Current and novel therapeutic targets in the treatment of rheumatoid arthritis.

Rheumatoid arthritis (RA), a multifactorial disease characterized by synovitis, cartilage destruction, bone erosion, and periarticular decalcification, finally results in impairment of joint function. Both genetic and environmental factors are risk factors in the development of RA. Unwanted side effects accompany most of the current treatment strategies, and around 20-40% of patients with RA do not clinically benefit from these treatments. The unmet need for new treatment options for RA has prompted research in the development of novel agents acting through physiologically and pharmacologically relevant targets. Here we discuss in detail three critical pathways, Janus kinase/signal transducer and activator of transcription (JAK/STAT), Th17, and hypoxia-inducible factor (HIF), and their roles as unique therapeutic targets in the field of RA. Some of the less developed but potential targets like nucleotide-binding and oligomerization domain-like receptor containing protein 3 (NLRP3) inflammasome and histone deacetylase 1 (HDAC1) are also discussed.