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Letter to the Editor

Plasmapheresis Decreases Belatacept Exposure: Requires Consideration for Dose and Frequency Adjustments

Jain, Ashokkumar MD1; Xu, Ruichao MS2; Venkataramanan, Raman PhD2; Farooq, Umar MD3; Butt, Fauzia MD1; Ghahramani, Nasrollah MD3; Kadry, Zakiyah MD1

Author Information
doi: 10.1097/TP.0000000000003840
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INTRODUCTION

Belatacept was approved for kidney transplantation (KTx) in 2011.1 Belatacept has a long half life (9.8 d) with a small volume of distribution (0.09 L/k).2,3 After KTx, patients may require plasmapheresis (PP).4 However, the effects of PP on belatacept serum concentrations have not been reported. The aim of the present report is to examine the changes in serum concentration of belatacept with each PP in between belatacept dosing.

CASE REPORT

A 43-y-old man received a deceased donor KTx for focal segmental glomerulosclerosis (FSGS) with induction immunosuppression of Rabbit antithymocyte globulin (rATG) and methylprednisolone. Post KTx he had a nonoliguric delayed graft function with proteinuria suggesting early recurrent FSGS. PP was commenced, and he received rituximab. Five weeks, post KTx, he was switched from tacrolimus to belatacept 10 mg/kg every 4 wk, maintaining mycophenolate mofetil 1000 mg twice a day and prednisolone 20 mg daily. Twice a week, PP was continued for persistent proteinuria. He experienced 2 episodes of Banff 1A acute rejection 9 and 13 wk postbelatacept therapy. These were treated with 2 doses of 1000 mg of methylprednisone for first rejection and rATG second rejection. Belatacept (10 mg/kg) frequency was increased from every 4–3 wk.

STUDY DESIGN

After institutional review board approval and patient’s consent, blood samples were obtained before and after eighth belatacept infusion (27 wk postbelatacept initiation) and before and after each subsequent 5 PP (3, 6, 10, 17, and 21 d posteighth belatacept dosing). Belatacept serum concentrations were measured by ELISA (PPD Richmond Virginia 23230). Simulation of standard dosing without PP was analyzed by MATLAB for comparison.5

RESULTS

Figure 1 compares the 5 pre and postbelatacept concentrations in between 2 doses of belatacept. Also shown in the figure simulations of 10 and 5 mg/kg belatacept infusion without PP at the corresponding time points. The percentage of decrease in belatacept concentration from pre PP to post PP was consistent across all PPs results in a decrease of 64%, 67%, 67%▾, 69%, and 67% (from first to fifth PP, ▾ = sample lost, estimated value). The calculated actual amount of belatacept removed from first PP to fifth PP was 260, 78, 26, 14, and 6.4 mg, respectively. The percentage of administered belatacept dose removed amounted to 25.8%, 7.8%, 5.6%, 1.4%, and 0.65% at the same time points. Belatacept concentrations are higher after dosing; hence, higher amount of belatacept is removed by PP early after belatacept dosing.

FIGURE 1.
FIGURE 1.:
Belatacept concentration µgm/mL pre and post PP or without PP. It shows the changes in belatacept serum concentration (µgm/mL) before and after each PP on day 3, 6, 10, 17, and 21 after the belatacept dosing, 10 mg/kg (solid line). Simulation of belatacept concentration without PP with 10 mg/kg (dotted line…..) and 5 mg/kg (broken line ----) without PP are depicted for comparison.5 ▾, estimated value, sample lost; PP, plasmapheresis.

CONCLUSION

There are two-thirds decreases in belatacept serum concentration with each PP. The actual quantity of belatacept removed decreased from 260 mg (25.6% of the dose) with first PP (day 3 from belatacept dosing) to 6.4 mg (0.65% of the dose) with fifth PP (21 d postbelatacept). The amount of belatacept removed from PP is dependent upon the interval of PP from the last belatacept dosing.

Belatacept dose and frequency adjustments are necessary with PP depending on the timing and frequency of PP from the previous dose of belatacept.

ACKNOWLEDGMENTS

Sandra Nayibizi, Jesse Combs, RN, BSN, HLA laboratory technologists for clinical progress, blood draws, processing, and storage of serum. Lisa McCully and Barbara Baker for figure and editing assistance.

REFERENCES

1. Archdeacon P, Dixon C, Belen O, et al. Summary of the US FDA approval of belatacept. Am J Transplant. 2012;12:554–562.
2. Moudgil A, Dharnidharka VR, Feig DI, et al. Phase I study of single-dose pharmacokinetics and pharmacodynamics of belatacept in adolescent kidney transplant recipients. Am J Transplant. 2019;19:1218–1223.
3. Shen J, Townsend R, You X, et al. Pharmacokinetics, pharmacodynamics, and immunogenicity of belatacept in adult kidney transplant recipients. Clin Drug Investig. 2014;34:117–126.
4. Salvadori M, Tsalouchos A. Therapeutic apheresis in kidney transplantation: an updated review. World J Transplant. 2019;9:103–122.
5. MATLAB Online. MathWorks. Available at https://www.mathworks.com/products/matlab-online.html. Accessed on December 8, 2020.
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