Alexandra Pyatt, Melissa McGowan, Ryota Tanaka, Bradley Miyagawa, Tomoyuki Mizuno, Adele Rike Shields, Annette Christianson, Patricia West-Thielke, John P. Leone, E. Steve Woodle, Dixon Kaufman, Alexander Wiseman, Arthur J. Matas, Alexander A. Vinks, Rita R. Alloway
{"title":"Belatacept早期类固醇停药试验（BEST）对临床结果的药代动力学分析，并与报道的获益和BENEFIT- ext药代动力学分析进行比较","authors":"Alexandra Pyatt, Melissa McGowan, Ryota Tanaka, Bradley Miyagawa, Tomoyuki Mizuno, Adele Rike Shields, Annette Christianson, Patricia West-Thielke, John P. Leone, E. Steve Woodle, Dixon Kaufman, Alexander Wiseman, Arthur J. Matas, Alexander A. Vinks, Rita R. Alloway","doi":"10.1111/ctr.70172","DOIUrl":null,"url":null,"abstract":"<p>Belatacept (BELA) pharmacokinetic (PK) studies informed dosing strategies used in phase 3 studies, where fixed mg/kg dosing compared a less intensive (LI) and more intensive (MI) regimen. The LI regimen was preferred due to a better risk/benefit profile. We compared PK parameters observed in the BELA Early Steroid Withdrawal Trial (BEST) with previous reports. BELA trough samples were analyzed using a validated quantitative enzyme-linked immunoassay. Clearance (CL) was estimated with Bayesian estimation using a published BELA population PK model. Significantly higher CL was observed in subjects <60 years old and African American (AA) patients, leading to decreased BELA exposure. No differences in allometrically scaled CL were observed by BMI or sex; however, overall BELA exposure was greater in males. There were no differences in exposure in subjects with rejection; however, subjects with infection had significantly higher exposure. BELA PK was not different between alemtuzumab and rabbit-antithymocyte globulin induction groups without steroids, but overall drug exposure was higher than previously reported in trials co-administering with basiliximab and steroids. Future studies to optimize BELA dosing strategies are warranted as BELA exposure in this analysis exceeded Phase 3 target thresholds.</p><p><b>Trial Registration</b>: ClinicalTrials.gov identifier: NCT 01729494</p>","PeriodicalId":10467,"journal":{"name":"Clinical Transplantation","volume":"39 8","pages":""},"PeriodicalIF":1.9000,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/ctr.70172","citationCount":"0","resultStr":"{\"title\":\"Belatacept Pharmacokinetic Analysis of Belatacept Early Steroid Withdrawal Trial (BEST) to Clinical Outcomes and Compared With Reported BENEFIT and BENEFIT-EXT Pharmacokinetic Analysis\",\"authors\":\"Alexandra Pyatt, Melissa McGowan, Ryota Tanaka, Bradley Miyagawa, Tomoyuki Mizuno, Adele Rike Shields, Annette Christianson, Patricia West-Thielke, John P. Leone, E. Steve Woodle, Dixon Kaufman, Alexander Wiseman, Arthur J. 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There were no differences in exposure in subjects with rejection; however, subjects with infection had significantly higher exposure. BELA PK was not different between alemtuzumab and rabbit-antithymocyte globulin induction groups without steroids, but overall drug exposure was higher than previously reported in trials co-administering with basiliximab and steroids. 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Belatacept Pharmacokinetic Analysis of Belatacept Early Steroid Withdrawal Trial (BEST) to Clinical Outcomes and Compared With Reported BENEFIT and BENEFIT-EXT Pharmacokinetic Analysis
Belatacept (BELA) pharmacokinetic (PK) studies informed dosing strategies used in phase 3 studies, where fixed mg/kg dosing compared a less intensive (LI) and more intensive (MI) regimen. The LI regimen was preferred due to a better risk/benefit profile. We compared PK parameters observed in the BELA Early Steroid Withdrawal Trial (BEST) with previous reports. BELA trough samples were analyzed using a validated quantitative enzyme-linked immunoassay. Clearance (CL) was estimated with Bayesian estimation using a published BELA population PK model. Significantly higher CL was observed in subjects <60 years old and African American (AA) patients, leading to decreased BELA exposure. No differences in allometrically scaled CL were observed by BMI or sex; however, overall BELA exposure was greater in males. There were no differences in exposure in subjects with rejection; however, subjects with infection had significantly higher exposure. BELA PK was not different between alemtuzumab and rabbit-antithymocyte globulin induction groups without steroids, but overall drug exposure was higher than previously reported in trials co-administering with basiliximab and steroids. Future studies to optimize BELA dosing strategies are warranted as BELA exposure in this analysis exceeded Phase 3 target thresholds.
期刊介绍：
Clinical Transplantation: The Journal of Clinical and Translational Research aims to serve as a channel of rapid communication for all those involved in the care of patients who require, or have had, organ or tissue transplants, including: kidney, intestine, liver, pancreas, islets, heart, heart valves, lung, bone marrow, cornea, skin, bone, and cartilage, viable or stored.
Published monthly, Clinical Transplantation’s scope is focused on the complete spectrum of present transplant therapies, as well as also those that are experimental or may become possible in future. Topics include:
Immunology and immunosuppression;
Patient preparation;
Social, ethical, and psychological issues;
Complications, short- and long-term results;
Artificial organs;
Donation and preservation of organ and tissue;
Translational studies;
Advances in tissue typing;
Updates on transplant pathology;.
Clinical and translational studies are particularly welcome, as well as focused reviews. Full-length papers and short communications are invited. Clinical reviews are encouraged, as well as seminal papers in basic science which might lead to immediate clinical application. Prominence is regularly given to the results of cooperative surveys conducted by the organ and tissue transplant registries.
Clinical Transplantation: The Journal of Clinical and Translational Research is essential reading for clinicians and researchers in the diverse field of transplantation: surgeons; clinical immunologists; cryobiologists; hematologists; gastroenterologists; hepatologists; pulmonologists; nephrologists; cardiologists; and endocrinologists. It will also be of interest to sociologists, psychologists, research workers, and to all health professionals whose combined efforts will improve the prognosis of transplant recipients.
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