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ObjectivesTo evaluate long-term kinetics of the BNT162b2 mRNA vaccine-induced immune response in adult patients with autoimmune inflammatory rheumatic diseases (AIIRD) and immunocompetent controls.MethodsA prospective multicentre study investigated serum anti-SARS-CoV-2 S1/S2 IgG titre at 2–6 weeks (AIIRD n=720, controls n=122) and 6 months (AIIRD n=628, controls n=116) after the second vaccine, and 2–6 weeks after the third vaccine dose (AIIRD n=169, controls n=45). T-cell immune response to the third vaccine was evaluated in a small sample.ResultsThe two-dose vaccine regimen induced a higher humoral response in controls compared with patients, postvaccination seropositivity rates of 100% versus 84.72%, pConclusionsThe two-dose BNTb262 regimen was associated with similar clinical efficacy and similar waning of the humoral response over 6 months among patients with AIIRD and controls. The third vaccine dose restored the humoral response in all of the controls and the majority of patients.

Background:Anti-IL17 agents, such as Secukinumab (SEC) and Ixekizumab (IXE) have been shown to be efficacious for the treatment of psoriasis and PsA12. In the field of psoriasis, there is growing evidence of a successful switching between the two anti-IL-17 agents in case of an insufficient response to one of the treatments3 There is no information on the efficacy of switching between anti IL17 agents in PsA.Objectives:To assess the clinical response to IXE in patients with PsA following SEC failure.Methods:A retrospective observational study was conducted in two rheumatology centers in Israel, including PsA patients with a history of treatment with SEC, further treated with IXE for a minimum of 3 months. Lack of efficacy, loss of efficacy, and side effects over time were reported as a reason for switching to another anti-IL17 agent. The mean difference between the beginning of the follow up period and the different follow up points (6 and 12 months) was tested using a one-sample t-test. Time until treatment failure was estimated using Kaplan–Meier curves, and compared using the log-rank test. Hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) were calculated using the Cox proportional-hazards model to test the association between each variable and the time to treatment failure.Results:The study included 23 PsA patients (11♀/12♂), mean age 58.7 years±13.4 SD. Most patients (n=20, 86%) received 2+ TNFi and 10 patients (43%) received both TNFi and ustekinumab. Median number of biologics prior to SEC was 3 (IQR 2-4). There was a significant improvement in TJC at 6 and 12 months (-2.16 [-4.0, -0.3]; p=0.025 and-1.69 [-3.09, -0.28]; p=0.022, respectively). SJC was significantly improved at 6 months but not at 12 months (-2.68 [-5.3, -0.04]; p= 0.046 and -1.50 [-4.25,1.25]; p=0.26, respectively). CDAI score was significantly improved at 6 months (-10.19, [-16.26, -4.1], p=0.002) and at 12 months (-9.29 [-14.8, -3.71], p=0.003) as was SDAI score (-10.13 [-16.4, -3.8], p=0.003 and -12.2 [-17.1, -7.2], p=0.0002). At six months, PASI50 was achieved by 81% (13 patients), PASI75 was achieved by 63% (10 patients), PASI90 was achieved by 50% (8 patients) and PASI100 by 31% (10 patients). At 12 months, PASI50 and PASI75 was achieved by 57% (8 patients), PASI90 was achieved by 43% (6 patients) and PASI100 by 21% (3 patients).Over time, of the 23 patients treated with IXE, 15 patients (65%) had experienced treatment failure, with a median treatment period of 8 months (IQR 6.5-13.5), of which 4 (17%) had primary treatment failure and 11 patients (48%) secondary treatment failure. Reasons for treatment cessation were: worsening psoriasis (4 patients (27%)), worsening peripheral arthritis (4 patients (27%)), both (7 patients (47%)), worsening of axial disease (2 patients (13%)) and adverse events (1 patient, 6%).Conclusion:patients after failure of multiple biologic treatments experienced significant response of peripheral arthritis and dermatologic disease on IXE after they had previously failed SEC. . However, in this refractory cohort of PsA, the effect was limited on time with 65% failure after a median time of 8 months.Within class switch from SEC to IXE is a plausible therapeutic option in PsA patients following secukinumab failure.References:[1]Mease PJ, McInnes IB, Kirkham B, et al. N Engl J Med. 2015;373(14):1329-1339.[2]Nash P, Kirkham B, Okada M, et al. Lancet Lond Engl. 2017;389(10086):2317-2327.[3]Bokor-Billmann T, Schäkel K. J Dermatol Treat. 2019;30(3):216-220Disclosure of Interests:None declared.

