Collagen-Induced Arthritis Model (CIA)

Rheumatoid arthritis (RA) is an autoimmune disease associated with chronic inflammation, primarily in the joints. RA is characterized by synovial inflammation, swelling, and autoantibody production, which result in the destruction of cartilage and bone in the small joints of hands, wrists, and feet. Vium offers a well-established rat collagen-induced arthritis (CIA) model against which to validate the efficacy of potential therapeutic compounds (1-2). In the rat CIA model, both B and T cells mediate joint inflammation and destruction with signature increases in the cytokines IL-1, IL-6, IL-17, and TNF-alpha which are validated targets for development for new therapeutics.


Study Metrics

Vium Arthritis IndexTM

The Arthritis Index provides an objective measure of function-related disease severity comparable to the traditional arthritis score.  The Arthritis Index is automatically scored using a computer algorithm removing the variability that may arise from manual measurements.

Available Conventional Measures 

  • Arthritis score
  • Ankle joint size (caliper)
  • Ankle joint histopathology
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Figure 1. Example of Vium Arthritis Index tracking increase in arthritis in rat CIA model compared with control.

Figure 2. Typical increase observed in arthritis score in Vium's CIA model after induction compared with control.

Figure 3. Increase in joint size after induction in rat CIA model tracks compared with control.  


Study Overview

We have validated our CIA model in both rats and mice following standard protocols.  Disease onset occurs between 11 to 15 days with average day of onset occurring between study day 12 & 13. Our induction rate is > 95%.

Study Design

Randomization

Subjects are randomized into groups using motion prior to induction and disease severity at time of onset.

Dosing

Subjects are enrolled into treatment groups following the onset of a significant Vium Arthritis Index score or an arthritis score of > 1.  A standard study may dose for 14 – 28 days.

Analysis

Treatment efficacy is assessed using Vium metrics and optional conventional measures to compare disease severity between vehicle and treated animals.   Study progress, subject videos and graphs are made available to you securely via your account on Vium's Research Suite.  

Positive control therapeutics

Several positive control therapeutics can be used including:

  • Methotrexate (daily, PO)
  • Enbrel (q3d, SC)
  • Dexamethasone (daily, PO or IP)
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Figure 4. Effect of Drug Treatment on Motion in Rat CIA RA Study.  Changes over time in Rat CIA study showing comparison between control and therapeutic treated groups.  Treated groups show significantly more motion than non-treated groups.

Figure 5. SOC testing in Rat CIA model showing Arthritis Score for groups treated with various SOC drugs vs control.


Learn More

References

  1. Hegen M, Keith JC Jr, Collins M, Nickerson-Nutter CL. (2008) Utility of animal models for identification of potential thereapeutics for rheumatoid arthritis. Ann Rheum Dis. 67: 1505-15.
  2. Bevaart L, Vervoordeldonk MJ, Tak PP. (2010) Evaluation of therapeutic targets in animal models of arthritis: how does it relate to rheumatoid arthritis? Arthritis Rheum. 62: 2192-205.
  3. Benedele A. (2001) Animal models of rheumatoid arthritis. J Muscoloskelet Neuronal Interact. 1: 377-85.
  4. Trentham DE, Townes AS, Kang AH. (1977) Autoimmunity to type II collagen an experimental model of arthritis. J Exp Med. 146:857-68.
  5. Courtenay JS, Dallman MJ, Dayan AD, Martin A, Mosedale B. (1980) Immunisation against heterologous type II collagen induces arthritis in mice. Nature 283: 666-8.

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