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Background:Systemic Sclerosis (SSc) is a rare autoimmune disease characterized by vascular abnormalities and diffuse fibrosis including patchy fibrosis of the myocardium and subsequent conduction abnormalities. As much as 27% of SSc deaths are due to cardiac impairment. The electrocardiogram (ECG) remains the most used screening tool for cardiac electrical activity [1].Objectives:To evaluate the prevalence and functional associations of ECG abnormalities in SSc patients.Methods:We performed a prospective cross-sectional analysis of patients fulfilling the 2013 American College of Rheumatology/ European League Against Rheumatism (ACR/EULAR) SSc classification criteria who were hospitalized in our Rheumatology Department from November 2022 to December 2023. A wide range of variables were collected, namely patients’ demographic data, personal and family history, disease history, comorbidities and treatment, blood tests which included the lipid profile, cardiac enzymes, thyroid markers, and complete antibody profile. Cardiac involvement was also evaluated with ECG at rest, performed at inclusion and by echocardiography (echo).Results:73 patients, 7 (9.6%) males and 66 (90.4%) females, with mean±SD age at inclusion of 59.3±11.7 years were included, 32 (44%) with diffuse cutaneous form, 40 (55%) with limited cutaneous form and 1 (1%) with sine scleroderma form.The descriptive ECG and echo parameters are presented in Table 1. The Intraventricular conduction disturbances (IVCD) were most frequently identified in our lot (n-38, 52%) with the highest prevalence for the right bundle branch block (RBBB).The IVCD was associated with the QRS complex width (r-379, p=0.023), higher PAPs level (34.4±12.2 vs 28.8±7.5, p=0.007), and also with the Rodnan results for the hand-fingers (2 (1;3) vs 0.5(0;2), p=0.028).Further, the RBBB was more frequent in patients with high cholesterol levels (148.7±53 vs 182.2±49.6 p=0,046).The N-terminal prohormones of brain natriuretic peptides (NT-proBNP) values were related with prolonged PR interval (p=0.006), laboratory parameters such as cholesterol fractions, creatinine, (147.2 (75.4;173.9) vs 175.7 (149.9;217.1), p=0.012, 0.87 (0.74;1.78) vs 0.71 (0.62;0.81), p=0.025). Furthermore, positive associations were identified for Rodnan total and hand score and azathioprine posology (14 (4.5;25.5) vs 6 (4;11), p=0.043, 2 (0;3) vs 0 (0;3), p=0.026, p r-624, p=0.013).Regarding the autoimmunity profile, there was no significant association with the criteria SSc antibodies and atrioventricular conduction disturbances (AVCD), even if the anti-SCL-70 antibodies were associated with QT interval duration (0.36±0.03 vs 0.38±0.03, p=0.039). However, the patients with anti-Ro antibodies (113.7±0.83 vs 18.19±4.6, p<0,001) were at more risk of developing AVCD.Regarding the immunosuppressant treatment, we found an interesting association between Azathioprine treatment and higher prevalence of IVCD and AVCD (19/59 (32.2%) vs 4/5 (80%), p=0,003 and 18/34 (53%) vs 5/30 (16.7), p=0,032).Conclusion:Standard ECG is a useful screening tool to identify cardiac involvement in patients with SSc. RBBB was identified most frequently on our patients’ ECG at inclusion. Laboratory tests such as cholesterol fraction, positive NT-proBNP, presence of anti-Ro and anti-SCL70 antibodies present significant correlations with ECG changes suggestive for conduction disturbances. Azathioprine treatment associated higher occurrence of conduction disorders, thus further analyzes of possible confounders should be considered.REFERENCES:[1] M. Vrancianu CA et al. „Arrhythmias and Conduction Disturbances in Patients with Systemic Sclerosis-A Systematic Literature Review.,” Int J Mol Sci. 2022 Oct 26;23(21):12963. doi: 10.3390/ijms232112963. PMID: 36361752; PMCID: PMC9658897.Acknowledgements:NIL.Disclosure of Interests:None declared.

