Daniel Mrak1, Elisabeth Simader1, Daniela Sieghart1, Peter mandl2, Helga Radner1, Thomas Perkmann3, Helmuth Haslacher3, Margareta Mayer4, Maximilian Koblischke4, Philipp Hofer5, Lisa Göschl1, Felix Kartnig1, Thomas Deimel6, Andreas Kerschbaumer6, Thomas Hummel1, Barbara Kornek6, Renate Thalhammer3, Karin Stiasny4, Stefan Winkler7, Josef Smolen6, Judith Aberle4, Daniel Aletaha8, Leonhard Heinz1 and Michael Bonelli1, 1Division of Rheumatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria, 2Division of Rheumatology, Department of Internal Medicine III, Medical University of Vienna, Wien, Austria, 3Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria, 4Center for Virology, Medical University of Vienna, Vienna, Austria, 5Department of Pathology, Medical University of Vienna, Vienna, Austria, 6Medical University of Vienna, Vienna, Austria, 7Division of Infectious Diseases and Tropical Medicine, Department of Internal Medicine I, Medical University of Vienna, Vienna, Austria, 8Medical University Vienna, Wien, Austria
Background/Purpose: Humoral immune response to COVID-19 vaccination is vastly diminished in B-cell depleted patients, resulting in lower antibody titers in patients with a potential higher risk of severe COVID-19. It has previously been shown that non-seroconverted patients partially seroconvert upon a third vaccination. However, it remains unclear whether rituximab treated patients benefit from a fourth vaccination and should therefore postpone rituximab therapy.
Methods: Within an open-label extension study, Rituximab treated patients who have received a third vaccination with either a vector (ChAdOx1 nCoV-19) or an mRNA vaccine were included to receive a fourth vaccination with an mRNA-based vaccine. Antibodies were quantified using the Elecsys Anti-SARS-CoV-2 S immunoassay against the receptor-binding domain (RBD) of the spike protein. SARS-CoV-2-specific T cell responses were quantified by IFN-γ ELISpot assays.
Results: Upon fourth vaccination, the number of patients who seroconverted could be increased from 12/36 (33%) to 22/36 (61%). Anti-RBD antibody titers could be raised from 11.6 [IQR 8.1, 25.5] to 344.5 BAU/ml [IQR 119.0, 1387.8] in patients who were already seroconverted after the third dose. Hereby, vaccine responses were diminished in patients who received rituximab in the last 6 months compared to those who didn't (antibody increase of 124 [IQR 64, 300] vs 1880 [IQR 1311, 2449] BAU/ml, respectively). Cellular immune responses were higher in patients who received a vector vaccine as a 3rd dose. No unexpected safety signals were detected, one serious adverse event not related to vaccination occurred.
Conclusion: A fourth COVID 19 vaccination is safe in patients undergoing rituximab treatment However, rituximab seems to have an adverse effect on an additional booster vaccination Indication of rituximab should be carefully assessed before application and pre/post exposure prophylaxis such as monoclonal antibodies should be evaluated in these high risk patients.
Disclosures: D. Mrak, Pfizer; E. Simader, Boehringer-Ingelheim; D. Sieghart, None; P. mandl, AbbVie, Bristol-Myers Squibb(BMS), Celgene, Janssen, Eli Lilly, Novartis, Merck/MSD, Roche, UCB; H. Radner, None; T. Perkmann, None; H. Haslacher, Glock Health, BlueSky Immunotherapies, Neutrolis; M. Mayer, None; M. Koblischke, None; P. Hofer, None; L. Göschl, None; F. Kartnig, Boehringer-Ingelheim, Eli Lilly; T. Deimel, None; A. Kerschbaumer, AbbVie/Abbott, Eli Lilly, Gilead, Merck/MSD, Amgen, Janssen, UCB; T. Hummel, None; B. Kornek, Biogen, BMS Celgene, Johnsson&Johnsson, Merck, Novartis, Roche, Sanofi-Genzyme, Teva; R. Thalhammer, None; K. Stiasny, Pfizer; S. Winkler, None; J. Smolen, AbbVie, AstraZeneca, Eli Lilly, Novartis, Amgen, Bristol Myers Squibb, Galapagos-Gilead, Janssen, Merck-Sharp-Dohme, Novartis-Sandoz, Pfizer, Roche-Chugai, Samsung, UCB; J. Aberle, None; D. Aletaha, Novartis, SoBi, Sanofi, Amgen, Lilly, Merck, Pfizer, Roche, Sandoz, Janssen, AbbVie; L. Heinz, None; M. Bonelli, Eli Lilly.
