Utility of animal models for identification of potential therapeutics for rheumatoid arthritis.
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.
Inflammation Discovery Research, Wyeth Research, Cambridge, MA 02140-2311, USA. mhegen@wyeth.com
M
M
Hegen
J C
JC
Keith
M
M
Collins
C L
CL
Nickerson-Nutter
D000818:Animals; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001169:Arthritis, Experimental / Q000188:drug therapy* / Q000473:pathology; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000473:pathology; D002986:Clinical Trials as Topic; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D006801:Humans; D051379:Mice; D051381:Rats; D013045:Species Specificity; D016896:Treatment Outcome
D018501:Antirheumatic Agents