Diminished responses to mRNA-based SARS-CoV-2 vaccines in individuals with rheumatoid arthritis on immune- modifying therapies

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disorder that causes debilitating swelling and destruction of the joints. People with RA are treated with drugs that actively suppress one or more parts of their immune system, and these may alter the response to vaccination against SARS-CoV-2. In this study, we analyzed blood samples from a cohort of patients with RA after receiving a 2-dose mRNA COVID-19 vaccine regimen. Our data show that individuals on the cytotoxic T lymphocyte antigen 4-Ig therapy abatacept had reduced levels of SARS-CoV-2-neutralizing antibodies after vaccination. At the cellular level, these patients showed reduced activation and class switching of SARS-CoV-2-specific B cells, as well as reduced numbers and impaired helper cytokine production by SARS-CoV-2-specific CD4+ T cells. Individuals on methotrexate showed similar but less severe defects in vaccine response, whereas individuals on the B cell-depleting therapy rituximab had a near-total loss of antibody production after vaccination. These data define a specific cellular phenotype associated with impaired response to SARS-CoV-2 vaccination in patients with RA on different immune-modifying therapies and help inform efforts to improve vaccination strategies in this vulnerable population.

Automated summary

This study analyzed blood samples from patients with rheumatoid arthritis (RA) after receiving a 2-dose mRNA COVID-19 vaccine. The findings showed that patients on the cytotoxic T lymphocyte antigen 4-Ig therapy had reduced levels of SARS-CoV-2-neutralizing antibodies after vaccination. Additionally, these patients had decreased activation and class switching of SARS-CoV-2-specific B cells, as well as impaired production of helper cytokines by SARS-CoV-2-specific CD4+ T cells. The study provides valuable insights into the impaired response to SARS-CoV-2 vaccination in RA patients on different immune-modifying therapies.