F. Pimentel-Santos

Comparative Effectiveness of Tocilizumab and TNF Inhibitors in Rheumatoid Arthritis Patients: Data from the Rheumatic Diseases Portuguese Register, Reuma.pt.

Objectives. To compare the effectiveness of TNF inhibitors (TNFi) and tocilizumab in rheumatoid arthritis (RA) treatment, according to different response criteria. Methods. We included RA patients registered in the Rheumatic Diseases Portuguese Register treated with TNFi or tocilizumab for at least 6 months, between January 2008 and July 2013. We assessed remission/low disease activity (LDA) at 6 months according to DAS28, CDAI, and SDAI, as well as Boolean ACR/EULAR remission and EULAR response rate, adjusting for measured confounders. Results. Tocilizumab-treated patients (n = 95) presented higher baseline disease activity and were less frequently naïve to biologics compared to TNFi users (n = 429). Multivariate logistic regression analysis including the propensity score for receiving tocilizumab showed that patients treated with tocilizumab were more likely to achieve remission or LDA according to DAS28 (OR = 11.0/6.2, 95% CI 5.6–21.6/3.2–12.0), CDAI (OR = 2.8/2.6, 95% CI 1.2–6.5/1.3–5.5), or SDAI (OR = 3.6/2.5, 95% CI 1.5–8.7/1.1–5.5), as well as a good EULAR response (OR = 6.4, 95% CI 3.4–12.0). However, both groups did not differ in Boolean remission (OR = 1.9, 95% CI 0.8–4.8) or good/moderate EULAR response (OR = 1.8, 95% CI 0.8–4.5). Conclusions. Compared with TNFi, tocilizumab was associated with greater likelihood of achieving DAS28, CDAI, and SDAI remission/LDA and EULAR good response. Boolean remission and EULAR good/moderate response did not differ significantly between groups.

DXA in the assessment of subchondral bone mineral density in knee osteoarthritis—A semi-standardized protocol after systematic review

INTRODUCTIONnSubchondral bone mineral density (sBMD) contributes to the initiation and progression of knee osteoarthritis (OA). Reliable methods to assess sBMD status may predict the response of specific OA phenotypes to targeted therapies. While dual-energy X-ray absorptiometry (DXA) of the knee can determine sBMD, no consensus exists regarding its methodology.nnnOBJECTIVEnConstruct a semi-standardized protocol for knee DXA to measure sBMD in patients with OA of the knee by evaluating the varying methodologies present in existing literature.nnnMETHODSnWe performed a systematic review of original papers published in PubMed and Web of Science from their inception to July 2014 using the following search terms: subchondral bone, osteoarthritis, and bone mineral density.nnnRESULTSnDXA of the knee can be performed with similar reproducibility values to those proposed by the International Society for Clinical Densitometry for the hip and spine. We identified acquisition view, hip rotation, knee positioning and stabilization, ROI location and definition, and the type of analysis software as important sources of variation. A proposed knee DXA protocol was constructed taking into consideration the results of the review.nnnCONCLUSIONSnDXA of the knee can be reliably performed in patients with knee OA. Nevertheless, we found substantial methodological variation across previous studies. Methodological standardization may provide a foundation from which to establish DXA of the knee as a valid tool for identification of SB changes and as an outcome measure in clinical trials of disease modifying osteoarthritic drugs.

Effect of comedication with conventional synthetic DMARDs on TNF inhibitors‐retention in patients with spondyloarthritis: A prospective cohort

To evaluate whether use of comedication with conventional synthetic disease‐modifying antirheumatic drugs (csDMARDs) influences the retention of tumor necrosis factor inhibitors (TNFi) in patients with spondyloarthritis (SpA).

