Asthma is one of the costliest diseases worldwide due to its high prevalence.

According to the Korean Academy of Asthma, Allergy and Clinical Immunology, asthma's direct and indirect costs are estimated to be around 4 trillion won ($2.85 billion). Patients with severe asthma have a 44.4 percent job interruption rate due to the threat of acute exacerbations. Acute exacerbations of asthma can be life-threatening with breathing difficulties, causing a significant burden on individuals and society.

Therefore, controlling asthma through treatment is cost-effective. According to the asthma awareness survey in eight Asia-Pacific countries, only 8 percent of Korean asthma patients are well-controlled.

A recent study analyzing the cost-effectiveness of Dupixent (dupilumab) in Korean patients with severe asthma was published in the international journal Health Economics Review.

Professor Rhee Chin-kook of the Department of Pulmonology and Critical Care Medicine at the Catholic University of Korea Seoul St. Mary's Hospital and his colleagues conducted the cost-effectiveness study, using data from the Korean subgroup of the pivotal phase 3 LIBERTY ASTHMA QUEST study and severe asthma patients at the hospital.

The study found Dupixent reduced 1,992 lifetime severe asthma exacerbations per patient compared to conventional treatment. This is significant, given that 47 percent of severe asthma patients in Korea have experienced acute exacerbations in the past year and complained about lost productivity.

Korea Biomedical Review caught up with Professor Rhee, who led the study, to learn more about its clinical value and the effect Dupixent could have on the Korean asthma treatment landscape.

Question: What is the problem with asthma treatment in Korea in general?

Answer: Inhalant treatment should be the foundation of asthma treatment, but it is under-prescribed in Korea. Even when it is prescribed, there is no reimbursement for outpatient disease and inhalant education. Compared to foreign countries, Korean doctors are paid less, so they must see many patients quickly. Asthma is often unrecognized by patients themselves, and there is not enough time to discuss the disease with them, leading to poor diagnosis.

Although secondary and tertiary healthcare institutions are better equipped than primary healthcare providers, Korea's highly polluted environment and four distinct seasons make for long in-between seasons and winters. These characteristics can lead to frequent viral infections and worsen asthma. These various factors affect the treatment of asthma in Korea.

Q: Are asthma patients more likely to have severe cases in Korea than abroad?

A: The line between mild and severe asthma is unclear. While diabetes and blood pressure take a long time to progress from mild to severe, some asthma is severe at the onset, some patients are severe and don't recognize it, and some patients think it's just a cold, but their lung function drops to 30-40 percent. In the end, there are not many severe cases per se, but rather a pattern of worsening and becoming severe due to missed opportunities to prevent or treat symptoms, such as “acute exacerbations” and “attacks,” which are part of the definition of severe asthma.

Q: What percentage of asthma patients in Korea have severe cases?

A: About 5-10 percent. Unlike overseas, where mild cases are often managed in primary care but inevitably progress to severe cases, severe asthma in Korea is often first diagnosed in the emergency room, which means that people are often diagnosed in the emergency room, having lost the opportunity to get adequate treatment earlier.

Q: What are severe symptoms, and what treatment should be sought? Also, how does this affect the patient socially and personally?

A: Acute exacerbation is the most dangerous event an asthma patient can experience. Symptoms, including extreme shortness of breath, hypoxia, fainting, and various forms of shock, characterize the clinical picture. At this point, most patients arrive at the hospital out of breath, and tests often show that their oxygen levels are too low to be dangerous without oxygen. In severe cases, respiratory failure often requires mechanical ventilation or admission to the intensive care unit.

Once this happens, it has a negative impact on the patient's health and socioeconomic status. Many asthma patients are young, economically active people who cannot work for one to two weeks after an acute exacerbation, suffering a significant economic loss.

Q: Does having an acute exacerbation increase the risk of repeating it?

A: Yes. Certain types of patients are prone to frequent acute exacerbations. If they continue to have recurrent episodes despite adequate treatment, they should be considered for treatment with a biologic, including Dupixent.

Q: Asthma is categorized into allergic and eosinophilic, and biologics are prescribed accordingly. Unlike other biologics, Dupixent inhibits IL-4 and IL-13. What makes it different?

A: Allergic asthma represents a small percentage of all severe asthma patients. In clinical practice, many older, non-allergic patients are not allergic. These patients are often unresponsive to existing treatments, including omalizumab, and need other treatment options, such as Dupixent.

Type 2 inflammatory asthma, which responds well to Dupixent, is caused by eosinophilic inflammation and inflammation of higher order, represented by increased fractional exhaled nitric oxide (FeNO). It is most seen in patients with middle-aged onsets and no pre-existing history of allergies. In Korea, the number of patients with type 2 inflammatory asthma is increasing due to the increasing number of older adults, posing a serious problem.

