4.6 Article

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

Journal

FRONTIERS IN MEDICINE
Volume 9, Issue -, Pages -

Publisher

FRONTIERS MEDIA SA
DOI: 10.3389/fmed.2022.914424

Keywords

SARS-CoV-2; kidney transplantation; immunosuppressant; mycophenolate; azathioprine

Funding

  1. Medical-Scientific Fund of the Mayor of the Federal Capital of Vienna [21182]
  2. Christine Vranitzky-Stiftung research
  3. Medical University of Vienna Transplantation Research Platform's Start-Up Grant

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Kidney transplant recipients are at high risk of severe COVID-19, but their vaccine response is impaired, especially for those on triple immunosuppression. Pausing of mycophenolic acid (MPA) or azathioprine (AZA) for two weeks around vaccination did not increase seroconversion rate, but one third of non-responders developed antibodies after an additional dose, supporting continued vaccination.
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.

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