Vidalba Rocher

Use of ultrasound-guided small joint biopsy to evaluate the histopathologic response to rheumatoid arthritis therapy: recommendations for application to clinical trials.

To examine in a cohort of rheumatoid arthritis (RA) patients undergoing serial ultrasound (US)–guided biopsies of small joints in the context of clinical trials whether sufficient synovial tissue could be obtained at both baseline and second biopsy to: 1) accurately evaluate the synovial immune phenotype, 2) permit adequate RNA extraction to determine molecular signatures, and 3) sensitively detect change in the number of synovial sublining macrophages (CD68+) following effective therapy.

A Multicenter Retrospective Analysis Evaluating Performance of Synovial Biopsy Techniques in Patients With Inflammatory Arthritis: Arthroscopic Versus Ultrasound-Guided Versus Blind Needle Biopsy

To evaluate whether the choice of synovial biopsy technique (arthroscopy, blind needle [BN] biopsy, ultrasound [US]–guided portal and forceps [P&F], or US‐guided needle biopsy [NB]) translates to significant variation in synovial tissue quality and quantity, with the aim of informing recommendations for the choice of synovial sampling technique within clinical trials.

OP0040 Synovial cell infiltration in acpa-ve patients displays similar signatures to other seronegative inflammatory arthritis. results from the pathobiology of early arthritis cohort (PEAC)

Background There is increasing evidence to suggest that ACPA +ve and ACPA-ve RA are distinct diseases. Current data demonstrates overlap in classification criteria between ACPA-ve RA and other sero negative inflammatory arthritidies such as PsA. Associated with this is a variable prognosis and response to treatment for patients with ACPA-ve RA. Biomarkers capable of refining diagnosis and improving on current classification criteria early in the disease course for patients with ACPA-ve RA are thus urgently needed. Data examining the synovial pathophysiological relationship between PsA and ACPA ±RA is currently limited although has the potential to identify disease specific synovial cellular and molecular signatures. Objectives Therefore, the aim of this study is to examine in a cohort of therapy naïve, early inflammatory arthritis patients, whether ACPA-ve RA can be defined at disease initiation according to synovial pathobiological signatures. Methods A total of 186 consecutive DMARD naïve inflammatory arthritis patients (disease duration <1 year) recruited as part of the multicentre PEAC study at Barts Health NHS Trust were evaluated. All patients underwent a baseline synovial biopsy of a clinically active joint along with collection of inflammatory markers (CRP). Following H and E staining, sections underwent immumohistochemical staining and semi-quantitative scoring (0–4) to determine the degree of CD20 +Bcells, CD3 +T cells, CD68 +lining (l) and sublining (sl) macrophage and CD138 +plasma cell infiltration. Sections were categorised into three pathotypes: (i) Fibroid(F):(CD68 SL <2 and or CD3, CD20, CD138 <1), (ii) Myeloid(M):(CD68SL >2, CD20 <1 and or CD3 >1) and (iii) Lymphoid(L):(grade 2–3 CD20 +aggregates, CD20 >2). Results 90/186 patients were classified as ACPA+ve RA, 55/186 as ACPA-ve RA and 41/186 as PsA. 80% of synovial samples were collected from small joints (wrist, MCP, PIP). All 186 samples were suitable for analysis. Results confirmed that C-reactive protein (CRP) as inflammatory marker does not differentiate between subgroups (p 0.41). Significantly higher degree of immune cell infiltration was seen between ACPA+ve vs ACPA-ve and ACPA+ve vs PsA but not between ACPA-ve and PsA (figure 1). When grouping patient between clinical subgroups (ACPA+ve vs ACPA-ve vs PsA) and pathotypes (fibroid, myeloid and lymphoid) (table1) we demonstrated a significantly higher prevalence of a lymphoid pathotype in ACPA+ve RA vs ACPA-ve or PsA. RA acpa +N909ungraded RA acpa-N5512ungraded PsAN410ungraded P value fisher test P value acpa+vs acpa- P value acpa+vs PsA P value acpa- vs PsA F 15 (16%) 17 (31%) 15 (36%) 0.01* 0.03* 0.005* 0.41 M 25 (28%) 14 (25%) 11 (27%) L 41 (45%) 12 (22%) 10 (24%) Conclusions Our results suggest that the synovial cell infiltrate (B cells, T cells, macrophages and plasma cells) in ACPA-ve RA is significantly different from ACPA +ve patients. They also suggest shared pathophysiological mechanisms between PsA and ACPA-ve RA and support a role for future refinement of diagnosis of ACPA-ve RA according to synovial pathobiology. Disclosure of Interest None declared

