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Background:There is evidence of subclinical activity in psoriatic arthritis (PsA) patients in remission detected by power Doppler ultrasound (PDUS), which represent a risk factor for relapse [1].Objectives:The study aimed to evaluate subclinical ultrasound changes in patients with PsA who reached the therapeutic target with biological therapy.Methods:This cross-sectional study included patients from the Romanian Registry of Rheumatic Diseases, with Disease Activity Index for Psoriatic Arthrititis (DAPSA) < 14, undergoing biological therapy. Clinical and musculoskeletal ultrasound examinations were performed. PDUS scanning protocol included bilateral evaluation of hands and feet joints for synovitis and bilateral assessment of elbow lateral epicondyle, quadriceps insertion, distal patella tendon insertion, and Achilles enthesis for enthesitis. Enthesitis and synovitis were defined using the OMERACT criteria [2] and they were considered active if they exhibited at least a score 1 for PDUS signal.Results:The study included 44 patients: mean age of 55.2 ± 15.2 years; 52.3% women; 36.4% obesity; 29.5% smokers; mean PsA duration of 15.4 ± 9.1 years; average psoriasis duration of 22.9 ± 13.0 years; 1 patient with PsA sine psoriasis; mean DAPSA of 4.5 ± 3.0. In total 15.9% of patients had active synovitis and 18.2% had active enthesitis. Only 12.5% of the active ultrasound enthesitis were painful on palpation. The comparison of clinical and PDUS findings at entheseal level showed a sensitivity of 12.5%, a specificity of 95.1% for clinical examination and an overall agreement of 93.2%. The probability of observing positive ultrasound changes in patients with painful enthesis was 2.5 times higher than in those with painless enthesis.Conclusion:A high proportion of active synovitis and enthesitis was detected in PsA patients considered within the therapeutic target. Clinical examination may be used as a guide for selecting the anatomic sites to scan, and patients with positive PDUS findings should be considered at risk of relapse.REFERENCES:[1] Ruta S et al. J Rheumatol. 2017; 44 (7): 1018-1023.[2] Bruyn GA, et al OMERACT Ultrasound Working Group.J Rheumatol. 2019 Oct;46(10):1388-1393.Acknowledgements:NIL.Disclosure of Interests:Mihaela Agache speaking fees in meetings sponsored by Abbvie, Novartis, Pfizer, Luminita Enache: None declared, Corina Mogosan speaking fees in meetings sponsored by Abbvie, Lilly, Novartis, Pfizer, Claudiu Popescu speaker fees from Abbvie, Norvartis, Pfizer, Emilio Filippucci speaking fees in meetings sponsored by Abbvie, Amgen, Bristol-Myers Squibb, Janssen-Cilag, Lilly, Novartis, Pfizer and UCB Pharma, Catalin Codreanu Support for clinical studies: AbbVie, Ewopharma, Lilly, Novartis, PfizerSpeaker fees & consultancy: AbbVie, Amgen, Boehringer Ingelheim, Ewopharma, Lilly, Novartis, Pfizer, Sandoz.

Liver disease is a major cause of morbidity and mortality worldwide. As in other fields of medicine, there is a stringent need for non-invasive markers to improve patient diagnostics, monitoring and prognostic ability in liver pathology. Cell-free circulating RNA molecules have been recently acknowledged as an important source of potential medical biomarkers. However, many aspects related to the biology of these molecules remain to be elucidated. In this review, we summarize current concepts related to the origin, transportation and possible functions of cell-free RNA. We outline current development of extracellular RNA-based biomarkers in the main forms of non-inherited liver disease: chronic viral hepatitis, hepatocellular carcinoma, non-alcoholic fatty liver, hepato-toxicity, and liver transplantation. Despite recent technological advances, the lack of standardization in the assessment of these markers makes their adoption into clinical practice difficult. We thus finally review the main factors influencing quantification of circulating RNA. These factors should be considered in the reporting and interpretation of current findings, as well as in the proper planning of future studies, to improve reliability and reproducibility of results.