BackgroundThe anti-Nucleolar Organizer Region 90 antibodies (NOR90) are rare antinuclear antibodies (ANA) identified in up to 6% of patients with systemic sclerosis (SSc). However, due to the small number of available studies, the clinical relevance of NOR90 in SSc remains uncertain.ObjectivesTo analyze clinical associations of NOR90 in patients with SSc in a multicentric cohort.MethodsPost-hoc, cross-sectional study of prospectively collected data from the European Scleroderma Trials and Research (EUSTAR) group database, with additional information on NOR90 provided by participating centers (EUSTAR project CP105). NOR90 was tested using immunoassays. Differences between patients with and without NOR90 were assessed using the U Mann-Whitney and the Chi-square test, and clinical associations were tested using regression models.ResultsOverall, 1318 patients with SSc were included (mean age 58.3±13.7 years, 81.3% female), of whom 44 (3.3%) were positive for NOR90, that were also positive for other SSc-specific antibodies: anti-topoisomerase I (20.5%), anti-centromere (42.9%), and anti-RNA polymerase III (12.5%). The demographic and clinical data of NOR90-positive and -negative patients are displayed in Table 1. There was no difference in the presence of severe organ manifestations including interstitial lung disease, pulmonary hypertension, and renal crisis, but NOR90-positive patients were more frequently female, had lower modified Rodnan skin score (mRSS), and lower prevalence of upper and lower gastrointestinal symptoms compared to NOR90-negative patients. In multivariable regression models adjusted for the presence of the most frequent SSc-specific antibodies, NOR90 remained significantly associated with lower mRSS and with less frequent gastrointestinal symptoms (Figure 1).ConclusionTo the best of our knowledge, this is the largest SSc cohort tested for NOR90 so far. Apart from negative associations with skin fibrosis and GI symptoms, which should be analyzed in further studies, we did not find any significant association of NOR90 with SSc-associated organ/ system involvement. However, these patients had a considerable prevalence of severe organ manifestations and should therefore be carefully evaluated.Table 1.Demographic and clinical SSc-related data of NOR90-positive and -negative patients.ParameterNOR90 (+)NOR90 (-)p-valueAge, years61.5 (48.0; 68.0)59.0 (50.0; 68.0)0.663Female, yes/total (%)43/44 (97.7%)1029/1274 (80.8%)0.005Disease duration, years15.5 (9.7; 21.2)12.0 (6.0; 21.5)0.061Anti-topoisomerase I, n/N (%)9/42 (20.5%)343/1241 (27.6%)0.375Anti-centromere positive, n/N (%)18/42 (42.9%)472/1252 (37.7%)0.498RNA Polymerase III positive, n/N (%)5/40 (12.5%)99/1186 (8.3%)0.354Diffuse cutaneous SSc, yes/ total (%)6/29 (20.7%)334/1089 (30.7%)0.249Digital ulcers, yes/ total (%)4/9 (44.4%)252/630 (40.0%)0.101mRSS2.0 (0.0; 7.0)5.0 (1.2; 11.0)0.001Pulmonary hypertension, yes/ total (%)6/26 (23.1%)118/850 (13.9%)0.185Lung fibrosis, yes/ total (%)11/26 (42.3%)427/897 (52.4%)0.594DLCO, % predicted73.0 (44.7; 84.0)69.5 (55.0; 83.0)0.756Upper gastrointestinal tract symptoms, yes/ total (%)17/40 (42.5%)592/930 (63.7%)0.007Lower gastrointestinal tract symptoms, yes/ total (%)5/40 (12.5%)360/937 (38.4%)0.001Renal crisis, yes/ total (%)1/42 (2.4%)34/1237 (2.7%)0.886Joint synovitis, yes/ total (%)1/31 (2.3%)138/914 (15.1%)0.066Data are presented as median (interquartile range) for the continuous variables and as number (percent) for the nominal ones. n = number of patients with positive results for the antibodies tested. N = total number of patients tested for the respective antibody. Significant p-values (p < 0.05) are marked in bold.Figure 1.Association of NOR90 and SSc-criteria antibodies (ATA; ACA; RNAP III) with the mRSS and gastrointestinal (GI) manifestations.AcknowledgementsAlina Dima, Alexandru Garaiman, and Madelon Vonk share equal contribution.Disclosure of InterestsAlina Dima Grant/research support from: EULAR Scientific training grant for young fellow, Alexandru Garaiman: None declared, Madelon Vonk Speakers bureau: Boehringer Ingelheim, Ferrer, Galapagos, GSK, Janssen, MSD and Novartis, Consultant of: Boehringer Ingelheim, Ferrer, Galapagos, GSK, Janssen, MSD and Novartis, Brigit Kersten: None declared, Radim Bečvář: None declared, Michal Tomcik: None declared, Anna-Maria Hoffmann-Vold Speakers bureau: Boehringer Ingelheim, Jannsen, Medscape, Merck Sharp & Dohme and Roche, Consultant of: ARXX, Boehringer Ingelheim, Genentech, Jannsen, Medscape, Merck Sharp & Dohme and Roche, Grant/research support from: Boehringer Ingelheim, Jannsen, Ivan Castellví Speakers bureau: Boehringer, Janssen-Cilag, BMS, Roche, UCB., Consultant of: Boehringer, Janssen-Cilag, Topandur, Jose Luis Tandaipan: None declared, Marek Brzosko: None declared, Marcin Milchert: None declared, Dorota Krasowska Speakers bureau: Novartis, Abbvie, Elli Lilly, Consultant of: Boehringer Ingelheim, Novartis, Janssen, Małgorzata Michalska-Jakubus: None declared, Paolo Airò Speakers bureau: Bristol Myers Squibb, Bohringer Ingelheim, Roche, Novartis, CSL Behring Janssen- Cilag, Consultant of: Bristol Myers Squibb, Bohringer Ingelheim, Roche, Novartis, CSL Behring Janssen- Cilag, Marco Matucci-Cerinic Speakers bureau: Biogen, Sandoz, Boehringer, Lilly, Galapagos, Grant/research support from: MSD, Janssen, Cosimo Bruni Speakers bureau: Eli Lilly, Consultant of: Boehringer Ingelheim, Grant/research support from: Gruppo Italiano Lotta alla Sclerodermia (GILS), European Scleroderma Trials and Research Group (EUSTAR), Foundation for research in Rheumatology (FOREUM), Scleroderma Clinical Trials Consortium (SCTC), AbbVie, Michele Iudici: None declared, Joerg Distler: None declared, Ana Maria Gheorghiu Speakers bureau: Sandoz, Boehringer Ingelheim, Ewopharma, Consultant of: Boehringer Ingelheim, Hadi Poormoghim: None declared, Francesca Motta Consultant of: Thermo Fisher, Maria De Santis: None declared, Magda Parvu: None declared, Oliver Distler Speakers bureau: 4P-Pharma, Abbvie, Acceleron, Alcimed, Altavant, Amgen, AnaMar, Arxx, AstraZeneca, Baecon, Blade, Bayer, Boehringer Ingelheim, Corbus, CSL Behring, Galderma, Galapagos, Glenmark, Gossamer, iQvia, Horizon, Inventiva, Janssen, Kymera, Lupin, Medscape, Merck, Consultant of: Miltenyi Biotec, Mitsubishi Tanabe, Novartis, Prometheus, Redxpharma, Roivant, Sanofi and Topadur, Carina Mihai Speakers bureau: from Boehringer Ingelheim, Janssen, MED Talks Switzerland, Mepha, and PlayToKnow AG, Grant/research support from: Boehringer Ingelheim, Roche.

