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Resumen Antecedentes y objetivos El conocimiento de los niveles de farmacos anti-TNFα puede modificar el tratamiento en pacientes con artritis reumatoide (AR) y espondiloartritis (EspA). Objetivos Comparar los niveles de anti-TNFα en los pacientes con AR vs. EspA, en diferentes situaciones clinicas. Materiales y metodos Se realizo un estudio retrospectivo, observacional donde se midieron los niveles de anti-TNFα y la presencia de anticuerpos antifarmacos en pacientes seleccionados consecutivamente, utilizando la tecnica de ELISA. Resultados Se estudiaron 53, 73 y 78 pacientes en tratamiento con infliximab, adalimumab y etanercept, respectivamente. Los niveles medios de farmaco en pacientes con dosis estandar fueron: infliximab 2,2 μg/ml (1,4-5,2), adalimumab 4,9 μg/ml (0,8-8,9) y etanercept 3,1 μg/ml (2,3-4,4). No se encontraron diferencias en los niveles farmacos segun la actividad de la enfermedad, sin embargo, hubo diferencias en los niveles de etanercept e infliximab segun el uso de farmacos modificadores de la enfermedad sinteticos (FAMEsc). Conclusiones Los niveles de farmacos anti-TNFα se veran modificados por el tratamiento con FAMEsc.

To assess the golimumab retention rate during up to 8 years of follow up, and any associated factors.Retrospective analysis of the BIOBADASER (Spanish registry of biological drugs) database, assessing all adults who had ever started golimumab6 months before the analysis for an approved indication (rheumatoid arthritis [RA], axial spondyloarthritis [SpA] or psoriatic arthritis [PsA]).Among 885 patients (RA 267, axial SpA 370, PsA 248) receiving 944 cycles of golimumab, the retention rate of golimumab was 71.1% (95% confidence interval: 68.0-73.9) at year 1% and 37.7% (95% CI: 33.3-42.1) at year 7 and at year 8. Retention was higher when golimumab was used as the first biological drug (81.7% at year 1, 49.9% at year 7, p 0.001). In Cox regression analysis, factors associated with golimumab retention included use as first-line therapy (hazard ratio [HR] for discontinuation 1.52 for second- and 1.79 for third/later-line vs. first-line), use in axial SpA or PsA rather than RA (HR for axial SpA vs. RA 0.59, for PsA vs. Rheumatoid arthritis 0.67), and treatment with concomitant methotrexate (HR 0.67). Factors associated with golimumab discontinuation were corticosteroid use (HR 1.46) and disease activity above median (HR 1.29) at golimumab initiation.Based on this retrospective analysis of the BIOBADASER registry, nearly two-fifths (37.7%) of adult rheumatology patients initiating golimumab will remain on treatment for 8 years, with a higher probability of retention in axial SpA or PsA indications and when golimumab is used as first biologic.

Aim: To evaluate the persistence of the initial strategy of targeted therapy, with or without conventional synthetic (cs) disease-modifying antirheumatic drugs (DMARDs) (combination and monotherapy strategies, respectively) in patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), and ankylosing spondylitis (AS), under real-life conditions. Methods: This is a nested cohort study within BIOBADASER III, a prospective Spanish registry of patients with rheumatic diseases who are undergoing treatment with targeted therapy including biologics (b) and targeted synthetic (ts) DMARDs. The primary outcome was to determine the initial treatment strategy persistence; switching drugs within the same class, but maintaining the initial strategy (combination or monotherapy) was considered persistence. Bivariate comparisons and multivariate Cox proportional hazard models were used for the analyses.Results: A total of 2,589 patients were included in our study. In the multivariate model, compared to monotherapy, the combination therapy strategy was associated with shorter persistence in patients with RA (hazard ratio [HR] 1.58, 95% confidence interval [CI] 1.00 to 2.50, p=0.049), PsA-Axial (HR 3.00, 95% CI 1.35 to 6.70, p=0.007), PsA-Peripheral (HR 2.58, 95% CI 1.51 to 4.39, p

