Pharmacokinetics of Risankizumab in Asian Healthy Subjects and Patients With Moderate to Severe Plaque Psoriasis, Generalized Pustular Psoriasis, and Erythrodermic Psoriasis

摘要

Abstract Risankizumab, a humanized monoclonal antibody that targets interleukin‐23 p19 subunit, was developed for the treatment of psoriasis. This work characterizes risankizumab pharmacokinetics in Japanese and Chinese healthy subjects compared with white healthy subjects and in Japanese patients with moderate to severe plaque psoriasis, generalized pustular psoriasis, or erythrodermic psoriasis. A phase 1, single‐dose study evaluated risankizumab pharmacokinetics and safety/tolerability in healthy white (18 and 300?mg subcutaneous [SC]), Japanese (18, 90, and 300?mg SC and 200, 600, and 1200?mg intravenous [IV]), and Chinese (18, 90, and 300?mg SC) subjects; pharmacokinetic data were analyzed using noncompartmental methods. Risankizumab pharmacokinetic data from phase 2/3 studies in Japanese patients with plaque psoriasis, generalized pustular psoriasis, or erythrodermic psoriasis following multiple SC doses of 75?mg or 150?mg were analyzed using a population pharmacokinetic approach along with data from the phase 1 and global phase 1 to 3 studies. Risankizumab plasma exposures (peak plasma concentration and area under the concentration‐time curve) were approximately dose‐proportional across 18‐ to 300‐mg SC or 200‐ to 1200‐mg IV doses. Risankizumab terminal elimination half‐life (harmonic mean 27–34 days) was comparable across doses and ethnicities. Risankizumab exposures were approximately 20% to 30% higher in Japanese and Chinese healthy subjects compared with white healthy subjects or in Japanese patients compared with non‐Japanese patients. After accounting for body‐weight differences, risankizumab exposures were comparable across ethnicities. Overall, there was no ethnic impact on risankizumab pharmacokinetics, and the small difference in exposure due to body weight has no clinical relevance.