Background:The treat-to target (T2T) concept is the standard for treating rheumatoid arthritis (RA) patients worldwide1. However, difficulties that patients encounter in achieving disease control may differ between regions, which may impact the type of support needed for successful T2T implementation.Objectives:To compare differences in patient-reported challenges to controlling RA-related issues between Romanian and US patients.Methods:A cross-sectional study that recruited 403 RA patients was conducted in six centers in Romania. Patients were invited to complete an RA-related questionnaire. We compared their responses to those from a previous published study that included patients with RA from the US2. The survey included items on subjective beliefs about RA treatment (e.g. adherence, cost, adverse events) and knowledge about T2T strategy. Approval for US data use was given by the study coordinator2.Results:All patients in the Romanian cohort were Caucasian, with a mean age of 58.7 years (SD 11.6). 78% were females and the mean disease duration was 11.2 years (SD 8.3). Data was concordant with results from the previously published study. More patients from US had college education (60% vs 43.9%).Among the respondents, 93.3% Romanians were on a synthetic DMARD versus 97.7% Americans and 64.01% were currently on a biologic of choice compared to 74% patients in the US. More than half of the patients in both regions had a history of biologic DMARD use.Asked to grade (0 very good, 10 very bad) their disease activity on the survey day, a large category of patients (37.4%, SD 14.1) marked an average state (4-6), while 19.08% (SD 11.2) were feeling poorly related to their disease.Patients were asked to define their adherence to RA treatment in the last 30 days. While the US study reported that 93% of patients were adherent2, in our study only 62.5% of the Romanian patients reported adherence (p<0.01). A significantly lower proportion of Romanian patients were aware of T2T strategy (35 %, p 0.04).Regarding patient beliefs on their disease, statements were grouped into categories such as difficulty managing pain, medication safety, adherence, lifestyle. Most European patients would agree to change treatment to lower pain. Almost 82% stated they would accept rare adverse events in order to avoid invalidity, to confirm a better future outcome. US patients were more prone to stick to current therapy than escalade to increase clinical response. However, asked about novel therapies, Romanians were reluctant to changing treatment despite insufficient benefit, if the risk of cancer was noted. There was a high agreement that a delay in treatment would be unsatisfactory for both familial and professional chores.Conclusion:There are regional differences in knowledge and perceptions about RA treatment. Romanian patients know less on T2T algorithm. Improving awareness of the T2T strategy among RA patients may need different types of support depending on the patient’s place of residence.References:[1]Smolen, J. S. et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2016 update. Ann. Rheum. Dis. 76, 960–977 (2017).[2]Owensby, J. K. et al. Patient- and Rheumatologist- Perspectives Regarding Challenges to Achieving Optimal Disease Control in Rheumatoid Arthritis. Arthritis Care Res. (Hoboken). 0–2 (2019).Disclosure of Interests:CLAUDIA COBILINSCHI Speakers bureau: novartis, Maria Danila Speakers bureau: as personally stated, Daniela Opris-Belinski Speakers bureau: as declared, Ioana Saulescu Speakers bureau: Eli-Lilly, Pfizer, Laura Groseanu Speakers bureau: novartis, eli-lilly, ucb, pfizer,sandoz, Sanziana Daia-Iliescu Speakers bureau: sandoz, Catalin Codreanu Consultant of: Speaker and consulting fees from AbbVie, Accord Healthcare, Alfasigma, Egis, Eli Lilly, Ewopharma, Genesis, Mylan, Novartis, Pfizer, Roche, Sandoz, UCB, Speakers bureau: Speaker and consulting fees from AbbVie, Accord Healthcare, Alfasigma, Egis, Eli Lilly, Ewopharma, Genesis, Mylan, Novartis, Pfizer, Roche, Sandoz, UCB, Razvan Ionescu Speakers bureau: as personally stated, Magda Parvu Consultant of: Speaker fee and consultant: Pfizer, Novartis, Roche, Abbvie, UCB, Eli-Lilly, Speakers bureau: Speaker fee and consultant: Pfizer, Novartis, Roche, Abbvie, UCB, Eli-Lilly, Horatiu Popoviciu Speakers bureau: as personally stated, CODRINA ANCUTA Consultant of: AbbVie, Pfizer, Roche, Novartis, UCB, Ewopharma, Merck Sharpe and Dohme, and Eli Lilly, Speakers bureau: AbbVie, Pfizer, Roche, Novartis, UCB, Ewopharma, Merck Sharpe and Dohme, and Eli Lilly, Elena Rezus: None declared, Claudia Mihailov Speakers bureau: as personally stated, Ruxandra Ionescu Consultant of: Consulting fees from Abbvie, Eli-Lilly, Novartis, Pfizer, Roche, Sandoz, Speakers bureau: Consulting and speaker fees from Abbvie, Eli-Lilly, Novartis, Pfizer, Roche, Sandoz

