Dupilumab (9) – Dupixent®

• Clinical trials
  • The CHRONOS trial was already cited in the early benefit assessments to evaluate the additional benefit of dupilumab compared with the appropriate comparator therapy in adults and adolescents with moderate to severe atopic dermatitis and children aged 6 to 11 years with severe atopic dermatitis for whom systemic therapy is an option. This is a randomised, double-blind, controlled, multicentre Phase 3 trial in which dupilumab in combination with TCS is compared with placebo in combination with TCS in adults.

a) Children aged 6 months to 5 years with severe atopic dermatitis who are eligible for systemic therapy and whose clinical presentation is sufficiently similar to that of adults

• For the treatment of severe atopic dermatitis in children aged 6 months to 5 years who are eligible for systemic therapy and whose clinical presentation is sufficiently similar to that of adults, there is a hint of a non-quantifiable additional benefit of dupilumab compared with the appropriate comparator therapy.
• The results from the age stratum ≥ 18 to < 40 years of the CHRONOS study were used to assess the additional benefit in the patient group of children aged 6 months to 5 years with severe atopic dermatitis. Given 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 finding.
• mortality
  • No deaths occurred in either of the relevant study arms up to week 52.
• Morbidity – pruritus (Peak Pruritus NRS)
  • Pruritus was assessed using the Peak Pruritus NRS scale, where a score of 0 corresponded to no pruritus and a score of 10 to the worst conceivable pruritus. The improvement of ≥ 4 points by week 52 is considered. For the pruritus endpoint, 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.
• Morbidity – Eczema Area and Severity Index (EASI 75 and EASI 90 response)
  • In the German healthcare context, the EASI is a standard tool used by doctors to assess disease severity and is relevant for diagnosis and monitoring the progression of disease severity in clinical practice.
  • 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).
• Morbidity – Scoring Atopic Dermatitis (SCORAD 75 and SCORAD 90)
  • A SCORAD 75 or SCORAD 90 response is considered clinically relevant. In the age group of ≥ 18 to < 40 years, there was a statistically significant difference in favour of dupilumab for the SCORAD 75 response threshold. The SCORAD 90 response threshold shows no statistically significant difference between the treatment groups.
• Morbidity – sleep disturbances (SCORAD-VAS)
  • Sleep disturbances are assessed via patient self-report using a visual analogue scale, on which the patient rates their sleep disturbances at the time of measurement. For the mean change in the patient-relevant endpoint of sleep disturbances, a statistically significant, positive effect in favour of dupilumab was observed. This represents a clinically relevant effect.
• Morbidity – Patient-reported symptoms (POEM)
  • 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.
• Morbidity – Health status (EQ-5D VAS)
  • 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 broad CMQ conjunctivitis
  • For the endpoint ‘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’ (broad CMQ), the supplementary results for the overall population at week 52 show a statistically significant disadvantage compared with dupilumab compared with the comparator therapy. Overall, for the endpoint of 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 side effect is observed in the adverse events endpoint category, which is caused by the eye diseases endpoint. This negative side effect is not observed in the supplementary PRESCHOOL study, 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.
  • Consequently, positive effects are observed for morbidity and quality of life, alongside a disadvantage with regard to side effects. However, these disadvantages do not call into question the positive effects of dupilumab.

b) Children aged 6 months to 5 years with severe atopic dermatitis who are eligible for systemic therapy and whose clinical presentation is not sufficiently similar to that of adults

• For the treatment of severe atopic dermatitis in children aged 6 months to 5 years who are eligible for systemic therapy and whose clinical presentation is not sufficiently similar to that of adults, the additional benefit is not proven.
• For children aged 6 months to 5 years with severe atopic dermatitis who are eligible for systemic therapy and whose clinical presentation is not sufficiently similar to that of adults, the results of the CHRONOS study cannot be extrapolated (see study description for patient population a).

Courtesy translation only, please refer to the German original.