Stopping of Mycophenolic Acid in Kidney Transplant Recipients for 2 Weeks Peri-Vaccination Does Not Increase Response to SARS-CoV-2 Vaccination—A Non-randomized, Controlled Pilot Study

Abstract

IntroductionKidney transplant recipients (KTR) are at high risk of developing severe COVID-19. However, vaccine response in this population is severely impaired with humoral response rates of 36–54 and 55–69% after two or three doses of SARS-COV-2 vaccines, respectively. Triple immunosuppression and specifically the use of anti-proliferative agents such as mycophenolic acid (MPA) or azathioprine (AZA) have been identified as risk factors for vaccine hypo-responsiveness.MethodsWe hypothesized that in vaccine non-responders to at least three previous vaccine doses, pausing of MPA or AZA for 1 week before and 1 week after an additional vaccination would improve humoral response rates. We conducted an open-label, non-randomized controlled pilot study including 40 KTR with no detectable humoral response after three or four previous vaccine doses. Primary endpoint was seroconversion following SARS-CoV-2 vaccination. MPA and AZA was paused in 18 patients 1 week before until 1 week after an additional vaccine dose while immunosuppression was continued in 22 patients.ResultsThere was no difference in the humoral response rate between the MPA/AZA pause group and the control group (29 vs. 32%, p > 0.99). Absolute antibody levels were also not statistically significantly different between the two groups (p = 0.716).Renal function in the MPA/AZA pause group remained stable and there was no detection of new onset donor-specific antibodies or an increase of donor-derived cell-free DNA serving as a marker of allograft damage throughout the study period.ConclusionPausing of MPA/AZA for 2 weeks peri-vaccination did not increase the rate of seroconversion in kidney transplant. However, one in three KTR without humoral immune response to at least three previous vaccinations developed antibodies after an additional vaccine dose supporting continued vaccination in non-responders.

Humoral immune response and live-virus neutralization of the SARS-CoV-2 omicron (BA.1) variant after COVID-19 mRNA vaccination in children and young adults with chronic kidney disease

“…The latter observation is consistent with the data obtained in adolescent [4,7] and adult [20][21][22][23][24][25][26][27] KTR. It is currently being investigated in adults whether the transient halt of MMF therapy increases the rate of vaccine responders without an undue risk of kidney allograft rejection [28,29]. However, severe COVID-19 in pediatric patients on immunosuppressive therapy is rare [30][31][32].…”

Development and validation of multivariable prediction models of serological response to SARS-CoV-2 vaccination in kidney transplant recipients

“…While belatacept treatment and MPA dose have been reported as negative predictors of serological vaccine response throughout the literature ( 10 ), it is still unclear, whether modulation of immunosuppression, and especially pausing MPA can increase serological response to SARS-CoV-2 vaccination, since most data originate from observational or small non-randomized controlled trials ( 5 , 31 – 33 ).…”

Benefits of Switching Mycophenolic Acid to Sirolimus on Serological Response after a SARS-CoV-2 Booster Dose among Kidney Transplant Recipients: A Pilot Study

“…A recent study of MPA dose pause for one week before and four weeks after vaccination also revealed improvement in serologic response [ 16 ]. In another study with a shorter period, two weeks of immunosuppressive drug modification revealed an inadequate immune response [ 31 ]. Since the immune system requires a certain amount of time to respond after suppression or cessation of immunosuppression [ 32 ], thus, a two-week duration of immunosuppressive regimen switching prior to vaccination will allow the immune system to be restored, and another two weeks after vaccination can help the body to build an immune response to vaccination.…”