BackgroundData on the efficacy and safety of biological therapies for Rheumatoid Arthritis (RA) that come from Patient Registries present the results of clinical practice all over the world. In terms of efficacy, treatment persistence in RA is largely related to reaching the therapeutic target, i.e. remission or low disease activity.ObjectivesTo measure drug persistence with tumor necrosis factor alpha (TNF) antagonists and anti CD20 monoclonal antibody, among RA patients in Romania, as well as identify/determine additional factors that could influence it.MethodsPopulation-based cohort study carried out with RA patients in Romania. Data was gathered from the Romanian Registry of Rheumatic Diseases. The study cohort included RA patients who initiated the first course of a TNF antagonist or anti CD20 monoclonal antibody, anytime between 2004 and 2015. Persistence was measured as the time period during which the drug had been administered to a patient. Drug discontinuation was defined as drug treatment being interrupted due to adverse events, primary or secondary non-responder, or switching to another molecule. The influence of any other factors on persistence used T test and persistence was estimated using survival analysis.ResultsThe study cohort included 4,395 RA patients, mean age 59.55 yrs, 85.3% women, mean RA duration 14.37 yrs, treated with etanercept (29.7%), adalimumab (23.5%), infliximab (original 7.1%, biosimilars 0.7%), rituximab (38.9%); 23.1% used steroids (19.8% with <7.5mg dayli); mean current DAS28 score 3.08 (±1.20) and mean SDAI 3.62 ((±7.39). The persistence estimated in weeks (95% confidence interval) with infliximab was 330.8 (303.8–357.8), with rituximab it was 301.0 (262.2–339.8), with etanercept it was 240.6 (232.7–248.4) and with adalimumab it was 200.4 (191.0–209.9). There was a poor positive correlation between general persistence and RA duration (r=0.2, p<0.001) and a negative association with DAS28 (r= - 0.3, p<0.001). The use of methotrexate resulted in longer persistence (170.5±139.8) compared to other csDMARDs (152.0±120.2), p<0.001. Using steroids in dosages less than 7.5mg/day resulted in a significantly longer persistence compared to larger doses (131.2±121.3 vs 100.1±110.7), p<0.005. Patients being in remission or LDA maintained the biologics significantly longer than those with MDA or HAD (190.9±139.0 vs 121.1±107.8), p<0.001. All other factors that were analysed (age, sex, residency, education, work status, disease characteristics) had no significant effect on drug persistence. Adverse events, primary non-responders, and secondary non-responders were comparable among these molecules.ConclusionsLonger persistence was observed with infliximab, followed by rituximab, etanercept, and adalimumab in RA patients in Romania, for more than 10 years of biologics use. Reaching the state of remission or LDA, as well as low steroids regimens and long-standing disease seem to positively correlate with drug persistence.Disclosure of InterestNone declared

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

Background In recent years, emphasis has shifted in rheumatoid arthritis (RA) to early intervention in the disease course. The introduction of tumour necrosis factor (TNF) inhibitors significantly changed the overall treatment goals and guidelines. Best practice use still needs to be determined in patients with oscillating or increased disease activity treated with TNF inhibitors over long periods of time. Objectives To determine patterns of clinical response that can predict failure of anti-TNF treatment over time, indicating the need for change to second line therapy in patients suffering from severe RA with high disease activity. Methods In this longitudinal, observational, population-based, cohort study we included a total of 400 patients treated with anti-TNF therapy. Data were retrieved from the National Health Insurance House (NHIH) database (2002-2011). Over time, 195(51.5%) patients received a single TNF inhibitor and 184(48.5%) had 1-2 anti-TNF therapies. The 28-joint