SAT0048 Synovial Lymphocytic Aggregates Predict Clinical Response to Certolizumab Pegol in Rheumatoid Arthritis (Clinical and Pathological Response to Certolizumab-Pegol (Clip-Cert) Study)

Background The identification of biomarkers of clinical outcome to guide therapeutic decisions in rheumatoid arthritis (RA) would bring major benefits to patients and considerable health-economic value. There is data suggesting that response to TNF alpha inhibitors (TNFi) in RA may partly be explained by modulation of synovial ectopic lymphocytic aggregates (ELN) within the synovial tissue, although this is still controversial. Certolizumab pegol is a pegylated fully humanized TNFi. Whether specific synovial pathotypes predict response to the drug is unknown. Objectives The aim of this study was to investigate whether the presence of synovial ELN at baseline predicts clinical response to treatment with certolizumab pegol in RA patients. Methods 25 biologic-naïve RA patients who qualified for TNFi therapy according to NICE guidance (National Institute for Health and Clinical Excellence, http://guidance.nice.org.uk/TA186) was recruited at Barts and the London Hospital. Patients underwent ultrasound guided synovial biopsy of an active joint prior to commencing therapy with certolizumab pegol. Following 3 months of therapy, response to treatment was assessed according to EULAR response criteria. Paraffin embedding sequentially cut sections of synovial tissue underwent H&E staining and immunohistochemical staining for CD20 to detect B cells. Sections were graded as either diffuse or aggregate infiltrate as previously described [Manzo, Eur J Immunol 2005]. The study received local ethics approval. Results Characteristics of patients at baseline and clinical outcome after 3 months of therapy with comparison between ELN- and ELN+ are shown in Table 1 (Chi square or Mann Whitney test, as appropriate) Table 1 All (25=100%) ELN− (14=56%) ELN+ (11=44%) P value Baseline Female, % 18 (72%) 10 (71%) 8 (72%) 0.94 Age, mean ± SD 51±12 52±12 50±13 0.45 Dis dur (yrs), mean ± SD 6±5 7±6 5±4 0.97 ESR, mean ± SD 26±18 23±18 30±18 0.26 CRP, mean ± SD 10±24 4±3 18±35 0.04 IgM RF, % 13 (52%) 7 (50%) 6 (54%) 0.82 CCP, % 16 (64%) 9 (64%) 7 (63%) 0.97 DAS28, mean ± SD 6.3±0.7 6.3±0.8 6.3±0.7 0.74 HAQ, mean ± SD 1.57±0.71 1.75±0.65 1.35±0.75 0.15 Erosive, % 10 (40%) 5 (35%) 5 (45%) 0.62 Post treatment DAS28, mean ± SD 4.1±1.4 4.7±1.5 3.3±0.9 0.01 Delta DAS28, mean ± SD 2.2±1.2 1.6±1.3 3.0±0.8 0.003 EULAR response, % 18 (72%) 7 (50%) 11 (100%) 0.006 Presence of ELN+ is strongly associated with a significant post- treatment lower DAS28 (0.01) and conversely significant high