Background:Psoriatic arthritis (PsA) is a chronic, immune-mediated, systemic inflammatory arthritis associated with comorbidities including metabolic syndrome, cardiovascular risk factors and cardiovascular disease (CVD).Objectives:To evaluate the prevalence of venous thromboembolism (VTE) in a PsA patient cohort using a large health care provider database.Methods:A large health care provider database serving 4.7 million healthcare subscribers was interrogated for an adult patient cohort who were newly diagnosed with PsA between January 2005 (start date) and 31 December 2018 with date of diagnosis considered the index date. A risk set was employed to randomly select 4 controls without PsA as a comparator group to the PsA cohort matched by age, sex, ethnic group, and index date. Both groups were followed from the index date until the first occurrence of VTE event, death, or end of follow-up 31 December 2019, whichever came first. Marginal model with robust covariant estimate counting for the matching was used to estimate the crude and adjusted hazard ratio (HR) for the association between PsA and VTE. Within the group of PSA patients, Cox proportional hazard regression models was used to calculate the risk of having VTE given demographic variables, SES, smoking, selected comorbidities, and conventional vs biologic disease modifying anti-rheumatic drugs (c/bDMARD). Continuous variables were summarized with mean ± standard deviation, and categorical variables were presented as numbers and proportions. All tests were 2-sided; p values of < = 0.05 were considered statistically significant. All data were analyzed using SPSS, 24 (IBM SPSS Statistics for Windows, version 24.0, 2016, Armonk, NY) and SAS, 9.4 (SAS institute Inc, Cary, NC).Results:The PsA cohort consisted of 5,275 patients, 53.2% females with mean age of 51.66 ±15.41. The control group consisted of 21,011 subjects matched for age and sex. In relation to the control group, the PsA cohort had a higher SES (25.1% vs 23.4%, p30, cancer, IHD, vascular disease, and previous VTE found to be associated with VTE in the PsA group relative to controls in both univariate and multivariate analyses. The higher prevalence of VTE in PsA patients relative to controls did not remain statistically significant in multivariate analysis following adjustment for risk factors. Within the PsA group, patients with VTE were more often of older age and with past history of VTE. Both cDMARD and bDMARD were not associated with increased risk of VTE among PsA patients.Conclusion:The prevalence of VTE was higher in PsA group compared to the general population, but after adjustment for comorbidities and risk factors, it no longer remained statistically significant. Among PsA patients, age and previous history of VTE were associated with increased risk of VTE. Addressing VTE risk in the management of patients with PsA is recommended especially in the era of Janus kinase inhibitors.Disclosure of Interests:None declared

Background:Angiogenesis is an important contributor to the development of Rheumatoid arthritis (RA). Tocilizumab (TCZ), an anti-IL-6 receptor antibody, is an immunosuppressant used in the treatment of RA patients, but its effects on angiogenesis and the molecular mechanisms regulating new blood vessel formation are not fully elucidated.Objectives:To evaluate the concentrations of pro- and anti-angiogenic factors in serum samples of RA patients, before and after the initiation of TCZ treatment and to explore in an in vitro co-culture system the mechanisms of TCZ action.Methods:We evaluated the concentrations of EMMPRIN, VEGF, MMP-9, IL-6, NGAL, endostatin and thrombospondin-1 (Tsp-1) using commercial ELISA kits from 40 RA patients, before and 4 months after the initiation of TCZ treatment. The levels of secreted EMMPRIN, VEGF MMP-9 and Tsp-1 were measured in an in vitro co-culture system of HT1080 fibroblasts and U937 monocytes with and without addition of anti-EMMPRIN blocking antibody. In the tube formation assay serum samples and supernatnats from the co-cultures were added to endothelial layer. Images were obtained after 6 hours of incubation and the number of closed lumens were counted in two separate fields. In the wound assay, supernatants from the co-cultures, with or without the addition of the anti-EMMPRIN antibody were added to the endothelial layer after scratching. The scratch site area was measured immediately and compared to the area after 24 hours of incubation to assess the distance of cell migration.Results:Study population included 40 RA patients, 33 (82.5%) females, mean age of 57.5±11.1 years, disease duration of 7.7±5.6 years, and 53.9% positive for rheumatoid factor initiating treatment with TCZ. In this patient cohort, 25/40 (62.5%) patients were classified as “responders” according to EULAR criteria.Following 4 mounts of treatment, statistically significant reductions in the levels of EMMPRIN/CD147 (p=0.035), without significant changes in serum levels of MMP-9, VEGF, MMP-3 and MMP-7 and of the anti-angiogenetic factors Tsp-1 and endostatin were found. A statistically significant decrease in the ratio between the pro-angiogenic factor EMMPRIN and the anti-angiogenic