Severe tophaceous gout in a woman with therapeuticnon-compliance

A 67-year-old female presented with large tophaceous gouty arthropathy with diagnosis since 2006. First symptoms occurred in 2004 with polyarticular involvement of the small joints of the hands. She mentioned since 2006 the appearance of gouty tophi in the hands, elbows and feet, initially of small dimensions. She had history of essential hypertension, active smoker and regular consumption of alcohol (20–24 g/day). History of chronic kidney disease or family gout history was unknown. She was medicated with prednisolone 5 mg/day, colchicine 1 mg/day, irbesartan + hydrochlorothiazide 300 + 12.5 mg/day. The patient presented an irregular followup in consultation and refusal to take medication with allopurinol. She was hospitalized in April 2015 at the Rheumatology Department of the Hospital Egas Moniz, after progressive worsening in the previous months, by exuberant tophaceous gout in the hands and feet with spontaneous drainage Figure 1 (A and B). Semiologically, it stood out, as large subcutaneous gouty tophi on the back of the right hand (10 cm x 10 cm), back of the left hand, forefoot (10 cm x 10 cm), with multiple tophi of small dimensions in the phalanges of the hands and feet, wrists and elbows. Analytically, uric acid of 9.0 mg/dl. During hospitalization, the importance of smoking and alcohol avoidance was explained. The reintroduction of

SAT0260 Eligibility criteria for tnfi therapy in axspa: going beyond basdai

Background A BASDAI ≥4 has been often required to start TNFi therapy in patients with axSpA. However, this cut-off of high disease activity (HDA) is largely arbitrary. Unlike BASDAI, ASDAS incorporates objective measures (e.g. CRP) and has a validated definition of HDA (≥2.1). It has thus been suggested that ASDAS could also be used to guide treatment decisions, but evidence to support this is still scarce. Objectives To compare the impact of applying the ASDAS and BASDAI definitions of HDA in selecting patients for TNFi-treatment in daily clinical practice Methods Patients from Reuma.pt (Rheumatic Diseases Portuguese Register), with diagnosis of axSpA according to their rheumatologists (both treated and not treated with their first TNFi), with complete baseline BASDAI and ASDAS data, and complete 6u2009month of follow-up (i.e. baseline, 3 and 6 months visits available) were included. Four subgroups [cross-tabulation between ASDAS (≥2.1) and BASDAI (≥4) definitions of HDA], were compared according to baseline demographic and clinical characteristics in the ‘eligible population’ (i.e. irrespective of TNFi-treatment). In addition, for patients starting TNFi and with complete follow-up BASDAI/ASDAS data (‘efficacy population’), the subgroups were also compared according to different response criteria (see table 1), at 3 and 6 months. Results In total, 466 patients were included (59% males and 66% HLA-B27 positive). The large majority (n=382; 82%) fulfilled the definition of HDA according to both BASDAI and ASDAS at baseline (i.e. BASDAI≥4u2009and ASDAS≥2.1). The frequency of ASDAS≥2.1, if BASDAI<4, was much higher than the opposite condition (i.e. ASDAS<2.1, if BASDAI≥4) (70% vs 0.5%). Compared to patients fulfilling both definitions, those who were ASDAS≥2.1u2009only, were more likely to be male (82.5% vs 54%), HLA-B27 positive (79% vs 54%), to show higher levels of CRP (2.6±2.5u2009vs 2.2±2.8u2009mg/dL) and lower BASFI (3.1±2.6u2009vs 5.6±2.3). In the ‘efficacy population’ (n=296), better responses were observed among patients with ASDAS≥2.1u2009only, especially for the most ’stringent’ outcomes [e.g. ASDAS inactive disease (ASDAS ID): 59% and 50%, at 3 and 6 months respectively], compared to patients fulfilling both definitions (ASDAS ID: 26% and 25% at 3 and 6 months respectively) (table 1).Abstract SAT0260 – Table 1 TNFi response criteria across subgroups according to BASDAI/ASDAS category (‘efficacy population’) Conclusions Our results show that the ASDAS-HDA definition (ASDAS≥2.1) is more inclusive than the BASDAI-HDA definition (≥4) in selecting axSpA patients for TNFi treatment. Importantly, the additionally ‘captured’ patients respond better and have higher likelihood of predictors thereof. These results support the use of ASDAS≥2.1u2009as a selection criterion for treatment decisions. Acknowledgements Supported in part by a research Grant from Investigator-Initiated Studies program of MSD Disclosure of Interest J. Marona Grant/research support from: MSD, A. Sepriano Grant/research support from: MSD, S. Rodrigues-Manica Grant/research support from: MSD, F. Pimentel-Santos Grant/research support from: MSD, A. Mourão Grant/research support from: MSD, N. Gouveia Grant/research support from: MSD, J. Branco Grant/research support from: MSD, F. Vinagre Grant/research support from: MSD, R. Roque Grant/research support from: MSD, J. Rovisco Grant/research support from: MSD, M. Marques Grant/research support from: MSD, J. Tavares-Costa Grant/research support from: MSD, J. Silva Grant/research support from: MSD, H. Santos Grant/research support from: MSD, N. Madeira Grant/research support from: MSD, E. Vieira-Sousa Grant/research support from: MSD, R. Machado Grant/research support from: MSD, M. Bernardes Grant/research support from: MSD, R. Ferreira Grant/research support from: MSD, S. Ramiro Grant/research support from: MSD

