Hutmacher M M, Papp K, Krishnaswami S, Ito K, Tan H, Wolk R, Valdez H, Mebus C, Rottinghaus S T, Gupta P
Ann Arbor Pharmacometrics Group (A2PG), Inc., Ann Arbor, Michigan, USA.
Probity Medical Research and K Papp Clinical Research Inc., Waterloo, Ontario, Canada.
CPT Pharmacometrics Syst Pharmacol. 2017 May;6(5):322-330. doi: 10.1002/psp4.12182. Epub 2017 Mar 20.
Tofacitinib is an oral Janus kinase inhibitor. An integrated analysis was conducted to evaluate dosage optimality for tofacitinib in patients with moderate-to-severe plaque psoriasis and the impact of body weight on optimality in this patient population. Data were pooled from one phase IIb trial (2, 5, and 15 mg twice daily (b.i.d.)) and four phase III trials (5 and 10 mg b.i.d.). A longitudinal exposure-response model for Psoriasis Area and Severity Index (PASI) improvement (percent change from baseline) was established. Body weight influenced potency; heavier subjects require higher doses to achieve comparable benefit to lighter subjects. Disease severity, sex, and prior biologic usage were also predictive of response. The 10 and 5 mg doses were predicted to achieve 81% and 65%, respectively, of the maximum effect based on a 75% improvement in PASI. The greater efficacy of 10 mg over 5 mg was clinically meaningful.
托法替布是一种口服的 Janus 激酶抑制剂。进行了一项综合分析，以评估托法替布在中度至重度斑块状银屑病患者中的剂量优化情况，以及体重对该患者群体剂量优化的影响。数据来自一项 IIb 期试验（每日两次，每次 2、5 和 15 毫克）和四项 III 期试验（每日两次，每次 5 和 10 毫克）。建立了银屑病面积和严重程度指数（PASI）改善情况（相对于基线的百分比变化）的纵向暴露-反应模型。体重影响药效；体重较重的受试者需要更高剂量才能获得与体重较轻的受试者相当的益处。疾病严重程度、性别和既往生物制剂使用情况也可预测反应。基于 PASI 改善 75%，预计 10 毫克和 5 毫克剂量分别可达到最大效应的 81%和 65%。10 毫克剂量比 5 毫克剂量具有更高疗效，具有临床意义。
