Clinical Symposium: Joint Damage in Rheumatoid Arthritis

Jill Wong, MD, Andrew Thompson, MD

This ACR session consisted of three components, which will be summarized separately.

1. Radiographic Data with DMARDs and Biologic Agents
This session was an overview of Phase III data of radiographic analysis of disease progression, following treatment with disease-modifying anti-rheumatic drugs (DMARDs) and biologic agents in rheumatoid arthritis. Radiographic progression was measured using the Sharp Score, which is calculated from joint erosions, and joint space narrowing, found in the small joints of the hands and feet. The medications included in the analysis were:
 • Methotrexate
 • Leflunomide
 • Infliximab
 • Etanercept
 • Anakinra.

Methotrexate was found to significantly retard radiographic progression versus placebo over a 12-month period. It was also found to be statistically equivalent to leflunomide in an active controlled trial over 12 months. Similarly, leflunomide was found to be superior to placebo in two randomized controlled trials (RCTs) over 12 months. It was also found to be statistically equivalent to methotrexate and sulfasalazine over a 12-month period.

Infliximab was superior to methotrexate alone (in patients who had previously failed methotrexate and with a long disease duration) in slowing the progression of erosions over a two-year period. Etanercept was equivalent to methotrexate in patients with early disease over a two-year period. Anakinra versus placebo was found to be effective over 24 weeks with continued efficacy to 48 weeks.

In summary, all DMARDs and biologic agents described were found to be effective in reducing radiographic progression in rheumatoid arthritis. Unfortunately, direct comparison between studies is difficult because of differences in disease severity, disease duration and rate of radiographic progression.

2. Why Joint Space Narrowing and Bone Erosions are Different Biologic Processes
Cartilage and bone matrices exhibit striking differences in composition and organization. Therefore, it has been speculated that the cellular and biochemical processes responsible for their degradation may differ. In rheumatoid arthritis, the degradation of bone is thought to be secondary to osteoclastic activity produced at the bone-pannus junction. In contrast, the degradation of cartilage is thought to be secondary to the actions of pannus-derived synovial fibroblasts and macrophages, as well as the chondrocytes themselves.

3. Poor Correlation of Radiographic Data and Functional Outcomes
In patients with early rheumatoid arthritis, there is significant disability as measured by the Health Assessment Questionnaire (HAQ). The HAQ indicates that disability increases by 1 to 2% annually. Joint damage is reflected by radiographic erosions and joint space narrowing. These indicators become evident within two years and increase by 1 to 2% per year. A correlation between disability and damage is only seen with disease duration greater than five years. Factors contributing to disability not only include joint damage, but also psychological, socio-economic and functional limitations. However, the largest contribution remains unexplained.

back to list of reports

This program has been provided through an unrestricted educational grant from McNeil Consumer Healthcare, the makers of TYLENOL*(acetaminophen).