Date: Sunday, June 6, 2021
Session Time: 6:00pm-7:00pm
Presentation Time: 6:05pm-6:10pm
*Purpose: Belatacept(BELA) pharmacokinetic(PK) studies informed dosing in phase 3 studies where fixed mg/kg dosing compared a less intense(LI) and more intense(MI) regimen. LI was preferred over MI due to better risk/benefit profile. We compared PK parameters observed in the BELA Early Steroid withdrawal Trial (BEST) with previous reports.
*Methods: Samples analyzed BELA troughs via a validated quantitative enzyme-linked immunoassay. Clearance(Cl) was estimated with Bayesian estimation using clinical software MWPharm++(Mediware). Published population PK model was employed as the Bayesian prior. Allometric scaling adjusted for body weight. Individual concentration profiles generated estimated exposure parameters; troughs, area under the curve(AUC), average concentration(Cave), cumulative AUC(cAUC), and cumulative average(cCave). PK parameters were analyzed by age >60, race, gender, BMI >30, rejection and infection.
*Results: 876 BELA troughs in 191pts were analyzed. Bayesian predicted concentrations agreed with observed concentrations(R2=0.88). Figure 1 illustrates the model-based BELA concentration profiles with observations. Exposure was higher compared to previous reports (Figure 2) especially during induction phase. There were no differences in PK parameters observed based upon alemtuzumab vs r-ATG induction. The allometrically standardized Cl was comparable (0.74 vs 0.86L/day/70kg) and inter-individual variability in Cl was low (CV=22% vs 21%) in BEST and Zhou et al. Positive correlation between body weight and Cl(Figure 3) and Cavg was consistent across body weights. Significantly higher Cl was observed for patients <60 and AA. No differences in allometrically scaled Cl was observed by BMI or sex. Exposure was greater when BMI>30 and male. There were no differences in exposure in rejecting pts, however, pts with any infection, viral, and BK had significantly higher exposure.
*Conclusions: BELA PK was no different between alemtuzumab and r-ATG, but was higher than observed in trials using basiliximab and steroids. Reducing BELA exposure during the induction phase by reduced mg/kg doses or other anthropometric measures may be warranted. BELA concentration controlled trials may be considered to further optimize dosing.
To cite this abstract in AMA style:Bickenbach A, McGowan M, Miyagawa B, Mizuno T, Shields A, Christianson A, West-Thielke P, Leone J, Woodle E, Kaufman D, Wiseman A, Matas A, Vinks A. Belatacept Pharmacokinetic Analysis Comparing Belatacept Early Steroid Withdrawal Trial (BEST) with Benefit and Benefit-ext Trials [abstract]. Am J Transplant. 2021; 21 (suppl 3). https://atcmeetingabstracts.com/abstract/belatacept-pharmacokinetic-analysis-comparing-belatacept-early-steroid-withdrawal-trial-best-with-benefit-and-benefit-ext-trials/. Accessed June 15, 2021.
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