Dupilumab Dose Reduction Successful in Controlled Atopic Dermatitis

Brandon May

August 12, 2022

Dupilumab dose reduction appears feasible in patients with controlled atopic dermatitis (AD) who have been on the monoclonal antibody therapy for at least 1 year, according to a recent study. The researchers suggest that the findings, published in Allergy, represent an initial step toward personalized dupilumab treatment in controlled AD.

The study included 90 adult patients with AD from the BioDay registry who were selected on the basis of their dupilumab administration interval. A total of 30 patients (group A) who did not fulfill criteria for interval prolongation continued to use the standard dupilumab dose of 300 mg every 2 weeks. Groups B (n = 30) and C (n = 30) received the standard dosage but prolonged the treatment interval to every 4 weeks and every 6-8 weeks, respectively -- thus effectively decreasing the standard dosage by 50% and 66%-75%.

In all groups, there were no significant changes in disease severity scores during the tapering period. Although the Numeric Rating Scale-pruritus score significantly increased in groups B and C after interval prolongation, the scores remained low. Additionally, levels of disease severity biomarkers (CCL17/CCL18) in all groups also remained low during the observation period.

Sheilagh Maguiness, MD, an associate professor of dermatology and pediatrics at the University of Minnesota, said in an email to Medscape Medical News that long-term dupilumab seems to be well tolerated, with minimal side effects or risks at standard dosing.

Maguiness, who was not involved in the study, commented that there are several considerations to be made in prescribing treatment for patients with AD. "As physicians, we typically aspire to use the least amount of medication required to achieve a sustained benefit," she explained. "However, this temptation must be balanced by the risk for unintended consequences."

She noted that in the case of biologic therapies, an unintended consequence could be the potential for the development of antidrug antibodies with less frequent dosing intervals.

While intrigued by the concept of patient-centered dosing and the ability to increase the duration between dosing intervals, Maguiness said she believes that there are still more questions than there are answers. "As a pediatric dermatologist," she said, "this is going to be one of the central most important questions to study and answer with respect to biologic and emerging therapies for AD."

When asked about the potential implications of the findings, Maguiness noted, "The ability to reduce the frequency of dosing but still maintain efficacy in the context of biologic therapies would indeed yield a huge cost-saving to the healthcare system as a whole."

Peter Lio, MD, FAAD, a clinical assistant professor of dermatology and pediatrics at Northwestern Medicine in Chicago, explained that many patients with AD want to know whether treatment with dupilumab will be a permanent fixture in their daily lives. "I think that psychologically, it can be very upsetting to hear that you will need medication for the rest of your life," said Lio, who was not involved in the study.

According to Lio, a board member of the National Eczema Association, the most important thing about AD is that it is a disease of cycles.

"The idea that we can reduce or take a break from medication is very empowering and very exciting," he said. "I think that it can help change our views on what our medium- and long-term treatment goals are, and I think that acknowledging this may open the door for some patients who are hesitant to start something without a good sense of how they might stop."

Lio added that there is a need for more research to determine whether a patient is more likely to develop antibodies to dupilumab if treatment "is spaced out too much" and whether therapeutic efficacy will be the same if there is a need to revert back to standard dosing. Also, he added, there is a critical need to understand what insurance companies and pharmacies will do if clinicians change the dosing outside of FDA-approved parameters.

"My main goal is for patients to get better safely and be able to minimize medications whenever possible," commented Lio. "While I fully acknowledge that not every patient may be able to decrease dosing and that there may be very real risks to 'playing around' with things like this, as a clinician I feel that we must keep pushing the boundaries. Otherwise we will not learn or grow."

Maguiness and Lio report no relevant financial relationships. The study received no commercial or financial grant/assistance from industry.

Allergy. Published online July 15, 2022. Full text

Brandon May is a freelance medical journalist who has written more than 2100 articles for medical publications in the United States and the UK. Twitter: @brandonmilesmay

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