Belatacept and Tacrolimus Corticosteroid-Free Regimens Lead to Elevated Mycophenolic Acid Exposure at 1 and 3 Months after Kidney Transplantation

A. Dao, S. Tremblay, A. Shields, A. Loethen, B. Abu Jawdeh, T. Diwan, A. Govil, E. Woodle, R. Alloway.

UCincinnati, Cincinnati.

Meeting: 2018 American Transplant Congress

Abstract number: C91

Keywords: Adverse effects, Area-under-curve (AUC), Immunosuppression, Mycophenolate mofetil

Session Information

Session Name: Poster Session C: Kidney Immunosuppression: Novel Regimens and Drug Minimization

Session Type: Poster Session

Date: Monday, June 4, 2018

Session Time: 6:00pm-7:00pm

Presentation Time: 6:00pm-7:00pm

Location: Hall 4EF

Mycophenolate mofetil (MMF) is generally administered as a fixed dose. Studies have shown a relationship between MPA exposure (MPAAUC) but no data evaluates this relationship in CNI/steroid-free regimens. Also, the relationship between MPAAUC and adverse effects (AEs) is not well-established. Our objective was to evaluate the incidence of adverse events per MPAAUC in a prospective trial.

Method: Prospective MPAAUC measurement protocol in renal transplants (RT) receiving CNI or belatacept-based steroid-free regimens with rATG or alemtuzumab induction at 1 (MPAAUC_M1) and 3 (MPAAUC_M3) months post RT using the Pawinski equation (7.75+6.49C₀+0.76C_0.5+2.43C₂). MPAAUC ranges were: low (< 30mg/L*h^-1), intermediate (30-60mg/L*h^-1) and high (AUC >60mg/L*h^-1). MMF dose was adjusted per MPAAUC, AEs (viremia, leukopenia, neutropenia, BPAR1_yr) and provider discretion. An AE was considered associated with an MPAAUC when it occured within 1 month of the measurement.

Results: 101 patients were analyzed. Demographics, MPAAUCs, and AEs per IS group are included in Tables 1 and 2. Mean MPAAUCs were elevated (range 56-62.4mg/L*h^-1). Following MMF dosage decrease at month 1 in >30% of patients, mean MPAAUC_M3 remains similar to MPAAUC_M1. Figure 2 (panels A-D) represents the distribution of overall AEs at 1 and 3 months per MPAAUC groups and panels E-F the distribution of BPAR_1yr.

Conclusion: Regardless of concomitant IS, MPAAUC_M1 was high in 1/3 of patients; low MPAAUC was rare. Despite similar MPAAUC_M1, leukopenia occurred more frequently in belatacept vs tacrolimus regimens. Similar MPAAUC_M3 following dose decrease at 1 month indicates potential increase in MPA exposure over time post RT. As no relationship between MPAAUC and AEs has been observed, studies to determine optimal MPAAUC should be conducted.

CITATION INFORMATION: Dao A., Tremblay S., Shields A., Loethen A., Abu Jawdeh B., Diwan T., Govil A., Woodle E., Alloway R. Belatacept and Tacrolimus Corticosteroid-Free Regimens Lead to Elevated Mycophenolic Acid Exposure at 1 and 3 Months after Kidney Transplantation Am J Transplant. 2017;17 (suppl 3).

To cite this abstract in AMA style:

Dao A, Tremblay S, Shields A, Loethen A, Jawdeh BAbu, Diwan T, Govil A, Woodle E, Alloway R. Belatacept and Tacrolimus Corticosteroid-Free Regimens Lead to Elevated Mycophenolic Acid Exposure at 1 and 3 Months after Kidney Transplantation [abstract]. https://atcmeetingabstracts.com/abstract/belatacept-and-tacrolimus-corticosteroid-free-regimens-lead-to-elevated-mycophenolic-acid-exposure-at-1-and-3-months-after-kidney-transplantation/. Accessed December 3, 2024.

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