Ab0085 Pre-Exposure Prophylaxis of Sars-Cov-2 Infection and Severe Covid-19 With Tixagevimab and Cilgavimab (Evusheld) in Rheumatologic Patients Treated With Rituximab at Risk of Severe Covid-19: Efficacy and Safety Analysis of an Italian Monocentric Cohort

Background: Pts (pts) with inflammatory rheumatic and musculoskeletal diseases (IRMD) treated with Rituximab (RTX) are at higher risk of severe SARS-CoV-2 infections and COVID-19-related death[1,2]. The monoclonal antibodies tixagevimab and cilgavimab (Evusheld (EVS)) were authorised at a 150 mg/150 mg dose for pre-exposure prophylaxis (PrEP) against SARS-CoV-2 in pts treated with RTX in the previous 12 months. Objectives: The primary endpoint was to test EVS efficacy in preventing SARS-CoV-2 infections and severe COVID-19 cases at 6 months in IRMD pts treated with RTX in the previous 12 months, comparing subjects treated and not treated with EVS. Secondary endpoint was assessing EVS' safety profile. Methods: From 1 October 2022 to 31 December 2022, we screened 90 adult IRMD pts treated with at our tertiary rheumatological centre. They could have received a dose of an anti-COVID-19 vaccine or recovered from a SARS-CoV-2 infection more than 2 weeks before EVS. Exclusion criteria included pregnancy, breastfeeding, coagulopathies, significant cardiovascular risk factors, and allergic reactions to EVS components. Demographic and clinical variables were assessed at baseline. Pts were followed longitudinally at 30 days and 6 months. Baseline characteristics were analysed via descriptive statistics. We used Chi-squared test and Student's t-test to compare categorical and continuous variables. Survival analysis with Kaplan-Meier and log-rank tests compared time to first infection between the 2 groups. Results: Out of 90 screened pts, 26 were treated with EVS, 28 were excluded for contraindications, and 36 refused EVS. Treated pts had a mean age of 56 ± 15.95 years, and 88.5% were female. Diagnoses, among others, included rheumatoid arthritis (RA) (50%), systemic lupus erythematosus (11.5%), and systemic sclerosis (7.7%). In the EVS group, 23 (88.5%) pts completed the anti-COVID19 2-dose primary vaccination series, 42.3% received one booster dose, 34.6% received a second booster dose, and 7.7% were unvaccinated; 42.3% reported at least one SARS-CoV-2 infection within the prior 12 months. The control group (n=64) had a mean age of 57 ± 13.34 years, with 82.8% females; RA was the predominant diagnosis (68.7%). In the control group, 87.5% completed the 2-dose primary vaccination series, 45.3% received one booster dose, and 25% received a second booster dose; 39% reported at least one infection in the preceding 12 months. No EVS pts reported infections or adverse events at 30 days. At 6 months, 1 (3.8%) EVS pt reported mild COVID-19. In the control group, 20.3% reported infection at 6 months, with 1 severe case. Comparison between groups did not show a statistically significant difference in infection rates (p=0.051). Survival analysis demonstrated a mean time to infection of 207 ± 4.15 days for the EVS group and 183 ± 7.54 days for the control group (p=0.053). Conclusion: EVS prevented SARS-CoV-2 infections in 25 (96.2%) pts at 6 months. Our small sample size could have influenced the lack of a statistically significant association between EVS and SARS-CoV-2 prevention. Despite its limitations, this study provides real-world data on PrEP with EVS in high-risk IRMD pts treated with RTX. REFERENCES: [1] Avouac, J. et al. COVID-19 outcomes in pts with inflammatory rheumatic and musculoskeletal diseases treated with rituximab: a cohort study. Lancet Rheumatol.3, e419–e426 (2021). [2] Florence, A. et al. Severity of COVID-19 and survival in pts with rheumatic and inflammatory diseases: data from the French RMD COVID-19 cohort of 694 pts. Ann. Rheum. Dis.80, 527–538 (2021). Acknowledgements: NIL. Disclosure of Interests: Manuel Sette: None declared, Maria Manara Novartis, Angelini, Lilly, MSD, Laura Giudice: None declared, Martina Biggioggero: None declared, Nicoletta Del Papa: None declared, Ennio Giulio Favalli AbbVie, BMS, Celltrion, Galapagos, Janssen, Lilly, MSD, Novartis, Pfizer, UCB, AbbVie, BMS, Celltrion, Galapagos, Janssen, Lilly, MSD, Novartis, Pfizer, UCB, Maria Gerosa: None declared, Francesca Ingegnoli: None declared, Roberto F. Caporali AbbVie, Amgen, BMS, Celltrion, Fresenius, Galapagos, Janssen, Lilly, Novartis, Pfizer, UCB, AbbVie, Fresenius, Galapagos, Lilly, Novartis, Pfizer, UCB.