BackgroundRheumatoid Arthritis (RA) treatment targets remission or low disease activity. Patient Registries offer real-world data about effectiveness on long term. Comparing different tools for assessing effectiveness (disease activity, functional status and utility) could provide a more comprehensive approach on the term “achieve and maintain” the therapeutic goal, as a measure of efficacy.ObjectivesTo evaluate interrelations of disease activity – functional status – utility in a group of RA patients, treated with tumor necrosis factor alpha (TNF) antagonists and anti CD20 molecule, as well as any factor that could influence it.MethodsCross-sectional study carried out over a cohort of RA patients in Romania. Data was gathered from the Romanian Registry of Rheumatic Diseases and included only RA patients treated with biologics, for who were available all three variables under study: EQ5D (for utility), HAQ score (for functional status), and DAS28 and SDAI (for disease activity). The interrelations of the efficacy parameters were analyzed using correlation tests, T test, ANOVA.ResultsThe study cohort included 777 RA patients, mean age 58.72 (±12.37) yrs, 84.4% women, mean RA duration 14.08 (±8.33) yrs, 77.1% retired, treated with etanercept (30.6%), adalimumab (22.7%), infliximab (original 6.3%, biosimilars 0.7%), rituximab (26.3%) with a mean treatment duration 174.90 (±143.40) weeks; 27.3% used steroids (20.2% with <7.5mg daily); mean current DAS28 score = 3.66 (±1.52), mean delta DAS28 = 0.13 (±1.28), mean SDAI = 14.27 (±13.79), mean HAQ score = 1.14 (±0.64), mean EQ5D = 0.61±0.31. There was a strong positive correlation between HAQ score and DAS28, as well as SDAI: r=0.5 (p<0.001) and a negative association between HAQ and EQ5D: r= -0.6 (p<0.001). Utility score showed a strong negative association with DAS28 and with SDAI: r= -0.7 (p<0.001), whereas disease activity dynamics (delta DAS28 for the last 6 months) had a poor negative association with EQ5D: r= -0.2 (p<0.01), but not with HAQ. Patient global assessment (PGA) on disease activity had a significant association both with HAQ (r=0.6, p<0.001) and EQ5D (r= -0.6, p<0.01). Analyzing distribution of EQ5D and HAQ in DAS28 categories, there was a significant difference between categories (p<0.001); for EQ5D-DAS28: <2.6 = 0.81 (±0.19), 2.6–3.2 = 0.68 (±0.17), 3.2–5.1 = 0.63 (±0.18), >5.1 = 0.16 (±.38); for HAQ-DAS28: <2.6 = 0.73 (±0.57), 2.6–3.2 = 0.98 (±0.5), 3.2–5.1 = 1.25 (±0.52), >5.1 = 1.76 (±0.56). Steroids use belongs to more active disease; doses >7.5 mg/day represent a cutoff for patients with severe disease activity [HDA]. Disease duration had not any influence on EQ5D, HAQ or DAS28, as well as all other factors (age, sex, residency, education, work status).ConclusionsDisease activity influences the patient well-being and functionality. Considering the dynamics of disease activity over time and the fluctuating values of utility and HAQ score within DAS28 categories, analyzing treatment efficacy from a combined perspective may be helpful in evaluating the time trends on achieving and maintaining the therapeutic goals.Disclosure of InterestNone declared

BackgroundThe efficacy of anti TNFblockers in active ankylosing spondylitis (AS) is widely accepted. In Europe, high costs related to biological treatment lead to significant differences regarding the patient's accessibility to treatment depending on the level of economic development of different countries. In Romania, according to the national reimbursement protocol, a patient is eligible for treatment with TNF blockers if the disease is active despite using at least two non-steroidal anti-inflammatory drugs and sulfasalazine (for peripheral arthritis).ObjectivesThe aim of the study is to assess the accessibility of patients with AS to biological therapy in Romania, depending on their area of residence and socio- economical indicators for each region.MethodsA cross-sectional study was performed in 41 counties and Bucharest. Data were collected from the Romanian Registry of Rheumatic Diseases and the socio- economic indicators from the yearbook of the National Institute for Statistics.ResultsData were gathered for 2013 AS patients treated with biologics. The mean age was 45.46 yrs (±12.07), 78% were male, 71% live in urban residences and the mean disease duration was 11.53 yrs. 74% (n=1498) of patients had access to biologics in their county of residence, while 26% (n=524) of patients had to travel for treatment to another county. Compared to