Objectives: To analyze the prevalence, incidence, survival and contribution on mortality of major central nervous system (CNS) involvement in systemic lupus erythematosus (SLE). Methods: Patients fulfilling the SLE 1997 ACR classification criteria from the multicentre, retrospective RELESSER-TRANS (Spanish Society of Rheumatology Lupus Register) were included. Prevalence, incidence and survival rates of major CNS neuropsychiatric (NP)-SLE as a group and the individual NP manifestations cere-brovascular disease (CVD), seizure, psychosis, organic brain syndrome and transverse myelitis were calculated. Furthermore, the contribution of these manifestations on mortality was analysed in Cox regression models adjusted for confounders. Results: A total of 3591 SLE patients were included. Of them, 412 (11.5%) developed a total of 522 major CNS NP-SLE manifestations. 61 patients (12%) with major CNS NP-SLE died. The annual mortality rate for patients with and without ever major CNS NP-SLE was 10.8% vs 3.8%, respectively. Individually, CVD (14%) and organic brain syndrome (15.5%) showed the highest mortality rates. The 10% mortality rate for patients with and without ever major CNS NP-SLE was reached after 12.3 vs 22.8 years, respectively. CVD (9.8 years) and organic brain syndrome (7.1 years) reached the 10% mortality rate earlier than other major CNS NP-SLE manifestations. Major CNS NP-SLE (HR 1.85, 1.29-2.67) and more specifically CVD (HR 2.17, 1.41-3.33) and organic brain syndrome (HR 2.11, 1.19-3.74) accounted as independent prognostic factors for poor survival. Conclusion: The presentation of major CNS NP-SLE during the disease course contributes to a higher mortality, which may differ depending on the individual NP manifestation. CVD and organic brain syndrome are associated with the highest mortality rates.

Objective Describe the objectives, methods and results of the first year of the new version of the Spanish registry of adverse events involving biological therapies and synthetic drugs with an identifiable target in rheumatic diseases (BIOBADASER III). Methodology Multicenter prospective registry of patients with rheumatic inflammatory diseases being treated with biological drugs or synthetic drugs with an identifiable target in rheumatology departments in Spain. The main objective of BIOBADASER phase III is the registry and analysis of adverse events; moreover, a secondary objective was added consisting of assessing the effectiveness by means of the registry of activity indexes. Patients in the registry are evaluated at least once every year and whenever they experience an adverse event or a change in treatment. The collection of data for phase III began on 17 December 2015. Results During the first year, 35 centres participated. The number of patients included in this new phase in December 2016 was 2664. The mean age was 53.7 years and the median duration of treatment was 8.1 years. In all, 40.4% of the patients were diagnosed with rheumatoid arthritis. The most frequent adverse events were infections and infestations. Conclusions BIOBADASER phase III has been launched to adapt to a changing pharmacological environment, with the introduction of biosimilars and small molecules in the treatment of rheumatic diseases. This new stage is adapted to the changes in the reporting of adverse events and now includes information related to activity scores.

Altres ajuts: Merck Sharp & Dohme Spain. This observational, longitudinal retrospective, noncomparative study was designed to assess the persistence and effectiveness of golimumab as a second anti-tumor necrosis factor (TNF) drug in patients with spondyloarthritis requiring discontinuation from a first anti-TNF drug.Data were collected retrospectively for all patients with axial spondyloarthritis or psoriatic arthritis from 20 rheumatology clinics in Spain who started golimumab as a second anti-TNF drug between January 2013 and December 2015. Golimumab persistence was assessed with Kaplan-Meier survival analysis, and associated factors were assessed with Cox regression analysis.210 patients started golimumab as a second anti-TNF drug: 131 with axial spondyloarthritis and 79 with psoriatic arthritis. In axial spondyloarthritis patients, the mean (standard deviation) Bath Ankylosing Spondylitis Disease Activity Index score at baseline was 5.5 (2.1), decreasing to 3.9 (2.0) at month 3 and 3.5 (2.0) at year 1, and remaining stable thereafter. In psoriatic arthritis patients, mean (standard deviation) baseline Disease Activity Score was 4.0 (1.3), reducing to 2.5 (1.2) at month 3 and to 2.2 (1.3) at year 1. Corresponding improvements were recorded from baseline in C-reactive protein levels and erythrocyte sedimentation rates. The probability of persistence of treatment with golimumab was 80% at year 1, 70% at year 2 and 65% at years 3 and year 4, and was similar in those who had stopped the first anti-TNF due to loss of efficacy or other reasons. Cox regression analysis showed that the probability of survival with golimumab was higher in patients with higher erythrocyte sedimentation rate, in patients with axial spondyloarthritis than with psoriatic arthritis, and in those who had discontinued adalimumab as first anti-TNF. Seventy-two patients (34.3%) discontinued golimumab during follow-up, 50 of them due to lack of efficacy.In patients with spondyloarthritis requiring discontinuation from a first anti-TNF drug, treatment with golimumab was effective and showed a high probability of persistence up to 4years of treatment.