factor Tsp-1 that was calculated for each patient 4 months after initiating TCZ was found(p=0.031). The decrease in angiogenesis was manifested by the reduced number of closed lumen tube-like structures formed by EaHy926 endothelial cell line after incubation with serum samples 4 months after initiation of TCZ, relative to the number of closed lumens formed prior to TCZ initiation (p=0.007). The ratio between EMMPRIN and Tsp-1 was significantly reduced in the responding patients versus non-responders (p=0.033), while the levels of VEGF, MMP-9, Tsp-1, and EMMPRIN were unchanged.In vitro, the accumulation of the pro-angiogenic factors EMMRPIN, VEGF and MMP-9 in the supernatants was increased in the co-culture, while the accumulation of the anti-angiogenic factor Tsp-1 was decreased. When EMMPRIN was neutralized with a blocking antibody, supernatants derived from these co-cultures exhibited reduced migration, proliferation, and tube-like structure formation in functional assays.Conclusion:Our findings suggest an important role for EMMPRIN in mediating pro-angiogenic signals in RA patients, with EMMPRIN/Tsp-1 ratio serving as a marker of angiogenesis in RA. When administered to RA patients, TCZ in turn, exerts an anti-angiogenic effect through its regulation of EMMRPIN/CD147 levels.Disclosure of Interests:None declared

Background:The epidemiology of COVID19 among patients with AIIRD may be influenced by a dysregulated immune system, immunosuppressive therapies and behavioral patterns. Data regarding the epidemiology of COVID19 among patients with AIIRD is scarce.Objectives:To assess the pattern of COVID19 pandemic among patients with AIIRD compared to the general population in IsraelMethods:At the beginning of the COVID-19 pandemic, we established a national registry of patients with AIIRD, diagnosed with COVID-19, based on voluntary reporting by the treating rheumatologist. All the members of the Israeli Society of Rheumatology were encouraged to participate and repeatedly reminded to report any new cases. Rheumatology centers from 11 hospitals from the Northern and Central part of Israel participated in this study. The registry included demographic data, AIIRD diagnosis and duration, systemic organ involvement, co-morbidities, treatment (conventional synthetic disease modifying drugs (csDMARDs), biologic/targeted (b/ts) DMARDs, corticosteroids use, dose and treatment duration, date of COVID19 diagnosis, severity of the viral disease and complications, duration of hospitalization, if required, treatment for COVID 19, laboratory results and outcome. The diagnosis of COVID 19 was made by a positive SARS CoV2 PCR. The indications for SARS CoV2 PCR testing in Israel comprise clinical symptoms or exposure to a confirmed close contact. Severe illness was defined by SpO2 30 breaths/min, PaO2/FiO2 50% on chest imaging.The epidemiological data regarding the number of COVID19 confirmed patients, the number of severe cases and the rate of mortality among the general population per day and per week, were extracted from the data dashboard of the Israeli Ministry of Health. We analyzed data from 02.2020 to 15.01.2021.Results:During the study period we experienced 3 waves of COVID 19 pandemic. The governmental management of COVID19 spread, at the beginning of the pandemic, included inforcement of severe travel restrictions and social distancing, followed eventually by a preventive lockdown, in spite of the relatively low number of cases. Easing of the restrictions, lifting the travel ban, opening of the commerce and schools led to 2 much more severe waves, which triggered 2 new lockdowns. Up to January 2021, 549763 Israelis had confirmed COVID19, 30% of whom had severe disease, 0.84% died (30% of the patients with severe disease).We identified 190 AIIRD patients (mean(SD) age 52(18), 30% males) who had confirmed COVID19. The weekly incidence curve of patients with rheumatic diseases correlated with the curve of the general population (Figure 1).Sixty-one % of the patients with AIIRD received csDMARDs, 41% were on b/tsDMARDs, 39% on chronic corticosteroids, 12% on ≥10mg prednisone. Forty-seven% of patients required hospitalization, 20% had severe COVID19. Sixteen patients (42% of patients with severe COVID19) (mean(SD), median age 64.7(15.4),67)) died (systemic sclerosis-4 patients, rheumatoid arthritis – 6, systemic lupus erythematosus – 2, antiphospholipid syndrome-2, granulomatous polyangiitis -1, polymyalgia rheumatica-1). The AIIRD was active in 56% of them, 50% received csDMARDs, none of them were on b/tsDMARDs, 31% received chronic prednisone>10 mg. All patients who died had at least 2 comorbidities.Conclusion:The pattern of spread of COVID19 in AIIRD patients is similar to the general population despite repeated mass media alerts for enhanced social distancing for elderly and immune suppressed patients. The disease tends to be more severe with enhanced mortality, especially in those with active AIIRD disease and organ involvement (lungs, heart, renal), older age and co-morbidities. A reporting bias cannot be excluded.Figure 1.Acknowledgements:Both first authors contributed equally to the manuscript.Disclosure of Interests:None declared.

