Novel Immunotherapeutic Avenues for Rheumatoid Arthritis

Rheumatoid arthritis (RA) is the most common inflammatory rheumatic disease. It leads to irreversible joint damage, physical handicap, and reduced life expectancy. The past two decades have seen considerable therapeutic advances with the development of biologic treatments to block proinflammatory cytokines or modulate lymphocyte function, followed by the development of small molecules to target intracellular signaling. Nevertheless, only a minority of patients can achieve disease remission, especially long term, warranting further investigation into newer therapeutic options. Targeting single proinflammatory pathways may not be sufficient, as suggested by variable results with T helper (Th)-17-related cytokine blockade. Multilevel information from ‘omics’ techniques along with data from mechanistic studies might facilitate the identification of pivotal checkpoints in RA disease pathogenesis and the subsequent development of new effective treatments.

TrendsCurrent standard therapeutic options for RA involve targeting proinflammatory cytokines [such as tumor necrosis factor (TNF)-α and interleukin (IL)-6] or intracellular signaling pathways, depleting B cells, and controlling T cell activation.Several novel specific inhibitors of Janus kinase (JAK) isoforms and new biologics targeting IL-6 or IL-6 receptor (IL-6R) may enrich the therapeutic armamentarium in the near future.Initial targeting of most Th17 cytokines may have been deceptive, but blockade of cytokines, such as granulocyte-macrophage colony-stimulating factor (GM-CSF), have provided good clinical results. However, further testing is required.In vivo expansion of regulatory T cells by different means is being tested in clinical trials, although this approach remains challenging and controversial.