B Cell Reconstitution is Associated With COVID-19 Booster Vaccine Responsiveness in Patients Previously Seronegative Treated With Rituximab.

OBJECTIVE: To assess factors associated with serologic response to the coronavirus 2019 (COVID-19) booster vaccine in patients with autoimmune rheumatic diseases treated with rituximab (RTX) who were previously serologically unresponsive to the initial vaccine series. METHODS: A retrospective chart review of patients treated with RTX who failed to demonstrate a serologic response to the first SARS-CoV-2 vaccination series and subsequently received an mRNA vaccine booster was performed. Serologic response ≥ 4 weeks after the booster was the primary outcome. Fisher exact tests, t tests, and Wilcoxon rank-sum tests were used for comparisons. RESULTS: In 31 patients who were previously seronegative, 68% seroconverted following a booster of the COVID-19 vaccine. B cell reconstitution was significantly different between those with positive (median 1.79, IQR 0.65-3.00) and negative (median 0, IQR 0-0) serologic responses to the booster. The days from last RTX dose were also statistically different among seroconverters (median 301, IQR 251-368) vs nonseroconverters (median 188, IQR 169-245). Demographic characteristics were not associated with serologic positivity. Positive predictive value of B cell presence was 90.9% (95% CI 70.8-98.9) and negative predictive value was 100% (95% CI 59-100) for serologic response to the mRNA booster vaccine. Positive predictive value of time ≥ 6 months from last RTX dose to booster was 78.3% (95% CI 56.3-92.5) and the negative predictive value was 62.5% (95% CI 24.5-91.5). CONCLUSION: Detectable B cells and longer time from last RTX exposure were associated with the development of anti-SARS-CoV-2 spike protein antibodies following the booster vaccine. These findings should be considered in timing boosters in patients treated with RTX.

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

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.