Upadacitinib (2) – Rinvoq®

• Clinical trials
  • For the benefit assessment, the pharmaceutical manufacturer has submitted the randomised controlled trial SELECT-PsA 1, in which upadacitinib is compared with adalimumab, either alone or in combination with methotrexate.
  • The pharmaceutical manufacturer submits the results of a placebo-controlled RCT (SELECT-PsA 2) for the patient population under assessment.

a) Adults with active psoriatic arthritis who have responded inadequately to, or are intolerant of, prior disease-modifying antirheumatic drug (DMARD) therapy.

• Hint of considerable additional benefit.
• Overall, there is a hint of a considerable additional benefit of upadacitinib compared with adalimumab in adults with active psoriatic arthritis who have responded inadequately to, or are intolerant of, prior disease-modifying antirheumatic drugs (DMARD) therapy or were unable to tolerate it.
• The assessment of additional benefit is based on a randomised, head-to-head study. At the data cut-off point used, all adults had been treated for at least 56 weeks. The potential for bias across endpoints is classified as low for the study.
• Overall, therefore, a hint for the reliability of the findings is established.
• mortality
  • No deaths occurred during the study period in the SELECT-PsA 1 trial.
• Morbidity – Minimal disease activity (MDA and DAPSA)
  • Results are available for the endpoint of minimal disease activity from two operationalisations (Minimal Disease Activity [MDA] and DAPSA). Unlike the MDA, the calculation of minimal disease activity based on DAPSA involves the measurement of an inflammatory marker (C-reactive protein). The assessment of the minimal disease activity endpoint is therefore primarily based on the MDA. For minimal disease activity assessed using the MDA, a statistically significant advantage was observed in favour of upadacitinib compared with adalimumab. This effect is confirmed in terms of statistical significance in only one of the three sensitivity analyses carried out using alternative imputation strategies (NRI with variance correction). For minimal disease activity as measured by DAPSA (≤ 15), no statistically significant difference was observed between the treatment groups.
• Morbidity – Remission (DAPSA ≤ 3.3)
  • For the endpoint of remission, as assessed by DAPSA ≤ 3.3, there is a statistically significant advantage in favour of upadacitinib compared with adalimumab.
• Morbidity – Tender joints (TJC68 ≤ 1)
  • For the endpoint of tender joints, there was no statistically significant difference between the treatment groups.
• Morbidity – Swollen joints (SJC66 ≤ 1)
  • For the endpoint of swollen joints, there was no statistically significant difference between the treatment groups.
• Morbidity – Enthesitis (LEI and SPARCC)
  • Results are available for the enthesitis endpoint from two operationalisations (LEI and SPARCC). The LEI was developed for the indication of psoriatic arthritis and the SPARCC for the indication of spondyloarthritis. The assessment of the enthesitis endpoint is therefore primarily based on the LEI. For enthesitis assessed using the LEI, there is a statistically significant advantage in favour of upadacitinib compared with adalimumab. For enthesitis assessed using the SPARCC, there is no statistically significant difference between the treatment groups.
• Morbidity – dactylitis (LDI)
  • For the endpoint of dactylitis assessed using the LDI, there is no statistically significant difference between the treatment groups.
• Morbidity – Fatigue (FACIT-Fatigue)
  • For the endpoint of fatigue, assessed using the FACIT-Fatigue, there was no major statistical difference between the treatment groups, neither for the proportion of adults showing an improvement of ≥ 7.8 points (corresponding to 15% of the scale range) nor for the proportion of adults showing an improvement of ≥ 4 points.
• Morbidity – Skin symptoms (PASI 100 remission, PASI 90 and PASI 75 response)
  • For the endpoint of skin symptoms assessed using the PASI, there was no statistically significant difference between the treatment groups, neither in remission of skin symptoms (PASI 100) nor in PASI 90 and PASI 75 response.
• Morbidity – Physical functional status (HAQ-DI)
  • For the endpoint of physical functional status assessed using the HAQ-DI, there was a statistically significant difference in favour of upadacitinib compared with adalimumab, both for the proportion of adults showing an improvement of ≥ 0.45 points (corresponding to 15% of the scale range) and for the proportion of adults showing an improvement of ≥ 0.35 points, a statistically significant advantage was observed in favour of upadacitinib compared with adalimumab.
• Morbidity – Health status (EQ-5D VAS)
  • For the health status endpoint assessed using the EQ-5D VAS, based on the responder analyses using a response threshold of 15% of the scale range, there was a statistically significant advantage in favour of upadacitinib compared with adalimumab.
• Side effects – overall rates of SUEs and discontinuations due to AEs
  • For the endpoints of SAEs and discontinuation due to AEs, no statistically significant difference was observed between the treatment groups in either case.
• Overall assessment
  • In the morbidity endpoint category, a statistically significant difference in favour of upadacitinib was observed for the endpoints minimal disease activity (MDA), remission (DAPSA), enthesitis (LEI), physical functional status (HAQ-DI) and health status (EQ-5D VAS), a statistically significant difference was observed in favour of upadacitinib compared with adalimumab.
  • In the health-related quality of life endpoint category, the SF-36 showed a statistically significant advantage for upadacitinib over adalimumab in terms of both the physical and mental total scores.
  • In the endpoint category of side effects, there was neither an advantage nor a disadvantage for treatment with upadacitinib compared with treatment with adalimumab.
  • Overall, the positive effects of upadacitinib on minimal disease activity (MDA), remission (DAPSA), physical functional status (HAQ-DI) and health status (EQ-5D VAS) as well as on health-related quality of life (physical and mental total scores of the SF-36) compared with the appropriate comparator therapy are assessed as a significant improvement in treatment-related benefit not previously achieved, and the extent of the additional benefit is classified as considerable.
• Overall assessment
  • In the overall assessment, the positive effects of upadacitinib on minimal disease activity (MDA), remission (DAPSA), physical functional status (HAQ-DI) and health status (EQ-5D VAS) as well as on health-related quality of life (physical and mental summary scores of the SF-36) compared with the appropriate comparator therapy are assessed as a significant improvement in treatment-related benefit not previously achieved, and the extent of the additional benefit is classified as considerable.

b) Adults with active psoriatic arthritis who have responded inadequately to, or are intolerant of, prior treatment with disease-modifying biological anti-rheumatic drugs (bDMARDs).

• The additional benefit is not proven.
• The pharmaceutical manufacturer has not provided any suitable data for the patient population under assessment, meaning that no conclusions can be drawn regarding the additional benefit of upadacitinib compared with the appropriate comparator therapy.
• Overall, no additional benefit of upadacitinib compared with the appropriate comparator therapy has been established in adults with active psoriatic arthritis who have responded inadequately to, or are intolerant of, prior treatment with disease-modifying biological antirheumatic drugs (bDMARDs).

Courtesy translation only, please refer to the German original.