Upadacitinib (8) – Rinvoq®

• Clinical trials
  • The SELECT-GCA trial was a completed, double-blind, multicentre, three--arm randomised controlled trial comparing upadacitinib at doses of 15 mg and 7.5 mg with placebo in adults with newly diagnosed or recurrent active giant cell arteritis.

a) Adults with giant cell arteritis who are eligible for monotherapy with glucocorticoids

• For adults with giant cell arteritis who are eligible for treatment with glucocorticoids alone, there is a hint of a minor additional benefit for upadacitinib.
• Overall, therefore, there is a hint of additional benefit.
• mortality
  • For the endpoint of overall survival, there is no statistically significant difference between the treatment groups.
• Morbidity – Remission
  • For the remission endpoint under consideration, ‘sustained remission’, there is a statistically significant advantage in favour of upadacitinib + GC compared with placebo + GC.
  • For the benefit assessment, the operationalisation using the GC threshold of ≤ 5 mg/day is applied.
  • According to the guidelines, achieving or falling below this threshold represents a target value after one year.
  • This endpoint is defined as ‘sustained remission’.
• Morbidity – Fatigue
  • There is no statistically significant difference between the treatment arms in the proportion of patients showing a clinically relevant improvement or deterioration in the FACIT-Fatigue score of ≥ 8 points (out of 52 points).
• Morbidity – Health status
  • For the health status endpoint, as assessed using the VAS of the European Quality of Life Questionnaire 5 Dimensions (EQ-5D), there was no statistically significant difference between the treatment arms in the proportion of patients with a clinically relevant improvement or deterioration of ≥ 15 points (out of 100 points).
• Morbidity – Pain (PGIC)
  • No statistically significant differences were observed between the treatment groups with regard to the operationalisation of ‘severe deterioration’.
• quality of life
  • The responder analyses for clinically relevant improvement or deterioration of ≥ 10 points show no statistically significant differences between the treatment arms for either of the two summary scores.
• Side effects
  • For the endpoints of serious adverse events (AEs), severe AEs and discontinuation due to AEs, as well as the specific AEs of infections and serious infections, there were no statistically significant differences between the treatment arms in any case.
• Overall assessment
  • For the endpoint categories of mortality, health-related quality of life and side effects, there are neither advantages nor disadvantages for upadacitinib + GC compared with placebo + GC.
  • For the endpoint category of morbidity, the endpoint ‘remission’ —defined as the absence of signs and symptoms of giant cell arteritis and the achievement of or falling below a daily GC dose of 5 mg from weeks 36 to 52—a statistically significant difference in favour of upadacitinib.
  • No statistically significant differences were observed between the treatment groups for the patient-reported endpoints of fatigue, health status and pain.
  • Achieving and maintaining freedom from symptoms whilst avoiding glucocorticoid-induced side effects is a key therapeutic objective in this therapeutic indication.
  • Against this background, an overall assessment of the available results for upadacitinib in the treatment of adults with giant cell arteritis in patient group a), based on the moderate advantage observed for the endpoint ‘sustained remission’, a minor additional benefit can be inferred compared with the appropriate comparator therapy.

b) Adults with giant cell arteritis who are not suitable for glucocorticoid monotherapy

• For adults with giant cell arteritis who are not suitable for glucocorticoid monotherapy, additional benefit is not proven.
• For adults with giant cell arteritis who are not suitable for glucocorticoid monotherapy, no data are available to assess the additional benefit of upadacitinib compared with the appropriate comparator therapy.

Courtesy translation only, please refer to the German original.