Exposure–Response Relationships for the Efficacy and Safety of Risankizumab in Japanese Subjects with Psoriasis

• Published in: Clinical pharmacokinetics Vol. 59; no. 5; pp. 575 - 589
• Main Authors: Suleiman, Ahmed A., Khatri, Amit, Oberoi, Rajneet K., Othman, Ahmed A.
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 01.05.2020; Springer Nature B.V
• Subjects: Arthritis; Clinical trials; Cytokines; FDA approval; Internal Medicine; Light therapy; Medicine; Medicine & Public Health; Monoclonal antibodies; NCT; NCT02054481; NCT02672852; NCT02684357; NCT02684370; NCT02694523; NCT03000075; NCT03022045; Original Research Article; Patients; Pharmacokinetics; Pharmacology/Toxicology; Pharmacotherapy; Psoriasis; Skin; Studies; Japan
• ISSN: 0312-5963; 1179-1926; 1179-1926
• DOI: 10.1007/s40262-019-00829-2

Background and objective Risankizumab, a humanized monoclonal interleukin-23 antagonist antibody, has efficacy for treatment of plaque psoriasis, generalized pustular psoriasis (GPP) and erythrodermic psoriasis (EP). These analyses characterized the relationships between risankizumab exposures and key efficacy and safety variables in Japanese patients with moderate-to-severe plaque psoriasis, GPP, or EP following treatment with 75 or 150 mg subcutaneous doses at weeks 0, 4, and every 12 weeks thereafter. Methods Risankizumab average plasma concentrations (Cavg) were correlated with probabilities of achieving efficacy end points (PASI 75, PASI 90, PASI 100, and sPGA 0/1) using data from Japanese patients (N = 225) and non-Japanese patients (N = 1678) with moderate-to-severe plaque psoriasis enrolled in global trials, or a Japan Phase 2/3 trial. Results The exposure–efficacy relationships in Japanese patients were consistent with relationships for patients in global Phase 3 trials. At Week 16, a plateau of efficacy was demonstrated for 150 mg subcutaneous dose providing estimated PASI 90 and sPGA 0/1 response probabilities of 77%, and 88%, respectively. The exposures for 75 mg dose appeared to be suboptimal for PASI 100 response and other efficacy responses in heavier patients. Exposure–safety analyses (N = 242) indicated no apparent relationship between risankizumab Cavg and key safety variables, including any adverse event, serious adverse event, infection and infestation, and serious infection during treatment, consistent with observations in the global trials. Conclusions Overall, risankizumab 150 mg maximized efficacy, including PASI 100 response, in Japanese patients with psoriasis with no apparent relationship between exposure and evaluated safety variables. Clinical Trial Registration NCT03000075, NCT03022045, NCT02672852, NCT02684357, NCT02684370, NCT02694523, NCT02054481.