ObjectivesTo analyse the effect of targeted therapies, either biological (b) disease-modifying antirheumatic drugs (DMARDs), targeted synthetic (ts) DMARDs and other factors (demographics, comorbidities or COVID-19 symptoms) on the risk of COVID-19 related hospitalisation in patients with inflammatory rheumatic diseases.MethodsThe COVIDSER study is an observational cohort including 7782 patients with inflammatory rheumatic diseases. Multivariable logistic regression was used to estimate ORs and 95% CIs of hospitalisation. Antirheumatic medication taken immediately prior to infection, demographic characteristics, rheumatic disease diagnosis, comorbidities and COVID-19 symptoms were analysed.ResultsA total of 426 cases of symptomatic COVID-19 from 1 March 2020 to 13 April 2021 were included in the analyses: 106 (24.9%) were hospitalised and 19 (4.4%) died. In multivariate-adjusted models, bDMARDs and tsDMARDs in combination were not associated with hospitalisation compared with conventional synthetic DMARDs (OR 0.55, 95% CI 0.24 to 1.25 of b/tsDMARDs, p=0.15). Tumour necrosis factor inhibitors (TNF-i) were associated with a reduced likelihood of hospitalisation (OR 0.32, 95% CI 0.12 to 0.82, p=0.018), whereas rituximab showed a tendency to an increased risk of hospitalisation (OR 4.85, 95% CI 0.86 to 27.2). Glucocorticoid use was not associated with hospitalisation (OR 1.69, 95% CI 0.81 to 3.55). A mix of sociodemographic factors, comorbidities and COVID-19 symptoms contribute to patients’ hospitalisation.ConclusionsThe use of targeted therapies as a group is not associated with COVID-19 severity, except for rituximab, which shows a trend towards an increased risk of hospitalisation, while TNF-i was associated with decreased odds of hospitalisation in patients with rheumatic disease. Other factors like age, male gender, comorbidities and COVID-19 symptoms do play a role.

Background Survival, or persistence in treatment with a biological drug can be considered an indirect measure of efficacy, safety and tolerability Objectives We assessed the probability of persistence (survival) of treatment with golimumab in patients with rheumatic diseases and the factors associated to persistence with up to 6 years of follow-up. Methods BIOBADASER is the Spanish registry of biological drugs of the Spanish Society of Rheumatology and the Spanish Medicines Agency. A data-base analysis was done in December 2018 on all the patients aged 18 years or more who had initiated golimumab for one of the approved indications (rheumatoid arthritis [RA], axial spondyloarthritis [SpA] or psoriatic arthritis [PsA]). The probability of persistence was calculated with a Kaplan-Meier test. Factors related to persistence were analyzed with a Cox-regression model. Results 581 patients were included (165 [28.4%] RA, 249 [42.9%] axial SpA and 167 [28.7%] PsA), mean age 51 [12] years, 53% women). Median duration of disease at the onset of golimumab was 8.0 (3.0-14.7) years. Golimumab was prescribed as first biological drug in 37.9% of the patients, as second in 32.1% and as third or further in 30.0%. Concomitant medications at golimumab initiation included steroids (28.2%), methotrexate (MTX) (35.5%), sulphasalazine (7.2%) and leflunomide (13.9%). The probability of persistence of treatment with golimumab since treatment initiation was 74.3% at year 1 (95% CI 70.3 – 77.8), 63.5% at year 2 (59.0 – 67.6), 60.5% at year 3 (55.9 – 65.8), 54.5% (49.1 – 59.7) at year 4 and 5, and 52.1% (44.9 – 57.7) at year 6. Persistence was higher when golimumab was used as first biological agent (p log-rank Conclusion The probability of persistence (survival) on therapy with golimumab was high up to 6 years of follow-up and was higher in patients treated with golimumab as first biological drug or for PsA and SpA, and lower in those needing steroids, DMARDs different to MTX and in women. Acknowledgement This study was funded by Merck Sharp & Dohme of Spain. Disclosure of Interests Manuel Pombo: None declared, Carlos Sanchez-Piedra: None declared, Eduardo Cuende: None declared, Raquel Martin-Domenech: None declared, Javier del Pino: None declared, Cristina Campos Fernandez: None declared, Javier Manero: None declared, Blanca Garcia-Magallon: None declared, Fernando Sanchez-Alonso: None declared, Federico Diaz-Gonzalez Grant/research support from: MSD, Abbvie, Roche, Novartis, Consultant for: Lilly, Novartis, Pfizer, Amgen, Biogen, Celgene, Speakers bureau: MSD, Lilly, Janssen, BMS, Roche, Maria J. Arteaga Employee of: MSD, Luis Cea-Calvo Employee of: MSD, Juan J. Gomez-Reino: None declared

