FRI0157 A Baseline Prediction Model for Response To Certolizumab-Pegol: Role of Synovial Histopathology

BackgroundRheumatoid Arthritis (RA) is a severe joint disease characterized by chronic inflammation of synovial tissue. The inflammatory infiltrate within the rheumatoid synovium may be differently arranged, defining three distinct histopathotypes: myeloid (prevalent macrophage infiltration), lymphoid (B/T lymphocyte aggregates), and fibroid (fibroblastic infiltration with paucity of immune cells)1. Despite enabling a remarkable improvement of the disease's outcome, biologics are not effective in around 30–40% of treated patients. To date, no reliable pre-therapy predictors of response have been identified. The histological characterization of synovitis may represent a valuable tool in predicting response to biologics prior to treatment.ObjectivesTo evaluate the role of synovial pathology in predicting clinical response to certolizumab-pegol combined with DMARD.Methods32 RA patients fulfilling UK NICE criteria for starting TNF-inhibitors were enrolled at Barts Health Trust. Patients underwent a baseline US-guided biopsy prior to commencing certolizumab-pegol and a second biopsy after 12 weeks of treatment. Synovial immune infiltrate was assessed through immunohistochemical staining for CD3/CD20/CD68/CD138 and quantified using a semi-quantitative scoring system (0–4); accordingly, patients were classified as lymphoid (B cells aggregates grade ≥2), myeloid (sub-lining macrophages >2, +/− grade 1 aggregates) and fibroid (sub-lining macrophages ≤2). Therapeutic response was evaluated at 3 months according to EULAR criteria. Logistic regression model was performed to identify factors associated with good EULAR response at 3 months; the factors included clinical and biochemical parameters (ESR, CRP) as well as histopathology. The model selection was implemented using forward processes by AIC with 5-fold cross-validation (error=0.25).ResultsOut of 32 baseline biopsies, 53% were classified as lymphoid, 19% myeloid and 28% fibroid. Decrease in the number of sub-lining CD68-positive macrophages significantly correlated with clinical response (p