Real-world study shows positive results for Dupixent regardless of skin color

Atopic dermatitis is commonly diagnosed in childhood and especially among young children, those under the age of 6. Topical treatments, such as topical corticosteroid creams and calcineurin inhibitors, remain an important part of the armamentarium, but biologics, especially Dupixent (dupilumab), have come on strong as a treatment choice. Clinical trials have led to FDA approvals for, first, adolescents, then young children and finally, infants and toddlers.

But there is a problem with those clinical trials. The prevalence of atopic dermatitis is higher in people with non-White skin compared with those of European ancestry, but the majority of those enrolled in the clinical trials have been White patents.

“We just have too few [people with skin of color] in our clinical trials,” says Amy S. Paller, M.D., chair of the Departments of Dermatology at Northwestern University Feinberg School of Medicine in Chicago and lead investigator of several of the pivotal trials of Dupixent as treatment for atopic dermatitis in children.

A race and ethnic mismatch between individuals enrolled in important clinical trials and those with disease being studied occurs in many areas of medicine. In dermatology, the Skin of Color Society, the National Medical Association Dermatology Section and the National Psoriasis Foundation have launched efforts to increase enrollment of people with skin of color. Last year, the lead investigators of the VISIBLE trial assessing Tremfya (guselkumab) as a treatment for psoriasis published an article in JAMA Dermatology describing their efforts to enroll and retain study participants with skin of color. Their strategies included consulting with a dermatologist with experience treating underrepresented populations, using objective measures of skin tones, using color-polarized photography to better erythema, and using census and claims data to identify study sites.

How this real-world study worked

Although it is too late to redo the clinical trials of Dupixent, Paller and her colleagues have attempted to address the underrepresentation problem with analysis of retrospective real-world research, which uses data collected on patients after a drug or another type of intervention has been introduced into clinical practice.

PEDISTAD (which stands for PEDIatric Study in Atopic Dermatitis) is a 10-year observational study that has enrolled children younger than 12 with moderate-to-severe atopic dermatitis who had been treated with or are candidates for systemic treatment with biologics, cyclosporine, methotrexate, azathioprine, mycophenolate mofetil, Janus kinase inhibitors, corticosteroids, phototherapy or topical treatment. The study is funded by Sanofi and Regeneron, the companies that developed Dupixent.

In an article published late last month in the Journal of the American Academy of Dermatology, Paller and her colleagues shared the results of an analysis that included up to four years of follow-up data collected for PEDISTAD. The article comes approximately four years after Paller led another PEDISTAD study that included roughly three years of follow-up. A total of 1,342 patents 12 years and younger had been recruited to participate in the PEDISTAD registry when Paller and her colleagues conducted this study, but only a small fraction (7.4%, or 99 children) had been followed for the full four years.

For this analysis, the researchers compared 240 children who were treated with Dupixent with the 125 who were treated with methotrexate and 135 who were treated with cyclosporine. Of those treated with Dupixent, 93 (39%) were non-White and 147 were White (61%). They categorized patients on an intention-to-treat basis. Because this was a real-world study, treatment was decided by clinicians in consultation with a child’s caregiver, not by randomization according to a study protocol. Patients were categorized by the first treatment they were given, even if they switched to a different treatment later. Race and ethnicity were determined by self-identification and grouped for the analysis in a binary fashion into White and non-White.

Paller and her colleagues looked at a number of different outcomes, including the Eczema Area and Severity Index (EASI), the percentage body surface area (BSA), the Worst Scratch Numeric Rating Scale (WS-NRS) and the Peak Pruritus Numeric Rating Scale (PP-NRS) that are commonly used in dermatology studies. They also analyzed data collected on a number of quality-of-life measures.

Non-White vs. White differences

With so many outcomes, three different treatments and the White and non-White comparison, the results of the analysis as reported by Paller and her colleagues are complicated. But the result that they emphasized in the discussion of the article is that the patients treated with Dupixent experienced the largest improvement on many of the important measures — EASI, BSA, PP-NRS, WW-NRS — regardless of skin color. They also note the lower discontinuation rate among the children treated with Dupixent.

“In this analysis of real-world data from the PEDISTAD Registry, dupilumab appears to provide consistent disease control irrespective of skin color,” is the summary statement from Paller and her colleagues in the discussion section of the paper. In a brief interview with Managed Healthcare Executive, Paller said of the result, “It was hoped for” and called it “reassuring.”