“Dupixent, a trusted AD treatment without safety concerns"

[Interview] Professor Dong Hun Lee (Department of Dermatology, Seoul National University Hospital)

Targets key drivers of type 2 inflammation such as IL-4, IL-13 to reduce side effects…can be safely used long term

The strict reimbursement standards leave much to be desired… “We need to comprehensively consider the improvements in itching and QoL in addition to EASI.”

The biologic agent ‘Dupixent (dupilumab)’ holds an 'unrivaled' position in the treatment of severe atopic dermatitis.

 

In the AD treatment environment that had used immunotherapies that bring a high burden of side effects, the introduction of a safe and effective option has greatly improved the symptoms and quality of life in AD patients.

 

Due to its strong effect, requests for reimbursement to be extended to cover the pediatric and adolescent indications have been flooding.

 

Unlike systemic immunosuppressants, Dupxient selectively inhibits IL-4, IL-13 signals, the key drivers of type 2 inflammation, and therefore is known as a drug that can be safely used without concern over side effects.

 

Dailypharm met with Dong Hun Lee, Professor of Dermatology at the Seoul National University Hospital to hear about the effect and safety of Dupixent.

 

The following is a full QA with Professor Lee.

 

Professor Dong Hun Lee

-How has the introduction of Dupixent changed the atopic dermatitis treatment environment? =Before Dupixent, we mainly prescribed immunosuppressants such as cyclosporine and methotrexate, etc.

 

to treat severe atopic dermatitis.

 

Atopic dermatitis is a chronic condition that requires continued treatment and management, however, immunosuppressants have limitations in their treatment efficacy or have side effects that occur with long-term use that prohibit continuous use.

 

This is why major practice guidelines do not recommend continued use of cyclosporin for over 1-2 years.

 

In addition to clinical trials that demonstrated Dupixent’s superior efficacy, the company also recently disclosed the drug’s long-term safety data in adult patients with moderate-to-severe atopic dermatitis.

 

Also, in clinical practice, Dupixent generally showed a good effect in patients whose symptoms were not controlled by immunosuppressants such as cyclosporine.

 

Unlike other immunosuppressants that require regular monitoring every 1-3 months after administration, no separate blood tests are required for the use of Dupixent.

 

In this aspect, patients may see this convenience in administration as a benefit.

 

-Dupixent is being reimbursed applied the special calculation system in adults, but it has been pointed out that the set standards are too strict.

 

What is your opinion on this? =First, I would like to say that I am glad and thankful that many patients with severe AD are now benefiting through the reimbursement and special calculation system.

 

The EASI score that is used to assess the severity of AD only considers a patient’s symptoms and the extent (area) of eczema.

 

However, adult AD patients with atopic dermatitis mainly show symptoms on exposed areas such as the face, neck, and hands, and even though the area is small, the quality of life is greatly reduced and itching is severe and requires aggressive treatment.

 

To address this, the Korean Atopic Dermatitis Association presented an atopic dermatitis severity guideline that comprehensively reviews the Dermatology Life Quality Index (DLQI) and Numerical Rating Scale (NRS) score, in addition to the EASI score to assess the severity.

 

-Recently, Dupixent was approved for the treatment of moderate-to-severe atopic dermatitis in pediatric patients aged 6 to 11 in addition to adults and adolescents.

 

What were the limitations of previous treatment options for pediatric patients with moderate-to-severe atopic dermatitis?

 

What should be considered when expanding Dupixent reimbursement to pediatric patients in the future? = Prevalence of AD is around 10% in children and 3% in adults.

 

Like adult patients with AD, pediatric patients also often have severe symptoms and are prescribed systemic immunosuppressants or Dupixent.

 

However, long-term use of systemic immunosuppressants is not recommended in major guidelines because of the risk of side effects with long-term administration.

 

The burden of disease, school, peer relationships, and the increased burden of care borne by the family is larger for pediatric and adolescent patients.

 

Considering the specificities, such as the importance of initial treatment and a relatively small number of patients who will be needing reimbursement, I do hope that the reimbursement standards are relieved to cover these patients.

 

-Recently, a JAK inhibitor, ‘Olumiant,’ was approved in Korea for AD, with more JAKis to come.

 

Some companies developing JAK inhibitors have been taking active steps to such as conducting head-to-head clinical trials with Dupixent in AD.

 

How do you see the use of JAK inhibitors will go in the treatment of AD? =JAK(Janus kinase) inhibitors block a range of cytokines related to inflammatory responses by acting on the JAK signal pathway.

 

Its MOA works broader than Dupixent but narrower than other immunosuppressants such as cyclosporine in blocking inflammatory responses.

 

Although clinical trial results for the use of JAK inhibitors in AD are available, no real-world data is yet available.

 

We would need to wait and observe these results from the field.

 

Therefore it is yet difficult to make short- and long-term comparisons of JAK inhibitors and Dupxient.

 

-I would like to know your opinion on the safety issue that recently arose for JAK inhibitors.

 

The FDA’s black box warning does not include Dupixentl.

 

Is Dupixent safe in this respect?

 

=The US FDA’s recent Dear healthcare Professional letter indicated that the use of the JAK inhibitor ‘tofacitinib’ in rheumatoid arthritis patients raises the risk of cardiovascular disease compared to the use of TNF inhibitors.

 

However, the JAK inhibitor in question is not approved for atopic dermatitis, and JAK inhibitors do not need to be avoided as a whole as drugs in the same class can also have different efficacy and safety.

 

However, in consideration of the commonality in MOA of JAK inhibitors, continued monitoring as well as caution when prescribing the class in high-risk patients may be needed until further data is available.

 

In the case of Dupixent, the 3-year long-term safety data of the drug in adult patients have been recently added to the product label.

 

Also, patients in Korea who have been using the drug for over 3 years with the ‘Early Access Program (EAP)' before it was approved in Korea, are continuing their treatment in satisfaction until now.

 

No notable adverse reactions have been observed in patients who received Dupxient long-term, therefore no separate monitoring is required for its prescription, such as blood tests.

 

Also, patients do not prefer such additional tests.

 

-What common characteristics do patients who do not respond to Dupixent have? =It is effective in most patients, however, there were occasional cases where the effect was relatively small in patients who have high lgE or LDH levels that reflect the severity of disease or in overweight patients.

 

However, the level of non-response was not particularly noteworthy.

 

Also, almost no notable side effects were observed in patients that were prescribed Dupixent.

 

Symptoms such as conjunctivitis or facial redness did appear, but at a controllable level.