*Purpose: Two belatacept(BELA) fixed mg/kg dosing regimens, less intense(LI) and more intense(MI) were compared. The LI regimen was approved due to the higher risk profile of MI. Incidence of BK and herpes tended to be higher in pts with higher BELA troughs and a 17% increase in odds of serious infection was observed for every 10mcg/mL increase in the concentration average at 6 months(Cavg6mo). BEST samples were utilized to explore associations between BELA PK and infections.

*Methods: Collected samples in BELA treated pts were utilized to analyze BELA troughs via validated quantitative enzyme-linked immunoassay. Clearance(Cl) was estimated using Bayesian estimation with a published population PK model as the Bayesian prior with the clinical software MWPharm++(Mediware). Allometric scaling accounted for body weight differences. Individual patient profiles were analyzed to estimate troughs, cumulative area under the curve(AUC) and Cavg. PK parameters were analyzed with clinical data of any infection, severe bacterial, fungal, or viral.

*Results: 876 troughs in 191 pts showed agreement between observed concentrations and both population model-predicted and Bayesian estimated concentrations (R²=0.84 and 0.88, respectively). BELA exposure was higher than reported previously. Inter-individual variability in Cl was low (CV=22%) and matched reports. No significant differences between allometrically standardized Cl estimates were observed. BELA AUC and Cavg were significantly higher in pts with any infection(n=132) including viral(n= 82) compared to those without(Figure 1). Logistic regression revealed increased probability of infection based on Cavg6 and 12mo exposure. No difference in exposure was observed in CMV(n=23) pts. Significant increases in AUC and Cavg were observed in BK(n=41). BK pts experienced 11.8-14.6% increase in AUC out to 12mo. The Cavg or AUC at infection event is shown in Figure 2. Mean time to BK was 190±163 days. No significant differences in exposure were observed in bacterial(n=163) or fungal infected(n=13) pts.

*Conclusions: Higher BELA exposure was observed in pts with infection, particularly viral and BK . Effective CMV prophylaxis may prevent CMV in BELA treated pts regardless of exposure. BELA concentration controlled trials at lower doses may improve the overall infection, viral, and BK infection profile.

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