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Synovial tissue rank ligand expression and radiographic progression in rheumatoid arthritis: Observations from a proof-of-concept randomized clinical trial of cytokine blockade
Rheumatology International, 10/27/09

Rooney T et al. – When potential predictors of radiographic outcome were evaluated, baseline RANKL expression correlated with erosive progression at 1 year (r = 0.71, P < 0.01). Distinct, though related, pathophysiologic processes mediate joint inflammation and destruction in RA. Elevated synovial tissue RANKL expression is associated with progressive joint erosion, and may be independent of the clinical response to targeted therapy. The potential therapeutic importance of modulating RANKL in RA is highlighted, if radiographic arrest is to be achieved

Methods

Patients with active RA entered randomized open-label 12-month study of anakinra 100 mg/day, administered as monotherapy or in combination with pegsunercept 800 ?g/kg twice weekly
Arthroscopic synovial tissue biopsies obtained at baseline, at 4 weeks and at final time point
Following immunohistochemical staining, RANKL and OPG expression was quantified using digital image analysis
Radiographic damage evaluated using van der Heijde modification of Sharp scoring system
22 patients randomized
Baseline expression of RANKL, but not OPG, correlated significantly with baseline CRP levels

Results

Significant reduction in OPG expression following treatment observed in clinical responders at final time point , RANKL levels did not change, and RANKL:OPG ratio remained unaltered, even at the highest levels of clinical response
When potential predictors of radiographic outcome were evaluated, baseline RANKL expression correlated with erosive progression at 1 year

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