THU0667 A qualitative and quantitative comparison of synovial biopsy techniques during clinical trials of inflammatory arthritis

Background Synovial tissue is an attractive area of research for biomarkers of disease outcome in RA. Currently acquisition of synovial tissue using an arthroscopic approach in clinical trials is recommended though two US-guided techniques have been described, a portal and forceps (P&F) approach and an adaptation using a quick core needle (NB). However before US-guided biopsy techniques are widely adopted into clinical trials validation of performance against arthroscopy is required. Objectives To evaluate whether there were significant differences in synovial sampling quality and quantity between arthroscopic, US-P&F and US-NB procedures within the context of clinical trials. Methods This was a multicentre retrospective analysis of inflammatory arthritis patients recruited to clinical trials utilizing US-guided NB (Barts Health NHS Trust), US-guided P&F (ICRSS Policlinico San Matteo and University Hospital Birmingham) and arthroscopic biopsy (Repatriation General Hospital). Paraffin embedded synovial sections from each procedure underwent H&E staining and sections examined for intact cell lining layer (graded sections). Biopsy procedures were segregated into large (knee) and small joint procedures (wrist/MCP) for analysis. Proportion of samples yielding graded tissue per procedure was recorded. Using CellSens Dimensions software the mean area of synovial tissue obtained per procedure was determined. In addition the degree of synovitis was assessed using semi-quantitiative scoring (0–9). Results 78 patient procedures were evaluated, 22 on small joints (11 US-NB, 11 US P&F) and 56 on large joints (11 US-NB, 35 US-P&F, 10 arthroscopic). 47 patients had RA, 11 undifferentiated arthritis and 10 psoriatic arthritis. Arthroscopic sampling resulted in a significantly higher area of tissue retrieved per procedure than US P&F or US-NB. There were no significant differences in proportion of graded samples per procedure suggesting quality of synovial tissue was preserved between techniques. Finally no significant differences in degree of histological synovitis were demonstrated between sampling techniques.Table 1 Mean (SD) Small joint biopsies Large joint biopsies US –NB (n=11) US P&F (n=11) P value US-NB (n=11) US P&F (n=35) Arthroscopic (n=10) P value Joint biopsied 7 wrist 1 wrist 10 knee 32 knee 10 knee 5 MCP 10 MCP 3 ankle % graded samples per procedure 82.3 (22.4) 91 (10) 0.34 89.8 (17.5) 83.23 (19) 97 (11) 0.08 Mean area of tissue (mm2) per procedure 3.19 (1.75) 7.95 (4.91) <0.005* 4.66 (3.19) 8.8 (8.17) 17.64 (7.56) <0.0001* Synovitis score 4.9 (3.2) NA NA 3.8 (2.6) 4.53 (2.26) 4.5 (1.71) 0.35 Conclusions The results suggest that US-guided biopsy provides a reliable method for sampling synovial tissue of comparable quality to that obtained from arthroscopy. However when sampling large joints arthroscopic techniques, and when sampling small joints US-P&F yield a significantly higher quantity, though not quality, of tissue per procedure than US-NB. These results may influence choice of biopsy technique when designing clinical trial protocols in inflammatory arthritis. Disclosure of Interest None declared

THU0100 In early inflammatory arthritis a lymphoid pathotype signficantly associates with requirement for biologic therapy at 12 months follow up: results from the pathobiology of early arthritis cohort (PEAC)