disease activity score (DAS28) response rates and the difference between values found at two consecutive evaluations (ΔDAS28) were calculated and tested. Patients were classified as low (LDA), moderate (MDA) and high (HDA) disease activity. Statistical analysis was performed using STATA SE 11.0 software Results The MDA group was divided into MDA1, MDA2 and MDA3 to determine the factors predicting treatment failure. In our clinical practice, we identified five patterns of treatment response: 1) Responder (R) DAS28<3.2 or ΔDAS28>1.2 at 6 months; 2) MDA1 (Stable MDA) - ΔDAS28<1.2 and 3.20.4 per year, predictor of therapeutic failure with oscillating clinical response, secondary loss of treatment efficacy and shift towards HDA; 4) MDA3 (Unstable MDA) - 3.85.1 at 6 months or ΔDAS28<0.6 ideally diagnosed at 3 months. Conclusions MDA3 (Unstable MDA) response showed similar response to HDA in our statistical analysis and therefore second line therapy should be considered at first evaluation (6 weeks). Likewise, change to second line therapy is indicated after two consecutive MDA2 evaluations. MDA1 response requires monitoring and re-evaluation of treatment options if patients reach MDA2 breakthrough stage. In current clinical practice in Romania, in all MDA patients, we recommend strict patient evaluation and tight control in the first 1-3 months after anti-TNF treatment initiation, according to ACR/EULAR criteria and ACR 2012 treat to target guidelines. Disclosure of Interest None Declared

Background The role of disease worsening or flares in taking important clinical decisions, such as dose adjustments or treatment change, is poorly understood in patients suffering from severe RA treated with TNF inhibitors over long periods of time. Objectives To determine whether the prevalence of flare episodes can predict the response to anti-TNF treatment over time and the change to second line therapy. Methods In this longitudinal, observational, population-based, cohort study we included a total of 400 patients. Data were retrieved from the National Health Insurance House (NHIH) database (2002-2011). Flare events were defined according to OMERACT criteria as increase in disease activity score DAS28 >3.2 or >0.6 if DAS28 >3.2. Prevalence of flare episodes, DAS28 response rates and EULAR response rates were calculated every six months. Results In our analysis, 379 (94.5%) patients presented 672 flare episodes (prevalence 168% in the analysed population). Conclusions In current clinical practice in Romania, a single flare episode in patients with a MDA should prompt change to second line therapy, including biological agents with other mechanisms. Our real life results, based on data collected before 2012, support OMERACT flares criteria and ACR/EULAR recommendations, emphasizing strict patient evaluation and tight control in the first 1-3 months after anti-TNF treatment initiation. Disclosure of Interest None Declared

Background Although anti-TNF therapies moved forward the treatment of rheumatoid arthritis (RA), failure of the first anti-TNF medication is not uncommon. Many times modifying dosage/frequency of the initial drug or prescribing a different TNF inhibitor proves to be still inadequate. Using instead a biologic with a different mechanism of action, such as Rituximab (RTX), may be beneficial in terms of RA treatment to target. Objectives Based on EULAR-T2T and ACR criteria we analysed response following each RTX course (2 g at every 24 weeks). Methods Longitudinal (2002 to date), observational, population-based, cohort study. The analysis was performed based on data from the National Health Insurance House (NHIH) for 400 out of 1126 patients treated with RTX for RA in October 2011 in the NHIH database. The patients’ selection is statistically representative and homogenous at national level. All patients had an anti-TNF medication as first treatment stage for 2.5 years (average). In the second stage, 208 patients were switched to RTX after the initial anti-TNF failure. The remaining 192 patients followed one or two more anti-TNF therapy and only then continued with RTX. A total of 5 RTX courses were administered to both groups. Before each RTX course patient were monitored for DAS28 and EULAR response. Results Average DAS28 before RTX was 6.7 (N=400), reaching 4.5 (before C2), then 3.41 (before C3). At the time of this analysis 335 patients followed C3 and 211 C4. Before RTX start, 93% of the