ObjectiveThe development of sufficient COVID-19 vaccines has been a big breakthrough in fighting the global SARS-CoV-2 pandemic. However, vaccination effectiveness can be reduced in patients with autoimmune rheumatic diseases (AIRD). The aim of this study was to identify factors that lead to a diminished humoral vaccination response in patients with AIRD.MethodsVaccination response was measured with a surrogate virus neutralisation test and by testing for antibodies directed against the receptor-binding-domain (RBD) of SARS-CoV-2 in 308 fully vaccinated patients with AIRD. In addition, 296 immunocompetent participants were investigated as a control group. Statistical adjusted analysis included covariates with a possible influence on antibody response.ResultsPatients with AIRD showed lower antibody responses compared with immunocompetent individuals (median neutralising capacity 90.8% vs 96.5%, p<0.001; median anti-RBD-IgG 5.6 S/CO vs 6.7 S/CO, p<0.001). Lower antibody response was significantly influenced by type of immunosuppressive therapy, but not by rheumatic diagnosis, with patients under rituximab therapy developing the lowest antibody levels. Patients receiving mycophenolate, methotrexate or janus kinase inhibitors also showed reduced vaccination responses. Additional negative influencing factors were vaccination with AZD1222, old age and shorter intervals between the first two vaccinations.ConclusionCertain immunosuppressive therapies are associated with lower antibody responses after vaccination. Additional factors such as vaccine type, age and vaccination interval should be taken into account. We recommend antibody testing in at-risk patients with AIRD and emphasise the importance of booster vaccinations in these patients.