Abstract
Objectives: Patients with inflammatory rheumatic diseases (IRDs) treated with the anti-CD20 mAb 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 the time frame 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), AZD1222 (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 factors influencing the antibody levels were evaluated.
Results: A total of 102 patients were included. Of these, 65 (64%) showed a negative antibody level (<24 IU (international unit)/ml) after the vaccination. The comparative univariate analysis of the antibody levels achieved a significant result (P = 0.0008) for the time between the last RTX infusion and first vaccination against SARS-CoV-2. No CD19+ peripheral B-cells could be detected 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 the antibody titre and the interval between the last RTX infusion and the first vaccination, the number of peripheral B-cells, and immunoglobulin quantity. Improved understanding of the effect of these parameters can help guide synchronization of vaccination in relation to the RTX therapy regimen.
Keywords: ANCA-associated vasculitis; COVID-19; RA; antibody; immunogenicity; rituximab; vaccination.
【저자키워드】 COVID-19, immunogenicity, antibody, rituximab, vaccination., ANCA-associated vasculitis, RA, 【초록키워드】 SARS-CoV-2, Vaccine, vaccination, therapy, severe COVID-19, ELISA, B cell, outcomes, Ad26.COV2.S, AZD1222, Immunoglobulin, International, therapeutic, Patient, humoral immune response, anti-CD20, Moderna, antibody level, mAb, Antibody titre, case-control study, B-cell, dose, Inflammatory, B-cells, humoral, rheumatic disease, regimen, Factor, Frame, increased risk, blood sample, help, Univariate analysis, first vaccination, CD19+, parameter, examined, the patient, evaluated, approved, reduced, treated, Improved, quantified, RNA-1273, RTX, synchronization, 【제목키워드】 Treatment, COVID-19 vaccine, Patient, case-control study, Inflammatory, rheumatic disease,