Dupilumab levels may be unrelated to treatment response, safety in atopic dermatitis

Serum dupilumab levels showed no correlation to treatment response or adverse events in patients with atopic dermatitis during the first year of treatment, according to a study.

“Overall, the effectiveness and safety of dupilumab have been demonstrated for the treatment of patients with AD,” Lotte S. Spekhorst, MD, of the department of dermatology and allergology and National Expertise Center for Atopic Dermatitis at University Medical Center Utrecht, the Netherlands, and colleagues wrote. “However, not all patients with AD respond equally to dupilumab treatment, and some patients develop adverse effects.”

In this prospective clinical cohort study, Spekhorst and colleagues evaluated the association of serum dupilumab (Dupixent, Sanofi Genzyme/Regeneron) levels with treatment response and adverse events in patients with AD.

The researchers extracted data from the BioDay Registry and included 295 adult patients (baseline EASI score, 14.1; interquartile range [IQR], 10-20.2) with AD who started dupilumab and had a serum sample available at 16 weeks of treatment. At baseline, patients were subcutaneously administered 600 mg of dupilumab followed by 300 mg every other week. The researchers defined treatment response as the percent reduction in EASI score vs. the baseline score and as an absolute EASI cutoff score of 7 or less, which would indicate controlled AD.

By 16 weeks of treatment, researchers noted a broad range of serum dupilumab levels among patients (median level, 86.6 g/mL; IQR, 64.6-110 g/mL; range, 10.1-382 g/mL). However, odds ratios were nonsignificant for serum dupilumab levels at week 16 and predicting response at 52 weeks of treatment (EASI 90, OR = 0.96; 95% CI, 0.9-1.04; and EASI 7, OR = 1.03; 95% CI, 0.93-1.14).

In the first year of treatment, 73.2% of patients reported adverse events, of whom 46.4% developed dupilumab-associated ocular surface disease. There was no significant correlation between serum dupilumab levels at 16 weeks for the prediction of adverse events (OR = 1.01; 95% CI, 0.95-1.07), including dupilumab-associated ocular surface disease (OR = 1.02; 95% CI, 0.97-1.08) during the first year of treatment.

Although the study suggests dupilumab levels are unrelated to treatment response or adverse events, the researchers emphasize that response may be dependent on target availability of the interleukin-4 receptor subunit alpha, with an interpatient variability producing heterogeneity in response.

“More research is necessary to confirm the hypothesis of interpatient variability of the [interleukin-4 receptor alpha] and the [pharmacokinetics] of dupilumab,” Spekhorst and colleagues wrote.