Background Uveitis is one of the major causes of disability of Behcet’s disease (BD). According to the “Expert panel recommendations”, anti-TNF therapy with infliximab (IFX) or adalimumab (ADA) may be considered as first- or second-line therapy for patients with BD-ophthalmic manifestations. Objectives To compare IFX versus ADA as first biologic drug in refractory uveitis due to BD for 1-year period. Methods Multicenter study of BD-associated uveitis refractory to conventional non-biologic treatment. Dosing schedule: IFX 3-5 mg/kg iv at 0, 2 and 6 weeks and then every 4-8 week, and ADA 40 mg/sc/every other week without loading dose. Main comparative outcome measures: safety and efficacy, assessing the intraocular inflammation, macular thickness, visual acuity, degree of immunosuppression load, drug retention, and glucocorticoid-sparing effect. Results 177 patients (316 affected eyes) were included. IFX was used in 103 and ADA in 74. No significant differences at baseline were observed regarding main demographic features, previous therapy and ocular severity. After 1 year of therapy, we observed an improvement in all ocular parameters in IFX vs ADA groups: AC inflammation (78.18% vs 92.31%), vitritis (78.95% vs 93.33%), retinal vasculitis (97% vs 95%), macular thickness (264.89±59.74 vs 250.62±36.85), and BCVA (0.67±0.34 vs 0.81±0.26). Drug withdrawal was observed in 57 (55.33%) of IFX group and in 21 (28.37%) of ADA group. Conclusion After 1 year of therapy in refractory BD-associated uveitis, ADA showed a statistically better outcome than IFX in improvement of BCVA, vitritis and drug retention. References [1] Levy-Clarke G, et al. Expert panel recommendations for the use of anti-tumor necrosis factor biologic agents in patients with ocular inflammatory disorders. Ophthalmology. 2014; 121:785-96. [2] Santos-Gomez M, et al. The effect of biologic therapy different from infliximab or adalimumab in patients with refractory uveitis due to Behcet’s disease: results of a multicentre open-label study. Clin Exp Rheumatol 2016; 34 (6 Suppl 102): S34-40 [3] Atienza-Mateo B, et al. Anti-IL6-Receptor Tocilizumab in Refractory Uveitis Associated With Behcet’s Disease. Multicenter Retrospective Study. Rheumatology (Oxford). 2018 May 1;57(5): 856-864. [4] Martin-Varillas JL, et al. Successful Optimization of Adalimumab Therapy in Refractory Uveitis Due to Behcet’s Disease. Ophthalmology. 2018 Mar 27. Disclosure of Interests Belen Atienza-Mateo: None declared, Jose Luis Martin-Varillas: None declared, Vanesa Calvo-Rio: None declared, Rosalia Demetrio-Pablo: None declared, Emma Beltran: None declared, Juan Sanchez-Burson: None declared, Marina Mesquida: None declared, Alfredo Adan : None declared, Victoria Hernandez: None declared, Marisa Hernandez-Garfella: None declared, Elia Valls-Pascual: None declared, Lucia Martinez-Costa: None declared, Agusti Sellas-Fernandez: None declared, Miguel Cordero-Coma: None declared, Manuel Diaz-Llopis: None declared, Roberto Gallego: None declared, Jose L. Garcia-Serrano: None declared, Norberto Ortego: None declared, Jose M. Herreras: None declared, Alejandro Fonollosa: None declared, Angel Garcia-Aparicio: None declared, Olga Maiz-Alonso Speakers bureau: Pfizer, Ana Blanco: None declared, Ignacio Torre-Salaberri: None declared, Cruz Fernandez-Espartero: None declared, Vega Jovani: None declared, Diana Peiteado: None declared, Esperanza Pato: None declared, Juan Cruz: None declared, Carlos Fernandez-Cid: None declared, Elena Aurrecoechea: None declared, Miriam Garcia-Arias: None declared, Santos Castaneda Consultant for: Amgen, BMS, Pfizer, Lilly, MSD, Roche, Sanofi, UCB, Miguel A. Caracuel-Ruiz: None declared, Carlos A. Montilla-Morales: None declared, Antonio Atanes-Sandoval: None declared, Felix Francisco: None declared, Santos Insua: None declared, Senen Gonzalez-Suarez: None declared, Amalia Sanchez-Andrade: None declared, Fernando Gamero: None declared, Luis F. Linares Ferrando: None declared, Fredeswinda Romero: None declared, A. Javier Garcia-Gonzalez: None declared, RAQUEL ALMODOVAR: None declared, Enrique Minguez: None declared, Carmen Carrasco-Cubero: None declared, Alejandro Olive: None declared, Julio Vazquez: None declared, Oscar Ruiz-Moreno: None declared, Fernando Jimenez-Zorzo: None declared, Javier Manero: None declared, Santiago Munoz Fernandez: None declared, Cristina Fernandez-Carballido: None declared, Esteban Rubio-Romero: None declared, Fred Anton Pages: None declared, Francisco J. Toyos Saenz de Miera: None declared, Myriam Gandia Martinez: None declared, David Diaz Valle: None declared, Francisco J Lopez-Longo: None declared, Joan Miquel Nolla: None declared, Enrique Raya: None declared, Marcelino Revenga: None declared, J. Luis Hernandez: None declared, Monica Calderon-Goercke: None declared, D. Prieto-Pena: None declared, Inigo Gonzalez-Mazon: None declared, Lara Sanchez Bilbao: None declared, Miguel A. Gonzalez-Gay: None declared, Ricardo Blanco: None declared

