October 2, 2023

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[PubMed] [Google Scholar]. were self-reported, and participants were stratified into 4 groups based on reported total daily dose of MMF: zero MMF, low dose ( 1000?mg/d), moderate dose (1000C2000?mg/d), and high dose (2000?mg/d). Patients receiving mycophenolic acid were excluded. Antispike antibody testing was performed at 1, 3, and 6 mo after dose 2 using commercially available assays, as previously described.1,3 The study was approved by the Johns Hopkins Institutional Review Board. Clinical characteristics were compared using Wilcoxon rank-sum test for continuous and Fisher exact test for categorical variables. Multivariable Poisson regression with robust SE was used to estimate the risk of a negative antibody response associated with the MMF dose categories, adjusting for age, sex, vaccine type (mRNA-1273 versus BNT162b2), time since transplant, and steroid use. Analyses were performed using Stata 15.1/SE for Windows (College Station, TX). At vaccination, 94 (44.3%) HLTRs reported receiving no MMF, 33 (15.6%) reported low-dose, 54 (25.7%) reported moderate-dose, and 31 (14.8%) reported high-dose regimens (Table ?(Table1).1). After adjustment, the risk of negative response in the low dose was comparable with that in the zero MMF group (risk ratio?=?0.651.152.05; em P /em ?=?0.63). However, the moderate- and high-dose groups had 2-fold higher risk of negative antibody response (risk ratio?=?1.34 2.043.10 and 1.83 2.774.21, respectively; em P /em ? ?0.01). TABLE 1. Demographics of heart and lung transplant recipients based on daily MMF dose category thead th align=”left” rowspan=”1″ colspan=”1″ Factor /th th align=”center” rowspan=”1″ colspan=”1″ Zero MMF /th th align=”center” rowspan=”1″ colspan=”1″ Low 1000?mg/d /th th align=”center” rowspan=”1″ colspan=”1″ Moderate1000C1999 mg /th th align=”center” rowspan=”1″ colspan=”1″ High2000 mg /th th align=”center” rowspan=”1″ colspan=”1″ em P /em /th /thead N94335431Vaccine series0.66?BNT162b249 (52.1%)18 (54.5%)30 (55.6%)20 (64.5%)?mRNA-127345 (47.9%)15 (45.5%)24 (44.4%)11 (35.5%)Age, median (IQR)58.5 (41.9C68.9)66.2 (50.8C70.2)65.4 (48.5C70.3)59.1 (41.2C66.4)0.26Sex0.88?Male45 (47.9%)16 (48.5%)25 (46.3%)17 (54.8%)?Female48 (51.1%)17 (51.5%)29 (53.7%)14 (45.2%)?Other1 (1.1%)0 (0.0%)0 (0.0%)0 (0.0%)Years since transplant at dose 1, Crizotinib hydrochloride median (IQR)6.6 (2.7C11.2)5.5 (3.0C10.7)5.2 (2.6C9.8)4.3 (2.8C11.0)0.64History of rejection em a /em 5 (5.61%)0 (0%)1 (1.81%)1 (3.33%)0.51Organ transplanted0.049?Lung36 (38.3%)23 (69.7%)22 (40.7%)13 Crizotinib hydrochloride (41.9%)?Heart55 (58.5%)10 (30.3%)32 (59.3%)18 (58.1%)?Heart and lung3 (3.2%)0 (0.0%)0 (0.0%)0 (0.0%)Azathioprine15 (16.0%)0 (0.0%)0 (0.0%)0 (0.0%) 0.001Calcineurin inhibitor92 (97.9%)30 (90.9%)53 (98.1%)28 (90.3%)0.081Tacrolimus84 (89.4%)28 (84.8%)52 (96.3%)27 (87.1%)0.23Steroids58 (61.7%)24 (72.7%)25 (46.3%)17 (54.8%)0.094mTOR inhibitor42 (44.7%)4 (12.1%)3 (5.6%)4 Rabbit Polyclonal to CAPN9 (12.9%) 0.001Triple immunosuppression em b /em 0 (0.0%)21 (63.6%)25 (46.3%)16 (51.6%) 0.001 Open in a separate window em a /em History of rejection in the 6 mo preceding vaccination. em b /em Triple immunosuppression consisted of any combination of MMF, calcineurin inhibitor, steroid, azathioprine, or mTOR inhibitor. IQR, interquartile range; MMF, mycophenolate mofetil; mTOR, mammalian target of Crizotinib hydrochloride rapamycin. In this study of the effect of MMF dosing on antibody response to mRNA vaccination against SARS-CoV-2 in HLTRs, an MMF dose of 1000?mg/d was associated with increased risk of negative antibody response after a 2-dose SARS-CoV-2 mRNA vaccine series. Though the association of MMF use with poor antibody responses to SARS-CoV-2 vaccination in HLTRs has been previously reported,4 this is the first study to delineate the effect Crizotinib hydrochloride of MMF dosing on the antibody response in this population. There was a possibility for recall bias, as MMF doses were self-reported. Data regarding changes to MMF dose leading up to vaccination were unavailable. Additionally, although antibodies to the S1/receptor-binding domain are correlated with plasma neutralizing activity,5 neutralizing titers were not formally assessed. In conclusion, higher MMF doses increase the risk of a negative antibody response to the 2-dose mRNA vaccine series in HLTRs. These findings may help guide approaches to third and booster doses, variant-specific next-generation vaccines, and the potential role for transient immunosuppression reduction strategies in ongoing trials where appropriate. ACKNOWLEDGMENTS The authors thank the participants of the Johns Hopkins transplant vaccine study, without whom this work would be impossible. They also thank the Johns Hopkins transplant vaccine study team, including Brian Boyarsky, MD, PhD; Mayan Teles, BS; Carolyn Sidoti, BS; Michael T. Ou, BS; Ross S. Greenberg, BA; Jake A. Ruddy, BS; Muhammad Asad Munir, MBBS; Michelle R. Krach, MS; and Iulia Barbur, BSE. They also thank Andrew.