Background Early aggressive treatment in RA equates to better long term outcomes, however targeting aggressive therapies including biologics to patients with the worse prognosis is critical to deliver acceptable risk/benefit ratios and health economic improvements. Such an approach requires prognostic biomarkers, whether the well recognised heterogeneity in synovial pathobiology in early RA translates to specific disease outcomes is currently unknown. Objectives The aim of this study was to investigate whether in a treatment naïve early inflammatory arthritis cohort, baseline synovial pathotype significantly associates with disease outcome at 12 months. Methods 166 consecutive DMARD naïve patients recruited as part of PEAC at Barts Health NHS Trust with synovial tissue suitable for analysis were included. At baseline patients were classified as RA (2010 ACR/EULAR criteria) or undifferentiated (UA). All patients underwent a baseline synovial biopsy of a clinically active joint along with collection of demographic data. Patients were subsequently treated with DMARD +/- steroid therapy with aim for low disease activity (DAS <3.3). At 6 month follow up patients were escalated to biologic therapy if fulfilling UK NICE guidelines. At 12 months patients were classified as: (i) no treatment, (ii) DMARDs, and (iii) Biologic +/- DMARDs. Sequentially cut sections of baseline synovial biopsies underwent immunohistochemical staining and semi-quantitative scoring (0–4) to determine the degree of CD20+Bcells, CD3+T cells, CD68+ lining (l) and sublining (sl) macrophage and CD138+ plasma cell infiltration. Sections were categorised into 3 pathotypes, (i) Fibroid: (CD68 SL<2 and or CD3, CD20, CD138<1), (ii) Myeloid: (CD68SL>2, CD20<1 and or CD3>1) and (iii) Lymphoid: (grade 2–3 CD20+ aggregates, CD20>2). Results 79% were classified as RA and 21% as UA. Mean disease duration was 9.27 months. 92% (153/166) patients had follow-up at 12months. 29% (44/153) of patients were classified as fibroid, 34% (52/166) as myeloid and 37% (57/166) as lymphoid. At baseline patients with a lymphoid pathotype had a significantly higher CRP and DAS28 and were significantly more likely to be sero positive for for RF and ACPA (p<0.05), suggesting that a lymphoid pathotype is associated with higher levels of disease activity. At 12 months follow up a significantly higher proportion of patients classified as lymphoid vs myeloid or fibroid (58% vs 21% vs 21%) required biologic therapy. N=153 Fibroid (44) Myeloid (52) Lymphoid (57) p-value No treatment (14) n (%) 6 (42%) 6 (42%) 2 (14%) <0.05* DMARD (101) n (%) 30 (29%) 38 (37%) 33 (32%) Biologic +/− DMARD (38) n (%) 8 (21%) 8 (21%) 22 (58%) Conclusions Results demonstrate that in an early inflammatory arthritis cohort a lymphoid pathotype significantly associates with higher disease activity at baseline, sero positivity for RF and ACPA and a requirement for more aggressive therapy at 12 month. This supports a direct role for synovial lymphoid structures in disease pathogenesis and suggests a role as a prognostic biomarker facilitating early stratification of aggressive therapeutic intervention. Disclosure of Interest None declared

FRI0088 Synovial pathobiology correlates with diagnostic subgroups in early inflammatory arthritis: results from the pathobiology of early arthritis cohort (PEAC)

Background Application of the 2010 ACR/EULAR Criteria for RA to early inflammatory arthritis cohorts permits an enhanced sensitivity for diagnosis compared to the historic 1987 ACR criteria but risks loss of diagnostic specificity. Heterogeneity in RA synovial pathobiology is well recognised with differences in qualitative and quantitative degree of immune cell infiltration, whether such heterogeneity correlates with classification criteria in early inflammatory arthritis is unknown, offering the potential to refine early diagnostic criteria. Objectives The aim of this study was to examine in a cohort of therapy naïve, early inflammatory arthritis patients whether synovial immune cell infiltration differed significantly between diagnostic categories of early inflammatory arthritis (ACR/EULAR 2010 vs ACR 1987 vs undifferentiated). Methods A total of 200 consecutive DMARD naïve early arthritis patients (disease duration <1 year) recruited as part of the multicentre PEAC study at Barts Health NHS Trust were categorised according to the following criteria: i. RA 1987 ACR, ii. RA 2010 ACR/EULAR, and iii. Undifferentiated Arthritis (UA). All patients underwent a baseline synovial biopsy of a clinically active joint along with collection of demographic data. Following H&E staining, degree of synovitis was assessed. Sections underwent immumohistochemical staining and semi-quantitative scoring (0–4) to determine the degree of CD20+Bcells, CD3+T cells, CD68+ lining (l) and sublining (sl) macrophage and CD138+ plasma cell infiltration. Sections were categorised into three pathotypes: (i) Fibroid: (CD68 SL<2 and or CD3, CD20, CD138<1), (ii) Myeloid: (CD68SL>2, CD20<1 and or CD3>1) and (iii) Lymphoid: (grade 2–3 CD20+ aggregates, CD20>2). Results 166/200 samples were suitable for analysis. 115 patients were classified as RA1987, 16 patients as RA 2010 ACR/EULAR and 35 as UA. 80% of synovial samples were collected from small joints (wrist, MCP, PIP). Although there were no significant differences in disease duration between diagnostic subgroups, patients classified as RA1987 criteria had significantly higher levels of CRP, tender and swollen joints, DAS28 and sero positivity for ACPA and RF. When patients were stratified into pathotypes, a numerically higher proportion of patients within the RA1987 group were categorised as lymphoid. Further, patients within the RA 1987 group had a significantly higher synovitis score and degree of immune cell infiltration. N=166 RA1987 (115) RA2010 (16) UA (35) P value Fibroid 47 (%) 27 (23.5%) 6 (37.5%) 14 (40%) Myeloid 57 (%) 38 (33%) 5 (31.2%) 14 (40%) 0.10 Lymphoid 62 (%) 50 (43.5%) 5 (31.2%) 7 (20%) CD3 T cells 3.19 1.21 0.60 <0.001 CD20 B cells 2.88 0.80 0.75 <0.05 CD68L macrophages 3.60 1.86 1.34 <0.001 CD68SL macrophages 3.60 2.18 1.79 <0.05 CD138 Plasma Cells 2.85 1.06 0.73 <0.05 Synovitis Score 6.17 3.26 3.24 <0.001 Conclusions Stratifying patients according to baseline clinical diagnosis translates into differences in synovial pathobiology. The capacity to refine early clinical classification criteria through application of synovial pathobiological markers offers the potential to predict disease outcome and stratify therapeutic intervention. Disclosure of Interest None declared

