Persistence is an important component of therapeutic success, which depends on a variety of factors. Persistence measured under optimal conditions during clinical trials does not necessarily coincide with persistence observed in the real-world settings. The aim of the present study was to compare persistence rate of TNF-alpha inhibitors and interleukin 12/23 inhibitor in all psoriasis patients in Hungary, as well as to analyze the predictors of persistence. Data collected from 1263 patients over a period of 46 months were subjected to a retrospective analysis. Drug survival rate has been calculated according to Kaplan-Meier analysis and Cox regression was used to study the predictors. The overall persistence rate for the four biologicals exceeded 60% after 3 years. The persistence rate of ustekinumab at 3 years was 67.83%, which was superior compared to that of the TNF-alpha inhibitors, where the mean persistence rate was shown to be 50.76% (p < .05). Male patients showed significantly higher persistence than females (HR ¼ .76, p < .05 CI: 0.63, 0.92). Age, therapy-naïve status and use of concomitant MTX did not have significant effect on drug survival. Persistence rate of ustekinumab was significantly higher than that of TNF-alpha inhibitors, and among predictors, only male gender influenced persistence significantly. ARTICLE HISTORY

Accelerated atherosclerosis, increased cardiovascular morbidity and mortality have been associated with rheumatoid arthritis (RA) and ankylosing spondylitis (AS). Vascular function, clinical and laboratory markers and the effects of anti-TNF therapy were assessed in arthritides. Fifty-three 53 patients including 36 RA patients treated with either etanercept (ETN) or certolizumab pegol and 17 AS patients treated with ETN were included in a 12-month follow-up study. Ultrasonography was performed to determine flow-mediated vasodilation (FMD), common carotid intima-media thickness (ccIMT) and arterial pulse-wave velocity (PWV) in all patients. All assessments were performed at baseline and 6 and 12 months after treatment initiation. A significant improvement of brachial artery FMD was observed after 6 months (p = 0.004). A tendency of FMD improvement was also observed after 12 months (p = 0.065). ccIMT did not change throughout the year. PWV significantly improved after 12 months (p = 0.034). Higher baseline ccIMT (p = 0.009) and PWV (p = 0.038) were associated with clinical non-response (cNR) versus response (cR) to biologics. Multiple analysis confirmed the association of baseline ccIMT with age (p = 0.003) and cNR (p = 0.009), as well as that of baseline PWV with age at diagnosis (p = 0.022) and current chest pain (p = 0.004). Treatment itself determined the 12-month changes in FMD (p = 0.020) and PWV (p = 0.007). In a mixed cohort of RA and AS patients, TNF inhibition improved or stabilized vascular pathophysiology. Inflammation may be associated with FMD, while, among others, cNR may influence vascular function.

Patients with severe psoriasis exhibit signs of subclinical cardiovascular disease compared to control, and prolonged anti-TNF-α therapy has a potentially beneficial effect on these signs.

Psoriasis is a common inflammatory skin disease and dendritic cells (DCs) play crucial role in the development of skin inflammation. Although the characteristics of skin DCs in psoriasis are well defined, less is known about their peripheral blood precursors. Our aim was to characterize the phenotypic features as well as the cytokine and chemokine production of CD1c myeloid DCs (mDCs) and plasmacytoid DCs (pDCs) in the blood samples of psoriatic patients. Blood DCs were isolated by using a magnetic separation kit, and their intracytoplasmic cytokine production and CD83/CD86 maturation/activation marker expression were investigated by 8-colour flow cytometry. In CD1c mDCs the intracellular productions of Th1, Th2, Th17, Th22 and Treg polarizing cytokines were examined simultaneously, whereas in pDCs the amounts of IFNα as well as IL-12, IL-23 and IL-6 were investigated. The chemokine production of both DC populations was investigated by flow-cytometry and ELISA. According to our results psoriatic CD1c mDCs were in a premature state since their CD83/CD86 maturation/activation marker expression, IL-12 cytokine, CXCL9 and CCL20 chemokine production was significantly higher compared to control cells. On the other hand, blood pDCs neither produced any of the investigated cytokines and chemokines nor expressed CD83/CD86 maturation/activation markers. Our results indicate that in psoriasis not only skin but also blood mDCs perform Th1 polarizing and Th1/Th17 recruiting capacity, while pDCs function only in the skin milieu.