Dupixent is superior to existing drugs because it blocks interleukin (IL)-4 and IL-13, cytokines that are major contributors to type 2 inflammation, reducing eosinophilic inflammation at higher levels while lowering nitric oxide in airway epithelial cells and reducing allergic inflammation. That explains why Dupixent has a broader indication in asthma than omalizumab and IL-5 inhibitors. Omalizumab is indicated for severe allergic asthma, and IL-5 inhibitors are limited to eosinophilic asthma. In contrast, Dupixent is approved for eosinophilic asthma, asthma with increased exhaled nitric oxide, and severe asthma in patients who have been taking oral steroids for a long time.

Q: What was the rationale for conducting this cost-effectiveness study of Dupixent?

A: Biologics are expensive, and healthcare delivery systems and costs vary widely by country. Even if a drug is evaluated as cost-effective overseas, there may be differences when applied in Korea. For example, the cost of a commonly used three-drug inhaler for asthma differs by several orders of magnitude between Korea and the U.S. Therefore, it is not feasible to evaluate the cost-effectiveness of a drug in Korea and abroad on the same lines. We decided to conduct this study to determine the cost-effectiveness of drugs within the Korean fee-for-service system based on Korean asthma patients.

Q: Explain the study findings.

A: Dupixent is a costly medication, but its use can reduce acute exacerbations and ultimately significantly save healthcare costs. The medication cost was superior to reducing the disease burden due to fewer exacerbations. In today's environment, where severe asthma is undertreated, it should be recommended and used more than in other countries.

Q: The study showed Dupixent was more effective in Korea than abroad. Why is that?

A: In the QUEST phase 3 study, the reduction in asthma exacerbations was around 60 percent, whereas in Korea, it was over 90 percent. There are two main reasons for this.

First, in the overseas studies, most patients were Western and Caucasian, so the difference in outcomes may be due to racial differences compared to Asians. Second, it could be due to differences in healthcare delivery systems. In other countries, patients may not be treated at university hospitals and may be classified as having severe asthma when they are not. In Korea, the severity may be higher because specialists at tertiary hospitals diagnose many patients who have severe symptoms that do not respond well to inhalers. In addition, Korea has low medical fees and a well-organized healthcare delivery system compared to many other countries. To date, no clinical trials are comparing the ratio of foreigners to Koreans on a 1:1 basis, so we cannot definitively conclude any one reason, but we believe that it is a result of a combination of the characteristics of Korean and foreign patients and the differences in healthcare delivery systems in each country.

Q: How much can Dupixent treatment impact domestic healthcare cost savings?

A: When an acute exacerbation occurs, and a patient visits the emergency room or is hospitalized, the direct healthcare costs are significant, but the indirect economic losses due to disruption of socioeconomic activities are also massive. The benefits to patients and domestic insurance finances are many times greater than the cost of Dupixent, which in turn adds to the burden on society. A drug like Dupixent should be used, and the right conditions should be in place. Still, unfortunately, it is an unreasonable and contradictory situation for Dupixent not to be reimbursed.

Regrettably, anti-IL-5 inhibitors have recently been approved for coverage, but Dupixent is not. I once published a paper in the Journal of Allergy and Clinical Immunology (JACI), a journal of the American Academy of Allergy, Asthma, and Immunology (AAAAI), with several asthma experts from Korea and abroad. No countries were more economically developed than Korea, where Dupixent was not covered, and even in countries with much lower GDPs than Korea, the drug was covered. It was an embarrassing realization that we were almost the only country that didn't have access to Dupixent, and we published it in an influential paper. The lack of coverage for a drug that global experts recognize reflects a problem with our insurance policy and system.

Q: This study has no better economic analysis of the Korean situation.

A: In this study, we collected patient data from actual clinical practice and observed patients for several years. I was stunned to realize that acute exacerbations of asthma are very costly, which are a massive burden on both the individual patient and the country. The benefits are enormous if we can treat patients and improve their quality of life so they can be socially and economically active and live happily. It would be great for governments to take this into account.

When I do research, I usually focus on the medical side and don't have the opportunity to consider the cost or the actual patient experience. Collecting data directly through this study was a valuable and personal learning experience.

Q: It is also important to prevent asthma from progressing from mild to severe. How can primary healthcare providers improve their ability to diagnose it early?

A: The most realistic way to do this is to create a new medical fee for education on the use of inhalants. In addition, lung function tests are often not performed in primary care because their fees are so low. Pulmonary function tests at primary healthcare centers have recently been set at one-third lower than the previous price, so there is no incentive for testing.

To resolve this situation, the Korean Academy of Tuberculosis and Respiratory Diseases has proposed a protocol to the government through the “Asthma and COPD Chronic Disease Management Project”' to ensure systematic management of diabetes and hypertension, but it has not been implemented. We recently held a public hearing with Rep. Lee Ju-young on the same topic.

The only way for change to happen is to change the system. Patients, doctors, and other members of society must adapt to the system, so the system must be changed, and there is a way to do it. There are examples of successful outcomes in other countries. The reality is that respiratory chronic diseases are often underfunded and underpaid, even though they don't require as much money or effort as other chronic diseases.