B Cell Reconstitution Is Strongly Associated With COVID-19 Vaccine Responsiveness in Rheumatic Disease Patients Who Received Treatment With Rituximab.

ABSTRACT

OBJECTIVE: To assess the association of a detectable antibody response to COVID-19 vaccination with factors including B cell depletion in patients who received treatment with rituximab (RTX). METHODS: We conducted a retrospective review of the charts of adult patients who received treatment with RTX and completed messenger RNA vaccination for SARS-CoV-2. The primary outcome measure was the presence or absence and strength of the serologic antibody response to vaccination. Comparisons between those with and those without a detectable serologic response were calculated using t-tests, Fisher's exact test, and Wilcoxon's rank sum test. The relationship between the serologic response to COVID-19 vaccination and B cell reconstitution status was assessed using negative predictive values and positive predictive values with data reported as percentages with 95% confidence intervals (95% CIs). RESULTS: In 56 patients being treated with RTX, a significant difference in terms of the level of B cell reconstitution was observed in those with a positive serologic response compared to those with a negative serologic response to vaccination (proportion of B cells reconstituted among total lymphocytes, median 2% [interquartile range (IQR) 0.13-10%] versus median 0% [IQR 0-0%]; P < 0.001).There was also a significant difference in the time since the last RTX infusion between patients with a positive serologic response compared to those with a negative serologic response to vaccination (median time since last infusion 594 days [IQR 262-1,163] versus median 138 days [IQR 68-197]; P < 0.001). There was no serologic response to COVID-19 vaccination after the last exposure to RTX in 13% of patients (3 of 24) at >12 months after last exposure, 55% of patients (6 of 11) at 6-12 months after last exposure, and 86% of patients (18 of 21) at <6 months after last exposure. CONCLUSION: B cell reconstitution and a longer time since a patient's last exposure to RTX are associated with a positive serologic response to the COVID-19 vaccine. Strategies for maximizing vaccine responsiveness in patients who receive treatment with RTX should incorporate assessment of B cell reconstitution.