Abstract
IntroductionBiological markers specifically reflecting pathological processes may add value in the assessment of inter-individual variations in the course of rheumatoid arthritis (RA). The current study was undertaken to investigate whether baseline serum levels of the chemokine CXCL13 might predict clinical and ultrasonographic (US) outcomes in patients with recent-onset RA.MethodsThe study included 161 early RA patients (disease duration < 12 months) treated according to a disease activity score (DAS) driven step-up protocol aiming at DAS < 2.4. Clinical disease activity measures were collected at baseline, 2, 4, 6, 9 and 12 months, and US examination of the hands was performed at baseline, 6 and 12 months. Grey-Scale (GS) and Power Doppler (PD) synovitis were scored (0 to 3), with overall scores as the sum of each joint score. CXCL13 levels were measured at baseline by enzyme-linked immunosorbent assay and evaluated in relation to the achievement of low disease activity (LDA, DAS < 2.4) and US residual inflammation (PD ≤ 1) at 12 months.ResultsBaseline levels of CXCL13 were significantly higher in RA compared to healthy controls (n = 19) (P = 0.03) and correlated with measures of synovitis, such as the swollen joint count (R 0.28, P < 0.001), the US-GS (R 0.27, P = 0.003) and US-PD (R 0.26, P = 0.005) score. Although CXCL13 did not predict the likelihood of achieving clinical LDA at 12 months within a structured treat-to-target protocol, elevated levels of CXCL13 were associated with more frequent increases of methotrexate dosage (P < 0.001). Using adjusted analyses, the highest levels of CXCL13 (> 100 pg/ml) were the only independent predictor of residual imaging inflammation (P = 0.005), irrespective of initial US-PD scores, disease activity status, acute phase reactants and autoantibodies. Among the patients in clinical LDA at 12 months, US-PD scores ≤ 1 were less frequently achieved in the high baseline CXCL13 (> 100 pg/ml) group, with an adjusted OR = 0.06 (95% CI 0.01 to 0.55, P = 0.01).ConclusionsCXCL13 emerges as a new biological marker in early RA, accurate in assessing the severity of synovitis and the persistence of US-PD activity over time in response to conventional treatments.
Highlights
Biological markers reflecting pathological processes may add value in the assessment of inter-individual variations in the course of rheumatoid arthritis (RA)
Study participants and study protocol Study subjects were 161 recent-onset RA patients recruited from the Early Arthritis Clinic (EAC) of the University Hospital of Pavia based on the availability of baseline serum
To confirm the association between CXCL13 and objective measures of joint inflammation, we examined disease activity assessed by US
Summary
Biological markers reflecting pathological processes may add value in the assessment of inter-individual variations in the course of rheumatoid arthritis (RA). Achievement of clinical remission itself may not coincide with true suppression of inflammation, as patients in clinical remission may continue to have synovitis detectable using ultrasound (US) [4]. In this context, the persistence of Power Doppler (PD) activity may predict subsequent joint damage [5] and short-term relapse [6] in disease-modifying anti-rheumatic drug (DMARD)-treated patients in remission. Individual differences in the course of the disease are not yet accurately explained by traditional factors at baseline, including clinical disease activity, the levels of acute-phase response and autoantibodies [7,8,9]. Identification of new variables derived from understanding pathogenic mechanisms that correlate with synovitis, at both the clinical and the sub-clinical level, might refine our ability to build early prognostic algorithms
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