‘Adtralza with adjustable dosing intervals increases satisfaction of people with atopic dermatitis’

With more than 970,000 people living with atopic dermatitis in Korea, there is a growing need for effective treatment options tailored to individualized symptoms and signs.

Atopic dermatitis is a chronic inflammatory skin disease characterized by flare-ups and remissions, so continuous management is essential. Since each patient responds differently to treatment, it is important to utilize various treatment options.

Adtralza (tralokinumab), launched in May, is a new treatment alternative. As the first fully human immunoglobulin G4 (IgG4) monoclonal antibody to selectively target IL-13, Adtralza binds to IL-13 with high affinity, preventing its interaction with IL-13Rα1 and blocking IL-13 downstream signaling.

The recently published long-extended clinical trial study (ECZTEND) and the global real-world study (TRACE) reported Adtralza's efficacy and safety.

In the ECZTEND study, 93 percent of patients maintained a high level of symptom improvement (EASI-75 or higher) over six years of long-term treatment, and the study confirmed safety over three years in adolescent patients. Notably, the six-year long-term safety profile was similar to the initial placebo-controlled treatment period. It was well tolerated, with no new safety signals.

The TRACE study, which was participated in by 167 institutions in 11 countries, showed particularly strong improvements in facial and neck lesions. Among patients with lesions in these areas, 33 percent had complete clearance after three months of treatment, 42 percent after six months, and approximately 48 percent after nine months, with significant reductions in pruritus scores from 6.3 to 3.3 and EASI (Eczema Area and Severity Index) scores from 20.1 to 3.6.

Based on these clinical benefits and safety, Adtralza is recommended in national and international guidelines for treating atopic dermatitis in adolescents and adults and is used for treating moderate-to-severe atopic dermatitis in Korea, the United States, Canada, many European countries, the Middle East, and Japan.

Korea Biomedical Review met with Professor Lee Dong-hun of the Department of Dermatology at Seoul National University Hospital, who participated in the phase 3 clinical trial study (ECZTRA) of Adtralza, to learn about its effectiveness and value in clinical practice, as well as the status and future of atopic dermatitis treatment in Korea.

Question: The number of atopic dermatitis patients in Korea is steadily increasing. How does the disease develop and what challenges do patients face?

Answer: First, in terms of prevalence, about 10 percent of school-age children and 3 percent of adults in Korea have atopic dermatitis. In recent years, the course of the disease has changed a lot. In the past, it was thought to get better with age, but nowadays, there are more new cases in the 40s and 50s. It is also not uncommon for patients to recover from the disease in childhood and then relapse in adulthood, and there are cases of first-time cases in the 60s and older.

The burden on patients in terms of quality of life is also significant. National and international studies have shown that atopic dermatitis patients have difficulty with daily activities, work, and relationships due to itching. Many patients also complain of mental distress, including depression and anxiety. Therefore, in recent clinical trials, not only symptomatic improvement but also improvement in patient's quality of life are essential endpoints when evaluating the effectiveness of treatment.

Q: What are some of the factors that weigh on patients in terms of quality of life?

A: In childhood and adolescence, the disease often affects folds, such as the elbows and knees, which are relatively inconspicuous and may have less impact on daily life.

However, in adults, lesions often occur in exposed areas, such as the face, neck, hands, and feet. In these cases, the psychological burden on the patient is much greater and interferes with their social life. Although it’s important to control itching, treating and managing the exposed areas is especially important, as this is directly related to the patient’s quality of life.

Q: What are the drug treatment options for atopic dermatitis, and what are their characteristics?

A: Treatments can be divided into two main categories: topical and systemic. In mild cases of atopic dermatitis that affect the face or neck, topical treatments, including steroids or non-steroidal immunomodulators, are used. However, systemic treatments are needed if the disease progresses to moderate or severe.

Traditionally, immunosuppressants, including cyclosporine or methotrexate, are used. However, these drugs can affect the liver and heart and have side effects, such as increased blood pressure, making long-term use difficult.

New therapies have been developed in the last decade as research into the mechanisms and inflammatory pathways of atopic dermatitis has increased. These include the biologic Adtralza, injectable drugs, including dupilumab (Dupixent), and oral drugs, such as the JAK inhibitors upadacitinib (Rinvoq in trademark name) and abrocitinib (Cibinqo).

Biologics have the advantage of being safer, do not require regular blood tests, and can be combined with other medications. JAK inhibitors are convenient because they can be taken orally and work faster than biologics but require regular blood tests.

Q: With so many treatment options, what are Adtralza’s characteristics, and to whom is it mainly prescribed?

A: Adtralza is a drug that blocks IL-13, a key trigger for atopic dermatitis. As a clinician involved in trials, I see some notable features.

First, the dosing interval is adjustable. Unlike the existing biologic dupilumab, which requires injections every two weeks, Adtralza can be given every four weeks after 16 weeks if symptoms are well controlled. This is convenient, as patients often find frequent injections burdensome.

Second, it has advantages in terms of side effects. While dupilumab can cause redness of the face or neck and conjunctivitis in some patients, Adtralza has a relatively low incidence of these side effects. It may be a good option, especially for patients with a history of conjunctivitis.

From a cost perspective, it is also less expensive for patients (compared to traditional biologics). Long-term administration does not result in benefit cuts, making it suitable for patients who need ongoing treatment. As more real-world clinical data is accumulated, the evidence for efficacy will become clearer.

Q: Are there any notable clinical data on the effectiveness of Adtralza?

