Dupilumab (7) – Dupixent®

• Clinical trials
  • To assess the additional benefit of dupilumab, the pharmaceutical manufacturer has submitted two multicentre, randomised, double-blind, placebo-controlled Phase III trials.
  • The PRIME and PRIME2 trials enrolled 151 and 160 patients respectively, aged between 18 and 80 years, with prurigo nodularis diagnosed at least 3 months previously.
  • Study participants were randomised in a 1:1 ratio to receive either dupilumab (PRIME: N = 75; PRIME2: N = 78) or placebo (PRIME: N = 76; PRIME2: N = 82), in each case in addition to background therapy.

Adults with moderate to severe prurigo nodularis who are eligible for systemic therapy

• For the treatment of adults with moderate to severe prurigo nodularis who are eligible for systemic therapy, there is a hint of a non-quantifiable additional benefit compared with the appropriate comparator therapy.
• Overall, there is a hint of a non-quantifiable additional benefit for dupilumab.
• The strength of the evidence is classified as ‘hint’, as there are uncertainties regarding high and varying proportions of missing values across the treatment groups.
• mortality
  • No deaths occurred during the course of either study.
• Morbidity – Symptoms – Itching, skin pain and sleep quality assessed using the Worst Itching Intensity Numerical Rating Scale (WI-NRS), Skin Pain NRS and Sleep Quality NRS
  • No usable data are available for the meta-analysis regarding the endpoints of itching (improvement of ≥ 4 points), skin pain (improvement of ≥ 1.5 points) and sleep quality (improvement of ≥ 1.5 points).
  • When considering the PRIME study alone, a statistically significant advantage of dupilumab over placebo is evident for all three endpoints listed when assessing improvement up to week 24.
• Morbidity – Symptoms – Lesions as measured by the Prurigo Activity Score (PAS)
  • For the endpoint ‘lesions’ (100% healed lesions), the meta-analysis of the PRIME and PRIME2 studies showed a statistically significant difference in favour of dupilumab.
• Morbidity – anxiety symptoms and depressive symptoms as measured by the Hospital Anxiety and Depression Scale (HADS)
  • For the endpoints of anxiety symptoms (improvement of ≥ 3.15 points) and depressive symptoms (improvement of ≥ 3.15 points), the meta-analysis of data at week 24 showed statistically significant advantages of dupilumab compared with the appropriate comparator therapy in each case.
• Morbidity – health status as measured by the Patient Global Impression of Change (PGIC), Patient Global Impression of Severity (PGIS) and the visual analogue scale of the EQ-5D questionnaire (EQ-5D VAS)
  • The meta-analysis of the PGIC, PGIS and EQ-5D VAS at week 24 compared with baseline showed statistically significant advantages for dupilumab compared with placebo in each case.
• Quality of life – Dermatology Life Quality Index (DLQI)
  • In the meta-analysis of the PRIME and PRIME2 studies, a statistically significant advantage of dupilumab compared with placebo was observed in the proportion of patients with a DLQI of 0 or 1.
• Side effects – severe adverse events (SUEs) and eye diseases (SOC, UEs)
  • For the evaluated population, the meta-analysis of the PRIME and PRIME2 studies revealed no statistically significant differences between the treatment groups in the assessment of the endpoints SUEs and eye diseases (SOC, AEs).
• Side effects – Discontinuation due to adverse events (AEs)
  • For the endpoint of discontinuation due to AEs, the meta-analysis showed a statistically significant difference in favour of dupilumab compared with placebo.
• Overall assessment
  • In summary, in the morbidity category at week 24, there were exclusively statistically significant, clinically relevant effects in favour of dupilumab compared with placebo.
  • The meta-analysis showed a statistically significant improvement with dupilumab compared with placebo in the disease symptom of lesions (assessed using PAS) and in symptoms of anxiety and depression (assessed using HADS).
  • When considering the PRIME study in isolation, major benefits of dupilumab over placebo were also demonstrated for the disease symptoms of pruritus (assessed using the WI-NRS), skin pain (assessed using the Skin Pain NRS) and sleep quality (assessed using the Sleep Quality NRS).
  • Furthermore, the meta-analysis showed that dupilumab, compared with placebo, had statistically significant advantages for the endpoints of health status (assessed using the EQ-5D VAS, PGIC and PGIS) and health-related quality of life (assessed using the DLQI), which are also considered clinically relevant in the meta-analysis.
  • In the category of side effects, no statistically significant differences were observed between the treatment groups when considering the results for SAE and, in detail, for adverse events (AEs) within the SOC eye diseases.
  • For the endpoint ‘discontinuation due to adverse events’, a statistically significant advantage for dupilumab over placebo was observed in the meta-analysis.
  • Overall, at week 24, only statistically significant, positive effects were observed for dupilumab compared with placebo.
  • The advantages in the categories of morbidity and health-related quality of life are not offset by any disadvantages in the categories of mortality and side effects.
  • Overall, however, these advantages cannot be quantified to any extent due to uncertainties regarding the implementation of the appropriate comparator therapy.

Courtesy translation only, please refer to the German original.