Research in context
Evidence before this study We screened studies published between Jan 1, 2020, and Aug 1, 2022, in PubMed using the terms “COVID-19”, “SARS-CoV-2”, AND “BNT162b2” AND “rheumatoid arthritis”, “systemic lupus erythematosus”, “ANCA-associated vasculitis” to find original articles and systematic reviews published in English, examining the humoral immune response against SARS-CoV-2, induced by the BNT162b2 mRNA vaccine, in patients with an autoimmune inflammatory rheumatic disease (AIRD) induced by the two doses of BNT162b2 mRNA vaccine. Most studies focused on short-term humoral immune responses within 4 months after the second BNT162b2 vaccination. These short-term observations revealed that the use of several immunosuppressants such as rituximab, mycophenolate mofetil, glucocorticoids, abatacept, and methotrexate, correlated with a decrease in SARS-CoV-2 antigen-specific antibodies. Regarding the immune response to variants of concern induced by BNT162b2, the level of antibody produced against the Delta variant was reported to be lower than that against the wild-type or Alpha variant in patients with AIRDs. However, no studies have evaluated the immune responses against the Omicron variant induced by BNT162b2 in patients with AIRDs. We screened studies published between Jan 1, 2020, and Aug 1, 2022, in PubMed using the terms “COVID-19”, “SARS-CoV-2”, AND “BNT162b2” AND “rheumatoid arthritis”, “systemic lupus erythematosus”, “ANCA-associated vasculitis” to find original articles and systematic reviews published in English, examining the humoral immune response against SARS-CoV-2, induced by the BNT162b2 mRNA vaccine, in patients with an autoimmune inflammatory rheumatic disease (AIRD) induced by the two doses of BNT162b2 mRNA vaccine. Most studies focused on short-term humoral immune responses within 4 months after the second BNT162b2 vaccination. These short-term observations revealed that the use of several immunosuppressants such as rituximab, mycophenolate mofetil, glucocorticoids, abatacept, and methotrexate, correlated with a decrease in SARS-CoV-2 antigen-specific antibodies. Regarding the immune response to variants of concern induced by BNT162b2, the level of antibody produced against the Delta variant was reported to be lower than that against the wild-type or Alpha variant in patients with AIRDs. However, no studies have evaluated the immune responses against the Omicron variant induced by BNT162b2 in patients with AIRDs. Added value of this study We enrolled 598 patients with AIRDs and 148 healthy controls in this study. We found that medium-term humoral immunity was attenuated in anti-neutrophil cytoplasmic antibody-associated vasculitis and rheumatoid arthritis (RA) patients treated with glucocorticoids, tumor necrosis factor-α inhibitors (TNFis), or abatacept. In patients with RA or systemic lupus erythematosus, the levels of anti-Omicron receptor-binding domain/spike IgG induced by two doses of BNT162b2 strongly correlated with neutralizing antibody titers but were lower than those of anti-SARS-CoV-2 wild-type antibodies. We enrolled 598 patients with AIRDs and 148 healthy controls in this study. We found that medium-term humoral immunity was attenuated in anti-neutrophil cytoplasmic antibody-associated vasculitis and rheumatoid arthritis (RA) patients treated with glucocorticoids, tumor necrosis factor-α inhibitors (TNFis), or abatacept. In patients with RA or systemic lupus erythematosus, the levels of anti-Omicron receptor-binding domain/spike IgG induced by two doses of BNT162b2 strongly correlated with neutralizing antibody titers but were lower than those of anti-SARS-CoV-2 wild-type antibodies. Implications of all the available evidence Previously, TNFis were thought to have few short-term effects on antibody titer production after vaccination, but our report reveals potential negative medium-term effects. Therefore, our results suggest that the recommended interval of consecutive vaccination for AIRD patients may differ depending on the disease and treatment. In particular, an early booster vaccination may be recommended for anti-neutrophil cytoplasmic antibody-associated vasculitis and RA patients receiving treatment with glucocorticoids, TNFis, or abatacept. Furthermore, not only were antibody titers against variants of concern lower in immunosuppressant users after two vaccinations lower, but cellular immune responses were also reduced compared to those in healthy controls, representing one of the reasons why multiple vaccinations are recommended for patients receiving immunosuppressants. Previously, TNFis were thought to have few short-term effects on antibody titer production after vaccination, but our report reveals potential negative medium-term effects. Therefore, our results suggest that the recommended interval of consecutive vaccination for AIRD patients may differ depending on the disease and treatment. In particular, an early booster vaccination may be recommended for anti-neutrophil cytoplasmic antibody-associated vasculitis and RA patients receiving treatment with glucocorticoids, TNFis, or abatacept. Furthermore, not only were antibody titers against variants of concern lower in immunosuppressant users after two vaccinations lower, but cellular immune responses were also reduced compared to those in healthy controls, representing one of the reasons why multiple vaccinations are recommended for patients receiving immunosuppressants.