A: The results of the ECZTEND study, a long-term study of Adtralza, are noteworthy. The study looked at the long-term effects of treatment for six years, and 93 percent of patients maintained a 75 percent or greater reduction in the Eczema Area and Severity Index (EASI). This means that more than nine out of 10 patients responded well.

A three-year extension study in adolescent patients also showed positive results. Both efficacy and safety have been well established, and importantly, long-term use has been stable and not significantly different from the initial clinical trials.

Q: How safe is Adtralza in long-term use?

A: Adtralza has six years of long-term study data; extension studies are ongoing. It is very encouraging to see that no significant safety issues or adverse events have been reported in the five—to six-year data, suggesting that there are no significant safety concerns with continued use.

For comparison, the older drug dupilumab has five to six years of published data. In addition, Adtralza was approved and used in some countries, including Europe, two to three years earlier than in Korea, and no significant safety issues have been reported in those countries. Therefore, long-term use is not a problem for patients who respond well to the drug.

Q: What is the awareness of Adtralza among patients, and what are their clinical experiences?

A: Adtralza has been available in Korea since July this year, and patients have used it for only four to five months. Compared to dupilumab, which has existed for more than four years, awareness is not yet high.

In clinical practice, Adtralza is working as well as it has in clinical studies and real-world data. In particular, the adjustable dosing interval is a big advantage. Initially, you can dose every two weeks and then adjust the interval after 16 weeks, which gives you more flexibility for uninsured patients. Patients who have increased their dosing intervals due to cost considerations are happy with the results.

To qualify for reimbursement, patients usually need to be on a conventional immunomodulator for three to four months before they can qualify for a reimbursement exception. However, it is often prescribed without reimbursement for patients with less severe cases because the existing treatment is insufficient. Still, the long-term use of immunomodulators is burdensome. In these cases, price is an important consideration, as well as efficacy and safety, and many patients prefer Adtralza because of the significant cost difference over long-term treatment.

Q: For patients with insurance coverage, switching to four-weekly dosing after 16 weeks is possible, but how many patients take advantage of this benefit?

A: It's too early to know exactly how many patients will switch to four-weekly dosing after 16 weeks, as we've only been prescribing Adtralza for about four months. However, based on patient response to date, we expect many patients to switch to four-weekly dosing in the future.

Importantly, increasing the dosing interval does not significantly reduce treatment effectiveness. Patients are concerned about the burden of frequent injections and clinic visits. They find it inconvenient to carry syringes with them when traveling or on business trips, which is greatly reduced by switching to a four-week interval. Therefore, increasing the dosing interval may be a good option for well-tolerated patients.

Q: What areas of the current atopic dermatitis treatment landscape could be improved?

A: Currently, atopic dermatitis treatment has very limited cross-drug interactions. Even if a drug lacks efficacy or causes side effects, a new insurance review is required to switch to a different drug. This is different from the treatment of psoriasis. In psoriasis, drug crossovers are possible and common, and there is a lot of discussion about expanding coverage, including exposed areas in the moderate criteria. Expect these discussions to be further refined in the coming year.

Q: As a clinician, how do you feel about allowing a one-time switching of atopic dermatitis medications?

A: Currently, six atopic dermatitis drugs are approved in Korea, three biologics, and three other drugs. Allowing only one replacement may not be enough in practice. If you find a treatment that works well, you may not need to switch, but if it becomes ineffective or has side effects, you need more opportunities to find the best drug for you. Of course, appropriate criteria are needed, but a more flexible approach is needed rather than overly limiting the number of switches.

Q: New atopic dermatitis medications are constantly emerging. How do you see the treatment landscape for atopic dermatitis improving in the future?

A: The current definition of severe atopic dermatitis, an EASI score of 23, must be reconsidered. Even with an EASI score of 16 to 23, patients with a severe itch index of seven or higher have a significantly reduced quality of life, and many of them are uninsured. Systemic improvements are needed to ensure these patients access appropriate treatment.

None of the six currently available treatments is 100 percent effective. Patients respond differently to the same medication, and some patients with higher severity may respond well, while others with lower severity may respond less than expected. This is why it is important to personalize treatment for each patient's condition.

Currently, no biomarkers can accurately predict drug response, so treatment is based on a decision made by the doctor and patient together, weighing the pros and cons of the drug. In this situation, a range of treatment options is essential, with the flexibility to switch to another drug if it lacks effectiveness or has side effects. This requires ongoing research and the development of new drugs.

Q: Is it possible that the target level for atopic dermatitis treatment will increase?

A: As therapeutic advances raise expectations for treatment effectiveness, the current EASI 75 target could be raised. For example, PASI (Psoriasis Area Severity Index) 75 was the goal in treating psoriasis. However, PASI 90 and even PASI 100 have been achieved in recent years. As treatments have become more effective, doctors and patients have come to expect higher improvement rates. However, it's important to note that it's not just about improving efficacy but also about safety.

Q: Do you have any advice for people with atopic dermatitis?

A: Atopic dermatitis is a chronic inflammatory skin disease that requires long-term management. Many factors can trigger or exacerbate symptoms, including allergic reactions, irritants, foods, cosmetics, particulate matter, pollution, sweating after exercise, and stress.

Fortunately, in most cases, symptoms can be mild and controlled with proper treatment. Many new medications are available, so don't go alone, and always consult a dermatologist to find the right treatment for you. Professional treatment can reduce the burden of the disease.