Abstract
Objective: The factors involved in the increase in antibody titers in rheumatoid arthritis（RA）patients who receive multiple doses of COVID-19 vaccines, as in Japan, are not fully understood. Therefore, we compared the antibody titers of RA patients with those of age- and sex-matched controls, and investigated the influence of various factors on antibody titers. In addition, people who have already been infected with COVID-19 and those who have not received the COVID-19 vaccine were excluded from the analysis.
Subjects and methods: We measured nucleotide（N）and spike protein（S）antibody titers in 446 RA patients and 30 control subjects, and investigated the number of vaccinations, vaccination date and time, and medication used. We also compared the two groups and examined the influence of medication used in the RA group. Finally we performed a multiple regression analysis with S antibody titers as the dependent variable. Patients with a history of COVID-19 infection and those who had not received the COVID-19 vaccine were excluded from the analysis.
Results: No significant difference in S antibody titers was observed between the RA group（median 8.58［interquartile range 7.56, 9.35］U/ml（natural logarithm transformed））and the control group（8.83, ［7.98, 9.49］）（p=0.472）. In RA patients, S antibody titers increased with age（Spearman rank correlation, ρ=0.158, P=0.004）, and elderly patients tended to receive more vaccinations. S antibody titers increased significantly with increasing number of vaccinations, but reached a plateau at four doses. S antibody titers were significantly lower in prednisolone users compared to non-users（P=0.023）, and among users of molecular targeted drugs, anti-TNF（tumor necrosis factor）agent users showed significantly lower S antibody titers compared to non-users（P < 0.001）. Multiple regression analysis showed that female gender, number of days since the last vaccination, and use of bDMARDs and prednisone were significant factors influencing S antibody titers. However, no effect was observed with the use of methotrexate（MTX）.
Conclusion: In RA patients using bDMARDs（anti-TNF agents）and prednisolone, the rise in S antibody titers after vaccination was suppressed, but there was no effect from the use of MTX.
