Targeting pathogenic immune cells in rheumatoid arthritis: emerging immunotherapeutic frontiers

Rheumatoid arthritis (RA) is a persistent autoimmune condition that predominantly affects the joints resulting in inflammation, pain and progressive disability. Immunological imbalance, especially the stimulation of pathogenic immune cells, including T and B cells, macrophages, amongst others, is the cause of the disease, as it is critical to the development of the disease. The limitation of traditional anti-RA medications, such as non-steroidal anti-inflammatory drugs (NSAIDs) and disease-modifying anti-rheumatic drugs (DMARDs), in the treatment of the disease led to the development of more specific medicines. One of the most promising biologic agents, including monoclonal antibodies, cytokine inhibitors and cell-based therapies, are specifically targeting immune cells and inflammatory pathways in RA. This review examines these new immunotherapies, their mechanisms of action, clinical efficacy, and challenges associated with them, including resistance to treatment, safety issues, and the necessity to use personalised therapy. Also, the new immunotherapeutic approaches, which include targeting autoantibodies, gene therapy, and precision medicine, are promising new approaches that could result in more effective and personalised treatments. Finally, the review concludes with a discussion of future directions, where in combination therapies, next-generation biologics, and personalised treatment regimens are also possible and can change the way RA can be managed in the future. To preserve analytical depth, this review explicitly distinguishes established (regulatory-approved) therapies from investigational and experimental approaches and indicates the level of clinical evidence for each.