Pos1202 b-Cell Reconstitution Is Strongly Associated With a Positive Serologic Response to the Covid-19 Booster Vaccine in Previously Serologically Unresponsive Rituximab Treated Rheumatic Disease Patients

Abstract

BackgroundBooster doses of SARS-CoV-2 vaccines have emerged as an important strategy for containing the pandemic and may be especially important to rituximab treated patients. B-cell depletion has been associated with worse outcomes from COVID-19 infection, and many rituximab treated patients demonstrate an inadequate serologic response to the initial vaccine series (1). Strategies to optimize serologic response to COVID-19 vaccine boosters in previously serologically unresponsive patients is, therefore, of particular relevance.ObjectivesTo assess factors associated with serologic response to COVID-19 booster vaccines in rituximab treated patients previously serologically unresponsive to the initial vaccine series.MethodsA retrospective chart review of rituximab treated patients 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 four weeks or more after the booster was the primary outcome. T-tests, Fisher’s exact tests, and Wilcoxon rank sum tests were used for comparisons. Box and whisker plots were constructed to visualize differences between serologic response.ResultsIn 31 rituximab treated patients who were seronegative following the initial vaccine series, demographic characteristics, concurrent therapies, rheumatologic diagnosis, and vaccine type were not associated with serologic positivity to the booster vaccine (Table 1). B-cell reconstitution was significantly different between those with positive (median, IQR 1.785 (0.65, 3)) and negative (median, IQR 0 (0,0)) serologic responses to the booster (p-value<0.001) as was time from last rituximab exposure (p-value = 0.030) (Figure 1). 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. Positive predictive value of time >6 months from last rituximab to the booster was 78.3% (95% CI 56.3%, 92.5%) and the negative predictive value was 62.5% (95% CI 24.5%, 91.5%).Table 1.Bivariate comparisons between seronegative and seropositive patients to the COVID-19 booster vaccine by patient characteristics and demographicsFactorValueNegativePositivep-valueaN311021Age, median (IQR)64 (51, 72)63 (51, 69)65 (51, 73)0.75Sex1.00 Female23 (74%)7 (70%)16 (76%) Male8 (26%)3 (30%)5 (24%)Any immunosuppressantb9 (29%)3 (30%)6 (29%)1.00Corticosteroid5 (16%)1 (10%)4 (19%)1.003rdVaccine dose type0.24 Pfizer19 (61%)8 (80%)11 (52%) Moderna12 (39%)2 (20%)10 (48%)Dichotomous B-cell status around booster dose<0.001 No detectable B-cells7 (23%)7 (70%)0 (0%) Detectable B-cells22 (71%)2 (20%)20 (95%) Missing2 (6%)1 (10%)1 (5%)Time from last RTX infusion to booster, median (IQR)260 (216, 379)188 (169, 245)301 (251, 368)0.030Time from last RTX infusion to booster dose0.10 <6months8 (25.81%)5 (50%)3 (14%) 6-12 months15 (48.39%)3 (30%)12 (57%) >12 months8 (25.81%)2 (20%)6 (29%)aP-values are from Fisher’s exact test, Student’s T-test and Wilcoxon rank sum testsbImmunosuppressants included Leflunomide, Azathioprine, Methotrexate, Mycophenolate Mofetil, and TocilizumabIQR= Interquartile rangeConclusionPresence of detectable B-cells and longer time from last rituximab were associated with the development of SARS-CoV-2 spike protein antibodies following the booster vaccine. These factors should be considered in timing of administration of booster vaccine doses in previously unresponsive rituximab treated patients.References[1]Levavi H, Lancman G, Gabriolove J. Impact of rituximab on COVID-19 outcomes. Ann Hematol 2021;100:2805-12.Disclosure of InterestsKaitlin Schultz: None declared, Deanna Jannat-Khah Shareholder of: Cytodyn, Astrazeneca, Walgreens, Robert Spiera Consultant of: AbbVie, Regeneron, Sanofi, Chemomab, Formation Biologics, GSK, Janssen Pharmaceuticals, Chemocentryx, Grant/research support from: GSK, Boehringer Ingelheim Pharmaceuticals, Corbus Pharmaceuticals, Formation Biologics, InflaRx, Kadmon, Astrazeneca, AbbVie, Sanofi, Genentech/Roche, Principia, Novartis