LEEDS, United Kingdom—Severe inflammation is associated with rapid, severe, extensive damage in rheumatoid arthritis (RA), but the subgroup of patients most at risk can be helped with modern treatments such as biologics. The damage can be identified by readily available clinical tools, according to Paul Emery, MD, head of the academic unit of musculoskeletal disease at Leeds University in the UK. Dr. Emery, reviewed in Rheumatology recent advances in clinical identification and treatment of rapidly progressing RA.¹

“Several biologic markers and clinical indicators have been identified to help predict or establish which of the patients have rapidly progressing disease or who are at most risk for rapid progression. Early diagnosis of patients with rapidly progressing RA enables immediate and intensive intervention (eg, with biologic therapy) and a greater opportunity to change the course of disease,” Dr. Emery said.

Inflammatory markers are prime target

Structural damage progression in RA is the target for intervention. “Initially, it is inflammation and subsequent radiological progression that derive disability in RA.”

Drugs targeting tumor necrosis factor-α (TNF-α) reduce inflammation and can slow the radiographic progression of joint damage. “Anti-TNFα therapy, therefore, presents an opportunity to change the disease course in RA and represents a way forward for the management of the disease.” However, most RA patients do not experience rapid joint destruction over the first few years of disease. Those likely to be at risk have the shared epitope (HLA-DR1/DR4/DR10), but many patients with this genetic marker do not have rapidly progressive RA.

Rheumatoid factor (RF) positivity early in the disease course predicts more severe RA but is not a very useful predictor later in the disease. Patients with anticyclic citrullinated peptide (anti-CCP) antibodies at the time of diagnosis are likely to have greater radiological progression than those without anti-CCP at baseline, but antibody levels do not predict changes in disease activity, according to Dr. Emery.  Assessing anti-CCP along with antikeratin antibodies (AKAs) gives better predictive power, but Dr. Emery pointed out that tests for AKAs are not routinely available in most clinical settings.

Measuring C-reactive protein (CRP) levels is widely done, and these levels correlate strongly with RA disease activity, radiological progression, and response to therapy. “Significantly, normalization of CRP levels by drug therapy may minimize new joint damage, supporting the immediate introduction of inflammation-suppressing therapy before the onset of erosive damage,” he said.

Serum markers of cartilage and collagen breakdown such as C1, 2C, C2C, CPII, as well as the CS846-epitope of proteoglycan turnover and circulating cartilage oligomeric matrix protein (COMP) can also help identify high-risk patients. “High aggrecan and COMP ratios are a strong predictor of joint destruction,” Dr. Emery said.

Perhaps the most useful clinical “red flags” for rapid disease progression are acute-phase response (high CRP levels) and joint swelling. Joint destruction also reduces functional ability, as can be shown using changes in health assessment questionnaire scores.

Monitoring synovitis and the extent of underlying joint damage and bone erosion are essential, and Dr. Emery warned clinicians against relying on X-rays for this task. “[W]hen patients first present, about 80% will have completely normal X-rays...damage needs to occur for a long period of time before it becomes visible (1 year). Consequently, ultrasound rather than X-ray should be used routinely in the assessment of synovitis.”

Translating research into practice

“Identifying patients with rapidly progressing RA is important because immediate and intensive intervention (eg, with biologic therapy) offers a greater opportunity to change the course of disease, and there are serious consequences for these patients if treatment is delayed. While not all rapidly progressing patients are eligible for biologic therapy, those who are may require the most intensive therapy. Furthermore, it has been shown that the immediate use of intensive and aggressive combination therapies (eg, methotrexate plus infliximab) provides symptomatic and radiological benefits in rapidly progressing patients,” Dr. Emery concluded.

Reference

1. Emery P, McInnes IB, van Vollenhoven R, Kraan MC. Clinical identification and treatment of a rapidly progressing disease state in patients with rheumatoid arthritis. Rheumatology. 2008;47:392-398.