Geert D'Haens, Maria Rosario, Daniel Polhamus, Nathanael L Dirks, Chunlin Chen, Krisztina Kisfalvi, Christian Agboton, Séverine Vermeire, Brian G Feagan, William J Sandborn
{"title":"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。","authors":"Geert D'Haens, Maria Rosario, Daniel Polhamus, Nathanael L Dirks, Chunlin Chen, Krisztina Kisfalvi, Christian Agboton, Séverine Vermeire, Brian G Feagan, William J Sandborn","doi":"10.1080/17512433.2024.2318465","DOIUrl":null,"url":null,"abstract":"<p><strong>Background and aims: </strong>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).</p><p><strong>Methods: </strong>A previously described population pharmacokinetic model was used to predict average serum and trough concentrations at steady state (C<sub>av,ss</sub>, C<sub>trough,ss</sub>) 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).</p><p><strong>Results: </strong>Data were from 1968 patients (GEMINI 1 [<i>n</i> = 334], VISIBLE 1 [<i>n</i> = 216], GEMINI 2 [<i>n</i> = 1009], VISIBLE 2 [<i>n</i> = 409]) who received maintenance treatment with vedolizumab IV-Q8W, IV-Q4W, SC-Q2W, or placebo. Model-predicted C<sub>av,ss</sub> for IV-Q8W and SC-Q2W was similar in UC and CD. C<sub>av,ss</sub> was higher for IV-Q4W than IV-Q8W and SC-Q2W. C<sub>trough,ss</sub> values from IV and SC aligned well with pooled observed C<sub>trough</sub> by treatment group in UC and CD. C<sub>av,ss</sub> 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.</p><p><strong>Conclusion: </strong>Exposure-efficacy relationships for IV and SC vedolizumab administration were comparable, confirming that both are equally effective during maintenance treatment.</p>","PeriodicalId":12207,"journal":{"name":"Expert Review of Clinical Pharmacology","volume":" ","pages":"403-412"},"PeriodicalIF":3.6000,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Exposure-efficacy relationship of vedolizumab subcutaneous and intravenous formulations in Crohn's disease and ulcerative colitis.\",\"authors\":\"Geert D'Haens, Maria Rosario, Daniel Polhamus, Nathanael L Dirks, Chunlin Chen, Krisztina Kisfalvi, Christian Agboton, Séverine Vermeire, Brian G Feagan, William J Sandborn\",\"doi\":\"10.1080/17512433.2024.2318465\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background and aims: </strong>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).</p><p><strong>Methods: </strong>A previously described population pharmacokinetic model was used to predict average serum and trough concentrations at steady state (C<sub>av,ss</sub>, C<sub>trough,ss</sub>) 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).</p><p><strong>Results: </strong>Data were from 1968 patients (GEMINI 1 [<i>n</i> = 334], VISIBLE 1 [<i>n</i> = 216], GEMINI 2 [<i>n</i> = 1009], VISIBLE 2 [<i>n</i> = 409]) who received maintenance treatment with vedolizumab IV-Q8W, IV-Q4W, SC-Q2W, or placebo. Model-predicted C<sub>av,ss</sub> for IV-Q8W and SC-Q2W was similar in UC and CD. C<sub>av,ss</sub> was higher for IV-Q4W than IV-Q8W and SC-Q2W. C<sub>trough,ss</sub> values from IV and SC aligned well with pooled observed C<sub>trough</sub> by treatment group in UC and CD. C<sub>av,ss</sub> 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.</p><p><strong>Conclusion: </strong>Exposure-efficacy relationships for IV and SC vedolizumab administration were comparable, confirming that both are equally effective during maintenance treatment.</p>\",\"PeriodicalId\":12207,\"journal\":{\"name\":\"Expert Review of Clinical Pharmacology\",\"volume\":\" \",\"pages\":\"403-412\"},\"PeriodicalIF\":3.6000,\"publicationDate\":\"2024-04-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Expert Review of Clinical Pharmacology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1080/17512433.2024.2318465\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/3/5 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q2\",\"JCRName\":\"PHARMACOLOGY & PHARMACY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Expert Review of Clinical Pharmacology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1080/17512433.2024.2318465","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/3/5 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
Exposure-efficacy relationship of vedolizumab subcutaneous and intravenous formulations in Crohn's disease and ulcerative colitis.
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 (Cav,ss, Ctrough,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 Cav,ss for IV-Q8W and SC-Q2W was similar in UC and CD. Cav,ss was higher for IV-Q4W than IV-Q8W and SC-Q2W. Ctrough,ss values from IV and SC aligned well with pooled observed Ctrough by treatment group in UC and CD. Cav,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.
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.
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