Calls mount for cross-dosing of atopic dermatitis treatments to alleviate insurance burdens as Dupixent dominates market

As the biologic drug Dupixent (dupilumab) accounts for over 80 percent of the market for severe atopic dermatitis treatment, calls are mounting for allowing cross-dosing if no other purpose than saving health insurance finance.

Experts emphasize that the current health insurance system induces the most expensive drugs to be used the most. They argue that the government should allow cross-dosing to improve the already aggravating health insurance finance.

According to the insurance claims status of severe atopic dermatitis drugs submitted by the Health Insurance Review and Evaluation Service to Rep. Jeon Jin-sook of the Democratic Party of Korea, as of June 30, 10,205 patients were treated for severe atopic dermatitis. The cost of medical treatment benefits was more than 72.8 billion won ($54.4 million).

Of these, 8,455 patients were administered with Sanofi’s Dupixent. In 2021, the first year of reimbursement for severe atopic dermatitis, 3,293 patients were prescribed Dupixent, followed by 4,992 in 2022 and 7,542 in 2023.

More than 90 percent of the 5,374 patients with severe atopic dermatitis in 2022 were prescribed Dupixent, even after AbbVie's Rinvoq (upadacitinib) and Lilly's Olumiant (baricitinib) won reimbursement in May 2022. In 2023 and the first half of 2024, Dupixent’s prescribing rate dropped slightly but remained above 80 percent.

Dupixent is chased by Rinvoq, Olumiant, and Pfizer's Cibinqo (abrocitinib), which became reimbursable in July 2023, but the three drugs combined account for less than 20 percent of prescriptions. Rinvoq, Olumiant, and Cibinqo are JAK inhibitors.

However, academics and industry have pointed out that Dupixent, the first drug to be covered by health insurance, is dominating the severe atopic asthma market less because of its efficacy than because of unreasonable health insurance reimbursement criteria. The current health insurance system is inevitably biased toward certain treatments.

Currently, cross-drug treatment is not allowed for severe atopy. To know which drug is the proper treatment for an individual, doctors must be able to prescribe drugs freely. Since cross-dosing is not allowed for severe atopy, if a drug is ineffective or has side effects, the patient has to pay 100 percent of the cost of replacing the drug.

Therefore, it is in the patient's best interest to be prescribed Dupixent first to reduce the likelihood of having to pay 100 percent of the cost of the drug if it needs to be switched due to side effects or lack of effectiveness.

For example, suppose patients are prescribed Dupixent and switch to Rinvoq. In that case, they will only have to pay half the cost of Dupigent. Still, if they are prescribed the cheaper Rinvoq on benefits and then switch to Dupixent, they will have to pay 100 percent of the cost of Dupigent. Currently, the injectable Dupixent, a biologic, costs about 1.4 million won per month, while the oral Rinvoq, a JAK inhibitor, costs about 600,000.

As a result, the current reimbursement system, which does not allow cross-dosing, encourages the most expensive drugs to be used the most, which is a loss for health insurance finances.

“Patients with severe atopic dermatitis choose the most expensive drugs when they receive paid treatment as a calculation exception, considering that they may use biologics or JAK inhibitors on a non-reimbursement basis, and if it doesn't work, they can feel comfortable choosing another drug,” said Park Jo-eun, head of the Severe Atopic Dermatitis Association, a patient group, as a designated panelist at the policy discussion on “How to Improve the Treatment Environment for Severe Atopic Dermatitis” co-hosted by the association and Rep. Jeon and sponsored by the Korean Atopic Dermatitis Association, a research body.

Dr. Han Tae-young, an insurance director at the research group and a professor of dermatology at Nowon Eulji Medical Center, said, “Different drugs have different efficacy rates. Some drugs can reach 80 percent, but others only reach 60 percent or 40 percent. Regarding the 80 percent achievement rate, 20 percent does not achieve the therapeutic goal.”

Professor Han emphasized that continued use of high-priced drugs due to blocked cross-dosing can also affect health insurance finances.

“Currently, Dupixent is overwhelmingly prescribed at 80 percent, and it is the most expensive of the drugs. However, some patients who use Dupixent sometimes experience side effects and want to replace the drug but are unable to do so because they cannot cross-dose,” Professor Han said. “If such patients can replace it, it will help health insurance finances.”

However, Kang Mi-young, director of the Pharmaceutical Management Department at the Health Insurance Review and Evaluation Service (HIRA), countered such allegations, saying, “It's not that the system induces prescribing of certain drugs, it's just that Dupixent is the first drug that comes in and is prescribed the most.”

In response to the demand to allow cross-dosing, Kang was more optimistic, though. “We discussed cross-dosing of biologics and JAK inhibitors with experts in early September, reflecting academic opinions and clinical realities. We will follow up. It will take some time due to issues such as drug price reduction,” she said.

Kang expected that cross-dosing between biologics and JAK inhibitors would be allowed, rather than the two-way cross-dosing requested by patient organizations and the research society.

“Cross-dosing between biologics and JAK inhibitors has a certain degree of evidence, but cross-dosing within a biologic class or a JAK inhibitor class is still weak, so we will review it while looking at clinical reality,” she said.

However, Dr. Choi Eung-ho, president of the Korean Atopic Dermatitis Association, reiterated the need to allow cross-dosing between biologics and JAK inhibitors within the same class.

“Cross-dosing between biologics and JAK inhibitors, between biologics and JAK inhibitors, and between biologics and JAK inhibitors is the only true cross-over,” Choi said. “HIRA requires randomized, double-blind data with clinical evidence. Still, how can a pharmaceutical company spend a lot of money to conduct a double-blind cross-over study for a drug already licensed and covered?”

“One of my patients was on Dupixent and wanted to switch to another drug because it didn't work, but after switching to Rinvoq, his symptoms disappeared completely. Since he is covered by health insurance, he is paying 100 percent of his salary out of pocket,” Choi said. “We ask for double-blind data, but expert opinions based on seeing real patients should be the basis.”