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.

Response to SARS-CoV-2 vaccines in patients receiving B-cell modulating antibodies for renal autoimmune disease

“…We show that the humoral response strongly correlates with B-cell counts and the interval between last anti-CD20 antibody administration and vaccination. Both, time from Rituximab to humoral response and CD19 counts necessary for vaccination response, are similar to results reported in parallel studies [ 15 – 20 ]. This provides crucial information on how to time anti-CD20 antibody application and SARS-CoV-2 vaccinations.…”

COVID-19 in people with rheumatic diseases: risks, outcomes, treatment considerations

“…Notably, BCDT also affects immune responses to influenza vaccination and pneumococcal vaccination in patients with RA 104,105 . The presence of peripheral B cells at >10 cells per microlitre around 6 months after treatment with BCDT seems to be a reliable indication that seroconversion will occur following SARS-CoV-2 vaccination in people with RA or ANCA-associated vasculitis 4,88,[106][107][108][109] . The use of mycophenolate (including mycophenolate mofetil and mycophenolic acid) is associated with substantial impairment of humoral immunity following SARS-CoV-2 vaccination.…”

Immunogenicity, breakthrough infection, and underlying disease flare after SARS-CoV-2 vaccination among individuals with systemic autoimmune rheumatic diseases

“…Duration since rituximab exposure may be an important contributor to improved humoral response 17 . In a retrospective study of 56 patients treated with rituximab, the longer the period between the patient’s last exposure of rituximab and SARS-CoV-2 vaccination was associated with a positive serologic response, with those who had exposure >12 months had the best response 18 . Additionally, B-cell reconstitution has been reported to be a reliable marker of seroresponse in those with vasculitis or rheumatoid arthritis 14 , 17 , 18 .…”