Background:Diagnostic delay is a major challenge in axial spondyloarthritis (axSpA) with an extended interval of 8-10 years in Europe and 14 years in the United States between symptom onset and disease diagnosis (1, 2).Objectives:To assess the delay in the diagnosis of axSpA over time in a real world axSpA cohort diagnosed in the last 3 decades and to evaluate factors associated with this delay.Methods:A cohort of axSpA patients was recruited from a national multicenter registry of inflammatory arthritis. This cohorts’ demographic, clinical and diagnostic variables were studied. The diagnostic delay was defined as the time interval between the year of first symptom and year of diagnosis. The mean and median diagnostic delay were calculated. A survival analysis was performed evaluating the association between the demographic, clinical and diagnostic variables on the diagnostic delay.Results:Of the 373 axSpA patients in the registry, 198 (47%) are men. Ankylosing spondylitis fulfilling New York criteria was diagnosed in 73% of the patients. HLA-B*27 positivity was found in 64% of patients. The majority of the patients (63%) reported symptom onset between the age of 21-45, 21% before the age of 21 and 16% after the age of 45. Nine percent were diagnosed before the age of 21, 28% between 21-30, 23% between 31-40, 21% between 41-50 and 18% after the age of 50. One hundred and ten patients were diagnosed before 2000, 133 between 2001-2009 and 130 between 2010-2020. The mean and median delay in diagnosis was 9.1, 6 (±8.4) years when diagnosed before 2000, 5, 4 (±4.1) years when diagnosed 2001-2009, and 2, 1 (±1.5) years when diagnosed 2010-2020, respectively (graph 1). The only variable which was found to be associated with a shorter delay was the interval between symptom onset and first rheumatology consult: HR of 5.86 (4.3-8, pConclusion:Delay in axSpA diagnosis has significantly improved in this real-world cohort during the last decade. The most significant factor associated with a faster diagnosis was the time of the first rheumatology consult relative to symptom onset. Increasing the awareness of disease manifestations and early referral to a rheumatology service can improve the diagnosis delay of axSpA.References:[1]Sorensen J, Hetland ML, all departments of rheumatology in D. Diagnostic delay in patients with rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis: results from the Danish nationwide DANBIO registry. Ann Rheum Dis. 2015;74(3):e12.[2]Deodhar A, Mittal M, Reilly P, Bao Y, Manthena S, Anderson J, et al. Ankylosing spondylitis diagnosis in US patients with back pain: identifying providers involved and factors associated with rheumatology referral delay. Clin Rheumatol. 2016;35(7):1769-76.Graph 1.The improvement in the delay in diagnosis of axial spondyloarthropathy over the last 3 decadesDisclosure of Interests:None declared.

