Rituximab, but not other biologics, impairs humoral immunity in patients with rheumatoid arthritis—a study using CoVariant protein arrays

Abstract Objectives RA is an autoimmune disease characterized by chronic inflammation and joint destruction. Biologics are crucial to achieving treat-to-target goals in patients with RA. The global spread and continuous variation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) necessitate the monitoring of variant-specific humoral responses post-vaccination. The aim of this study was to investigate how different biologic treatments for vaccinated RA patients might affect their neutralizing antibodies against multiple SARS-CoV-2 variants. Methods We recruited RA patients who had received three doses of conventional SARS-CoV-2 vaccines and were treated with various biologics, e.g. TNF inhibitor (etanercept), IL-6 inhibitor (tocilizumab), CTLA4-Ig (abatacept) or anti-CD20 (rituximab). Serum samples were used to profile the binding and neutralizing antibodies using our own SARS-CoV-2 variant (CoVariant) protein array, developed previously. Results Compared with healthy controls, only RA therapy with rituximab showed a reduction in neutralizing antibodies capable of targeting spike proteins in SARS-CoV-2 wild-type and most variants. This reduction was not observed in binding antibodies against SARS-CoV-2 wild-type or its variants. Conclusion After receiving three doses of SARS-CoV-2 vaccination, RA patients who underwent rituximab treatment generated sufficient antibodies but exhibited lower neutralizing activities against wild-type and multiple variants, including current Omicron. Other biological DMARDs, e.g. TNF inhibitor, IL-6 inhibitor and CTLA4-Ig, did not show obvious inhibition. Lay Summary What does this mean for patients? This research examined the impact of various biologic treatments (a type of drug) on the immune response of rheumatoid arthritis (RA) patients to coronavirus disease 2019 (COVID-19) vaccination. The study revealed that RA patients treated with rituximab had significantly lower levels of neutralizing antibodies against various severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants, including Omicron, even after receiving three vaccine doses. Neutralizing antibodies defend the body from organisms that cause disease, such as viruses, by preventing them from entering cells. In contrast, RA patients receiving other biologic therapies, including TNF inhibitors, IL-6 inhibitors or CTLA4-Ig, did not experience the same reduction in neutralizing antibodies. No significant difference was found in serum antibodies