Atopic dermatitis experts have agreed that health insurance coverage standards should be relaxed to allow the cross-dosing of biologics and JAK inhibitors in cases of ineffectiveness or side effects.

The Korean Atopic Dermatitis Association recently held its 23rd congress and unveiled revised “Atopic Dermatitis Treatment Guidelines.”

The society has been operating the “Task Force for Guideline Revision,” headed by Professor Cho Sang-hyun of the Catholic University of Korea College of Medicine, since May of last year to reflect the introduction of various biologics and JAK inhibitors in recent years and their health insurance coverage.

During the conference, Professor Ko Hyun-chang of the Department of Dermatology at Pusan National University Yangsan Hospital presented “Revised Korean Guidelines for the Treatment of Atopic Dermatitis.”

"The guidelines reflect the opinions (consensus) of 50 atopic dermatitis experts in Korea based on the academic evidence published to date," Ko said. "The evidence level is divided into levels 1 (randomized controlled trials (RCTs)) to 5 (expert opinion), and the recommendation level is divided into A (strongly recommended), B (optionally recommended), C (not recommended except for unusual circumstances), and D (not recommended)."

The guidelines recommend the use of moisturizers to improve symptoms and prevent acute exacerbations of atopic dermatitis and the elimination of dust mites as much as possible to control symptoms in patients with atopic dermatitis who are sensitized to dust mite antigens and have a history of dermatitis exacerbations after antigen exposure.

For topical treatment, topical steroids for symptom control are recommended (A), and the appropriate strength of topical steroids should be selected according to the severity, treatment area, and age (A).

They also recommended the use of topical calcineurin inhibitors for symptom control and for lesions in sensitive areas (face, folds, and groin) and maintenance treatment with moderate topical steroids or topical calcineurin inhibitors applied regularly two to three times per week to prevent recurrence of lesions that have improved (A).

However, if there is a severe local reaction, such as a burning sensation after applying a topical calcineurin inhibitor, it was recommended first to use a topical steroid and consider changing the topical calcineurin inhibitor (B).

In systemic treatment, the immunosuppressant cyclosporine was strongly recommended (A) in patients with moderate or severe atopic dermatitis not adequately controlled by topical therapy or is not recommended. However, it advised that selective use of methotrexate and azathioprine should be considered (B).

In particular, the use of long-term oral steroids is not recommended due to the risk of adverse effects (D), but the immunosuppressant mycophenolate mofetil in patients with moderate or severe atopic dermatitis not adequately controlled by topical treatments or not recommended, and alitretinoin to improve symptoms of hand eczema in patients with atopic dermatitis with hand eczema should be considered for limited use (C).

Regarding biologics, dupilumab (Dupixent) was strongly recommended (A) for adult and pediatric patients with moderate to severe atopic dermatitis not adequately controlled with topical therapy or not recommended. The recommendation grade for tralokinumab (Adtralza) was A, although evidence is still lacking in adolescents.

In contrast, Lilly's lebrikizumab (Ebglyss in Europe) and Galderma's nemolizumab were considered for use (B), while Novartis' allergy treatment omalizumab (Xolair) was recommended for limited use (C) in patients with moderate to severe atopic dermatitis not adequately controlled with topical therapy or not recommended.

Concerning JAK inhibitors, the oral JAK 1/2 inhibitor baricitinib (Olumiant, A), the oral JAK1 inhibitor upadacitinib (Rinvoq, A), and the oral JAK1 inhibitor abrocitinib (Cibinqo, A) were recommended for adult patients with moderate to severe atopic dermatitis not adequately controlled with topical therapy or not recommended. However, oral JAK inhibitors in patients with moderate or severe atopic dermatitis should be monitored regularly, and the benefit-risk ratio should be considered, according to the guidelines.

‘Cross-dosing is appropriate if there is no response after 3-month treatment’

In particular, the guideline revisions favored allowing cross-dosing between biologics and JAK inhibitors.

For severe atopic dermatitis, switching between biologics and JAK inhibitors is not covered by health insurance. To get health insurance coverage, the first-line treatment must be administered for three months and meet the criteria of EASI (Eczema Area and Severity Index) of 23 or more. Therefore, many patients with severe atopic dermatitis complain about why they have to stop taking medication and worsen their atopy to get insurance coverage while they experience side effects without positive due biologics or JAK inhibitors and must change their medications.

"If EASI 50 is not achieved for three months or if the NRS does not decrease by more than four points or DLQI by more than six points despite treatment, it is considered refractory to treatment, and cross-treatment is appropriate," Professor Ko said. "Therefore, the task force proposes to consider switching to another biologic or JAK inhibitor if the biologic or JAK inhibitor is ineffective or has side effects (B)."

There was a consensus among experts on switching between biologics and JAK inhibitors, with 96 percent of Korean atopic specialists agreeing that switching should be possible, Ko explained. However, the level of recommendation was set at B because the evidence for switching from JAK inhibitors to biologics is currently only anecdotal, compared to the evidence for switching from biologics to JAK inhibitors, so there are not enough studies to support it, he noted.

"There was strong disagreement on the addition of systemic immunosuppressants or oral JAK inhibitors in patients with moderate or severe atopic dermatitis not adequately controlled by biologics (C)," Professor Ko added.

Besides, biologics was recommended in patients with moderate to severe pediatric and adolescent atopic dermatitis not adequately controlled by other topical therapies or not recommended (A).

In older patients with persistent chronic pruritus with skin lesions, the panel suggested treating them as if they had atopic dermatitis if other causes of pruritus have been ruled out by a dermatologist (B). In older patients with atopic dermatitis refractory to conventional topical therapy, the panel recommended selective use of biologics and low-dose JAK inhibitors based on benefit-risk and comorbidities.

For pregnant or lactating patients with atopic dermatitis, topical steroids were recommended (B). Still, they advised them to use oral cyclosporine during pregnancy sparingly (C) based on the patient benefit-risk ratio.

A long way for cross-dosing, which requires evidence for insurance coverage

Although the guidelines for treating atopic dermatitis were revised to reflect the latest treatment trends, the reimbursement criteria were not changed, so it will be some time before they are applied in practice, experts said.

"For the government to change the reimbursement standard, studies on cross-dosing, such as changing the duration or dose, must be published to support the academic evidence. However, no papers can be used as evidence in Korea or abroad yet. So, it is unlikely to be reflected immediately," said Professor Choi Eung-ho of Wonju Severance Hospital, elected as the new chairman of the society, in an interview with Korea Biomedical Review. "We will make more efforts to produce papers that can be used as evidence."