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Background: Patients with immune-mediated rheumatic diseases (IMRD) are commonly treated with immunosuppressors and prone to infections. Recently introduced mRNA SARS-Cov2 vaccines have demonstrated extraordinary efficacy across all ages. Immunosuppressed patients were excluded from phase III trials with SARS-Cov2 mRNA vaccines.
Objectives: To fully characterize B and T cell immune responses elicited by mRNA SARS-Cov2 vaccines in patients with rheumatic diseases under immunotherapies, and to identify which drugs reduce vaccine´s immunogenicity.
Methods: Humoral, CD4 and CD8 immune-responses were investigated in 100 SARS-Cov2-naïve patients with selected rheumatic diseases under immunosuppression after a two-dose regimen of SARS-Cov2 mRNA vaccine. Responses were compared with age, gender, and disease-matched IMRD patients not receiving immunosuppressors and with healthy controls.
Results: IMRD patients showed decreased seroconversion rates (80% vs 100%, p= 0.03) and cellular immune responses (75% vs 100%, p= 0.02). Patients on methotrexate achieved seroconversion in 62% of cases and cellular responses in 80% of cases. Abatacept decreased humoral and cellular responses. Rituximab (31% responders) and belimumab (50% responders) showed impaired humoral responses, but cellular responses were often preserved. Antibody titers were reduced with mycophenolate and azathioprine but preserved with leflunomide and anticytokines.
Conclusion: IMRD patients exhibit impaired SARS-CoV-2 vaccine-immunogenicity, variably reduced with immunosuppressors. Among commonly used therapies, abatacept and B-cell depleting therapies show deleterious effects, while anticytokines preserved immunogenicity. The effects of cumulative methotrexate and glucocorticoid doses on immunogenicity should be considered. Humoral and cellular responses are weakly correlated, but CD4 and CD8 tightly correlate. Seroconversion alone might not reflect the vaccine’s immunogenicity.
Graph 1: Multivariate analysis
| Abatacept | HCQ | Cumulative glucocorticoid dose | Cumulative methotrexate dose | Age > 65 years | Disease duration >10 years | |
|---|---|---|---|---|---|---|
| Seronversion | β - 0.1p= 0.04 | β 0.22 p= 0.01 | β - 0.26p= 0.44 | β - 0.19p= 0.03 | β - 0.27p= 0.002 | β - 0.10 p= 0.22 |
| IgG anti-spike levels | β - 0.13p= 0.001 | β 0.27p= 0.01 | β - 0.25p= 0.004 | β - 0.29p= 0.001 | β - 0.19p= 0.02 | β - 0.14p= 0.04 |
| CD4 T-cell response | β - 0.1p= 0.03 | β 0.10p= 0.24 | β - 0.04p= 0.61 | β - 0.03p= 0.64 | β - 0.05 p= 0.56 | β - 0.14 p= 0.11 |
| CD8 T -cell response | β - 0.08p= 0.02 | β 0.20 p= 0.12 | β - 0.1p= 0.43 | β - 0.02p= 0.24 | β - 0.1 p= 0.56 | β - 0.1 p= 0.15 |
REFERENCES:
[1]Arad U, Tzadok S, Amir S, et al. The cellular immune response to influenza vaccination is preserved in rheumatoid arthritis patients treated with rituximab. Vaccine 2011; 29:1643-1648
[2]Amanna IJ, Slifka MK. Contributions of humoral and cellular immunity to vaccine-induced protection in humans. Virology. 2011;411(2):206-215.
[3]Spiera R, Jinich S, Jannat-Khah D. Rituximab, but not other antirheumatic therapies, is associated with impaired serological response to SARS- CoV-2 vaccination in patients with rheumatic diseases. Ann Rheum Dis. 2021 May 11:annrheumdis-2021-220604. doi: 10.1136/annrheumdis-2021-220604. Epub ahead of print. PMID: 33975857.
Disclosure of Interests: None declared