Animal models of rheumatoid arthritis: How informative are they?
Kay McNamee1, Richard Williams1, Michael Seed2
1Kennedy Institute of Rheumatology, University of Oxford, Roosevelt Drive, Oxford OX3 7FY, UK.
Abstract:
Animal models of arthritis are widely used to de-convolute disease pathways and to identify novel drug targets and therapeutic approaches. However, the high attrition rates of drugs in Phase II/III rates means that a relatively small number of drugs reach the market, despite showing efficacy in pre-clinical models. There is also increasing awareness of the ethical issues surrounding the use of animal models of disease and it is timely, therefore, to review the relevance and translatability of animal models of arthritis. In this paper we review the most commonly used animal models in terms of their pathological similarities to human rheumatoid arthritis as well as their response to drug therapy. In general, the ability of animal models to predict efficacy of biologics in man has been good. However, the predictive power of animal models for small molecules has been variable, probably because of differences in the levels of target knockdown achievable in vivo.
Insights
Animal models are crucial for arthritis research but show variable success in predicting human drug efficacy. This review assesses their relevance and translatability for developing new arthritis therapies.
Area of Science:
- Rheumatology
- Translational Medicine
- Pharmacology
Background:
- Animal models are essential tools for understanding arthritis pathogenesis and discovering new treatments.
- High drug attrition rates in clinical trials highlight limitations in current preclinical models.
- Ethical considerations increasingly prompt a re-evaluation of animal model utility.
Purpose of the Study:
- To review the pathological relevance of common animal models to human rheumatoid arthritis.
- To assess the translatability of these models in predicting drug efficacy.
- To identify factors contributing to the variability in predictive power.
Main Methods:
- Review of commonly utilized animal models for arthritis research.
- Comparison of pathological features with human rheumatoid arthritis.
- Analysis of drug response data, differentiating between biologics and small molecules.
Main Results:
- Animal models generally show good predictive power for biologic therapies in humans.
- Predictive accuracy for small molecule drugs is variable.
- Differences in achievable target knockdown in vivo may explain variable small molecule efficacy prediction.
Conclusions:
- While valuable, animal models have limitations in predicting the efficacy of small molecule drugs for arthritis.
- Further refinement of models is needed to improve translatability, particularly for small molecules.
- The review provides insights into optimizing the use of animal models for arthritis drug development.