the group treated inside their county of residence, those treated outside, originated from areas with a lower gross domestic product per capita (5701.77 € compared to 8722.44 €; p<0.001; t test) and with high deficit of physicians (1.28 physicians/ 1000 inhabitants, comparated to 2.63 physicians/ 1000 inhabitants; p<0.001; t test). The urban habitat was associated with a higher accessibility to biologics (75.9%) inside their county of residence compared to patients living in rural areas (69.2%) (p=0.002, χ2 test); so the latter have to travel in order to being cared by a rheumatologist. The patients' age had a great influence on the accessibility to biologics: the patients treated outside of their county of residence were younger than those treated inside (44.1 yrs compared to 45.9 yrs; p=0.003, t test). On a national scale, the majority of AS patients treated outside their county of residence (86%; 449); were treated in Bucharest (the capital city); so the majority of patients treated with biologics in Bucharest are originating from other counties (60%; n=449/751).ConclusionsIn Romania, although there is a national protocol for biological therapy in AS, applied in the same way in every region of the country, the accessibility to biologic therapy varies a lot, mostly due to differences in the socio- economic status of each area of residence.Disclosure of InterestNone declared

BackgroundRomania fully reimburses through the National Insurance Health House (NIHH) six biological products for patients with active rheumatoid arthritis (RA), non-responders to at least 2 conventional remissive drugs: infliximab (IFX) original and biosimilars: inflectra (IFN), remsima (REM), etanercept (ETA), adalimumab (ADA), rituximab (RTX). All RA patients treated with biologics are registered in the national electronic database of the Romanian Registry of Rheumatic Diseases (RRBR) - application developed in 2013. Currently, 39.000 cases of RA are treated in Romania, according to NIHH data.ObjectivesCharacteristics of RA population treated with biological agents in Romania, efficacy and safety data from RRBR, after 2 years of initiation.MethodsObservational cross sectional study, which included all RA patients treated with biologics.Results4470 RA patients were included, mean age 57.11 years (±12.02), 85.5% women, mean RA duration 13.51 years (±7.97), 64.8% living in urban areas, 77.4% retired (50% of them permanently work disabled due to RA), 33% with elementary education; mean body mass index (BMI) 26.09 (±4.60). Current treatment: 7.27% IFX, 0.08% IFN, 0.23% REM, 20,74% ADA, 27.21% ETA, 39.91% RTX. Methotrexate is used in 56.3% cases, leflunomide in 41.2%, sulphasalasine in 12.6% and hydroxychloroquine in 9.4%. 23% patients use steroids (20.8% <10mg prednisone daily). The current mean DAS28 is 2.86 (±1.32) and SDAI 6.88 (±7.98); 52.4% cases are in remission (according to DAS28), but only 41.4% according to SDAI; 21.5% cases are in LDA (according to DAS28) and 41.8% (SDAI). Mean EuroQoL 5D (EQ-5D) is 0.73 (±0.26). There is a strong negative association between EQ-5D and DAS28 (r = - 0.7, p<0.01). DAS28 levels correlate positively with BMI (r =0.2, p<0.05). On safety issues, 105 severe adverse events have been reported (2.34%), 21 infections, other than tuberculosis (TB), 21 cases of TB, 15 solid malignancies, 1 case of Hodgkin lymphoma, 11 major cardiovascular events; 13 cases were fatal.ConclusionsIn Romania, the use of biologics in RA is on a positive trend (11.5% of all RA treated cases). 1/3 of patients have low education and 38.7% are permanently work disabled. Overall treatment efficacy of biological class in terms of T2T strategy (remission) reaches 52.4% (DAS28) and 41.4% (SDAI). Compared with other patients Registries from Europe or USA (1) in Romania there is a higher proportion of women treated and the percentage of steroids use is lower; DAS28 value is significantly lower (near-remission) compared to literature data (1), probably due to the strict evaluations imposed by the NIHH, while the adverse events seem less common (perhaps a lack of registration of all clinical situations). The impact of active disease on quality of life (EQ-5D) is major.ReferencesCurtis JR, Jain A, AsklingJ et al. A Comparison of Patient Characteristics and Outcomes in Selected European and U.S. Rheumatoid Arthritis Registries, Semin Arthritis Rheum. Aug 2010; 40(1): 2–14.e1., doi: 10.1016/j.semarthrit.2010.03.003, PMCID: PMC2958101, NIHMSID: NIHMS234142Disclosure of InterestNone declared

