Exposure-efficacy relationship of vedolizumab subcutaneous and intravenous formulations in Crohn's disease and ulcerative colitis.

IF 3.6 3区医学 Q2 PHARMACOLOGY & PHARMACY

Expert Review of Clinical Pharmacology Pub Date : 2024-04-01 Epub Date: 2024-03-05 DOI:10.1080/17512433.2024.2318465

Geert D'Haens, Maria Rosario, Daniel Polhamus, Nathanael L Dirks, Chunlin Chen, Krisztina Kisfalvi, Christian Agboton, Séverine Vermeire, Brian G Feagan, William J Sandborn

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引用次数: 0

Abstract

Background and aims: This posthoc analysis of the GEMINI and VISIBLE studies in ulcerative colitis (UC) and Crohn's Disease (CD) assessed exposure-efficacy of vedolizumab intravenous (IV) and subcutaneous (SC).

Methods: A previously described population pharmacokinetic model was used to predict average serum and trough concentrations at steady state (C_av,ss, C_trough,ss) and simulate the transition from vedolizumab IV to SC. Efficacy was defined as clinical remission at week 52: complete Mayo score ≤ 2 points and no individual subscore > 1 point (UC), and CD activity index score ≤ 150 points (CD).

Results: Data were from 1968 patients (GEMINI 1 [n = 334], VISIBLE 1 [n = 216], GEMINI 2 [n = 1009], VISIBLE 2 [n = 409]) who received maintenance treatment with vedolizumab IV-Q8W, IV-Q4W, SC-Q2W, or placebo. Model-predicted C_av,ss for IV-Q8W and SC-Q2W was similar in UC and CD. C_av,ss was higher for IV-Q4W than IV-Q8W and SC-Q2W. C_trough,ss values from IV and SC aligned well with pooled observed C_trough by treatment group in UC and CD. C_av,ss was equivalent for SC and IV. For UC and CD, efficacy rates were greater in patients in the highest quartiles of vedolizumab exposure for both formulations.

Conclusion: Exposure-efficacy relationships for IV and SC vedolizumab administration were comparable, confirming that both are equally effective during maintenance treatment.

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维多珠单抗皮下注射和静脉注射制剂在克罗恩病和溃疡性结肠炎中的暴露-疗效关系。

背景与目的这项针对溃疡性结肠炎（UC）和克罗恩病（CD）的GEMINI和VISIBLE研究的事后分析评估了静脉注射（IV）和皮下注射（SC）维多利珠单抗的暴露-疗效：方法：使用先前描述的群体药代动力学模型预测稳态时的平均血清浓度和谷浓度（Cav,ss, Ctrough,ss），并模拟从静脉注射维多珠单抗到皮下注射维多珠单抗的转变。疗效定义为第52周时的临床缓解：梅奥综合评分≤2分，且无单项亚评分>1分（UC），CD活动指数评分≤150分（CD）：数据来自1968名患者（GEMINI 1 [n = 334]、VISIBLE 1 [n = 216]、GEMINI 2 [n = 1009]、VISIBLE 2 [n = 409]），他们接受了维多珠单抗IV-Q8W、IV-Q4W、SC-Q2W或安慰剂的维持治疗。在 UC 和 CD 中，IV-Q8W 和 SC-Q2W 的模型预测 Cav,ss 相似。IV-Q4W 的 Cav,ss 值高于 IV-Q8W 和 SC-Q2W。在 UC 和 CD 中，IV 和 SC 的 Ctrough,ss 值与按治疗组汇总观察到的 Ctrough 值非常一致。SC和IV的Cav,ss值相同。对于 UC 和 CD，两种制剂中维多利珠单抗暴露量最高的四分位数患者的有效率更高：结论：静脉注射和皮下注射维多珠单抗的暴露-疗效关系相当，这证实了两种制剂在维持治疗期间同样有效。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Expert Review of Clinical Pharmacology PHARMACOLOGY & PHARMACY-

CiteScore

7.30

自引率

2.30%

发文量

127

期刊介绍： Advances in drug development technologies are yielding innovative new therapies, from potentially lifesaving medicines to lifestyle products. In recent years, however, the cost of developing new drugs has soared, and concerns over drug resistance and pharmacoeconomics have come to the fore. Adverse reactions experienced at the clinical trial level serve as a constant reminder of the importance of rigorous safety and toxicity testing. Furthermore the advent of pharmacogenomics and ‘individualized’ approaches to therapy will demand a fresh approach to drug evaluation and healthcare delivery. Clinical Pharmacology provides an essential role in integrating the expertise of all of the specialists and players who are active in meeting such challenges in modern biomedical practice.