New post-hoc analysis: consistent symptom improvement over 52 weeks.

In atopic dermatitis, long-term symptom control is one of the overriding therapeutic goals. A recently published post-hoc analysis demonstrated that patients treated with dupilumab achieved sustained and consistent improvement in symptoms and an increase in quality of life over the 1-year treatment period.

The pathogenesis of atopic dermatitis is characterized by a Th2-mediated immune response dominated by cytokines such as interleukin(IL)-4 and IL-13, causing an inflammatory response and epidermal barrier dysfunction [1]. The expression of IL-4 and IL-13 correlates with disease activity [2]. In addition to inflammatory lesions, excruciating pruritus is one of the leading symptoms of this chronic recurrent dermatosis. The therapeutic effect of dupilumab (Dupixent®) in atopic dermatitis was demonstrated in a phase III study in 2017 [3]. After 16 weeks of treatment (300 mg dupilumab, subcutaneously, at weekly or biweekly intervals), there was significant relief of itching, skin lesions, and skin infection rate with corresponding improvement in quality of life. Long-term studies support the safe side effect profile, which is very beneficial for long-term treatment [4,5].

LIBERTY AD CHRONOS Study

The double-blind, randomized-controlled LIBERTY AD CHRONOS study evaluated the treatment effects of dupilumab (s.c.) in combination with topical glucocorticoids (TCS) over the course of one year compared with placebo [4,6]. In this parallel-group design study, 740 adult patients with moderate to severe atopic dermatitis were randomized to the following trial arms: Dupilumab (300 mg, weekly) + TCS; Dupilumab (300 mg, every 2 weeks) + TCS; Placebo + TCS. At week 52, a significantly greater proportion of the dupilumab groups met the primary endpoint of complete/nearly complete healing as measured by Investigator’s Global Assessment (IGA), 39%, compared with 12% in the placebo group [6]. A 75% reduction in EASI (Eczema Area and Severity Index) was achieved at 16 weeks in 64% and 69%, respectively, in both dupilumab groups and in 23% in the placebo group; these values remained constant over the 52-week study period. No laboratory abnormalities were documented throughout the treatment period; local reactions at the injection site and conjunctivitis (14% and 19% in the dupilumab groups versus 8% in the placebo group) were the most common adverse events [4].

Results of the post-hoc analysis

To examine long-term symptom control with dupilumab therapy, a post-hoc analysis of the LIBERTY AD CHRONOS trial was conducted [4,7]. This determined the proportion of study participants treated with 300 mg q2w* dupilumab+TCS who achieved significant improvement in various endpoints over the 1-year treatment period compared with placebo+TCS. There were 10 measurement time points from week 16 to 52, each at four-week intervals. Across all these follow-up measurements, the dupilumab q2w* + TCS group (n=106) showed consistent symptom improvement in a higher proportion compared to placebo+TCS (n=315). EASI-50 was achieved by 70.8% with dupilumab and 19.7% with placebo. Regarding EASI-75, the corresponding values were 48.1% vs. 8.6%. As expected, the quality of life assessed by DLQI (Dermatology Life Quality Index) was also clearly superior to the placebo condition. Thus, 64.2% in the dupilumab study arm achieved an improvement in the DLQI by at least 4 points; in the placebo group, this proportion was 18.4%. As another patient-reported outcome, scores on the POEM (“Patient-Oriented Eczema Measure”) were measured: an improvement of 4 points was observed in 62.3% of patients treated with dupilumab+TCS compared with 13.0% in the placebo+TCS-treated group. Last but not least, in the weekly peak pruritus NRS score, a reduction of at least 3 points was documented in 65.1% of patients treated with dupilumab + TCS in at least six follow-up measurements, whereas this rate was 17.1% under placebo+TCS.

* every 2 weeks = q2w

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