Dupilumab (3) – Dupixent®

• Clinical trials
  • The AD-1526 study (n=251) is a randomised, controlled, double-blind study comparing dupilumab with placebo, conducted in adolescents aged 12 to < 18 years.
  • The CHRONOS trial (n=740) is a randomised, double-blind, controlled, multicentre Phase 3 trial comparing dupilumab in combination with topical glucocorticoids (TCS) with placebo in combination with TCS in adults.

Adolescents aged 12 to 17 years with moderate to severe atopic dermatitis who are eligible for systemic therapy

• For the treatment of moderate to severe atopic dermatitis in adolescent patients aged 12 to < 18 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.
• 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 findings.
• 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.
  • The EASI was operationalised based on the number of patients who achieved a 90 per cent improvement in their EASI score (EASI 90) and a 75 per cent improvement (EASI 75) from the start of the study to week 52.
  • An EASI 75 – or an EASI 90 – response is considered clinically meaningful. 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)
  • The SCORAD is another established tool for assessing the severity of atopic dermatitis.
  • The SCORAD was operationalised based on the number of patients who achieved an improvement in their SCORAD score of 90 per cent (SCORAD 90) and 75 per cent (SCORAD 75), respectively, from the start of the study to week 52.
  • A SCORAD 75 – or a SCORAD 90 – response is considered clinically relevant. For the SCORAD 75 response threshold, a statistically significant difference in favour of dupilumab was observed in the age group of ≥ 18 to < 40 years. The SCORAD 90 response threshold showed 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 + TCS compared with placebo + TCS was observed. This represents a clinically relevant effect.
• Morbidity – Patient-reported symptoms (POEM)
  • The POEM is a tool for assessing symptoms in patients with atopic dermatitis.
  • 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)
  • Health status was assessed using the visual analogue scale (VAS) of the EQ-5D questionnaire.
  • 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
  • The DLQI is a validated questionnaire used to assess disease-specific health-related quality of life in adult patients with dermatological conditions.
  • For the proportion of patients with a DLQI score 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 any conjunctivitis and blepharitis
  • For the endpoint ‘eye diseases’, a statistically significant disadvantage was observed compared with dupilumab compared with the comparator therapy in the age stratum ≥ 18 to < 40 years.
• Overall assessment
  • In summary, based on the data presented under the endpoint category of morbidity for the symptoms of pruritus 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 category of side effects, treatment with dupilumab is associated with disadvantages regarding the endpoints of eye diseases, including conjunctivitis.
  • Thus, there are positive effects on morbidity and quality of life, as well as a disadvantage in terms of side effects. However, these disadvantages do 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 disadvantages 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.