Inflammatory Arthritis: Current therapeutics and emerging CAR-based cell therapies

Abstract

Inflammatory Arthritis (IA) encompasses a heterogeneous group of chronic immune-mediated disorders, such as rheumatoid arthritis (RA), characterized by synovial inflammation, pain, and progressive joint and bone destruction. Despite major advancements in the pharmacological management of IA that includes non-steroidal anti-inflammatory drugs (NSAIDs), glucocorticoids (GCs), conventional and biologic disease-modifying anti-rheumatic drugs (DMARDs) and a new class of Janus kinase (JAK) inhibitors, a substantial proportion of patients fail to achieve sustained remission or disease control. This review provides a comprehensive overview of the current therapeutic landscape for IA, highlighting the successes and limitations of existing treatment strategies. Importantly, we examine the rapidly evolving field of chimeric antigen receptor (CAR)-based cell therapies, focusing primarily on CAR-T cells and the emerging concept of CAR-macrophages (CAR-M), as innovative approaches to target key pathogenic cell populations in IA. We synthesize preclinical evidence and systematically review the latest clinical applications of CAR-T cell therapy in RA. Furthermore, we explore in depth for the first time in the context of IA, the potential of CAR-M to resolve synovial inflammation and drive tissue repair. By integrating insights from both oncology and rheumatology, this review oUers a forward-looking perspective on how CAR-based adoptive immunotherapies may complement or surpass conventional IA treatments.