Background:Secukinumab (Cosentyx) is a human IgG1 monoclonal antibody that selectively binds to and neutralizes IL-17A. Several prospective randomized control trials have demonstrated the efficacy and safety of secukinumab in PsA, but there is a paucity of real life data in the PsA population.Objectives:To prospectively study secukinumab’s safety, efficacy, and tolerability in the cohort of PsA patients from the Israeli registry of inflammatory diseases.Methods:PsA patients fulfilling the CASPAR criteria from the Israeli registry of inflammatory diseases were included in the analysis, from 2010 to November 2019. The primary end point was secukinumab drug survival compared to other available TNFi drug. Bivariate and multivariate analysis of the factors that affect the drug event free survival was done by cox regression analysis. Drug survival according to treatment line (all treatment lines, or 2ndand above treatment lines) was examined using Kaplan-Meier curves.Results:Four hundred and four PsA patients were included, which had 709 treatment episodes (initiations) during the study period. Ninety patients had been treated with secukinumab (22%). Secukinumab treated patients were significantly older at time of initiation of treatment, and disease duration was longer. Secukinumab was more likely to be a second, third or forth line of treatment than the TNFi. . Time to an inefficacy event was longer for secukinumab than any other anti-TNF treatment. As a first line treatment secukinumab had drug survival similar to other TNFi. As a second or third line treatment, secukinumab had a better drug survival than other TNFi. Methotrexate did not have a significant effect on inefficacy event rate in combination treatment with secukinumab. Secukinumab, as infliximab and golimumab, was as effective in the higher BMI group as it was in the normal weight to obese groups. Smokers (current or past) did better on secukinumab than on TNFi. Secukinumab had a similar rate of adverse events compared to TNFi.Conclusion:In this multicenter real world study, secukinumab had a comparable drug survival to TNFi. As a second and beyond line of treatment secukinumab had a better drug survival and lower HR for an inefficacy event. IL-17 inhibition is an effective mechanism of action to treat PsA in real life, and should be used more frequently as a first and second line treatment.Tables and a graph:Table 1.Inefficacy events according to treatment and drug survival in 1, 2, and 3 years.DrugTotal episodesInefficacy events (%)HR95% CIP value1styear survival %2ndyear survival %3rdyear survival %SEC9030 (33.3)10.095865841ETA20286 (42.6)1.160.77-1.760.479755850IFX8734 (39.1)1.010.62-1.650.966826452ADA227103 (45.4)1.360.9-2.040.143715346GOL103103 (50)1.641.05-2.590.031635042Table 2.inefficacy events and drug survival according to line of treatment.DrugTotal episodesInefficacy events (%)HR95% CIP value1styear survival %2ndyear survival %3rdyear survival %1stlineSEC132 (15.4)10.216929276ETA13055 (42.3)3.250.79-13.340.101765951IFX2811 (39.3)2.880.64-13.010.168816352ADA10337 (35.9)2.630.63-10.910.183796359GOL2514 (56)4.551.03-200.0456050402ndand 3rdlinesSEC347 (20.6)10.039906666ETA6829 (42.6)1.680.74-3.850.218735751IFX5120 (39.2)1.420.6-3.360.431856454ADA11962 (52.1)2.51.15-5.480.022654635GOL5223 (44.2)2.260.97-5.270.066550464thlineSEC4321 (48.8)10.082824424ETA42 (50)1.10.25-4.730.9026733–IFX83 (37.5)0.830.25-2.790.7626969–ADA54 (80)4.871.6-14.810.00530––GOL2613 (50)1.290.64-2.580.473625231Figure 1.Cumulative survival without an inefficacy event of secukinumab compared to TNFα inhibitors regardless of treatment line.Disclosure of Interests:Tali Eviatar: None declared, Devy Zisman Consultant of: Novartis, Merav Lidar Consultant of: Novartis, Tatyana Reitblat Consultant of: Novartis, Alexandra Balbir-Gurman Consultant of: Novartis, Ori Elkayam Speakers bureau: AbbVie, BMS, Pfizer, Roche, Sanofi-Aventis, Novartis, Jansen