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Background and Objectives Cardiovascular (CV) morbidity and mortality are increased in patients with rheumatoid arthritis (RA) and ankylosing spondylitis (AS). Biologics may influence vascular function and lipids in arthritides, however, most studies have been short-term and less information has become available on etanercept (ETN) and certolizumab pegol (CZP). We wished determine the effects of these TNF blockers on common carotid intima-media thickness (ccIMT), brachial artery flow-mediated, endothelium-dependent vasodilatation (FMD) and the arterial stiffness marker pulse wave velocity (PWV) in context with laboratory assessments in RA and AS patients after 12 months of biological therapy. Materials and Methods Twenty-seven RA patients (23 female, 4 male) and 17 AS patients (14 males, 3 females) were included. RA patients received either ETN or CZP and AS patients were treated with ETN for 12 months. Brachial and carotid ultrasonography was performed to determine FMD, ccIMT and PWV, respectively. We also assessed immunological, inflammatory and metabolic laboratory markers. Results In RA, at baseline, mean ccIMT was 0.56 mm (normal range: 0.4-0.9 mm), mean FMD was 6,5% (normal: >10%) and the mean PWV was 8.4 m/s (normal range: 4-20m/s). At baseline, ccIMT correlated with disease duration (R = 0.446, p = 0.015), while FMD and PWV did not. ccIMT (R = 0.393, p = 0.023) and PWV (R = 0.511, p = 0.005) also correlated with age at RA onset. PWV correlated with serum triglyceride levels. In AS, at baseline, mean ccIMT was 0.47 mm (normal range: 0.4-0.9 mm), mean FMD was 6,9% (normal: >10%) and the mean PWV was 6.4 m/s (normal range: 4-20m/s). At baseline, a significant inverse correlation was observed between CRP and HDL-C levels (R = -0.518, p = 0.033). ccIMT strongly correlated with BASDAI R = 0.881, p = 0.001). After 12 months of anti-TNF treatment in RA, DAS28 (p < 0.001), CRP (p = 0.004). FMD (p = 0.04) and PWV (p = 0.035) significantly improved. In AS, 12 months of ETN treatment resulted in significant improvement in BASDAI (from 6.14 to 1.25; p < 0.001), CRP (from 13.4 to 2.3 mg/l; p = 0.002). FMD (from 6.9% to 9.3%; p = 0.01) and PWV (from 6.4 to 5.4 m/sec, p = 0.045), while ccIMT showed no change. There have been no significant changes in lipid levels in AS. Conclusions In patients with RA and AS, FMD, a marker of endothel dysfunction and PWV, a marker of arterial stiffness significantly improved after 12 months of anti-TNF treatment. ccIMT may require more time to improve. These beneficial vascular changes were associated with improved disease activity.

