Dupilumab Effective Among Individuals with Atopic Dermatitis, Obesity

Dupilumab has comparable efficacy among adults with atopic dermatitis and obesity to that of the general population of adult patients, according to new findings, though an optimized dosage may be considered among those in the former population.¹

These data were the result of new research—led by Joséphine Dupuis from the Service de Dermatologie at the Hôpital Huriez in France—conducted to assess the effectiveness and tolerance of dupilumab among those with moderate-to-severe atopic dermatitis as well as obesity. Dupuis et al. noted the underrepresentation of patients with obesity in clinical trials of drugs for inflammatory conditions impacting the skin.

“Pharmacokinetic studies of dupilumab showed lower residual concentrations in patients with a higher body mass index (BMI), with no impact on efficacy,” Dupuis et al. wrote. “However, no patients with obesity were included in these studies. Due to the increasing obesity prevalence in the general population and possibly in AD patients, a specific study was performed accordingly.”^{1, 2}

Background and Design

The investigators worked to evaluate the results of dupilumab therapy among individuals with obesity, identified with a body mass index (BMI) ≥30 kg/m². They collected standardized data from a multicentre cohort of adult individuals with eczema, also known as atopic dermatitis.

The percentage of individuals achieving a 0 or 1 Investigator's Global Assessment (IGA) score, or a 2 point reduction at the 5-month mark compared to baseline was the main outcome assessed. The research team also made a comparison of efficacy scores and Dermatology Life Quality Index (DLQI) scores between 2 age- and sex-matched cohorts of subjects who either had and or did not have obesity, all of which were given dupilumab at a single reference center.

A total of 96 participants with obesity were treated with dupilumab in the timeframe between July 2017 - March 2023. At the point of baseline and a follow-up interaction, information was collected on Scoring Atopic Dermatitis (SCORAD), IGA, Pruritus Numerical Rating Scale (PNRS), Eczema Area and Severity Index (EASI), and adverse events (AEs).

Findings

Most of those featured had severe eczema. By the 5-month mark and the 12-month mark, the investigators concluded that 74% and 78%, respectively, had been shown to respond to the drug, regardless of the grade of their obesity. They also found that the median duration of treatment was 18 months, adding that there were interquartile ranges of 10 - 32 months.

Dupilumab dosage was adjusted during follow-up interactions among 19% of subjects. The effectiveness of a dose escalation to 300 mg every 7-12 days was reported by the research team in terms of decreasing subjects’ IGA scores among 4 of the 6 participants without an initial response.

The team noted that 53% of subjects had at least a single AE, finding that weight shifts were seen among 41% of participants, as 17 had gained and 8 had lost weight. They found that conjunctivitis and facial redness had been seen among 34% and 17% of subjects, respectively. Among 13%, AEs resulted in discontinuation.

Baseline disease severity was shown to be similar by the research team when they compared the 26 matched subjects with and without obesity. By the 5-month mark, the team reported that 62% with obesity had responded to the drug versus 85% without obesity, though the distinction was not found to be statistically significant.

DLQI shifts were less pronounced at 5 months among those with obesity versus those without. The investigators noted the slightly increased frequency of AEs among individuals with obesity (62%) versus controls (46%), adding that shifts in weight were observed in both cohorts.

Despite the investigators’ conclusion that the efficacy of dupilumab in subjects with obesity was comparable to the general population with eczema, they added that exploratory comparisons indicate a possibly lower rate of response among those with obesity, and an optimized dosage could show some benefit for this group.

“Weight changes observed under dupilumab in our cohort were unexpected,” they wrote. “A Swedish study reported a mean weight gain of 6.1 kg (0.1–18) in a small cohort of 12 patients (mean BMI 27.3 kg/m2 at baseline) receiving dupilumab. Even if the mechanisms underlying these weight changes remain unknown, weight monitoring might be recommended during the follow-up.”

References

1. ^{Dupuis J, Tauber M, Staumont-Salle D, et al. French Atopic Dermatitis Network from the Group of Research and Study in Atopic Dermatitis (GREAT), the French Society of Dermatology (SFD). Efficacy and tolerance of dupilumab in patients with moderate-to-severe atopic dermatitis and obesity. J Eur Acad Dermatol Venereol. 2024 Jul 31. doi: 10.1111/jdv.20264. Epub ahead of print. PMID: 39082796.}
2. ^{Clot PF, Kamal M, Sun J, Xu C, Kong F, Gu Y, et al. Dupilumab pharmacokinetics in Chinese healthy subjects and patients with atopic dermatitis: results of two randomized, double-blind, placebo-controlled studies. Int Immunopharmacol. 2021; 99:107985.}