AB0016 B-cell subsets differences in inflammatory rheumatic diseases

Background Targeting humoral immunity has been proved effective in several inflammatory rheumatic diseases (IRD). Though clinical trials have shown some efficacy of B-cell depletion in ankylosing spondylitis (AS), results are less convincing. Other studies have revealed an association between mutations and expression of immune regulatory genes suggesting B-cell dysfunction in the development and progression of AS. Yet, there is still lack of data describing B-cell subsets in AS, how these compare to other IRD and an evaluation of B cell compartment homeostasis in the pathophysiology of this disease. Objectives To assess and compare the immature, naive and antigen differentiated subsets of peripheral B-cell compartment in AS with those in healthy controls (HC) and other IRD Methods Patients (pts) with AS, RA and SLE according to respective classification criteria were included in this study. Pts under biologic DMARDS were not included. Sociodemographic and clinical variables were recorded. Blood samples were collected for quantification of inflammatory markers (ESR and CRP), immunoglobulin serum levels and assessment of B-cell immature transitional stages and mature subsets by flow cytometry (figure). Mann-Whitney and Fishers exact test were used for comparison of AS with other groups Results Overall, 60 pts and 12 HC were included (Table). All patient groups presented similar and rather low levels of inflammation, as measured by CRP, ESR and immunoglobulins, in addition to a decreased lymphocyte count by comparison with HC. There were no differences in the B-cell counts between AS pts and HC, with both groups having higher B-cell counts than RA and SLE pts. Regarding B-cell subsets, the immature transitional compartment of AS pts was found in normal range, but not in the RA and SLE groups. In fact, the latter presented a significant decrease in all transitional cell maturity stages (T1-T3). The next step in B-cell differentiation is mature naïve cells, also found in normal levels in AS and decreased in RA and in particular in SLE. AS pts presented slightly higher counts of CD27+IgD+ MZ-like and class able to switch memory cells with reference to HC and these cell numbers were found to be low in RA and even lower in SLE pts. Switched memory CD27+IgD- B-cells were reduced in all patient groups, however, only SLE pts presented highly decreased cell levels. Conclusions We found that while a severe dysfunction is present in the homeostasis of the B-cell compartment in RA and in particular SLE pts, which are lymphopenic in both immature and mature B-cell compartments, it appears that AS pts are not affected in the same way. At this stage, functional studies appear to be necessary in order to identify differences in key mechanisms of B cell development and differentiation that may play a role in the aetiology and progression of these inflammatory rheumatic diseases. Our first results, however, establish that pathophysiological mechanisms involving B-cells clearly differentiate AS from RA and SLE Disclosure of Interest None declared

OP0070 The role of individual and country-level socio-economic factors in work participation in patients with spondyloarthritis across 22 countries worldwide: results from the comospa study

Background Spondyloarthritis (SpA) carries substantial financial costs, including direct costs (use of medical services and treatments) and indirect costs (loss of work productivity). While disease related factors have been repeatedly shown to be associated with work outcomes, information on the role of educational attainment and the economic wealth of the patients country of residence is scarce. Objectives To explore the role of individual and country level socio-economic (SE) factors on employment, absenteeism and presenteeism across 22 countries. Methods Patients with a clinical diagnosis of SpA, fulfilling the ASAS SpA criteria and in working age (≤65 years old) from COMOSPA were included. Outcomes explored were employment-status, absenteeism and presenteeism according to the Work Productivity and Activity Impairment Specific Health Problem (WPAI-SHP) questionnaire. Absenteeism and presenteeism were assessed in employed patients. Multilevel logistic (for work status) and linear (for absenteeism and presenteeism) regression models with random intercept for country were constructed. Independent contribution of individual (education) and country level socio-economic factors (country healthcare expenditures and gross domestic product (GDP) (all low vs medium/high tertiles) were assessed in models adjusted for clinical factors. Results In total 3,114 patients from 22 countries were included (mean (SD) age 40.9 (11.8) years; 66% males; and 63% employed). Of these, 89% had axial SpA and 11% a peripheral SpA. Unadjusted employment rates ranged from 28% (Colombia) to 83% (Canada). After adjustment for relevant socio-demographic and clinical variables, differences between countries in work status persisted (Figure). High healthcare expenditures were associated with higher employment (OR=2.42; 95% CI=1.53;3.81) and lower presenteeism (β=-4.53;CI=-8.90;-0.17). Similarly, higher GDP was associated with higher employment (OR=1.70; 95% CI=1.02;2.83), and in the same direction with presenteeism but without reaching statistical significance (β=-3.42;CI=-13.07;6.23). No significant association between any country SE indicators and absenteeism was found. At individual level, higher education was positively associated with employment-status, presenteeism and absenteeism. Conclusions Individual- and country-level SE factors affect work participation in SpA, and this varies significantly across countries. Better socio-economic welfare seems to support SpA patients to stay employed and productive. Disclosure of Interest None declared

