A single-center review of pre-exposure prophylaxis with tixagevimab–cilgavimab in solid organ transplant recipients

Background: Coronavirus disease 2019 (COVID-19) continues to negatively impact solid organ transplant recipients (SOTr). Data on the use of tixagevimab–cilgavimab (tix-cil) in vaccinated SOTr during circulation of Omicron and its subvariants are limited. Therefore, this single-center review was conducted to evaluate tix-cil efficacy in multiple organ transplant groups during a study period where Omicron B.1.1.529, BA.2.12.1, and BA.5 predominated. Methods: In this single-center retrospective study, we evaluated the incidence of COVID-19 infection in adult SOTr who did or did not receive pre-exposure prophylaxis (PrEP) with tix-cil. SOTr were included if they were at least 18 years of age and met emergencyuseauthorizationcriteriafortix-ciluse.Theprimaryoutcomeanalyzedwas the incidence of COVID-19 infection. Results: Ninety SOTr met inclusion criteria and comprised of two groups, tix-cil PrEP ( n = 45) and no tix-cil PrEP ( n = 45). Of SOTr who received tix-cil PrEP, three (6.7%) developed COVID-19 infection, compared to eight (17.8%) in the no tix-cil PrEP group ( p = .20). Of the 11 SOTr diagnosed with COVID-19, 15 (82.2%) were fully vaccinated againstCOVID-19priortotransplantation.Moreover,18.2%and81.8%oftheCOVID-19 cases observed were asymptomatic and mild-to-moderate, respectively. Discussion: Our study results, which included months when BA.5 was in increased circulation,suggestnosignificantdifferenceinCOVID-19infectionwithorwithoutuseof tix-cil PrEP in our solid organ transplant groups. As the COVID-19 pandemic continues to evolve, clinical utility of tix-cil should be evaluated against new, emerging strains.

COVID-19 infection and mortality. 2 This risk is further increased in SOT recipients (SOTr) who are either unvaccinated or partially vaccinated against COVID-19. 3 Since many populations remain vulnerable to COVID-19 despite vaccination, there have been advancements with other pre-exposure prophylaxis measures, including the development of tixagevimab-cilgavimab (tix-cil).
Tixagevimab and cilgavimab are neutralizing IgG1 monoclonal antibodies that bind to non-overlapping regions of the receptor binding domain of the SARS-CoV-2 spike protein, thereby preventing virus attachment via the angiotensin-converting enzyme 2 (ACE2) receptor in humans. 4 The Food and Drug Administration (FDA) issued an Emergency Use Authorization (EUA) for tix-cil in December 2021 largely due to early results of a Phase III clinical trial, PROVENT, that was conducted in unvaccinated and largely immunocompetent patients during the circulation of Alpha (B.1.1.7) and Delta (B.1.617.2) variants. 5 However, tix-cil became available for use in healthcare institutions in January 2022 during the emergence of the Omicron wave.
Importantly, since the early results of PROVENT, several in vitro studies have suggested reduced activity of tix-cil against more recent variants of SARS-CoV-2, including Omicron. 6 Therefore, data on the use of tix-cil in vaccinated SOTr during circulation of Omicron and its subvariants are scarce and limited by a small number of observations.
As a result, this single-center review of tix-cil was conducted to evaluate its efficacy in multiple organ transplant groups including heart, lung, liver, and kidney, during a study period where Omicron B.1.1.529, BA.2.12.1, and BA.5 predominated.

METHODS
We performed a single-center, retrospective review of all adult SOTr who received or did not receive tix-cil for SARS-CoV-2 pre-exposure prophylaxis (PrEP) at Keck Medical Center of USC. Patients were included if they were SOTr, at least 18 years of age, and met EUA criteria for tix-cil. 4 Patients were excluded if they were unvaccinated against COVID-19, and if we were unable to confirm the administration of tix-cil through review of our electronic health record (EHR)

Definitions
Severity of illness was defined based on the criteria outlined by the

Immunosuppression protocols
Institutional protocols for induction and maintenance immunosuppression differed depending on organ type. The protocol for kidney transplantation includes induction with anti-thymocyte globulin (ATG) or basiliximab with methylprednisolone followed by maintenance immunosuppression with tacrolimus, mycophenolate, and prednisone. Liver transplant recipients receive basiliximab induction with or without methylprednisolone based on immunological risk, followed by maintenance immunosuppression consisting of tacrolimus and mycophenolate with or without prednisone. Heart transplant recipients receive induction with ATG or basiliximab with methylprednisolone followed by triple maintenance immunosuppression with tacrolimus, mycophenolate, and prednisone. Last, lung transplant recipients receive basiliximab induction with methylprednisolone, followed by triple maintenance immunosuppression with tacrolimus, mycophenolate, and prednisone.

RESULTS
A total of 70 SOTr receiving tix-cil PrEP were identified at our cen- 68.9%; p = .04). There were no significant differences between the two groups with respect to the remaining baseline characteristics.
Immunosuppression management was organ specific as mentioned in the methods section. Use of basiliximab induction was similar between the tix-cil PrEP group compared to the no tix-cil PrEP group (66.7% vs. 82.2%; p = .09). There was also no difference in ATG use between the two groups (20.0% vs. 11.1%; p = .38). There was also no difference between the two groups with respect to maintenance immunosuppression and steroid usage.
As seen in Figure 1, the incidence of COVID-19 infections in the tix-cil PrEP group was 6.7% over a median follow-up period of 639  Table 3.

DISCUSSION
The current study reports our early experience with using tix-cil for PrEP against SARS-CoV-2 infection in a cohort of SOTr. Since SOTr are at higher risk for severe COVID-19 due to immunosuppressive medications, comorbidities, and suboptimal responses to COVID-19 vaccines, these individuals were universally referred to receive tix-cil.
However, our usage of tix-cil was markedly less than the number of transplants performed. While our institution performed over 250 SOTs in 2022, about one-fourth of these individuals received tix-cil. In this retrospective review, we report the safety and efficacy of tix-cil use.
Although not statistically significant, we found that the occurrence of