TABLE 3.

Summary of studies of TDM or TCI concentration‐controlled dosing of mycophenolate

Study	Design	Dosing strategy in CCD arms	Therapeutic exposure	Outcomes
Hale et al 27 and van Gelder et al 28	Multitarget RCCT in kidney transplant recipients (n = 150)	Target MPA AUC0‐12 of either 16.1, 32.2 or 60.6 mg/L·h (low, medium or high target arms)	Successful separation of intervention arms into three distinct MPA exposure groups	BPAR 27.5%, 14.9% and 11.5% in low, medium and high target groups respectively (P = 0.043, low vs medium target group)
		Dose recommendation from MAPBE supplied to clinician
Le Meur et al 29	RCT of TCI vs fixed dosing in kidney transplant recipients (n = 137)	Target MPA AUC0‐12 target of 40 mg/L·h	In TCI arm, increased proportion within range of 30‐60 mg/L·h at all post‐adjustment time points over the 12‐month period	Treatment failure in 47.7% vs 29.2% (P = 0.03) and BPAR in 24.6% vs 7.7% (P = 0.01), fixed dose vs. TCI arm respectively
		Dose recommendation from MAPBE supplied to clinician
Van Gelder et al 30	RCT of TDM vs fixed dosing in kidney transplant recipients (n = 901)	MPA AUC0‐12 between 30 and 60 mg/L·h deemed acceptable	TDM failed to improve exposure, with similar mean MPA AUC0‐12 and proportion in range between treatment arms	No difference in outcomes. Treatment failure in 25.7% vs 25.6% (P = 0.81) and BPAR in 15.5% vs 14.9%, in the fixed dose and TDM arm, respectively
		Observed MPA AUC0‐12 supplied to clinician without dose adjustment recommendation
Gaston et al 31	RCT of TDM vs fixed dosing in 720 kidney transplant recipients: TDM and reduced CNI (group A), TDM and standard CNI (group B), fixed dosing and standard CNI (group C)	Goal trough MPA > 1.3 mg/L (cyclosporine co‐therapy) or >1.9 mg/L (tacrolimus co‐therapy)	TDM failed to improve exposure, with MPA trough concentrations “identical at all time points with or without monitored dosing”	Noninferiority group A vs group C (primary outcome measure)
				Treatment failure in 55 (22.6%), 67 (28.3%), and 67 (27.9%) subjects in groups A, B and C, respectively (P = 0.13 for A vs B and P = 0.18 for A vs C)
		Observed MPA trough concentration supplied to clinician without dose adjustment recommendation

Abbreviations: AUC, area under the concentration‐time curve; BPAR, biopsy proven acute rejection; CCD, concentration‐controlled dosing; CNI, calcineurin inhibitor; MAPBE, maximum a posteriori Bayesian estimation; MPA, mycophenolic acid; RCCT, randomized concentration‐controlled trial; RCT, randomized controlled trial; TCI, target concentration intervention; TDM, therapeutic drug monitoring.