anti-interleukin 5 receptor antibodies and anti-interleukin 4 receptor antibodies according to their targets. The following article briefly introduces the appropriate population, usage and dosage, safety and other aspects of these biological agents.

Anti-Immunoglobulin E Monoclonal Antibody

Anti-Immunoglobulin E antibody, or omalizumab, is the first targeted therapeutic drug in the field of asthma. It was approved in my country in August 2017 and officially put into clinical use in my country in March 2018. Related studies have shown that omalizumab can make about 80% of allergic asthma patients free of daytime and nighttime asthma symptoms and no severe attacks within 1 year; about 60% of patients can reduce or stop oral hormones; long-term use can control asthma and stabilize the condition.

The drug is mainly suitable for adults, adolescents (≥12 years old) and children (6-12 years old) with allergic asthma mediated by immunoglobulin E. Generally speaking, the initial use of omalizumab needs to be continued for 12 to 16 weeks to evaluate its effectiveness. For patients who are indeed effective, the course of treatment should last for 12 months, during which the asthma control should be evaluated in the outpatient clinic every 3 months, including recent symptoms, lung function, etc.

At present, Omalizumab has been included in my country's medical insurance catalogue and its price has been greatly reduced, bringing new hope to patients with severe asthma whose symptoms are difficult to control.

Anti-IL-5 monoclonal antibody

Interleukin-5 is a cytokine that can regulate the growth and activation of eosinophils and is closely related to the pathogenesis of asthma. Anti-interleukin-5 antibodies can reduce eosinophil levels and reduce related inflammatory responses by binding to interleukin-5. Common drugs are mepolizumab and reslizumab, and the main indications are additional treatments for patients with severe eosinophilic asthma over 12 years old. Among them, mepolizumab was officially approved for marketing in China in November 2021. Related studies have shown that mepolizumab can reduce asthma attacks and reduce the amount of oral hormones taken by patients. Mepolizumab has good safety, and common adverse reactions are fever, headache, local reactions at the injection site, etc.

Anti-IL-5 receptor monoclonal antibody

Anti-interleukin-5 receptor antibodies can control asthma inflammation by consuming eosinophils in the blood and airways. This type of drug, benralizumab, was launched in the United States in 2018. Its main indication is additional treatment for severe eosinophilic asthma in patients over 12 years old. Clinical studies have shown that benralizumab can significantly reduce the frequency of exacerbations in patients with severe, uncontrolled eosinophilic asthma, and has good safety and few adverse reactions.

Anti-IL-4 receptor monoclonal antibody

Dupilumab, an anti-interleukin-4 receptor monoclonal antibody, can reduce eosinophil levels by blocking the interleukin-4 receptor-related pathway, thereby inhibiting airway inflammation. The drug was first launched globally in 2017 as a treatment for atopic dermatitis and is currently approved for add-on treatment of patients with moderate to severe eosinophilic or oral steroid-dependent asthma in people over 12 years of age. Common adverse reactions are injection site reactions, oropharyngeal pain, and eosinophilia.

Other biological targeted drugs

The above drugs are all included in the Global Asthma Prevention and Control Initiative and the Domestic Bronchial Asthma Prevention and Control Guidelines (2020 Edition). In addition, there are still a variety of biological targeted preparations that are still in asthma-related clinical research, such as prostaglandin D2 receptor antagonists and thymic stromal lymphopoietin antibodies. Among them, tezepelumab, a drug corresponding to thymic stromal lymphopoietin antibodies, was approved for marketing in the United States in November 2021. Related studies have shown that tezepelumab can not only reduce acute asthma attacks, reduce airway hyperresponsiveness, and improve lung function, but also reduce blood eosinophils, exhaled nitric oxide and total immunoglobulin E levels, indicating that it will affect multiple pathways of asthma (interleukin-4, interleukin-5, interleukin-13), and may become a more important therapeutic drug in the field of severe asthma in the future.

Biologics efficacy evaluation and medication course

Compared with traditional drugs, biological preparations have the advantages of more precise treatment and better efficacy, but they also have disadvantages such as long dosing intervals, the need to go to the hospital for injections, and inconvenient treatment. Therefore, for asthma patients, it is very important to follow the doctor's orders, receive treatment and follow-up on time, and actively communicate with the doctor to jointly evaluate the efficacy. Good treatment effects can increase patients' confidence and compliance in treatment; if the treatment effect is not good, patients should change to other treatment plans under the guidance of a doctor. In addition, there are currently no relevant guidelines to provide clear medication course recommendations for biological targeted treatment of asthma. If the patient is indeed effective after the efficacy evaluation period, the duration of medication can be determined under the doctor's advice based on factors such as the severity of the disease and economic situation.

Figure 2 Copyright image, no permission to reprint

For patients with severe asthma who cannot be controlled by conventional medications and whose quality of life has been severely reduced, the emergence of biologics has brought new possibilities and hope. At the same time, as a heterogeneous disease, the pathogenesis and phenotype of asthma patients are also different, and biologics also need to be selected and treated individually according to the patient's condition. In short, I believe that more and more patients with severe asthma will be able to get their asthma well controlled through targeted treatment with biologics, allowing them to breathe freely under the blue sky.

Figure 3 Copyright image, no permission to reprint