Humoral immunogenicity of COVID-19 vaccines in patients with inflammatory rheumatic diseases under treatment with Rituximab: a case–control study (COVID-19VacRTX)

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.

Optimal time for COVID-19 vaccination in rituximab-treated dermatologic patients

“…Experts suggest waiting at least five months after the last rituximab administration (21,22). Our study, corresponding to others, found that vaccinating at less than six months post-rituximab is extremely low yielded since the humoral immune response to COVID-19 vaccines was virtually blocked by rituximab during this period (42)(43)(44)(45). IMDD patients who required rituximab every six months should be considered for alternative COVID-19 preventive measures, for instance, passive immunization with Tixagevimab/Cilgavimab injection (i.e., human monoclonal antibodies against the surface spike protein of SARS-CoV-2).…”

Do quantitative levels of antispike‐IgG antibodies aid in predicting protection from SARS‐CoV‐2 infection? Results from a longitudinal study in a police cohort

“…In this cohort, a high vaccination rate and a low infection rate were observed during the first 11 months of the study period. 7,8 COVID-19 vaccines do generate anti-S1 IgG, [22][23][24] and a significant association between the anti-S1 IgG levels and infection risk reduction was observed in this study. In the prediction model, values above 900 BAU/mL added little to the infection risk reduction in the pre-Omicron period.…”

High T-cell response rate after COVID-19 vaccination in belimumab and rituximab recipients

“…B-cell-targeted therapies are the cornerstone of treatment for many systemic autoimmune diseases, and they often represent non-deferrable treatment for some clinical conditions. It has been suggested that B-cell recovery before vaccination increases the chances of an adequate humoral response to the vaccine [ 29 ]. However, our results indicate that B-cell depletion cannot preclude SARS-CoV-2 vaccination, since a cellular immune response can be elicited even in the absence of circulating B cells.…”