MTOR inhibitors, mycophenolates, and other immunosuppression regimens on antibody response to SARS-CoV-2 mRNA vaccines in solid organ transplant recipients

Abstract

A recent study concluded that SARS‐CoV‐2 mRNA vaccine responses were improved among transplant patients taking mTOR inhibitors (mTORi). This could have profound implications for vaccine strategies in transplant patients; however, limitations in the study design raise concerns about the conclusions. To address this issue more robustly, in a large cohort with appropriate adjustment for confounders, we conducted various regression‐ and machine learning‐based analyses to compare antibody responses by immunosuppressive agents in a national cohort (n = 1037). MMF was associated with significantly lower odds of positive antibody response (aOR = 0.090.130.18). Consistent with the recent mTORi study, the odds tended to be higher with mTORi (aOR = 1.001.452.13); however, importantly, this seemingly protective tendency disappeared (aOR = 0.470.731.12) after adjusting for MMF. We repeated this comparison by combinations of immunosuppression agents. Compared to MMF + tacrolimus, MMF‐free regimens were associated with higher odds of positive antibody response (aOR = 2.394.267.92 for mTORi+tacrolimus; 2.345.5415.32 for mTORi‐only; and 6.7810.2515.93 for tacrolimus‐only), whereas MMF‐including regimens were not, regardless of mTORi use (aOR = 0.811.542.98 for MMF + mTORi; and 0.811.512.87 for MMF‐only). We repeated these analyses in an independent cohort (n = 512) and found similar results. Our study demonstrates that the recently reported findings were confounded by MMF, and that mTORi is not independently associated with improved vaccine responses.