LAUSR

OBJECTIVE The effectiveness of COVID-19 vaccinations wanes due to immune evasion of the B.1.1.529 (Omicron) variant and diminished antibody titers over time. We aim to evaluate the benefit of a fourth vaccination dose in patients with autoimmune rheumatic diseases (ARD). METHODS A retrospective analysis included ARD patients 18 years or older in the Clalit health management organization in Israel, insured 52% of the entire population, from January 16, 2022, to March 31, 2022, when the predominant SARS-CoV-2 variant was Omicron. We compared patients without previous COVID-19 infection who received three doses of the BNT162b2 vaccine (control) to those who received the fourth dose. The primary outcome was COVID-19 infection, which was analyzed using multivariate Cox regression in the entire cohort and within ARD subgroups. Secondary outcomes were COVID-19-related hospitalizations and death. RESULTS We included 43,748 ARD patients, of whom 27,766 and 15,982 were in the control and fourth vaccination groups, respectively. COVID-19 infection occurred in 6,942 (25.0%) of the control group and 1,754 (11.0%) of the fourth dose group (p < 0.001). Patients vaccinated with the fourth dose had a lower risk for COVID-19 infection in the entire cohort (HR 0.54, 95% CI 0.52-0.58) and throughout every subgroup regardless of the baseline characteristic or medical treatment except for rituximab. A similar association was observed in COVID-19-related hospitalization (HR 0.36, 95% C.I 0.22-0.61) and COVID-19-related death (HR 0.41, 95% C.I 0.24-0.71). CONCLUSION Fourth BNT162b2 vaccination of ARD patients was associated with favourable outcomes compared to three doses among patients with no history of COVID-19 infection.