Assessing the post hoc effectiveness of tixagevimab-cilgavimab for prevention of SARS-CoV-2 infections in solid organ transplant recipients

BackgroundTixagevimab-cilgavimab (Tix-Cil) was authorized for prophylaxis against COVID-19 in immunocompromised patients from December 2021 through January 2023. Real-world effectiveness for solid organ transplant (SOT) recipients has been unclear.MethodsWe enrolled 911 SOT recipients into a longitudinal COVID-19 serology study, of whom 381 (42%) received >= 1 dose of Tix-Cil. We collected and analyzed data on incident SARS-CoV-2 infections and antibody kinetics for all patients from January 2022 to March 2023, including periods dominated by Omicron BA and BQ subvariants.ResultsOver 253 +/- 131 days of follow-up, there were 324 new-onset SARS-CoV-2 infections: 117 (31%) in Tix-Cil treated and 207 (39%) in Tix-Cil untreated patients (p = .012). In analyses adjusting for demographic, clinical, and COVID-19 exposure factors, any Tix-Cil treatment was associated with lower infection risk (OR 0.52, 95% CI 0.27-0.96, p = .039) throughout the surveillance period including when more resistant BQ.1 and BQ.1.1 subvariants had emerged (12/1/2022 onwards). Among treated patients, receiving a Tix-Cil dose was associated with substantial and sustained increase in anti-spike IgG antibody and angiotensin-converting enzyme 2 binding inhibition levels (Abbott Architect assay) that together also demonstrated association with lower infection risk (p = .042). During the full surveillance period, the frequency of infections requiring hospitalization was low overall (N = 26, 2.9% of the total cohort) and not significantly different between Tix-Cil recipients (N = 12, 3.2% of treated patients) and non-Tix-Cil recipients (N = 14, 2.6% of untreated patients) with unadjusted p = .31 for between-group difference.ConclusionIn a large cohort of SOT recipients, we found that Tix-Cil reduced infection risk even amidst emergent Omicron subvariants. Additionally, the extent of measurable humoral response to Tix-Cil may indicate relative effectiveness. Pre-exposure monoclonal antibody therapy may represent a strategy that will continue to offer clinical benefit for immunocompromised persons who are known to derive limited protection from vaccinations.image In a surveillance study of solid organ transplant recipients, tixagevimab-cilgavimab reduced infection risk even amidst emergent Omicron subvariants. Measures of circulating humoral response to treatment also appeared to predict clinical effectiveness. Monoclonal antibody therapies may continue to offer protection from SARS-CoV-2 for immunocompromised patients who gain limited benefit from vaccinations.image

Automated summary

In a study of solid organ transplant recipients, Tixagevimab-cilgavimab exhibited a reduction in infection risk even in the presence of emergent Omicron subvariants. Measures of circulating humoral response to treatment also seemed to serve as indicators of clinical effectiveness. Monoclonal antibody therapies may continue to offer protection against SARS-CoV-2 for immunocompromised patients who have limited benefit from vaccinations.