Progressive Joint Damage in Rheumatoid Arthritis

What Are the Risk Factors?

X-ray of arthritic knees
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Progressive joint damage is what doctors, researchers, and patients with arthritis and rheumatic diseases strive to control. It is the consequence of chronic synovial inflammation. Treatments are developed with specific goals in mind—one of which is to slow disease progression.

First and foremost, it is important to understand that progressive joint damage, if not controlled, may be associated with functional limitations and disability.

What factors are predictive of a poor prognosis with progressive joint damage?

Usual Factors Associated With Progressive Joint Damage

The strongest indicator of progressive joint damage in rheumatoid arthritis is said to be seropositivity. That said, seronegativity does not preclude progressive joint damage. I can attest to that from first-hand experience.

Rapid progression of joint damage tends to be associated with being positive for both rheumatoid factor and anti-CCP—more likely than if someone is positive for either, rather than both. Factors which point to a poor prognosis with progressive joint damage include:

  • Positive for anti-CCP
  • Positive for HLA-B27, HLA-B39, or HLA-DQw3.
  • High level of medication use, including corticosteroids, used to treat inflammation in the affected joints
  • An inadequate response to medications
  • Decreased joint function as determined by the Health Assessment Questionnaire
  • Declining quality of life

    Goals of Treatment

    The emphasis of most rheumatoid arthritis research is on early disease, as well as how early diagnosis and treatment can impact progression. According to study results published in Arthritis and Rheumatism, between 60 percent and 95 percent of people with rheumatoid arthritis develop at least one erosion evident radiographically (i.e., on x-ray) within 3 to 8 years after the onset of the disease.

    According to results presented at the 2012 annual meeting of the American College of Rheumatology, researchers also determined that progressive joint damage is still common among people who have had rheumatoid arthritis for at least 5 years. That also appears to be the case in nearly half of rheumatoid arthritis patients who are treated with biologic drugs.

    The FDA has recognized that the prevention or slowing of radiographic joint damage in rheumatoid arthritis is a major goal of treatment. The FDA approved labeling claims for certain DMARDs (disease-modifying anti-rheumatic drugs) and biologic drugs that state the medications slow the progression of radiographic joint damage.

    A goal of achieving remission in rheumatoid arthritis is to halt joint damage. But, established criteria for achieving remission still leaves room for there to be radiographic progression of joint damage.

    Remission is defined by parameters of disease activity as it is associated with joint inflammation, rather than joint damage. Controlling inflammation is crucial to controlling disease activity in rheumatoid arthritis. Immune processes are involved. A complex network of immune cells is in command of a network of inflammatory cytokines and chemokines. That's the crux of disease activity in rheumatoid arthritis. At the same time as cytokine activity, there are more specialized activities occurring between local synovial cells, especially fibroblasts, and cartilage and bone tissue. This activity, localized at the margins of affected joints, causes joint damage.

    The local synovial activity can act independently and cause cartilage and bone destruction, separate from general synovial inflammation. It is complicated, but the bottom line is that progressive joint damage can occur despite well-controlled inflammation.

    A Word From Verywell

    There are people with rheumatoid arthritis who do not have the usual factors or biomarkers for progressive joint damage, yet they still have progressive joint damage. I'm referring to those who may be negative for rheumatoid factor (seronegative), negative for anti-CCP, or who have a sed rate or CRP that is not significantly elevated. It has been determined that, in such cases, there is expression and activation of MMP-3 (stromolysin-1) and MMP-1 (collagenase-1) which contributes to progressive joint damage. MMP-3 and MMP-1 are the matrix metalloproteinases (enzymes). Elevated serum levels of MMP-3 and MMP-1 are significantly associated with disease activity and may also be predictive of radiological joint damage and functional decline.


    Gladman, Ritchlin. Risk Factors for Progressive Joint Damage. Treatment for Psoriatic Arthritis. UpToDate. Updated September 28, 2016.

    Lafeber Floris PJG et al. Progression of Joint Damage Despite Control of Inflammation in Rheumatoid Arthritis: A Role for Cartilage Damage Driven Synovial Fibroblast Activity. BMJ Journals. 2012.

    Lillegraven, S et al. Progressive Radiographic Joint Damage in Established Rheumatoid Arthritis: Common and Strongly Associated With Seropositivity. ACR Abstracts: 2660. 2012 ACR Annual Meeting.

    Paulus HE et al. Classifying Structural Joint Damage in Rheumatoid Arthritis as Progressive or Nonprogressive Using a Composite Definition of Joint Radiographic Change. Arthritis and Rheumatism. April 2004.

    Al-Bayyoumy SA, et al. Correlation Between Progressive Joint Damage and Serum Level of Matrix Metalloproteinases: MMP-3 and MMP-1 in Early Rheumatoid Arthritis. Egyptian Rheumatology and Rehabilitation. July 2007.