Abstract
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.
Keywords: rheumatoid arthritis, ANCA-associated vasculitis, rituximab, vaccination, COVID-19, antibody, immunogenicity
Contributor Information
Falk Schumacher, Department of Rheumatology, Krankenhaus Porz am Rhein, Cologne, Germany.
Nikola Mrdenovic, Department of Rheumatology, Krankenhaus Porz am Rhein, Cologne, Germany.
Dennis Scheicht, Department of Rheumatology, Krankenhaus Porz am Rhein, Cologne, Germany.
Jörn Pons-Kühnemann, Medical Statistics, Institute of Medical Informatics, Justus Liebig University, Giessen, Germany.
Christine Scheibelhut, Medical Statistics, Institute of Medical Informatics, Justus Liebig University, Giessen, Germany.
Johannes Strunk, Department of Rheumatology, Krankenhaus Porz am Rhein, Cologne, Germany.
Supplementary Material
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