Background Accelerated atherosclerosis, increased cardiovascular (CV) morbidity and mortality, as well as the perpetuation of angiogenesis and abundant production of angiogenic factors have been associated with rheumatoid arthritis (RA) and ankylosing spondylitis (AS). Biologics may influence both vascular function and angiogenesis. However, the effects of targeted therapies on vascular function and angiogenesis have been poorly studied in a comparative manner. Objectives Vascular function, markers of atherosclerosis and angiogenesis, as well as the effects of anti-TNF therapy on these biomarkeres were assessed in the very same arthritis patient cohort. Methods Altogether 31 arthritis patients including 18 RA patients treated with either etanercept (ETN) or certolizumab pegol (CZP) and 13 AS patients treated with ETN were included in a 12-month follow-up study. Ultrasonography was performed to determine flow-mediated vasodilation (FMD), a marker of endothelial dysfunction; common carotid intima-media thickness (ccIMT), a marker of atherosclerosis and pulse-wave velocity (PWV), an arterial stiffness parameter in all patients. Furthermore, circulating markers of angiogenesis including vascular endothelial growth factor (VEGF), platelet-derived growth factor-BB (PDGF-BB), angiopoietin 1 (Ang1), Ang2 and thrombospondin 1 (TSP-1) were assessed in the sera by ELISA. DAS28, BASDAI and CRP, markers of disease activity, were also determined. All assessments were performed at baseline, as well as 6 and 12 months after treatment initiation. Results Anti-TNF treatment was highly effective in both diseases, as the mean DAS28 decreased from 5.00 to 2.97 (p<0.001) in RA, mean BASDAI decreased from 5.99 to 1.82 (p<0.001) in AS and CRP decreased from 13.8 to 3.9 mg/l (p=0.021) in RA+AS over a 12-month period. Anti-TNF treatment resulted in significant improvement in FMD (from 7.15% to 9.11%; p=0.009) and a tendency of improvement in PWV (from 7.57 to 6.82 m/sec; p=0.190). Among markers of angiogenesis, mean VEGF (from 268.3 to 222.6 pg/ml; p=0.006) and PDGF-BB (from 8187 to 6020 pg/ml; p=0.012) levels significantly decreased after 12 months of therapy. Moreover, PDGF levels after 12 months, as well as Ang2 levels at all time points correlated with disease duration (p<0.05) and Ang1, Ang2 and TSP1 levels all correlated with CRP at baseline (p<0.05). When markers of vascular function and angiogenesis were compared, baseline PDGF levels correlated with baseline ccIMT (p<0.05). Conclusions In a mixed cohort of RA and AS patients, anti-TNF therapy improved endothelial function and decreased the circulating levels of some angiogenic markers. Both impaired vascular function and the perpetuation of angiogenesis may be due to active systemic inflammation associated with these arthritides. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.2799

Background Cardiovascular (CV) morbidity and mortality are increased in patients with rheumatoid arthritis (RA). Biologics may influence vascular function and lipids in RA, however, most studies have been short-term and less information has become available on etanercept (ETN) and certolizumab pegol (CZP). Objectives We wished determine the effects of these TNF blockers on common carotid intima-media thickness (ccIMT), brachial artery flow-mediated, endothelium-dependent vasodilatation (FMD) and the arterial stiffness marker pulse wave velocity (PWV) in context with laboratory assessments in RA patients after 12 months of biological therapy. Methods Twenty-six patients (22 female, 4 male) were studied. They received either ETN or CZP for 12 months. Brachial and carotid ultrasonography was performed to determine FMD, ccIMT and PWV, respectively. We also assessed immunological, inflammatory and metabolic laboratory markers. Results At baseline, meanccIMT was 0.56 mm (normal range: 0.4-0.9 mm), mean FMD was 6,5% (normal: >10%) and the mean PWV was 8.4 m/s (normal range: 4-20m/s). At baseline, ccIMT correlated with disease duration (R=0.446, p=0.015), while FMD and PWV did not. ccIMT (R=0.393, p=0.023) and PWV (R=0.511, p=0.005) also correlated with age at RA onset. PWV correlated with serum triglyceride levels. After 12 months of anti-TNF treatment, DAS28 (p<0.001), CRP (p=0.004). FMD (p=0.04) and PWV (p=0.035) significantly improved. Conclusions In patients with RA, FMD, a marker of endothel dysfunction and PWV, a marker of arterial stiffness significantly improved after 12 months of anti-TNF treatment with ETN or CZP. ccIMT may require more time to improve. Disclosure of Interest None Declared