Utility of animal models for identification of potential therapeutics for rheumatoid arthritis

Abstract

Animal models of rheumatoid arthritis (RA) are widely used for testing potential new therapies for RA. However, the question of which animal model is most predictive of therapeutic efficacy in human RA commonly arises in data evaluation. A retrospective review of the animal models used to evaluate approved, pending RA therapies, and compounds that were discontinued during phase II or III clinical trials found that the three most commonly used models were adjuvant-induced arthritis (AIA) in rats and collagen-induced arthritis (CIA) in rats and mice. Limited data were found for more recently developed genetically modified animal models. Examination of the efficacy of various compounds in these animal models revealed that a compound's therapeutic efficacy, rather than prophylactic efficacy, in AIA and CIA models was more predictive of clinical efficacy in human RA than data from either model alone.

Endothelial dysfunction in rat adjuvant‐induced arthritis: Up‐regulation of the vascular arginase pathway

“…In addition, data on endothelial dysfunction in experimental models of arthritis are scarce. In the present study, we investigated endothelial function in the AIA model, which is commonly accepted as having many histologic and clinical features in common with human RA (31) and which is widely used to predict clinical efficacy of new therapies in RA (32). In accordance with previous studies (12)(13)(14)(15)(16)(33)(34)(35), our data show that endothelial function assessed by the vasodilating response to ACh is impaired in AIA rats.…”

Therapeutic Effect of Human Amniotic Membrane–Derived Cells on Experimental Arthritis and Other Inflammatory Disorders

“…Having demonstrated the immunosuppressive activity of HAMCs on RA cells, we investigated their potential in the treatment of CIA, an experimental model of arthritis in mice that shares a number of histopathologic and immunologic features of RA (29). Two separate intraperitoneal injections of HAMCs to mice with signs of established clinical arthritis progressively attenuated the severity and incidence of the disease ( Figure 3A).…”

Hesperidin and Experimentally-Induced Arthritis in Male Rats

“…Adjuvant arthritis models by as SC. injection of CFA to rats lead to development of RA and is predictive of the clinical efficacy of many drugs in human RA (18) . AIA can be compounded by systemic disease, infiltration of inflammatory cells, and hyperplasia of synovial membrane in association with destruction of joints looking like RA in humans (19) .…”