Background:Persistence in biologic therapy in psoriatic arthritis is critical to optimize symptom remission, functional capacity and health care costs.Objectives:To estimate the persistence to biologic treatment prescribed to PsA patients in a real-life setting as well as factors associated with improved biologic drug survival in these patients.Methods:Patients with PsA from a large health care provider database with at least two consecutive dispensed prescriptions of a biologic agent indicated for PsA from January 1st, 2002 until December 31st, 2018 were identified and followed until medication stop date or the end of observation period. Patients were considered non-persistent whenever a new prescription was dispensed and a permissible gap of 6 months was exceeded prior to starting on this biologic agent from the prescription date. Treatment changes were based on physician decisions and patient preferences.Demographic data including age, sex, BMI, ethnicity, smoking history and socioeconomic status as well as Charlson comorbidity index were retrieved. Data regarding use of steroids and non-biologic disease-modifying anti-rheumatic drugs were also extracted. Descriptive statistics, including means (standard deviations) for continuous variables and frequencies (%) for categorical variables, were used. Persistence estimates were derived using non-parametric survival analysis using Kaplan-Meier functions, with treatment discontinuations as failure events. Cox regression hazard ratio models were conducted to investigate factors associated with drug persistence.Results:2301 PsA patients with 2958 treatment periods were identified and included in the analyses. The mean age was 50.9±14 years of whom 54% were females, 70.4% of the study population had a BMI>25, and 36% were obese(BMI>30), 40% were current smokers, and 76% had a Charlson comorbidity index higher than 1. The most commonly prescribed drug was etanercept, followed by adalimumab, golimumab, secukinumab, ustekinumab and infliximab at 33%, 29%, 12%, 10%,8% and 8%, respectively. Only about 20% of patients remained on a particular biologic agent after 5 years, whereas about 40% persisted on therapy following 20 months of treatment. A Kaplan-Mayer survival analysis with pairwise comparisons of all treatment choices with respect to lines of therapy was conducted. When analyzing the data for all treatment periods and taking into account all lines of therapy, secukinumab had a higher persistency than adalimumab, infliximab and ustekinumab, with a Log Rank of 0.022, 0.047 and 0.001, respectively, as is shown in figure 1. Female sex and smoking were associated with lower drug persistence (HR=1.25, 95%CI 1.13-1.38 and HR=1.109, 95%CI 1.01-1.21, respectively). When analyzing the data regarding second-line biologic agents, secukinumab was found to be superior to adalimumab, etanercept, infliximab and ustekinumab but not to golimumab with a Log-Rank P value of 0.001, 0.004, 0.025 and 0.002, respectively (figure 2). On analyzing the data using only the first indicated biologic line, no superiority of any single anti-Tumor Necrosis Factor-alpha (anti-TNFα) agent was observed.Conclusion:In this large observational cohort, in the era of biologic therapy, a relatively low persistence was observed, with female sex and smoking having a negative impact on persistency. None of the anti-TNFα agents as first line therapy was found to be more persistent than others, while secukinumab was found to be superior to other biologics when indicated as second line of therapy.References:NoneFigure 1.Figure 2.Acknowledgments:noneDisclosure of Interests:None declared

Objectives To study the association between traditional disease-modifying antirheumatic drugs (c-DMARD) or anti-TNF-α agents and herpes zoster (HZ) in patients with psoriatic arthritis (PsA). Methods A retrospective cohort study was conducted in patients with PsA between 2002 and 2013. Patients were grouped as follows: no DMARDs (Group A); c-DMARDs (Group B); anti-TNF-α agents (Group C); anti-TNF-α agents in combination with c-DMARDs (Group D). Crude incidence rates (IR) were calculated as number of HZ episodes per 1000 patient-years. A Cox regression model was used to adjust for HZ risk factors (age, gender, steroid use, Charlson Comorbidity Index score, and previous treatment) in order to estimate their contribution to the risk of the first HZ event. Results The study included 3128 patients, mean age 50.26±14.54 years; 46.2% male. During a period of 20 096 person-years 182 HZ events were observed. The crude IR (95% CI) of HZ in the study population was 9.06 per 1000 patient-years, and in Groups A-D 7.36 (5.41 to 9.79), 9.21 (7.5 to 11.21), 8.64 (4.84 to 14.26), 17.86 (10.91 to 27.58), respectively. In a multivariate analysis, age (HR 1.01, 95% CI 1.00 to 1.02), treatment with steroids (HR 1.08, 95% CI 1.04 to 1.13), and a combination of anti-TNF-α agents and c-DMARDs (HR 2.37, 95% CI 1.32 to 4.22) were significantly associated with HZ events. Conclusions In our database, the risk of HZ was significantly increased with age, treatment with steroids, and combination of anti-TNF-α agents and c-DMARDs, but not with c-DMARDs or anti-TNF-α therapy alone. Time to HZ event was shorter in patients treated with anti -TNF-α agents.

