Time Since Rituximab Treatment Is Essential for Developing a Humoral Response to COVID-19 mRNA Vaccines in Patients With Rheumatic Diseases

Objective. We aimed to investigate (1) whether patients with rheumatic disease (RD) treated with rituximab (RTX) raise a serological response toward the coronavirus disease 2019 (COVID-19) mRNA vaccines, and (2) to elucidate the influence of time since the last RTX dose before vaccination on this response. Methods. We identified and included 201 patients with RDs followed at the outpatient clinic at the Department of Rheumatology, Aarhus University Hospital, who had been treated with RTX in the period 2017-2021 and who had completed their 2-dose vaccination series with a COVID-19 mRNA vaccine. Total antibodies against the SARS-CoV-2 spike protein were measured on all patients and 44 blood donors as reference. Results. We observed a time-dependent increase in antibody response as the interval from the last RTX treatment to vaccination increased. Only 17.3% of patients developed a detectable antibody response after receiving their vaccination <= 6 months after their previous RTX treatment. Positive antibody response increased to 66.7% in patients who had RTX 9-12 months before vaccination. All blood donors (100%) had detectable antibodies after vaccination. Conclusion. Patients with RDs treated with RTX have a severely impaired serological response toward COVID-19 mRNA vaccines. Our data suggest that the current recommendations of a 6-month interval between RTX treatment and vaccination should be reevaluated.