AB0300 Association of vitamin d status with rheumatoid arthritis disease activity and uv index

Background Lower serum vitamin D levels have been shown to be associated with various autoimmune disorders, including Rheumatoid Arthritis (RA). Vitamin D deficiency is common in RA patients, despite profiting from a sunny country. Objectives The aim of the study is to evaluate (1) – the association between vitamin D serum levels and disease activity in patients with RA; (2) – seasonal distribution of vitamin D levels. Methods Patients fulfilling the 2010 EULAR/ACR Rheumatoid Arthritis Classification Criteria, which had serum vitamin D [25(OH)D3] levels measured between January 2013 and December of 2016 were included. Demographic data, disease activity scores, including DAS283v-CRP and DAS283v-ESR, vitamin D supplementation with cholecalciferol and other therapeutic approaches were recorded. Vitamin D insufficiency was considered between 25–75 nmol/L and deficiency if <25 nmol/L. According to the national agency for the study of sea and atmosphere, UV Index levels were grouped into low UV Index 3–6 (October to April) and high UV Index 9–10 (May to September). Correlation between variables was analyzed using Spearmans rho. Results A sample composed by 95 patients, 79 females (83.16%), with an average age (SD) of 68.57 (11.92) years within 40–88 years range were included. Average disease duration was 13.46 (11.41) years. The average age at diagnosis was 57.10 (14.25) years. The average vitamin D levels were 78.13 (60.98) nmol/L in a range between 20–400 nmol/L. Vitamin D levels were not significantly different in male vs. females patients. The prevalence of vitamin D insufficiency and deficiency was 53.68% and 8.42% respectively, despite 57.89% of the patients taking supplementation (average 6141 (4800) UI/week). The univariable analysis showed that albeit vitamin D levels presented a negative poor correlation with DAS283v-CRP (rho=-0.348, p-value<0.001) and DAS283v-ESR (rho=-0.271, p-value<0.01), there was a direct reduction in dispersion of the vitamin D values for increasing values of DAS283v-CRP and ESR. It was observed that vitamin D levels increase with patient age and decrease with disease duration. Sazonality and supplementation didnt affect vitamin D levels in our population. Conclusions Vitamin D insufficiency/deficiency was frequent among RA patients (62.1%), independently of seasonality or supplementation. An interesting pattern behavior was observed in this study, which indicates that the likelihood of encountering a very narrowband of vitamin D values for patients with high disease activity is very high, and thus, the forecast capability of vitamin D values for patients with increasingly active disease is quite good. Future research will aim at strengthening the statistical parameters of relevance, identifying and characterizing the more specific behaviours of this global pattern. Disclosure of Interest None declared

AB0954 A New Ultrasonography Protocol for The Assessment of Primary Knee Osteoarthritis

