Shivan Shah (@idoncology.bsky.social)

Replacing Mycophenolate Mofetil by Everolimus in Kidney Transplant Recipients to Increase Vaccine Immunogenicity: Results of a Randomized Controlled Trial Vaccine immunogenicity is reduced in kidney transplant recipients (KTRs), especially in those using mycophenolate mofetil (MMF). Whether replacement of MMF by everolimus improves vaccine immunogenicity is unknown.MethodsKTRs were randomized 1:1 to continue MMF or switch to everolimus. Participants received one coronavirus disease 2019 (COVID-19) booster vaccination and two herpes zoster (HZ) vaccinations at 6, 10 and 14 weeks postrandomization. Primary outcome was the neutralizing antibody response 28 days after COVID-19 vaccination. Secondary outcomes included antibody and T-cell responses 28 days after COVID-19 and HZ vaccination, and safety.ResultsIn 110 KTRs, COVID-19 vaccination resulted in comparable Omicron XBB.1.5 neutralizing antibody titers in the everolimus versus MMF group (308 [74.4–1314] vs 327 [115–897]; P = .83), whereas severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) Spike-specific T-cell responses were slightly lower with everolimus (118 [32.1–243] vs 228 [113–381] spot-forming cells [SFCs]/106 peripheral blood mononuclear cells [PBMCs]; P = .02). HZ vaccination led to higher varicella zoster virus (VZV) glycoprotein E (gE)–specific immunoglobulin G titers with everolimus (2192 [888–4523] vs 1101 [440–2078] 50% endpoint titer; P = .004), while VZV gE-specific T-cell responses were similar (85.0 [27.5–155] vs 115 [50.0–258] SFCs/106 PBMCs; P = .24). Besides known side effects, everolimus led to more bacterial infections (27.3% vs 11.1%; P = .03).ConclusionsSix weeks’ replacement of MMF by everolimus in KTRs does not improve COVID-19 booster vaccine immunogenicity, whereas 10 weeks’ replacement enhances humoral HZ vaccine immunogenicity. While replacing MMF by everolimus may improve vaccine responses, its timing and potential risks require careful consideration. https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciaf107/8113296?rss=1