EBioMedicine (Nov 2024)

Cilgavimab and tixagevimab as pre-exposure prophylaxis in vaccine non-responder kidney transplant recipients during a period of prevalent SARS-CoV-2 BA.2 and BA.4/5 variants—a prospective cohort study (RESCUE-TX)Research in context

  • Roman Reindl-Schwaighofer,
  • Andreas Heinzel,
  • Lukas Raab,
  • Robert Strassl,
  • Carsten T. Herz,
  • Florina Regele,
  • Konstantin Doberer,
  • Oliver Helk,
  • Paul Spechtl,
  • Constantin Aschauer,
  • Karin Hu,
  • Rahel Jagoditsch,
  • Bianca Reiskopf,
  • Georg A. Böhmig,
  • Bernhard Benka,
  • Benedikt Mahr,
  • Karin Stiasny,
  • Lukas Weseslindtner,
  • Michael Kammer,
  • Thomas Wekerle,
  • Rainer Oberbauer

Journal volume & issue
Vol. 109
p. 105417

Abstract

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Summary: Background: The response to severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) vaccination is severely impaired in patients on maintenance immunosuppression after kidney transplantation. Methods: We conducted a prospective cohort study of 194 kidney transplant recipients (KTR) who exhibited no response to SARS-CoV-2 vaccinations (i.e., SARS-CoV-2 spike protein antibodies ≤264 U/mL) and had no prior documented infection. Patients received 300 mg of cilgavimab/tixagevimab as SARS-CoV-2 pre-exposure prophylaxis (PrEP) between March 4, 2022, and May 3, 2022 and were contrasted to a matched cohort of 186 KTRs also without immunization again defined as SARS-CoV-2 spike protein antibodies ≤264 U/mL and no documented prior infection. The primary outcome was the serum kinetics of cilgavimab/tixagevimab, the secondary endpoints were time to SARS-CoV-2 breakthrough infection, severity of disease and variant specific live viral in vitro neutralization tests of patient sera. Findings: Longitudinal serum level monitoring showed a half-life of 91 days for both antibodies (95% CI 86–95 days for cilgavimab and 85–96 days for tixagevimab) in KTRs. In vitro neutralization tests showed effectiveness against the BA.2 omicron subvariant but not BA.5. The cumulative incidence of SARS-CoV-2 infections until May 15, 2022, (BA.2 dominance) was 15/194 vs 36/186 in the PrEP and control group respectively (OR = 0.35, 95% CI 0.18–0.66) but was not different thereafter (BA.4/5 dominance). The number of severe infections during the BA.2 period was lower in the prophylaxis than in the control group (OR = 0.37, 95% CI 0.17–0.79). Interpretation: This study showed that SARS-CoV-2 PrEP with cilgavimab/tixagevimab demonstrated clinical effectiveness against variants that are neutralised (BA.2) but not against BA.4/5. Funding: This study was funded by the Medical University of Vienna and an unrestricted grant from AstraZeneca (ESR-21-21585).

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