Objective: To assess changes in macrophage phenotype and function after rituximab-induced B cell depletion in patients with rheumatoid arthritis (RA). Methods: 10 patients with RA were treated with rituximab, achieving significant B cell depletion 4 months later. Clinical improvement, rheumatoid factor (RF), anti-cyclic citrullinated peptide (anti-CCP) antibodies, mRNA of B cell activating factor (BAFF), interleukin (IL) 10 and CD86 in human monocyte-derived macrophages (HMDMs) and tumour necrosis factor α (TNFα) secretion from cultured HMDMs were assessed at baseline and after the depletion. Results: A clinical response of American College of Rheumatology (ACR) 50% improvement was noted in six patients, and another two patients responded with moderate improvement, equivalent to ACR 20–50% improvements. RF and anti-CCP antibodies were positive at baseline in seven of ten patients. RF disappeared or declined in six patients 4 months after treatment, correlating with clinical improvement. By contrast, anti-CCP remained unchanged in six patients. After rituximab treatment, and in association with clinical improvement, BAFF, IL10 and CD86 mRNA expression in HMDM were significantly upregulated compared with values at baseline. A significant decrease in TNFα in the supernatant of cultured HMDM was also noted. Conclusions: In addition to B cell depletion and attenuation in some of the specific autoantibodies, clinical improvement in rituximab-treated patients with RA occurred in association with changes in macrophage function.

Background Dysregulated expression levels of different microRNAs are reported in both serum and inflamed joints of RA patients. Objectives To determine whether administration of Tocalizumab (TCZ), a neutralizing anti-IL-6 receptor antibody, changes expression levels of selected miRNAs, which were previously described in the context of RA. Methods 40 RA patients diagnosed with moderate to severe disease activity according to both DAS28 and CDAI scores, and were started on TCZ therapy, were enrolled in the study. Serum samples that were obtained before treatment and 4 months after TCZ treatment initiation, were analyzed for the relative expression of miR-16, -21, -132, -146a, -150, -155, -203, -221, and -323 by qPCR. Results No significant changes in the expression levels of the tested miRNAs were found after TCZ treatment. However, when patients were stratified to responders and non-responders according to both the CDAI and DAS28 scores, the levels of miR-203 alone, out of the 9 miRNAs examined, were increased by 8.2% (p Conclusions The expression levels of miR-203 could serve as a potential biomarker that predicts a positive response to TCZ treatment in RA patients. References O9Connell, R. M., Rao, D. S., Baltimore, D. (2012) microRNA regulation of inflammatory responses. Annu Rev Immunol 30, 295-312. Fu, L., Jin, L., Yan, L., Shi, J., Wang, H., Zhou, B., Wu, X. (2014) Comprehensive review of genetic association studies and meta-analysis on miRNA polymorphisms and rheumatoid arthritis and systemic lupus erythematosus susceptibility. Hum Immunol Sep 2014. Bottini, N. and Firestein, G. S. (2013) Epigenetics in rheumatoid arthritis: a primer for rheumatologists. Curr Rheumatol Rep 15, 372. Duroux-Richard, I., Jorgensen, C., Apparailly, F. (2012) What do microRNAs mean for rheumatoid arthritis? Arthritis Rheum 64, 11-20. Murata, K., Yoshitomi, H., Tanida, S., Ishikawa, M., Nishitani, K., Ito, H., Nakamura, T. (2010) Plasma and synovial fluid microRNAs as potential biomarkers of rheumatoid arthritis and osteoarthritis. Arthritis research & therapy 12, R86. Stanczyk, J., Ospelt, C., Karouzakis, E., Filer, A., Raza, K., Kolling, C., Gay, R., Buckley, C. D., Tak, P. P., Gay, S., Kyburz, D. (2011) Altered expression of microRNA-203 in rheumatoid arthritis synovial fibroblasts and its role in fibroblast activation. Arthritis Rheum 63, 373-81. Acknowledgements The first and second authors are equal contributors. Disclosure of Interest None declared

Background Psoriatic arthritis (PsA) is associated with higher prevalence and risk for cardiovascular morbidities [1,2]. Objectives The aim of the study is to substantiate these findings in our population and to examine additional aspects of cardiovascular morbidities, including congestive heart failure and cardiomyopathy. Methods A retrospective, longitudinal, cohort case control study was performed on records of patients with PsA between 2000 and 2013 from the database of Israel9s largest health care provider, Clalit Health Services. For each patient with PsA, 5 control patients without history of psoriasis or rheumatoid arthritis were chosen, matched for age and gender. The following morbidities were analyzed: ischemic heart disease (IHD), valvular heart disease excluding mitral valve