Upadacitinib (4) – Rinvoq®

• Clinical trials
  • For the benefit assessment, the pharmaceutical manufacturer has submitted the Heads-Up randomised controlled trial, in which upadacitinib is compared with dupilumab.

a) Adults with moderate to severe atopic dermatitis who are eligible for continuous systemic therapy, for whom 30 mg of upadacitinib is the appropriate dose

• For the treatment of moderate to severe atopic dermatitis in adults who are eligible for continuous systemic therapy and for whom 30 mg is the appropriate dose, there is an indication of considerable additional benefit of upadacitinib compared with the appropriate comparator therapy.
• Overall, there is evidence of a considerable additional benefit of upadacitinib compared with dupilumab in adults with moderate to severe atopic dermatitis who are eligible for continuous systemic therapy and for whom 30 mg is the appropriate dose.
• The assessment of additional benefit is based on a randomised, double-blind, head-to-head study in which all adults were treated for 24 weeks.
• Overall, an indication is drawn regarding the certainty of the evidence.
• mortality
  • No statistically significant difference was observed between the treatment arms for the endpoint of overall survival.
• Morbidity – Eczema Area and Severity Index (EASI 75 and EASI 90 response, EASI 100 remission)
  • Whilst there is no statistically significant difference between the treatment groups for EASI 75, a statistically significant difference in favour of upadacitinib is observed for the EASI 90 response threshold.
  • In this study, a statistically significant difference in favour of upadacitinib was observed for EASI 100.
• Morbidity – pruritus (Worst Pruritus Numerical Rating Scale, WP-NRS)
  • Pruritus was assessed using the Worst Pruritus NRS scale, a self-report instrument measuring the worst pruritus experienced within the last 24 hours, where a score of 0 corresponds to no pruritus and a score of 10 to the worst conceivable pruritus.
  • The analysis considered, on the one hand, complete freedom from the symptom of pruritus (WP-NRS = 0) and, on the other hand, an improvement of ≥ 4 points by week 24. Statistically significant differences in favour of upadacitinib were observed for both measures.
• Morbidity – Patient-reported symptoms (Head and Neck Patient Global Impression of Severity, HN-PGIS)
  • The HN-PGIS is a patient-reported measure used to assess the severity of atopic dermatitis symptoms in the head and neck region on a scale from 0 (no symptoms) to 6 (cannot be ignored and significantly restricts my daily activities).
  • For the benefit assessment, the proportion of patients with an HN-PGIS score of 0 at week 24 is used. This shows a statistically significant effect in favour of upadacitinib compared with dupilumab.
• Health-related quality of life
  • Quality-of-life endpoints were not assessed using either an established and validated disease-specific instrument (e.g. DLQI) or a generic one (e.g. SF-36).
• Overall assessment
  • In the morbidity endpoint category, for adults for whom 30 mg is the appropriate dose, a statistically significant difference was observed in the endpoints of 90% improvement in EASI (EASI 90), remission (EASI 100), pruritus (WP-NRS 0 and an improvement of ≥ 4 points) and patient-reported symptoms (HN-PGIS 0), a statistically significant difference in favour of upadacitinib compared with dupilumab.
  • No endpoints were assessed in the health-related quality of life category. Consequently, no quality-of-life data are available for the benefit assessment.
  • In the side effect category, the overall rate of severe side effects (CTCAE grade ≥ 3) shows a disadvantage for upadacitinib; however, this does not call the positive results into question.
  • In detail, specific adverse events show both advantages (conjunctivitis and eye diseases) and disadvantages (infections and acne) of upadacitinib compared with dupilumab.
  • Overall, the positive effects of upadacitinib on pruritus, EASI 90 and remission (EASI 100) compared with dupilumab are assessed as a significant improvement in treatment-related benefit not previously achieved, and the extent of this benefit is classified as considerable.
  • Consequently, it can be concluded that, overall, upadacitinib offers considerable additional benefit compared with dupilumab in adults with moderate to severe atopic dermatitis who are eligible for continuous systemic therapy and for whom 30 mg is the appropriate dose.

b) Adults with moderate to severe atopic dermatitis who are eligible for continuous systemic therapy and for whom 15 mg of upadacitinib is the appropriate dose

• For the treatment of moderate to severe atopic dermatitis in adults who are eligible for continuous systemic therapy and for whom 15 mg is the appropriate dose, the additional benefit is not proven.
• Overall, no additional benefit of upadacitinib compared with the appropriate comparator therapy has been established in adults with moderate to severe atopic dermatitis who are eligible for continuous systemic therapy and for whom 15 mg is the appropriate dose.

c) Adolescents aged 12 to < 18 years with moderate to severe atopic dermatitis who are eligible for continuous systemic therapy

• For the treatment of moderate to severe atopic dermatitis in adolescents eligible for continuous systemic therapy, the additional benefit is not proven.
• Overall, no additional benefit of upadacitinib compared with the appropriate comparator therapy has been established in adolescents with moderate to severe atopic dermatitis who are suitable for continuous systemic therapy.

Courtesy translation only, please refer to the German original.