Dupilumab (5) – Dupixent®

• Clinical trials
  • The AD-1652 study (n=367) is a randomised, controlled, double-blind trial comparing dupilumab with placebo, conducted in children aged 6 to 11 years with severe atopic dermatitis.
  • The CHRONOS trial (n=740) is a randomised, double-blind, controlled, multicentre Phase 3 trial comparing dupilumab in combination with TCS against placebo in combination with TCS in adults.

Children aged 6 to 11 years with severe atopic dermatitis who are eligible for systemic therapy

• For the treatment of severe atopic dermatitis in children aged 6 to 11 years who are eligible for systemic therapy, there is a hint of a non-quantifiable additional benefit of dupilumab compared with the appropriate comparator therapy.
• Due to the limitations of the available evidence and the evidence transfer, a hint of a non-quantifiable additional benefit can be inferred in terms of the certainty of the evidence.
• mortality
  • No deaths occurred in either of the relevant study arms up to week 52.
• morbidity
  • In this assessment, morbidity is presented using pruritus (Peak Pruritus NRS), EASI, SCORAD, sleep disturbances (SCORAD–VAS), patient-reported symptoms (POEM) and health status (EQ-5D-VAS).
  • For the endpoint of pruritus, a statistically significant difference in favour of dupilumab compared with the appropriate comparator therapy was observed in the age stratum of ≥ 18 to < 40 years for the relevant patient population of the CHRONOS study.
  • In the age group of ≥ 18 to < 40 years, a statistically significant difference in favour of dupilumab was observed for both response thresholds (EASI 75 and EASI 90).
  • A SCORAD 75 or SCORAD 90 response is considered clinically relevant. In the age group of ≥ 18 to < 40 years, a statistically significant difference in favour of dupilumab was observed for the SCORAD 75 response threshold. The SCORAD 90 response threshold showed no statistically significant difference between the treatment groups.
  • For the mean change in the patient-relevant endpoint of sleep disturbances, a statistically significant, positive effect in favour of dupilumab + TCS compared with placebo + TCS was observed. This is a clinically relevant effect.
  • For the mean change in patient-reported symptoms, a statistically significant, clinically relevant, positive effect in favour of dupilumab + TCS compared with placebo + TCS was observed in the age stratum of ≥ 18 to < 40 years.
  • For the health status endpoint (EQ-5D-VAS), there was no statistically significant difference between the treatment groups in the mean change at week 52 compared with baseline.
• Quality of life – Dermatology Life Quality Index (DLQI) response
  • For the proportion of patients with a DLQI of 0 or 1, a statistically significant advantage was observed for dupilumab compared with placebo + TCS at week 52.
• Side effects – eye diseases (SOC) and Narrow CMQ conjunctivitis
  • For the endpoint of eye diseases, a statistically significant disadvantage compared with dupilumab compared with the comparator therapy was observed in the age stratum ≥ 18 to < 40 years.
  • For the endpoint ‘conjunctivitis’ (Narrow CMQ), the supplementary results for the overall population at week 52 show no statistically significant difference between the treatment arms.
  • Overall, for the endpoint ‘eye diseases’ (SOC), there is a statistically significant disadvantage for dupilumab compared with the comparator therapy.
• Overall assessment
  • In summary, based on the data presented under the morbidity endpoint category, there is a statistically significant advantage in favour of dupilumab + TCS over placebo + TCS for the symptoms of itching and sleep disturbances, patient-reported symptoms, and the improvement in the EASI score by 75 per cent and 90 per cent, as well as a 75 per cent improvement in the SCORAD score, a statistically significant advantage in favour of dupilumab + TCS compared with placebo + TCS.
  • Similarly, in the quality of life endpoint category, a statistically significant advantage in favour of dupilumab + TCS over placebo + TCS is observed in terms of achieving a DLQI of 0 or 1.
  • In the relevant age stratum, a negative effect is observed in the side effects endpoint category, which is caused by the eye diseases endpoint. This negative effect is not observed in the supplementary study AD-1652, which involved patients from the target population.
  • Overall, the negative effect observed in the ‘eye diseases’ endpoint within the relevant age stratum of the CHRONOS study does not call into question the positive effects of dupilumab.
  • Taking the study results as a whole, the positive effects of dupilumab on morbidity and quality of life outweigh the disadvantage in terms of side effects; consequently, there is evidence of a non-quantifiable additional benefit for dupilumab.

Courtesy translation only, please refer to the German original.