Background There is a lack of adequate outcome measures of treatment response in Knee Osteoarthritis (KOA). The role of Ultrasonography (US) in the management of inflammatory articular and periarticular diseases is well established, but it has been less extensively used in OA. Objectives To develop a new high-resolution US protocol for the assessment of structural and inflammatory changes in primary KOA and to evaluate its inter-observer reliability. Methods A scanning protocol was developed by consensus among 3 senior Rheumatologists with similar high levels of experience in musculoskeletal US. The protocol includes both inflammatory elementary lesions (synovitis, power Doppler, Bakers cyst) and structural damage lesions (medial collateral ligament bulging, meniscal lesions and osteophytes) measured as dichotomous variables (present/absent). Cartilage thickness (in millimeters) is assessed at the notch and 10mm towards the lateral and medial condyles (mean value of 3 measurements). The OMERACT definitions for elementary lesions were used whenever available. In addition, global scores were calculated for joint inflammation (range: 0–3) and structural damage (range 0–11). Patients with primary KOA according to the American College of Rheumatology classification criteria underwent Knee US assessment in the same day by the 3 experts using the same device. For dichotomous parameters, Inter-observer agreement was estimated by the free-marginal multirater Kappa and the proportion of agreement (Agt). For continuous parameters two-way mixed effects models were used and absolute-agreement Intraclass Correlation Coefficients (ICC) was measured between individual ratings and global scores. Results In total, 7 patients were included (14 knees), corresponding to 42 US assessments by the 3 readers. Patients were 6 females and 1 male, with a mean age of 58.6 years. Concerning inflammatory lesions, agreement was good for synovitis (κ=0.714; Agt=85.7%) and Baker cyst (κ=0.714;Agt=85.7%). All power Doppler analysis were negative, thus achieving excellent agreement (κ=1; Agt=100%). As a result, agreement was good for the inflammatory score (ICC: 0.774; 95% CI). Results were not as homogenous for structural damage lesions. In one hand, agreement was excellent for medial meniscus cyst (κ=0.810; Agt=90.5%), good for lateral and medial femoral osteophytes [κ=0.619; Agt=80.9%) and κ=0.714; Agt=85.7%) respectively] and for lateral meniscus extrusion and cyst κ=0.619 and 0.619; Agt=81.0%). On the other hand, it was poor for lateral meniscus fracture κ=0.143; Agt=57.1%). For cartilage thickness, agreement was good for notch and medial condyle (ICC=0.652 and 0.619). Finally, the overall structural score agreement was moderate (ICC: 0.484). Conclusions The proposed protocol has shown to be reliable in patients with KOA, therefore a promising tool to be used both in clinical practice and for research purposes. Long-term reproducibility and responsiveness to change is needed to become a valid outcome measure, thus filling in an important gap in OA assessment. Disclosure of Interest None declared

AB0835 Association Between Sociodemographic and Clinical Features with Radiographic Severity in Knee Osteoarthritis – Results from Epireumapt

Objectives To assess patient characteristics associated with radiographic severity in knee osteoarthritis (KOA) in a population-based study. Methods EpiReumaPt is a national epidemiologic, cross-sectional study of rheumatic diseases (RD) in the Portuguese population conducted from September 2011 to December 2013. From the 3877 patients assessed by a rheumatologist on the second phase of the study, we included all cases of KOA defined according to the American College of Rheumatology clinical and/or radiographic classification criteria. Knee x-rays were acquired using a standardized protocol and centrally scored according to the Kellgren-Lawrence (KL) scale. The knee osteoarthritis outcome score (KOOS) was used to assess KOA clinical features. Weighted stepwise multivariate logistic regression was used to assess which features associated with radiographic severity, after stratifying the disease in mild (grade 0 to 2) and severe (grade 3 and 4) KOA according to the KL scale. Results A total of 981 (weighted prevalence: 12.4%) patients were classified as KOA patients. Knee radiographs were available for 553 patients. From those, 318 (63.7%) had mild disease and 235 (36.3%) had severe disease. On the multivariate analysis, several patients features were significantly and independently associated to radiographic severity: age (OR: 1.08; p<0.001), obesity (OR: 2.7; p=0.014); dyslipidemia (OR: 2.73; p=0.002), the total number of non-rheumatic comorbidities (OR: 0.63; p<0.001); Country region (OR: 0.61; p<0.001); orthopedic intervention of the knee (OR: 4.71; p=0.004); KOOS symptoms subscale (OR: 0.96; p=0.001; higher KOOS, less symptoms). Alentejo region had the higher proportion of severe disease [56.0% (36.2-75.7)], whereas Lisbon area had the lowest [36.4% (26.9-45.8)]. Conclusions We found several clinical and sociodemographic features associated with radiographic severity in KOA patients. Our findings contribute to the understanding of disease progression mediators. A longitudinal evaluation is needed to validate these results. Disclosure of Interest None declared