prolapse, congestive heart failure (CHF), cardiomyopathy, idiopathic hypertrophic subaortic stenosis (IHSS), cerebrovascular accident (CVA), carotid artery disease, peripheral vascular disease (PVD), and aortic aneurism. T-test was used to compare continuous variables and Chi square test was used for categorical variables. Age, gender, socioeconomic status and ethnicity were entered into a multivariate regression model. Results The study included 3161 patients with PsA, 1474 males (46.6%) and 1687 (53.4%) females with a mean age of 58.29±15.44 years, and 15,805 controls. Comparative analysis demonstrated higher prevalence of the following in the case cohort: IHD (18.95% vs. 14.49%) p Conclusions A high prevalence of cardiovascular co-morbidities was found in this cohort of PsA patients. The spectrum of cardiac involvement was not limited to IHD, carotid artery disease and PVD, and included also increased risk of CHF, cardiomiopathies and valvular heart disease. A high index of suspicion, and close monitoring and treatment of cardiovascular risk factors are recommended. References Husni ME, Mease PJ. Managing comorbid disease in patients with psoriatic arthritis. Curr Rheumatol Rep 2010;12:281–287. Horreau C, Pouplard C, Brenaut E, Barnetche T, Misery L, Cribier B, et a l. Cardiovascular morbidity and mortality in psoriasis and psoriatic arthritis: a systematic literature review. J Eur Acad Dermatol Venereol 2013;27(Suppl. 3):12–29. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.3830

Background Arthritis is estimated to precede skin psoriasis in approximately 15% of psoriatic arthritis patients (PsA) (1). However this data is based on studies published prior to the development of the Classification for Psoriatic Arthritis (CASPAR) criteria(2). Objectives The aim of this study is to characterize clinical, laboratory and radiological features that distinguish PsA patients diagnosed based on CASPAR criteria, who present with arthritis before psoriasis from those who develop either concomitant skin or joint manifestations or arthritis following psoriasis. Methods A retrospective cohort study of patients with PsA fulfilling the CASPAR criteria and followed in two rheumatology clinics was conducted. All charts were reviewed and clinical, laboratory and radiological manifestations at the first rheumatology evaluation were analyzed. Patients were divided into 3 groups according to the relation between the onset of the cutaneous psoriasis and arthritis: Group A (skin before joints), Group B (joints before skin), and Group C (simultaneous presentation). Analysis of variance and t-test were used to compare continuous variables. A Chi square test was used for categorical variables. Results Overall 160 patients were included: 121(75.6%) in Group A, 12 (7.5%) in Group B and 27 (16.9%) in Group C. Of these, 63 (39.4%) were males. Their mean age was 55.2±14.4 years. The mean age at onset of psoriasis and PsA were 39.7±16.3 and 48.3±14.3, respectively. No statistically significant difference across the groups with respect to age, gender, ethnicity and family history of psoriasis was observed. A polyarthritis pattern was observed in 81 (68.1%), 11 (91.7%), and 22 (81.5%) patients, respectively (p=0.11); oligoarthritis in 31 (26.5%), 1 (9.1%), and 4 (16%) patients, respectively (p=0.26); spinal involvement in 22(18.3%), 4 (33.3%), and 4 (14.8%) patients, respectively (p=0.37); and distal interphalangeal joint involvement in 16 (13.3%), 3 (27.3%) and 0 (0%) patients, respectively (p=0.04). No statistically significant differences were noted in the prevalence of entheseal, nail and dactylitis involvement. Radiographic studies revealed bone erosions in 28 (28%), 4 (33.3%) and 5 (25%) patients, respectively; radiographic sacroiliitis in 20 (20%), 3 (25%) and 3 (15.8%), patients, respectively; and new bone formation in 9 (8/9%), 1(8/3%) and 1(5.6%) patients, respectively, with no statistically significant differences. No statistically significant differences were noted in c-reactive protein levels, the prevalence of rheumatic factor and antinuclear antibody positivity. Conclusions A lower prevalence of PsA (7.5%) preceding skin manifestation was observed in our study using stringent CASPAR criteria compared to previous data published. No statistically significant differences in clinical, laboratory and radiological manifestations were noted across the analyzed groups. Polyarthritis is the most common pattern of PsA presentation. References Gladman DD, Shuckett R, Russeii ML, et al: Psoriatic arthritis-an analysis of 220 patients. Q J Med1987; 62:127-141. Taylor W, Gladman D, Helliwell P, et al: Classification criteria for psoriatic arthritis: development of new criteria from a large international study. Arthritis Rheum. 2006; 54:2665-73. Disclosure of Interest None Declared