TY - JOUR
T1 - Mycophenolic acid exposure determines antibody formation following SARS-CoV-2 vaccination in kidney transplant recipients
T2 - a nested cohort study
AU - Meziyerh, Soufian
AU - Bouwmans, Pim
AU - van Gelder, Teun
AU - van der Helm, Danny
AU - Messchendorp, Lianne
AU - van der Boog, Paul J M
AU - de Fijter, Johan W
AU - Moes, Dirk Jan A R
AU - de Vries, Aiko P J
AU - RECOVAC Collaborators
N1 - Funding Information:
The RECOVAC consortium received funding by The Netherlands Organization for Health Research and Development (ZonMw) and the Dutch Kidney Foundation. Peer-review has been conducted by the ZonMW committee. The consortium is endorsed by the Dutch Federation of Nephrology (NFN), Dutch Transplant Society (NTV), Dutch Kidney Patient Association (NVN), and the Dutch Kidney Foundation (Nierstichting). The RECOVAC consortium will share data with the RIVM and Netherlands Pharmacovigilance Center (LAREB) whenever deemed relevant. We would kindly like to thank all the collaborators of the national multicenter RECOVAC consortium in the Netherlands.
Funding Information:
The RECOVAC consortium received funding by The Netherlands Organization for Health Research and Development (ZonMw) and the Dutch Kidney Foundation. Peer‐review has been conducted by the ZonMW committee. The consortium is endorsed by the Dutch Federation of Nephrology (NFN), Dutch Transplant Society (NTV), Dutch Kidney Patient Association (NVN), and the Dutch Kidney Foundation (Nierstichting). The RECOVAC consortium will share data with the RIVM and Netherlands Pharmacovigilance Center (LAREB) whenever deemed relevant.
Publisher Copyright:
© 2023 The Authors. Clinical Pharmacology & Therapeutics published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.
PY - 2023/7
Y1 - 2023/7
N2 - Despite (repeated) boosting, kidney transplant recipients (KTRs) may remain at increased risk of severe COVID-19 since a substantial number of individuals remain seronegative or with low antibody titers. In particular, mycophenolic acid use has been shown to affect antibody formation negatively and may be an important modifiable risk factor. We investigated the exposure–response relationship between mycophenolic acid 12-hour area under the curve (AUC
0–12h) exposure and seroconversion including antibody titers after vaccination using mRNA-1273 SARS-CoV-2 vaccine (Moderna) in 316 KTRs from our center that participated in the national Dutch renal patients COVID-19 vaccination – long term efficacy and safety of SARS-CoV-2 vaccination in kidney disease patients vaccination study. After two vaccination doses, 162 (51%) KTRs seroconverted. KTRs treated with mycophenolic acid showed less seroconversion and lower antibody titers compared with KTRs without mycophenolic acid (44% vs. 77%, and 36 binding antibody units (BAU)/mL vs. 340 BAU/mL; P < 0.001). The mean mycophenolic acid AUC
0–12h exposure was significantly lower in KTRs who seroconverted compared with KTRs who did not (39 vs. 29 mg⋅h/L; P < 0.001). High mycophenolic acid exposure (±90 mg⋅h/L) and no exposure to mycophenolic acid resulted in a seroconversion rate ranging from 10% to 80%. Every 10 mg⋅h/L increase in mycophenolic acid AUC
0–12h gave an adjusted odds ratio for seroconversion of 0.87 (95% confidence interval (CI), 0.79–0.97; P = 0.010) and 0.89 (95% CI, 0.85–0.93; P < 0.001) for KTRs on dual and triple maintenance immunosuppressive therapy, respectively. Higher mycophenolic acid AUC
0–12h correlated with lower antibody titers (R = 0.44, P < 0.001). This study demonstrates the exposure–response relationship between gold standard mycophenolic acid exposure and antibody formation to support interventional studies investigating mycophenolic acid adjustment to improve antibody formation after further boosting.
AB - Despite (repeated) boosting, kidney transplant recipients (KTRs) may remain at increased risk of severe COVID-19 since a substantial number of individuals remain seronegative or with low antibody titers. In particular, mycophenolic acid use has been shown to affect antibody formation negatively and may be an important modifiable risk factor. We investigated the exposure–response relationship between mycophenolic acid 12-hour area under the curve (AUC
0–12h) exposure and seroconversion including antibody titers after vaccination using mRNA-1273 SARS-CoV-2 vaccine (Moderna) in 316 KTRs from our center that participated in the national Dutch renal patients COVID-19 vaccination – long term efficacy and safety of SARS-CoV-2 vaccination in kidney disease patients vaccination study. After two vaccination doses, 162 (51%) KTRs seroconverted. KTRs treated with mycophenolic acid showed less seroconversion and lower antibody titers compared with KTRs without mycophenolic acid (44% vs. 77%, and 36 binding antibody units (BAU)/mL vs. 340 BAU/mL; P < 0.001). The mean mycophenolic acid AUC
0–12h exposure was significantly lower in KTRs who seroconverted compared with KTRs who did not (39 vs. 29 mg⋅h/L; P < 0.001). High mycophenolic acid exposure (±90 mg⋅h/L) and no exposure to mycophenolic acid resulted in a seroconversion rate ranging from 10% to 80%. Every 10 mg⋅h/L increase in mycophenolic acid AUC
0–12h gave an adjusted odds ratio for seroconversion of 0.87 (95% confidence interval (CI), 0.79–0.97; P = 0.010) and 0.89 (95% CI, 0.85–0.93; P < 0.001) for KTRs on dual and triple maintenance immunosuppressive therapy, respectively. Higher mycophenolic acid AUC
0–12h correlated with lower antibody titers (R = 0.44, P < 0.001). This study demonstrates the exposure–response relationship between gold standard mycophenolic acid exposure and antibody formation to support interventional studies investigating mycophenolic acid adjustment to improve antibody formation after further boosting.
U2 - 10.1002/cpt.2872
DO - 10.1002/cpt.2872
M3 - Article
C2 - 36789469
SN - 0009-9236
VL - 114
SP - 118
EP - 126
JO - Clinical Pharmacology & Therapeutics
JF - Clinical Pharmacology & Therapeutics
IS - 1
ER -