Safety of Bivalent SARS-CoV-2 Vaccines as a Second Booster Dose in Arthritis Patients on Immunosuppressive Therapies

Background Safety and efficacy of updated bivalent vaccines, containing both the original vaccine variant of SARS-CoV-2 Spike and either Omicron variants BA.1 or BA.4/5, are of particular interest in arthritis patients on immunosuppressive therapies. With the continuous emergence of new viral variants, it is important to evaluate whether updated vaccines induce more adverse events in this patient group. Objectives To examine if a second booster dose with updated bivalent vaccine increases the risk of adverse events, compared to the first booster dose with monovalent vaccines. Methods The prospective Nor-vaC study investigates vaccine responses in patients with immune mediated inflammatory diseases using immunosuppressive therapies (1). The present analyses included arthritis patients who received two booster doses. Patients received available vaccines according to the Norwegian vaccination program. The current recommendation in the Norwegian arthritis population is a three-dose primary vaccination series followed by two booster doses. Adverse events following vaccines doses were self-reported through questionnaires. Adverse events following the first (monovalent) and second (bivalent) booster were compared with McNemar’s test. Results Between 7 th of July 2021 and 6 th of December 2022 a total of 243 arthritis patients (127 rheumatoid arthritis, 65 psoriatic arthritis, 51 spondyloarthritis) on immunosuppressive therapies (Table 1) received a first, monovalent (BNT162b2, mRNA-1273) and a second, bivalent booster dose (BNT162b2 (WT/OMI BA.1), mRNA-1273.214, BNT162b2 (WT/OMI BA.4/BA.5)). Adverse events were recorded within 2 weeks in all patients (Figure 1). In total, 45 vs 49 (19% vs 20 %) patients reported any adverse event after a second, bivalent booster dose, compared to the first, monovalent booster, respectively. There was no significant difference in adverse events overall (p= 0.57). The most common adverse events after the second booster were pain at injection site (12 %), flu-like symptoms (9 %) and headache (6 %). No new safety signals emerged. A total of 15 (6 %) patients reported a disease flare after receiving the second, bivalent booster, compared to 21 (8 %) after the first, monovalent booster. Conclusion There was no difference in adverse events between the monovalent, first booster, and the bivalent, second booster, indicating that bivalent vaccines are safe in this patient group. Reference [1]Syversen S.W. et al Arthritis Rheumatol 2022 Table 1. Demographic characteristics and immunosuppressive medication in patients receiving a 1 st monovalent and a 2 nd bivalent booster dose. Characteristics Patients, n (%) Total 243 Age (years), median (IQR) 61 (52-67) Female 152 (63) Immunosuppressive medication TNFi mono a 75 (31) TNFi combo a+b 72 (30) Methotrexate 62 (26) Rituximab 9 (4) IL-inhibitors c 6 (2) JAK-inhibitors d 11 (5) Other e 8 (3) 1st booster BNT162b2 106 (44) mRNA-1273 137 (56) 2nd booster BNT162b2 (WT/OMI BA.1) 65 (25) BNT162b2 (WT/OMI BA.4/BA.5) 120 (47) mRNA-1273.214 (WT/OMI BA.1) 58 (23) Results in n (%) unless otherwise specified. a Tumor necrosis factor inhibitors: infliximab, etanercept, adalimumab, golimumab, certolizumab pegol. b Combination therapy: methotrexate, sulfasalazine, leflunomide, azathioprine. c Interleukin inhibitors: tocilizumab, secukinumab. d Janus kinase inhibitors: filgotinib, baricitinib, upadacitinib, tofacitinib. e Other: abatacept, sulfasalazine, leflunomide, azathioprine. Figure 1. Adverse events after bivalent vaccine as a 2 nd booster dose compared to a monovalent vaccine as a 1 st booster dose. Acknowledgements We thank the patients and health-care workers who have participated in the Norwegian study of vaccine response to COVID-19. We thank the patient representatives in the study group, Kristin Isabella Kirkengen Espe and Roger Thoresen. We thank all study personnel, laboratory personnel, and other staff involved at the clinical departments involved, particularly Synnøve Aure, Margareth Sveinsson, May Britt Solem, Elisabeth Røssum-Haaland, and Kjetil Bergsmark. Disclosure of Interests Hilde Ørbo: None declared, Ingrid Jyssum: None declared, Anne Therese Tveter: None declared, Ingrid E. Christensen: None declared, Joseph Sexton: None declared, Kristin Hammersbøen Bjørlykke Speakers bureau: Janssen-Cilag, Grete B. Kro: None declared, Tore K. Kvien Speakers bureau: Amgen, Celltrion, Egis, Evapharma, Ewopharma, Hikma, Oktal, Sandoz, Sanofi, Consultant of: AbbVie, Biogen, Celltrion, Eli Lilly, Gilead, Mylan, Novartis, Pfizer, Sandoz, Sanofi, Grant/research support from: AbbVie, Amgen, BMS MSD, Novartis, Pfizer, UCB, Ludvig A. Munthe Speakers bureau: Novartis, Cellgene, Gunnveig Grodeland Speakers bureau: Bayer, Sanofi, ThermoFisher, Consultant of: AstraZeneca, Siri Mjaaland: None declared, John Torgils Vaage: None declared, Espen A Haavardsholm Speakers bureau: Pfizer, UCB, Consultant of: AbbVie, Boehringer-Ingelheim, Eli Lilly, Gilead, Kristin Kaasen Jørgensen Speakers bureau: Bristol-Myers Squibb, Roche, Sella Aarrestad Provan: None declared, Silje Watterdal Syversen: None declared, Guro Løvik Goll Speakers bureau: AbbVie/Abbott, Galapagos, Pfizer, UCB, Consultant of: AbbVie/Abbott, Galapagos, Pfizer, UCB.