Clinical Background

Arthritis is the leading cause of disability in the United States causing at least 9,500 deaths, 750,000 hospitalizations and 36 million ambulatory care visits annually within the United States. Approximately 10% of all arthritis is rheumatoid arthritis.

The cause of rheumatoid arthritis (RA) is not  well understood, and there is an on-going debate about whether RA is in fact a single disease or a collection of related diseases. Most theories about the causes of RA involve some sort of autoimmune mechanism, possibly secondary to an as yet undefined infection.

Current treatment for RA includes the use of NSAIDs, but may also include the use of more potent anti-inflammatory compounds such as corticosteroids. In addition, disease specific anti-rheumatic drugs (DMARDs) are used in RA. The most commonly used of these is methotrexate, which has well known anti-mitotic properties, but also seems to have specific affects on the pro-inflammatory pathways. Other cytotoxic agents are less commonly used and have more significant side effects.

Animal Models

Biomodels offers collagen-induced arthritis (CIA) models in rats and mice based on the method of Trentham et al (1).   Rats are given a single injection of collagen in an adjuvant on day 1 and arthritis is scored clinically on days 10 through 21.  Mice require more extensive immunization and are generally score from day 28 on.   The extent of the arthritis is evaluated by scoring each paw for erythema (redness) and/or swelling on a 0-4 scale for each paw and then adding them together for a cumulative score up to 16. The scoring is done on all 4 paws so each animal and the different groups can then be compared using a variety of statistical methods.

0= No swelling or erythema
1= Slight swelling and/or erythema
2= low to moderate swelling
3= pronounced swelling with limited joint usage
4= excessive swelling with joint rigidity

In addition, X-rays can be taken of the paws and histological endpoints can also be used to evaluate the extent of the disease.

Collagen-induced arthritis in rodents. A combined score correlating to the extent of arthritic symptoms in rodents with (open clear circles) that can be reversed using the anti-inflammatory dexamethasone (solid red circles).