AB0089 SUPERIOR SARS-CoV-2 ANTIBODY RESPONSE ACHIEVED IN RITUXIMAB-TREATED PATIENTS WHEN VACCINATED AGAINST COVID-19 BEFORE COMPARED TO AFTER RITUXIMAB INITIATION – GUIDANCE FOR FUTURE VACCINATION STRATEGIES

Background: Rituximab (RTX) treated patients with autoimmune inflammatory rheumatic diseases have suboptimal responses to COVID-19 vaccines and increased risk of severe COVID-19, which has sparked debates regarding the future use of RTX. However, existing research was conducted on patients already receiving RTX when vaccines became available, failing to account for the current landscape where patients can receive vaccinations before initiating RTX. Objectives: We aimed to compare the serological response to COVID-19 vaccines in patients vaccinated before or after RTX treatment initiation. Methods: Patients treated with RTX at the Dep. of Rheumatology, Aarhus University Hospital, from 2017 to 2022 were eligible for inclusion (n=368). Patients were categorized based on the order of RTX treatment to their primary COVID-19 vaccination: RTX pre (RTX only prior to vaccination), RTX pre+post (RTX prior to and after vaccination), and RTX post (RTX only after vaccination). Additionally, we investigated the effect of vaccines administered ≥ 9 months since the last RTX treatment, "RTX-free" vaccinations. Serological response was evaluated by measuring 2 different SARS-CoV-2-IgGs (Spike & Neutralizing). Blood donors (BDs) were enrolled as controls, n=113. Results: We included 254 patients; 67% female, aged 62 years. The predominant diagnoses were ANCA-vasculitis (31%), rheumatoid arthritis (26%) and myositis (12%). Patients had on average four COVID-19 vaccinations and one infection, while BDs had respectively three and one. The RTX pre+post group had significantly lower concentrations of spike and neutralizing abs compared to the RTX pre and RTX post group, Figure 1a and b. Only 65% of RTX pre+post developed neutralizing abs compared to 91% for the RTX post and 93% for the RTX pre, Figure 1b. There was no difference between the RTX pre or RTX post in seroconversion of the 3 abs measured (all p's ≥ 0.08). Univariate and multivariate logistic regression analysis were performed with seroconversion of SARS-CoV-2-Spike IgG as the dependent variable, Figure 2. The final model had number of "RTX-free" vaccinations (OR 1.93) and number of RTX infusions (OR 0.94) as the significant predictors. There was a significant dose-dependent correlation between "RTX-free" vaccinations with both antibody concentrations and seroconversion (Figure 1c, P< 0.001). The patients with 0 "RTX-free" vaccinations had a seroconversion rate of 50%, compared to 89% for patients with 3 "RTX-free" vaccinations and 40-fold higher median ab levels. Similar dose-dependent associations for both seroconversion and antibody concentrations were also seen for total RTX infusions received, Figure 1d. There were no significant differences in the number of SARS-CoV-2 infections among patient groups. Hospital admissions for COVID-19 were infrequent, and most infections were mild. Conclusion: Our study demonstrates that COVID-19 vaccination administered before initiating RTX will induce a superior serological response compared to vaccination after RTX treatment. Additionally, our findings highlight the importance of timing vaccinations for individuals undergoing RTX treatment. The concept of "RTX-free" vaccinations with a minimum gap of 9 months since last RTX treatment may be useful in guiding vaccination strategies. Finally, our finding underscores the reversibility of the antibody impairment experienced after RTX treatment cessation, provided patients receive an adequate number of "RTX-free" vaccinations. While previous vaccine studies have primarily involved patients already receiving RTX during vaccination, the future landscape will involve vaccinating patients before initiating RTX treatment. This approach yields more favorable serological responses and mitigates the risks associated with SARS-CoV-2 infection during immunosuppression. Our findings have implications for clinical decision-making and highlight the importance of optimizing vaccination strategies in general in patients initiating RTX treatment. Finally, the results should alleviate the current fear and concerns regarding vaccination and the use of RTX. REFERENCES: [1] DOI: 10.3899/jrheum.211152 Acknowledgements: The Danish Rheumatism Association. Disclosure of Interests: None declared.