Novel therapeutic strategies for autoimmune and inflammatory rheumatic diseases

Drugs of unknown mechanisms of action are no longer being developed because we have largely capitalized on our improved understanding of the immunopathogenesis of immune-mediated inflammatory diseases (IMIDs) to develop therapeutic monoclonal antibodies (mAbs) and targeted treatments. These therapies have profoundly revolutionized the care of IMIDs. However, because of the heterogeneity of IMIDs and the redundancy of the targeted molecular pathways, some patients with IMIDs might not respond to a specific targeted drug or their disease might relapse secondarily. Therefore, there is much at stake in the development of new therapeutic strategies, which include combinations of mAbs or bispecific mAbs (BsMAbs), nanobodies and nanoparticles (NPs), therapeutic vaccines, small interfering RNA (siRNA) interference, autologous hematopoietic stem cell transplan-tation (aHSCT), or chimeric antigen receptor (CAR)-T cells. With the broad pipeline of targeted treatments in clinical development, the therapeutic paradigm is rapidly evolving from whether new drugs will be available to the complex selection of the most adequate targeted treatment (or treatment combination) at the patient level. This paradigm change highlights the need to better characterize the heterogeneous immunological spectrum of these diseases. Only then will these novel therapeutic strategies be able to fully demonstrate their potential to treat IMIDs.