OP0240 Synovial Lymphocytic Aggregates Associate with Highly Active RA and Predict Erosive Disease Progression at 12 Months: Results from The Pathobiology of Early Arthritis Cohort

Background The synovial cellular infiltrate in RA has for some time been recognised to organise into lymphocytic aggregates with a number observations suggesting they are immunologically competent and can support chronic inflammation. However, their clinical significance has been controversial with conflicting publications reporting diverse associations with disease outcome. Objectives The aim of this study was to examine in a cohort of therapy naïve, early RA patients whether baseline synovial pathotype: i)associated with specific clinical phenotypes, ii)predicted response to DMARD therapy, and iii)predicted joint damage progression Methods 135 DMARD-naïve early RA patients were recruited as part of the Pathobiology of Early Arthritis Cohort at Barts Health NHS Trust. Following pre-treatment synovial biopsy clinical data was collected at baseline and 12 months. Following immunohistochemical staining the degree of synovial infiltration by CD20+B cells, CD3+T cells, CD68+macrophages and CD138+plasma cells was determined. Patients were then categorised into synovial pathotypes: lymphoid, myeloid or fibroid according to the degree of immune cell infiltration. Samples also underwent nanostring analysis of 238 genes. Significant differences in clinical parameters at baseline and progression in radiographic damage at 12 months between synovial pathotypes was determined. Results At baseline a lymphoid pathotype significantly associated with ACPA+ve (0.017) and highly active disease (DAS28, CRP, ESR and swollen joint count, p<0.01). Furthermore a significantly higher number of patients with a baseline lymphoid pathotype (vs myeloid/fibroid) developed radiographic progression (9/26 vs 5/53, p=0.026). A cohort of 79 genes were identifed from the nanostring analysis that were differentially upregulated in patients with joint damage progression. Logistic regression analysis was used to develop a clinical model for predicting radiographic progression (final model ESR, RF and ACPA) with an AUC of 0.86. Integration of synovial gene expression profiles into the clinical model improved the AUC to 0.96. Conclusions The demonstration in this early RA cohort of a significant association between a lymphoid pathotype and a severe clinical phenotype/sero positivity for ACPA supports a direct role for synovial lymphoid structures in disease pathogenesis. Furthermore patients with a lymphoid pathotype were significantly more likely to develop radiographic damage. Integration of synovial gene expression profiles into a clinical model of radiographic progression enhanced performance. This data strongly supports a role for integration of synovial biomarkers into clinical prediction models of radiographic progression in early RA with critical implications for future patient stratification. Disclosure of Interest None declared

