THE EFFECT of IMMUNOSUPPRESSIVE AGENTS on ANTIBODY FORMATION after COVID-19 VACCINATION in RHEUMATOID ARTHRITIS PATIENTS

ABSTRACT

Background: There is still controversy about the efficacy of COVID-19 vaccination and its extent in lowering immunogenicity of Rheumatoid Arthritis (RA) patients. The guideline in whether immunosuppressive agents need to be discontinued before the vaccination is continuously updated because it is considered to lower immunogenicity. Furthermore, there is great discussion on the effectiveness of the COVID-19 booster vaccine and interest in antibody generation in different types of vaccine, as in South Korea there are many patients who were prescribed the mRNA booster vaccine after two doses of ChAdOx1-S nCoV-19 vaccine. Objectives: Thus, we investigated the differences of antibody production between patients who received only two doses of ChAdOx1-S nCoV-19 and those who received the mRNA booster vaccine. Also, antibody production under different types of immunosuppressive agents was analyzed. Methods: From October 14, 2021 to January 21, 2022 at a tertiary referral center, two patient groups diagnosed with RA were studied prospectively;one group that completed 1st and 2nd doses of ChAdOx1-S nCoV-19 vaccine, second group that completed mRNA booster vaccine as well as two doses of ChAdOx1-S nCoV-19 vaccine. SARS-CoV-2 antibody testing on the semiquantitative anti-SARS-CoV-2 S enzyme immunoassay was done, and differences in antibody titers were analyzed in patients who received different immunosup-pressive agents such as csDMARD, TNF inhibitor, JAK inhibitor, Tocilizumab, Abatacept and Corticosteroid. Statistical analysis with a multivariate logistic regression model was performed. Results: In a total of 261 patients, 153 patients had completed two doses of ChAdOx1-S nCoV-19, 108 patients had completed third mRNA booster vaccine. Anti-SARS-CoV-2 RBD antibody positive rate (titer>0.8U/mL) was 97%(149/153) and 99%(107/108) respectively, and only 5 patients showed negative result. In the aspect of high antibody titer(>250U/mL), which is the upper limit of the RBD antibody immunoassay, the result showed rate of 31% (47/153) in the non-booster group and 94%(102/108) in the booster group respectively. Among the different immunosuppressive agents and other clinical aspects, multivariate analysis revealed that corticosteroid use (OR 0.91;95% CI 0.86-0.98), older age(OR 4.33;95% CI 1.34-13.91), and male gender(OR 0.35;95% CI 0.16-0.75) were signifcantly associated with low rate of high antibody titer. Furthermore, out of 14 patients who underwent antibody test twice before and after the mRNA booster vaccine, other than four patients who already showed high titer of >250U/mL before the mRNA booster vaccine, 10 patients showed an increase in titer after the booster vaccine and 7 patients were acquired high titer of >250U/mL. Conclusion: Anti-SARS-CoV-2 RBD antibody positive rate was 97% or more regardless of the mRNA booster vaccination. However, patients who received the mRNA booster vaccine after two doses of ChAdOx1-S nCoV-19 vaccine showed high antibody titer (>250U/mL) three times more than those who did not receive the booster shot. Our fndings also showed that corticosteroid use, old age, and male gender is signifcantly associated with low rate of acquiring high antibody titer.