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Population pharmacokinetic and exposure–response analysis of apremilast in Japanese subjects with moderate to severe psoriasis
Author(s) -
Okubo Yukari,
Ohtsuki Mamitaro,
Komine Mayumi,
Imafuku Shinichi,
Kassir Nastya,
Petric Rosemary,
Nemoto Osamu
Publication year - 2021
Publication title -
the journal of dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.9
H-Index - 65
eISSN - 1346-8138
pISSN - 0385-2407
DOI - 10.1111/1346-8138.16068
Subject(s) - apremilast , psoriasis , medicine , population , pharmacokinetics , psoriasis area and severity index , dermatology , gastroenterology , psoriatic arthritis , environmental health
Apremilast is an orally available phosphodiesterase 4 inhibitor used for the treatment of moderate to severe psoriasis. The aims of this analysis were to develop a population pharmacokinetic (PPK) model of apremilast based on observed data from phase 1 studies combined with clinical trial data from subjects with moderate to severe psoriasis, and to develop exposure–response (E‐R) models to determine whether Japanese subjects with moderate to severe psoriasis achieve response to apremilast treatment similar to that observed in non‐Japanese, predominantly Caucasian subjects with moderate to severe psoriasis. The PPK model demonstrated that apremilast plasma concentrations and overall apparent clearance rate were comparable between the Japanese and Caucasian subgroups. The E‐R analyses of ≥75% or ≥50% improvement from baseline in Psoriasis Area and Severity Index score and achievement of static Physician Global Assessment score of 0 (clear) or 1 (almost clear) at week 16 indicated that apremilast treatment in Japanese subjects approached the maximal effect with response rates comparable to those in predominantly Caucasian subjects. Overall, the analyses confirm that the approved apremilast 30 mg b.i.d. dose is appropriate for Japanese subjects with moderate to severe psoriasis, with an efficacy profile similar to that previously observed in Caucasian subjects.