total number of patients was in HDA and 8% in MDA. After 2 RTX courses 38.25% of the patients reached LDA or remission. After 18 months (before C4) 63.88% patients were in LDA or remission, while before C5 86.73% of the 211 patients having C4 were in LDA or remission (48.82% in remission). In terms of EULAR response after 4 RTX cycles 84.36% had a good response and 15.64% a moderate response, compared to previous treatment with anti-TNF in the same interval (2 years): 5.03% good response and 91.82% moderate response. BaselineW24W48W72W96 DAS286.74.53.4132.6 LDA %05.2526.2537.9137.91 Remission %00.0012.0025.9748.82 Eular Good Response %02.0032.2560.9084.36 Eular Moderate Response %085.567.2538.5115.64 Conclusions Each RTX course led to an increased and cumulative clinical DAS28 response compared to the previous one. With each following RTX course all patients registered consolidation of lower DAS28 response, and continuously growing LDA or remission percentage. Response was sustained and cumulated regardless their rheumatoid factor status. Introducing Rituximab to patients with no response or intolerance to anti-TNF agents proved to be an adequate choice, therefore we consider its prescription after the first anti-TNF failure as a preferred option in terms of clinical response. Disclosure of Interest None Declared

Background Rheumatoid arthritis (RA) is a chronic inflammatory disorder, affecting patient’s quality of life. Therefore the National Health Insurance House invests important budgets each year for RA treatments, while not all drugs and/or therapeutic approaches proved to be effective for the vast majority of patients. Finding treatment protocols that bring most benefits for the patients becomes thus an important concern and topic for research. Objectives Compare efficiency of two different RA therapy approaches: (1) switching to Rituximab (RTX) after a first anti-TNF failure or (2) switching to RTX after a second/third anti-TNF failure. Methods Longitudinal (2002 up to date), observational, population-based, cohort study. The analysis was performed for 400 RA patients over 18 years old: 75.1% female (average age 54), 24.9% male (average age 52), all having an anti-TNF α medication as first treatment stage for 2.5 years (average). In the second stage, 208 patients (Group 1) were switched to RTX after the initial anti-TNFα failure, having a median 2.3 RTX cycles (2g at 24 weeks). All the remaining 192 patients (Group 2) continued with one more anti-TNF (10.8 months) and 32 of them had also a third one (7.9 months). Only then, Group 2 continued with RTX therapy for a median 2.2 cycles. We evaluated the effectiveness of the 2 approaches using: DAS28, Δ DAS28, and EULAR response. Results For all 400 patients average DAS28 was 6.55 before RTX therapy, and 3.50 after 2 complete RTX cycles (12 months). For Group 1, DAS28 decreased from 6.31 to 3.25 (medium values) after 2 complete RTX cycles (N=208). For Group 2 we noticed an increase of DAS28 during the cure, medium ΔDAS28 reached 0.9 thus evidencing development of resistance to the anti-TNF medication. DAS28 decreased consistently for all patients in RTX therapy but reached its lowest value for Group 1 patients: after the first RTX cycle, ΔDAS28 = - 2.3. All patients receiving RTX, achieved LDA or remission, but for Group 1, these results have been obtained sooner and in a higher percentage. After 2 RTX cycles (12 months) Group 1 obtained 36.5% LDA and 15.4% remission, vs. only 15.1% LDA and 8.3% remission in Group 2. At the end of the study (five RTX cycles), 91% of Group 1 patients experienced LDA and remission (54.9% remission) vs. 80.8% of the patients in Group 2 (40.4% remission). Conclusions Introducing RTX after the first anti-TNF therapy proved to be the most effective option, leading to cumulating of clinical benefits (fast LDA or remission) and to consolidation of lower DAS28 response with each following RTX therapy. This strategy proved to lead to a very good EULAR response, sooner and better than the RTX therapy initiated only after 2 or 3 anti-TNF treatments. The clinical response is very good irrespective of the rheumatoid factor status, and no resistance appeared to the RTX treatment. Based on these results, we consider RTX treatment after the first anti-TNF failure as a preferred treatment option and in terms of clinical response it follows the EULAR–ACR principles on RA treat-to-target. Disclosure of Interest None Declared