BackgroundTherapeutic target in rheumatoid arthritis (RA) aims at achieving remission or low disease activity (1). Among the known poor prognostic factors are anti–citrullinated protein antibody (ACPA) and rheumatoid factor (RF). Clinical significance and therapeutic implications of the positivity of antinuclear antibodies (ANA) in serum of RA patients is still under debate.ObjectivesThe implications of ANA positivity, as a prognostic factor, in the therapeutic response to biologic therapy in RA, as measured by DAS28 score.MethodsCross sectional, observational study; all data were gathered from the electronic database of Romanian Registry of Rheumatic Diseases (RRBR) which comprises all RA patients following biological treatment in the country. There were included only RA patients who were evaluated for the presence of ANA, before initiating biologic therapy.Results740 RA patients were included in the study, mean age 56.50 years (±12.59), 84.5% women, mean disease duration 12.54 years (±7.67), 66.4% from urban areas, 74.7% retired. At baseline (prior to biologic start), 26.9% patients were positive for ANA, 89.8% for RF and 37% for anti-CCP antibodies and the mean DAS28 was 5.09±2.35. 72.4% patients were treated with TNF-alpha blockers, while 27.6% with anti-CD20 drugs. During evolution, 22% of subjects required switch of therapy. Biologics persistency (the duration of therapy under one drug) was on average 31.70 (±29.95) months (for those without switch) and the latest DAS 28 score was 2.90±1.41. There were statistically significant differences between DAS28 values at all assessments, depending on the presence of ANA. At biological start, DAS28 score in ANA positive group was 5.70±2.06, while in ANA negative group was 4.86±2.41 (p<0.001). In terms of treatment efficacy, assessed by the latest DAS28, ANA positive group had a score of 3.32±1.61, compared to 2.74±1.30 of the ANA negative patients (p<0.001). The drug persistence in ANA positive patients was 22.65±25.68 months, versus 34.86±30.71 months in ANA negative group (p<0.001). For patients who required switch of therapy, DAS28 score at switch time was 5.42±1.52 in ANA positive group, versus 4.79±1.80 in ANA negative group (p=0.05). There is a poor positive association between ANA positivity and DAS28 at all assessments (r =0.2, p<0.01) and ACPA positivity (r =0.2, p<0.01) and a negative correlation between ANA positivity and drug persistence (r = - 0.2, p<0.01). Linear regression showed that ANA positivity best predicts the treatment efficacy, evaluated by DAS28 dynamics (t =4.5, p<0.001) (followed by ACPA positivity).ConclusionsANA positivity in patients with RA, before initiating the biological therapy, may be a poor prognostic factor for the therapeutic efficacy, as well as for the drug persistence. More studies are needed to confirm these observations.ReferencesSmolen JS, Landewe R, Breedveld FC, Buch M, Burmester G, Dougados M et al,EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2013 update Ann Rheum Dis. Mar 2014; 73(3): 492–509.Disclosure of InterestNone declared

Chronic hepatitis C (CHC) is a major burden for public health worldwide. Although newer direct-acting antivirals show good efficacy, their cost precludes their wide adoption in resource-limited regions. Thus, strategies are being developed to help identify patients with high susceptibility to response to classic PEG-interferon + ribavirin therapy. IL28B polymorphism rs12979860 C/T is an important predictor for an efficient response to interferon-based therapy. A genetic variant in adiponutrin (PNPLA3) gene, rs738409 C/G, is associated with steatosis, severity, and progression of liver fibrosis in CHC patients, and predicts treatment outcome in difficult-to-cure HCV-infected patients with advanced fibrosis. We developed a rapid and inexpensive assay based on duplex high-resolution melting (HRM) for the simultaneous genotyping of these two polymorphisms. The assay validation was performed on synthetic DNA templates and 132 clinical samples from CHC patients. When compared with allele-specific PCR and sequencing, our assay showed 100% (95% CI: 0.9724–1) accuracy, with 100% sensitivity and specificity. Our assay was robust against concentration and quality of DNA samples, melting curve normalization intervals, HRM analysis algorithm, and sequence variations near the targeted SNPs (single nucleotide polymorphism). This duplex assay should provide useful information for patient-oriented management and clinical decision-making in CHC.