470. Clinical Effectiveness of The Monoclonal Antibody Combination Tixagevimab-Cilgavimab (T/C) as Pre-Exposure Prophylaxis (PReP) of COVID-19 among Patients (pts) with Moderate to Severe Immunocompromised (IC) Conditions across a Large U.S. Healthcare System: A Propensity Score-Matched Retrospective Cohort Study

BACKGROUND: T/C authorization in the US for PrEP of COVID-19 in IC individuals was initially based on a randomized trial (PROVENT). However, < 5% of enrollees in PROVENT were IC. We sought to assess real-world effectiveness of T/C PrEP among IC pts. METHODS: We conducted a retrospective, observational, propensity-score matched cohort study at UPMC from Jan 1, 2022, to Mar 31, 2023. We assessed effectiveness at ≤ 6 months of T/C 600 mg (as initial dose, or as 300 mg then 300 mg ≤ 3 months later) against chart confirmed COVID-19 hospitalizations and COVID-19–related deaths among IC pts. RESULTS: Before matching, there were 2931 T/C vs 157,225 non-T/C pts. After matching, 2301 matched pairs remained (78.5% vs 1.8% of all eligible T/C vs non-T/C pts). Most pts had moderate/severe IC conditions (Table 1). During the study period encompassing circulating variants both susceptible and resistant to T/C, there were 15 vs 18 COVID-19 hospitalizations across 377,832 person-days in T/C vs non-T/C pts (Table 2). Thus, 0.72% vs 0.87% of T/C exposed vs unexposed pts were hospitalized for COVID-19 (HR 0.833, 95% CI 0.39 – 1.75, p = 0.73) (Table 2; Figure 1). There was no difference in effectiveness by T/C dosing pattern (Table 2). Effectiveness was numerically higher in the BA.5 period, although there were few events in other variant eras (Table 2). There was a non-significant 50% lower risk of hospitalization in T/C patients with solid tumors or autoimmune conditions, and no significant difference by exposure status in patients with organ transplant or hematologic cancer (Table 2). There were 5 COVID-19 ICU admissions per exposure group, and 2 inpatient COVID-19–related deaths (1 per group) (Table 3). Limitations included overall low event rate limiting power and an open healthcare system leading to possibility of missing hospitalizations due to pts seeking care elsewhere. [Figure: see text] [Figure: see text] [Figure: see text] CONCLUSION: The overall low number of chart-confirmed COVID-19 hospitalizations for the entire cohort limited our ability to detect a statistical difference between T/C exposed vs. unexposed patients. Possible clinical benefit of T/C is suggested for solid tumor and autoimmune patients, although larger studies will need to confirm this observation. [Figure: see text] DISCLOSURES: Ghady Haidar, MD, Allovir: Grant/Research Support|AstraZeneca: Advisor/Consultant|AstraZeneca: Grant/Research Support|Karius: Advisor/Consultant|Karius: Grant/Research Support|NIH: Grant/Research Support Graham M. Snyder, MD, SM, Infectious Diseases Connect: Advisor/Consultant Cátia Ferreira, PhD, AstraZeneca: Employee Lisa Glasser, MD, AstraZeneca: Stocks/Bonds Kathleen Heil, RN, BSN, AstraZeneca: Employee Andrew Lee, MSc, AstraZeneca: Employee Carla Talarico, PhD, MPH, AstraZeneca: Stocks/Bonds Sudhir Venkatesan, MPH, PhD, AstraZeneca: Employee Sylvia Taylor, PhD, MPH, MBA, AstraZeneca: Stocks/Bonds Erin K. McCreary, PharmD, Abbvie: Advisor/Consultant|Ferring: Advisor/Consultant|GSK: Honoraria|La Jolla (Entasis): Advisor/Consultant|LabSimply: Advisor/Consultant|Merck: Advisor/Consultant|Shionogi: Advisor/Consultant|Shionogi: Honoraria John W. Mellors, MD, AstraZeneca: Grant/Research Support|Gilead Sciences: Grant/Research Support