HUMORAL IMMUNE RESPONSE AGAINST BNT162B2 MRNA COVID-19 VACCINE in JAPANESE RHEUMATIC DISEASE PATIENTS RECEIVING IMMUNOSUPPRESSIVE THERAPY: A MONOCENTRIC STUDY

ABSTRACT

Background: Patients with immune-mediated infammatory diseases are inherently susceptible to infections and are at high risk of developing COVID-19. COVID-19 vaccination in patients with rheumatoid and musculoskeletal disease (RMD) is strongly recommended [1]. BNT162b2 is the most used COVID-19 vaccine in Japan. The safety and efficacy of this vaccine has been demonstrated in the general population [2], but patients receiving immunosuppressive therapy were excluded from the study. Although data on the immunogenicity of COVID-19 vaccine in the immunocompromised adult population is rapidly increasing, the immunogenicity of mRNA COVID-19 vaccine in RMD patients receiving medication has been reported in various and still inadequate ways. Furthermore, the immunogenicity of mRNA COVID-19 vaccine may vary depending on the medication. In addition, most of these data were reported from Western countries, and data on Japanese patients with RMD are limited. Objectives: To investigate serum antibody titre against SARS-CoV-2 spike protein following BNT162b2 vaccination in Japanese RMD patients on various immunomodulatory treatment. Methods: Two hundred and twelve RMD outpatients undergoing treatment at Kagawa University Hospital and 43 healthy volunteers, who had received two doses of BNT162b2, were included in the study. Serum sample was collected at least 14 days after the second dose. Antibody titer against SARS-CoV-2 spike protein in serum was measured by ELISA (Elecsys Anti-SARS-CoV-2 S RUO). We analyzed the relationship between clinical characteristics, including the type of disease and treatment of RMD, and antibody titer against SARS-CoV-2 spike protein. Results: The antibody titer against SARS-CoV-2 spike protein in RMD patients was signifcantly lower than that in healthy subjects. In the analysis with therapeutic agents, the mean antibody titer in RMD patients treated with rituximab (RTX) was much lower than that in healthy controls. Patients treated with baricitinib, azathioprine, mycophenolate mofetil, abatacept, TNF inhibitors, cyclosporine, IL-6 inhibitors, methotrexate (MTX), or glucocorti-coids (GC) had only moderately lower antibody titers. Patients treated with tacrolimus, an immunosuppressive drug commonly used for treatment in Japan, showed a slight decrease in antibody titer, but the difference was not signifcant compared with healthy subjects. IL-17 and IL-23 inhibitors did not impair the humoral response. In addition, the combination of MTX with various immunosuppressive agents reduced titers, although this was not statistically signifcant. Conclusion: Many of the immunosuppressants impaired the immunogenicity to BNT162b2 in Japanese RMD patients. The degree of decline of antibody titers differed according to immunosuppressant. MTX potentially impairs the immunogenicity of BNT162b2 also in the case of concomitant use with other immunosuppressant.