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.