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

Background Rheumatoid 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 diseases 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. Objectives To evaluate the role of synovial pathology in predicting clinical response to certolizumab-pegol combined with DMARD. Methods 32 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). Results Out 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<0.05). Baseline demographic and clinical parameters were comparable between the three histological groups; the CRP level was significantly higher in the myeloid compared to fibroid. The histological pathotype adjusted for baseline VAS pain and patient global health score, ESR, HAQ score and concomitant steroid treatment, was identified as a significant predictor of good response to certolizumab-pegol by forward selection (AUC 0.97, CI 0.92–1). The chance of achieving a good EULAR response to certolizumab-pegol was 91% lower in patients classified as a fibroid pathotype at baseline compared to myeloid/lymphoid pathotypes (OR 0.09, CI 0, 1.75). Conclusions Our study shows that patients with a fibroid pathotype at baseline are less likely to respond to Certolizumab-pegol. Moreover, we identified a novel prediction model of response based on clinical parameters and synovial histopathological classification. Histological assessment of synovial tissue may be of critical importance for developing personalised treatment for RA. References Pitzalis C et al, New learnings on the pathophysiology of RA from synovial biopsies. Curr Opin Rheumatol. 2013 Disclosure of Interest None declared

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 higher Delta DAS28 (0.003) as well as good/moderate EULAR response. A stepwise logistic regression analysis was performed by entering several baseline variables: gender, age, disease duration, presence of erosions, RF and CCP status, use of steroids, DAS28, HAQ, presence of ELN. Only presence of ELN was identified as a potential predictor of EULAR response (Fisher exact test p<0.001; Logistic Regression OR=11.0, 95% CI=1.10-109.67, p=0.041). Conclusions Our findings strenghts the relevance of synovial pathotype in relationship with clinical outcome. In particular, the presence of ELN may be a potential predictor of primary clinical response to certolizumab pegol treatment, in line with previous data observed for other TNFi. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.5564

OP0032 Baseline Synovial B-Cell Status Predicts Response to Rituximab Therapy in RA

Background B-cells are key mediators in RA pathogenesis through the initiation of several pathways that lead to the perturbation of the immune system. Rituximab, an anti-CD20 monoclonal antibody is recommended for use after failure with traditional disease modifying agents and anti-TNF therapy. Despite using peripheral blood B-cells as a marker to ensure depletion, the clinical response to Rituximab remains variable, highlighting an unmet need for further biomarkers of response. Mechanisms that underpin the variation in clinical outcome are yet to be fully elucidated but may relate to distinct differences in cellular infiltrate and target expression within the synovium. Objectives The aim of this open-labelled pilot study was to test the hypothesis that patients with a B-cell rich versus B-cell poor synovial pathotype have an enhanced response to B-cell depletion following therapy with Rituximab. Methods Synovial biopsy (Ultrasound guided n=34, arthroscopic n=6) was performed at baseline in 40 patients with active RA (as defined by a DAS-28 score of >5.1) who had failed treatment with standard disease modifying therapy. 35 patients had received prior anti-TNF therapy, a subset of 5 patients were anti-TNF naïve. Rituximab was administered, with appropriate pre-medication, as two intravenous infusions at a dose of 1g 14 days apart. Synovial tissue was fixed in formalin, paraffin-embedded and cut to serial sections (3μm). Histological grading and lymphoid organization of the synovium was assessed by immunohistochemical analysis. After staining for CD20, the presence or absence of B-cells was determined by a semi-quantitative score (0-4)1. CD21 staining was carried out on samples with large aggregates to determine the presence of FDC in germinal centres (GC) within the synovium. Disease response to treatment (improvement in DAS-28>1.2) at 16 weeks was correlated with the presence or absence of B-cells and GC using Fishers exact test and Chi-squared testing, respectively. Results IHC for CD20 results were available from 39 patients. 29 [74%] patients were females, mean age 58.5 [29-80], 36 [92%] were anti-CCP positive and 32 [82%] were RF positive. 12 [30%] showed a response (DAS-28 >1.2) improvement at 3 months. 24 [62%] patients had little or no B-cell infiltrate within the synovium. In this subgroup, 20 [83%] did not exhibit a significant clinical response. (p=0.031). In B-cell rich non-responders, the presence of GC was noted in 5 out of 6 individuals [83%]; only 1 patient who was GC positive responded to Rituximab. (p=0.01, n=37) Conclusions This open-labeled pilot study strongly suggests that response to Rituximab therapy is determined by the presence or absence of B-cells within the synovium. In patients with B-cell rich synovium, the presence of GC appears to be an important marker of resistance to Rituximab therapy. This pilot study also highlights the potential to utilize synovial pathotype as a biomarker to predict disease outcomes and response. References Kraan, M.C., Haringman, J.J., Post W.J., Versendaal, J., Breedveld, F.C., Tak. P.P. Immunohistological analysis of synovial tissue for differential diagnosis in early arthritis. Rheumatology 1999; 38:1074–1080. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.5609