OP0208 Synovial Immunopathology Defines Clinical Responsiveness to Dmard Therapy in Early Psoriatic Arthritis: A Pre- and Post-Treatment Mechanistic Study Using a Minimally Invasive Ultrasound-Guided Synovial Biopsy Procedure
Authors: W.S. Tan, M. Bellan, A. Nerviani, M. Di Cicco, A. Mahto, I. Lazarou, R. Hands, F. Humby, S. Kelly, C. Pitzalis
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> Although the pathogenesis of psoriatic arthritis is well-explored, the mechanisms underlying patients9 differential response to disease-modifying treatment remains unknown. <h3>Objectives</h3> This analysis was undertaken to explore the potential utility of synovial tissue examination in measuring and predicting response to disease-modifying treatment in an early PsA cohort. <h3>Methods</h3> Patients were selected from a prospective study containing clinical, serological and histological data on over 200 patients with early inflammatory arthritis. Patients with 1 or more swollen joint, who had symptoms for less than 12 months, and who were DMARD-naïve, were recruited. Each patient underwent a clinical assessment of arthritis activity and an ultrasound-guided needle synovial biopsy of an affected joint. Patients were started on therapy in line with local standard care guidelines and followed up for 1 year. At 6 months, a repeat synovial biopsy was performed. 16 patients diagnosed clinically with PsA were analyzed. Clinical and histological (inflammatory, CD3, CD20, CD68L, CD68SL, CD138) responses to treatment were compared using the paired-samples Wilcoxon Signed Rank test. The Spearman Correlation method was used to explore the relationships between the following: a) IHC and clinical markers of disease activity at baseline; b) change in IHC and change in clinical markers at 6 months; and c) IHC at baseline and change in clinical markers at 6 months. <h3>Results</h3> The median duration of symptoms at baseline was 4 (1-11) months. 15/16 patients were initiated on non-biologic DMARD therapy after histological sampling (10 on MTX, 1 on SSZ, 3 on MTX + SSZ and 1 on MTX + HCQ). By 6 months, 14 patients remained on non-biologic DMARD only, and 2 patients had initiated anti-TNF treatment. At 6 months, 8/16 patients (50%) achieved a good or moderate EULAR response. ESR, CRP and DAS28 were reduced. Reductions in histological scores were achieved for inflammation, CD3 and CD68SL. At baseline, there was no strong correlation between IHC markers and clinical variables. Changes in CD3 and in CD68SL scores at 6 months correlated with changes in tender joint count (r=0.646 and 0.700), DAS28 (r=0.608 and 0.646) and HAQ (r=0.662 and 0.665). High baseline IHC scores for CD3 and CD68SL were associated with greater reductions in TJC (r=-0.602 and -0.625) and DAS28 (r=-0.609 and -0.612) at 6 months. A high CD138 score correlated strongly with greater reductions in ESR (r=-0.796), CRP (r=-0.693), TJC (r=-0.796) and DAS28 (r=-0.812). <h3>Conclusions</h3> In early psoriatic arthritis, clinical response to disease-modifying treatment is accompanied by, and correlated with, a reduction in synovial CD3 and CD68SL scores. This suggests that CD3 and CD68SL may be useful as surrogate histological markers for clinical response. Higher CD3, CD68SL and CD138 scores at baseline predicted enhanced therapeutic response, suggesting that a higher inflammatory infiltrate in affected synovium at baseline indicates greater responsiveness to disease-modifying immune modulatory treatments. In-depth cellular and molecular (targeted gene array) analyses are underway to investigate the immunological pathways underlying differential responses. <h3>Disclosure of Interest</h3> None declared