AB0069 MRNA VACCINES EXERT A BIPOLAR CLINICAL EFFECTIVENESS IN PATIENTS WITH RITUXIMAB-TREATED IMMUNE-MEDIATED INFLAMMATORY DISEASES OF VARYING DISEASE ACTIVITY STATUSES
Authors: P. H. Lai, C. H. Lu, T. W. Chang, S. H. Lan, C. F. Cheng, S. C. Hsieh
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> Rituximab (RTX) is a cornerstone therapy in immune mediated inflammatory disease (IMID) in addition to conventional treatment. Immune responses to vaccination can be impaired by RTX therapy[1,2]; however, real-world data regarding SARS-CoV-2 vaccine effectiveness in RTX-treated IMID patients suffering from COVID-19 infection remained limited. <h3>Objectives:</h3> This study aims to explore the associations between the exposure mechanism of the SARS-CoV-2 vaccine and the outcomes of COVID-19 infection in IMID patients who have previously received RTX treatment. <h3>Methods:</h3> In the NTUH-RTX cohort, IMID patients hospitalized for COVID-19 infection during April 2021 to April 2023 were retrospectively identified, and 1:2 matched with non-hospitalized COVID-19-infected controls by age, gender and diagnosis. COVID-19 infection was diagnosed by SARS-CoV-2 RNA rRT-PCR assay and/or antigen test. Patients without any SARS-CoV-2 vaccination or received the first RTX therapy after vaccination were excluded. The demographics, serum markers, and subsequent medical outcomes were systematically reviewed from the electronic health records. Using the National Immunization Information System (NIIS), the vaccination history of each patient was identified, and divided into three types: mRNA vaccines (BNT162b2/Pfizer–BioNTech and mRNA -1273/Moderna), protein-based vaccines (MVC-CoV1901/Medigen and NVX-CoV2373/Novavax), and adenoviral vectored vaccine (ChAdOx1/AstraZeneca). In the analysis, patients were categorized based on their vaccination history: exclusively exposed to mRNA vaccines (pure-mRNA), protein-based with/without other vaccines, and others. The time interval between the date of the last SARS-CoV-2 vaccination and the COVID-19 diagnosis (abbreviated as Vac_COV) was calculated. Associations between outcomes (hospitalization, very delayed viral shedding, and all-cause mortality) and vaccination history were explored using the Mann-Whitney U-test. Multivariate analysis was conducted with logistic regression. <h3>Results:</h3> A total of 22 hospitalized cases and 49 matched non-hospitalized controls were included. Their characteristics are shown in Table 1. mRNA vaccine exposure was numerically higher in the non-hospitalized group (Figure 1A). In the lower baseline serum IgG group, Vac_COV was associated with hospitalization (Figure 1B). In the hospitalized cases, 11 (50.0%) had severe disease, 14 (64.0%) had very delayed viral shedding, and 12 (55.0%) died. Pure-mRNA vaccines were correlated with very delayed viral shedding and all-cause mortality (Figure 1C). In multivariate analysis, pure-mRNA vaccines were correlated with very delayed viral shedding (odds ratio: 21.589, 95% CI 0.804, 6.374; p= 0.019). Protein-based vaccine exposure protected against all-cause mortality (odds ratio: 0.062, 95% CI 0.002, 0.636; p = 0.040). In the hospitalized cases with lower serum albumin, pure-mRNA vaccines were linked to very delayed viral shedding and all-cause mortality (Figure 1Dand E) while the effects were explicitly not seen in the higher serum albumin group. In univariate analysis, pure-mRNA vaccines were correlated with all-cause mortality (odds ratio: 18.000, 95% CI 1.634, 488.469; p = 0.034). In multivariate analysis, protein-based vaccine exposure protected against all-cause mortality (odds ratio: 0.016, 95% CI 3.955x10-5, 0.363; p = 0.039). <h3>Conclusion:</h3> mRNA vaccines protect against hospitalization in patients with higher serum albumin levels, but they are correlated with worse outcomes in patients with lower serum albumin levels. Albumin, being a negative acute-phase reactant, can serve as a marker of disease activity in patients with IMID. Vaccine effectiveness varies according to individual disease activity status. Protein-based vaccines may offer better efficacy in patients with lower serum albumin levels. Future research needs to elucidate the optimal SARS-CoV-2 vaccination strategies in IMID patients previously received RTX. <h3>REFERENCES:</h3> [1] Jena A, Mishra S, Deepak P, et al. Autoimmun Rev. 2022 Jan;21(1):102927. [2] Magliulo D, Wade SD, Kyttaris VC. Clin Immunol. 2022 Jan;234:108897. <h3>Acknowledgements:</h3> National Taiwan University Hospital, Department of Internal Medicine. <h3>Disclosure of Interests:</h3> <b>None declared.</b>