Background The synovial membrane is the primary site of inflammation in rheumatoid arthritis and as such the study of pathobiological synovial specimens has led to a greater understanding of disease pathogenesis. A number of studies have suggested that clinical response to treatment correlates with a significant decrease in synovial sublining macrophage (CD68sl) number. As such CD68sl has been recommended as a valid biomarker of response to treatment in clinical trials. There is however limited data examining synovial CD68sl response in treatment naïve early arthritis patients.
Objectives This study was undertaken to investigate the association between changes in infiltration of synovial CD68sl and clinical response to treatment in early treatment naїve RA patients.
Methods The study included 32 consecutive early RA patients (disease duration <12 months, >/=1 swollen joint) naïve to all disease modifying therapy, recruited at Barts and the London Hospital as part of the MRC funded Pathobiology of Early Arthritis Cohort (PEAC), http://www.peac-mrc.mds.qmul.ac.uk. The study was approved by the hospital’s ethics committee (REC 05/Q0703/198).
Baseline disease characteristics assessed included erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) level, rheumatoid factor (RF), anti-cyclic-citrullinated peptides (anti-CCP) antibodies and 28 joint-disease activity score (DAS28). All patients underwent ultrasound (us)-guided synovial biopsy of an affected joint at baseline and were then treated according to a standardised protocol with a combination of methotrexate and sulfasalazine. A repeat us guided synovial biopsy and clinical assessment was performed at 6 months follow up and patients were classified as good (GR), moderate (MR) or non responders (NR) according to EULAR response criteria. Sections of paraffin embedded RA synovial tissue from each time point underwent standard immunohistochemical staining for macrophages. The number of CD68sl were semi-quantitatively scored (0-4) at baseline and 6 month follow up.
Results All 32 patients had active disease (DAS28 ≥2.4). The median disease duration was 6 months (± 3.5). 59.4% and 68.8% of the patients were RF and anti-CCP antibody positive, respectively. After initiation of therapy, the mean (±SD) DAS28 decreased from 6.04 (±1.25) to 3.84 (±2.2 (p<0.005). In total, 10 patients (31.3%) fulfilled the EULAR criteria for GR, 9 patients (28.1%) for MR, and 13 patients (40.6%) were NR. There was a significantly reduction of CD68sl in GR and MR versus NR (p<0.04 Chi square test).
Conclusions These findings indicate that a reduction in CD68sl is associated with effective treatment in early RA patients and provides further evidence to support their use as a biomarker of response to treatment in clinical trials.
References Breisnihan B, GerlagDG, et al. Synovial Macrophages as a biomarker of response to therapeutic intervention in rheumatoid arthritis: standardization and consistency across centers. J Rheum 2007;34:620-2)
De Hair MJH, Harty LC, et al. Synovial tissue analysis for discovery of diagnostic and prognostic biomarkers in patients with early arthritis. J Rheum 2011;38:2068-72
Acknowledgements The authors would like to thank our research nurses Celia Breston and Victoria Katsande for their assistance in data collection.
Disclosure of Interest None Declared
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