Objectives Patients with inflammatory rheumatic diseases (IRD) treated with the monoclonal anti-CD20 antibody rituximab (RTX) have been identified as high-risk for severe COVID-19 outcomes. Additionally, there is increased risk due to reduced humoral immune response, induced by therapeutic B cell depletion. This study sought to quantify humoral response after vaccination against SARS-CoV-2 in patients with IRD treated with RTX. It also sought to elucidate the influence of timeframe between the last RTX dose and the first vaccination or the status of B cell depletion on antibody titre. Methods In this case-control study patients with IRDs previously treated with RTX were examined for humoral immune response after completing the first series of vaccinations with approved vaccines (BNT162b2 (Biontech/Pfizer), RNA-1273 (Moderna), (AstraZeneca/Oxford), Ad26.COV2.S (Janssen/Johnson & Johnson). Antibody levels were quantified using the Euroimmun Anti-SARS-CoV-2 QuantiVac ELISA [EI-S1-IgG-quant]. Blood samples were taken just before the next infusion with RTX after the vaccination. The interval between the last RTX infusion and the first vaccination against SARS-CoV-2 and other possible influencing factors on the antibody levels were evaluated. Results 102 patients were included. 65 (64%) showed a negative antibody level (<24IE/ml) after the vaccination. The comparative univariate analysis of the antibody levels achieved a significant result (p= 0.0008) for the time between last RTX infusion and first vaccination against SARS-CoV-2. No CD19+ peripheral B-cells could be measured in 73 of the patients (72%). Conclusion The study confirms the negative impact of RTX on antibody level after vaccination against SARS-CoV-2. A clear relationship exists between antibody titre and interval of the last infusion to the first vaccination, number of peripheral B-cells and immunoglobulin quantity. These parameters help improve synchronization of vaccination and RTX therapy regimen.
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