Rheumatoid factors revisited in the age of biologic therapy

The discovery of RF has been instrumental in diagnosing and classifying RA. Various RF isotypes, including IgM-RF and IgA-RF, have been linked to disease severity and treatment responses. The role of RF in RA pathogenesis, primarily through the formation of immune complexes, also carries the potential to influence the response to different medications. Recent progress in biologic therapies has further elucidated the role of RF in RA management. Treatments such as rituximab, abatacept and tocilizumab have shown differential efficacy based on RF status, with RF-positive patients often exhibiting better responses. Recent research also suggests that TNF inhibitors (TNFi) lacking the IgG1-Fc fragment like certolizumab pegol (CZP) may offer advantages over TNFi with an IgG1-Fc fragment, in RF-positive patients by preventing immune complex formation. Since this early observation is predominantly derived from previous multicentre studies with heterogeneous populations and potentially varying RF measurement methods, prospective randomized studies directly addressing this issue are essential for a more thorough and reliable evaluation. This paper is a narrative review outlining the evolving understanding of RF in the context of biologic therapies, emphasizing the need for personalized treatment approaches based on serological profiles and underlying immune mechanisms.