Menon Sujatha, Shoji Satoshi, Tsuchiwata Shinichi, Fallon Lara, Kanik Keith
Pfizer Inc., Groton, CT, USA.
Pfizer R&D Japan, Tokyo, Japan.
J Clin Pharmacol. 2025 Mar;65(3):369-377. doi: 10.1002/jcph.6147. Epub 2024 Oct 25.
Tofacitinib is an oral Janus kinase inhibitor for the treatment of psoriatic arthritis (PsA). These post hoc exposure-response (E-R) analyses of pooled data from two Phase 3 studies (NCT01877668 and NCT01882439) characterized the relationships between tofacitinib exposure and efficacy (American College of Rheumatology [ACR] criteria), and changes in hemoglobin (Hgb) in patients with PsA. Efficacy data for the proportion of patients receiving tofacitinib 5 or 10 mg twice daily, or placebo, achieving ACR ≥20%, ≥50%, or ≥70% response criteria (ACR20, ACR50, and ACR70, respectively) at Month 3, were modeled jointly using a four-category ordered categorical exposure-response model (ACR20 non-responder, ACR20 responder but not ACR50 responder, ACR50 responder but not ACR70 responder, and ACR70 responder). A maximum drug effect (E) model (using average concentrations of tofacitinib at steady state [C]) adequately described the exposure-ACR response rate relationship. Model-predicted response rates for tofacitinib 5 and 10 mg twice daily were 51% and 58%, respectively, for ACR20; 29% and 36% for ACR50; and 15% and 20% for ACR70. The E-R relationship between tofacitinib exposure and changes in Hgb was assessed using an indirect response model, which generally predicted Hgb concentration-time profiles across treatments well. The proportions of patients experiencing a decrease in Hgb of >2 g/dL were similar with tofacitinib 5 mg twice daily or placebo. These results were generally consistent with previous analyses in rheumatoid arthritis and psoriasis, and support the use of tofacitinib 5 mg twice daily for active PsA.
托法替布是一种用于治疗银屑病关节炎（PsA）的口服Janus激酶抑制剂。这些对两项3期研究（NCT01877668和NCT01882439）汇总数据进行的事后暴露-反应（E-R）分析，描述了托法替布暴露与疗效（美国风湿病学会[ACR]标准）以及PsA患者血红蛋白（Hgb）变化之间的关系。对于接受每日两次5或10mg托法替布或安慰剂治疗的患者，在第3个月达到ACR≥20%、≥50%或≥70%反应标准（分别为ACR20、ACR50和ACR70）的患者比例的疗效数据，使用四类有序分类暴露-反应模型（ACR20无反应者、ACR20反应者但非ACR50反应者、ACR50反应者但非ACR70反应者以及ACR70反应者）进行联合建模。最大药物效应（E）模型（使用托法替布稳态平均浓度[C]）充分描述了暴露-ACR反应率关系。托法替布每日两次5mg和10mg的模型预测反应率，ACR20分别为51%和58%；ACR50分别为29%和36%；ACR70分别为15%和20%。使用间接反应模型评估托法替布暴露与Hgb变化之间的E-R关系，该模型通常能很好地预测各治疗组的Hgb浓度-时间曲线。每日两次5mg托法替布治疗的患者与安慰剂组患者中血红蛋白降低>2g/dL的比例相似。这些结果总体上与先前类风湿关节炎和银屑病的分析一致，并支持每日两次使用5mg托法替布治疗活动性PsA。
