AbbVie announced that the European Commission (EC) has approved Skyrizi (risankizumab, 150 mg, subcutaneous injection at week 0, week 4 and every 12 weeks thereafter) alone or in combination with methotrexate (MTX), for the treatment of active psoriatic arthritis in adults who have had an inadequate response or who have been intolerant to one or more disease-modifying anti-rheumatic drugs (DMARDs). Marking the second indication for Skyrizi, the Marketing Authorization will be valid in all member states of the European Union, as well as Iceland, Liechtenstein, Norway and Northern Ireland.
“People living with psoriatic arthritis struggle with psoriatic lesions and joint inflammation that causes swelling and pain. Reducing these symptoms may give people the ability to resume their daily activities and improve their quality of life,” said Michael Severino, M.D., vice chairman and president, AbbVie. “We are excited by the EC approval of Skyrizi for the treatment of adults with active psoriatic arthritis.”
Skyrizi received EC approval based on data from two Phase 3 clinical studies, KEEPsAKE-1 and KEEPsAKE-2.1-3,6 In these studies, SKYRIZI met the primary endpoint of ACR20 response at week 24 versus placebo, and ranked secondary endpoints including, but not limited to, improvements in several clinical manifestations of psoriatic arthritis such as physical function (as measured by the Health Assessment Questionnaire Disability Index [HAQ-DI]) and minimal disease activity (MDA) at week 24.
In KEEPsAKE-1 and KEEPsAKE-2, 57.3 and 51.3 per cent of patients receiving SKYRIZI achieved the primary endpoint of ACR20 response at week 24, respectively, versus 33.5 and 26.5 per cent receiving placebo (p<0.001).
Skyrizi-treated patients showed significantly greater improvement from baseline in physical function as measured by HAQ-DI -0.31 and -0.22, compared to placebo -0.11 and -0.05 at week 24 (p<0.001) in KEEPSAKE-1 and KEEPSAKE-2, respectively.
At week 24, 25.0 per cent and 25.6 per cent of Skyrizi-treated patients achieved MDA, in KEEPSAKE-1 and KEEPSAKE-2 respectively, compared to 10.2 per cent and 11.4 per cent of those on placebo (p<0.001).
“Millions of people living with psoriatic arthritis are impacted by psoriatic lesions, joint pain, stiffness and fatigue,” said Lars Erik Kristensen, M.D., Ph.D., consultant and head of science at the Parker Institute in Copenhagen Denmark, associate professor, Lund Sweden, SUS University Hospital. “As seen in this phase 3 clinical trial program in psoriatic arthritis, Skyrizi has the potential to be a valuable new treatment option, helping to improve the signs and symptoms of the disease.”
The safety profile of Skyrizi in psoriatic arthritis was consistent with the safety profile of Skyrizi in plaque psoriasis, with no new safety risks observed. Through week 24, serious adverse events occurred in 2.5 per cent and 4.0 per cent of patients treated with Skyrizi in KEEPsAKE-1 and KEEPsAKE-2, respectively, compared with 3.7 percent and 5.5 per cent on placebo. Rates of serious infections were 1.0 and 0.9 per cent in Skyrizi-treated patients in KEEPsAKE-1 and KEEPsAKE-2, respectively, and 1.2 and 2.3 per cent in patients who received placebo. The rates of adverse events leading to discontinuation of the study drug were 0.8 per cent and 0.9 per cent of patients treated with Skyrizi in KEEPsAKE-1 and KEEPsAKE-2, respectively, compared with 0.8 percent and 2.3 per cent on placebo. In KEEPsAKE-1, there was one death in the Skyrizi group not related to the study drug per investigator. There were no deaths reported in KEEPsAKE-2.
Skyrizi (risankizumab) is part of a collaboration between Boehringer Ingelheim and AbbVie, with AbbVie leading development and commercialization globally.
Psoriatic arthritis is a heterogeneous, systemic inflammatory disease with hallmark manifestations across multiple domains including joints and skin. In psoriatic arthritis, the immune system creates inflammation that can lead to pain, fatigue, stiffness in the joints and the presence of psoriatic lesions.
KEEPsAKE-1 and KEEPsAKE-2 are both phase 3, multicenter, randomized, double-blind, placebo-controlled studies designed to evaluate the safety and efficacy of Skyrizi in adult patients with active psoriatic arthritis. KEEPsAKE-1 evaluated SKYRIZI in patients who had an inadequate response or intolerance to at least one DMARD. KEEPsAKE-2 evaluated Skyrizi in patients who had an inadequate response or intolerance to biologic therapy and/or DMARDs. Patients were randomized to Skyrizi 150 mg or placebo followed by Skyrizi 150 mg at week 24. Patients randomized to Skyrizi received four maintenance doses a year, following two initiation doses.
The primary endpoint for both studies was the achievement of ACR20 response at week 24. Ranked secondary endpoints included, but were not limited to, the achievement of MDA as well as the change from baseline in HAQ-DI at week 24. The studies are ongoing, and the long-term extension remains blinded to the original randomization and evaluates the long-term safety, tolerability and efficacy of Skyrizi in patients who have completed the placebo-controlled period.
Skyrizi is an interleukin-23 (IL-23) inhibitor that selectively blocks IL-23 by binding to its p19 subunit. IL-23, a cytokine involved in inflammatory processes, is thought to be linked to a number of chronic immune-mediated diseases, including psoriasis. The approved dose for Skyrizi is 150 mg (either as two 75 mg pre-filled syringe injections or one 150 mg pre-filled pen or pre-filled syringe injection), administered by subcutaneous injection at week 0 and 4, and every 12 weeks thereafter. The Skyrizi 150 mg formulation was approved by the European Union in May 2021. Phase 3 trials of Skyrizi in psoriasis, Crohn’s disease, ulcerative colitis and psoriatic arthritis are ongoing.