Dupilumab is a recombinant human monoclonal antibody that inhibits signalling of interleukins-4 and -13, two key cytokines thought to contribute to the inflammatory symptoms associated with atopic dermatitis.
The recommended dose of dupilumab is 300mg via subcutaneous injection every other week, following an initial dose of 600mg.
The efficacy and safety of dupilumab were assessed in three double-blind, placebo-controlled phase III studies in adults with moderate to severe atopic dermatitis who had responded inadequately to topical treatment (n=2119).
were identical monotherapy trials in which patients were randomised in a 1:1:1 ratio to receive dupilumab or placebo weekly, or dupilumab every other week alternating with placebo, for 16 weeks. All patients were required to apply moisturiser twice daily throughout the trial period.
In , patients were randomly allocated in a 3:1:3 ratio to receive dupilumab weekly, every other week or placebo weekly, for 52 weeks. All three groups also used topical steroids.
In all three trials, dupilumab was found to be superior to placebo in terms of the co-primary endpoints, ie, the percentage of patients achieving a score of ‘clear’ or ‘almost clear’ in the Investigator's Global Assessment (IGA 0/1) with a reduction from baseline of ≥2 points and the percentage achieving ≥75% improvement in Eczema Area and Severity Index (EASI 75), both assessed at week 16.
After 16 weeks of treatment, a significantly greater proportion of patients receiving a weekly dose of dupilumab scored IGA 0/1 with a reduction of ≥2 points than patients receiving placebo (SOLO 1: 37.2% vs 10.3%, p<0.001; SOLO 2: 36.4% vs 8.5%, p<0.001; CHRONOS: 39.2% vs 12.4%, p<0.0001).
The proportion of patients who achieved EASI 75 at 16 weeks in SOLO 1 was 52.4% with a weekly dose of dupilumab compared to 14.7% with placebo (p<0.001). The corresponding rates were 48.1% vs 11.9% (p<0.001) in SOLO 2 and 63.9% vs 23.2% (p<0.0001) in CHRONOS.
Similar outcomes in the co-primary endpoints were seen in patients receiving the licensed fortnightly dose of dupilumab in all three trials and at week 52 in the LIBERTY AD CHRONOS trial.
Improvement in quality of life
At week 16, an improvement of ≥4 points in the peak score on the pruritus Numerical Rating Scale (NRS) was observed in significantly more patients receiving a once-weekly dose of dupilumab than in those given placebo (SOLO 1: 40.3% vs 12.3%, p<0.001; SOLO 2: 39.0% vs 9.5%, p<0.001; CHRONOS: 50.8% vs 19.7%, p<0.0001).
Dupilumab also showed superiority to placebo in terms of scores on the additional secondary endpoints of the Dermatology Life Quality Index (DLQI), the Patient Oriented Eczema Measure and the Hospital Anxiety and Depression Scale, indicating positive effects on quality of life.
The most commonly seen adverse effects of dupilumab in trials were injection site reactions, conjunctivitis, blepharitis and oral herpes.