Modeling human rheumatoid arthritis in NHP: Type II collagen induced arthritis in cynomolgus macaques (167.4)

Abstract Collagen induced arthritis (CIA) rodent models have been extensively used in rheumatoid arthritis (RA) research. An RA model in non-human primate (NHP) is particularly demanded because of the close phylogenesis that provides the cross-reactivity to human for different development compounds using most modern drug technologies. However, NHP RA model has been reported extremely difficult because of the low and inconsistent disease incidence. We studied type II collagen induced arthritis in Cynomolgus monkeys. Following immunization with collagen, the disease progression was monitored for 8 weeks. Overall the arthritic incidence reached 87% and the average arthritic incidence of proximal interphalangeal (PIP) joint reached near 90%, significantly higher than what was previously reported. The average swelling of PIP joint increased approximately by 45%. Radiography, histopathology and histomorphometry analysis of the joint bones well supported the arthritic disease with the similar characteristics of human RA joints. The average arthritic score was significantly reduced with the single agent treatment of Methotrexate or Dexamethasone. Our results demonstrated the successful establishment of an reliable CIA in Cynomolgus monkeys, providing a valuable tool for studies of RA disease in pathogenesis, biomarker, translational research, and most importantly, anti-arthritic therapeutics as well as other relevant diseases, such as anemia of chronic disease and arthritic pain.