Objectives. This article estimates the frequency of polyautoimmunity and associated factors in a large retrospective cohort of patients with SLE. Methods. RELESSER (Spanish Society of Rheumatology Lupus Registry) is a nationwide multicentre, hospital-based registry of SLE patients. This is a cross-sectional study. The main variable was polyautoimmunity, which was defined as the co-occurrence of SLE and another autoimmune disease, such as autoimmune thyroiditis, RA, scleroderma, inflammatory myopathy and MCTD. We also recorded the presence of multiple autoimmune syndrome, secondary SS, secondary APS and a family history of autoimmune disease. Multiple logistic regression analysis was performed to investigate possible risk factors for polyautoimmunity. Results. Of the 3679 patients who fulfilled the criteria for SLE, 502 (13.6%) had polyautoimmunity. The most frequent types were autoimmune thyroiditis (7.9%), other systemic autoimmune diseases (6.2%), secondary SS (14.1%) and secondary APS (13.7%). Multiple autoimmune syndrome accounted for 10.2% of all cases of polyautoimmunity. A family history was recorded in 11.8%. According to the multivariate analysis, the factors associated with polyautoimmunity were female sex [odds ratio (95% CI), 1.72 (1.07, 2.72)], RP [1.63 (1.29, 2.05)], interstitial lung disease [3.35 (1.84, 6.01)], Jaccoud arthropathy [1.92 (1.40, 2.63)], anti-Ro/SSA and/or anti-La/SSB autoantibodies [2.03 (1.55, 2.67)], anti-RNP antibodies [1.48 (1.16, 1.90)], MTX [1.67 (1.26, 2.18)] and antimalarial drugs [0.50 (0.38, 0.67)]. Conclusion. Patients with SLE frequently present polyautoimmunity. We observed clinical and analytical characteristics associated with polyautoimmunity. Our finding that antimalarial drugs protected against polyautoimmunity should be verified in future studies., The RELESSER Registry was partially funded by GlaxoSmithKline (GSK), Roche, Union Chimique Belge (UCB), Lilly and Novartis. The sponsors had no role in the study design, data collection, analysis or interpretation, in writing the report, or in the decision to submit the article for publication. J.M.P.-R. is supported by grant 316265 (BIOCAPS) from the European Union 7th Framework Program (FP7/REGPOT-2012-2013.1). The study was supported by FIS Grant PI11/02857 (Instituto Carlos III, Fondos FEDER). Grant for medical researchers of the 'Fundacion Espanola de Reumatologia'.

Background Currents medical advances are allowing patients with chronic arthritis to live to advanced ages. Although the risks of biological therapies in elderly patients have been previously evaluated, data are scarce since they are mainly derived from clinical trials, in which elderly populations are often underrepresented or event excluded (patients up to 75 years old). In addition, comparisons between such studies are difficult in the absence of a consensus in defining the groups’ age. Objectives To evaluate the impact of age on the appearance of adverse events (AE) in patients with rheumatic diseases (rheumatoid arthritis -RA-, ankylosing spondylitis -AS- and psoriatic arthritis -PsA) at the start of biological treatment. Methods Multicenter prospective study in a real-world setting. Information was obtained from BIOBADASER, a national safety registry of patients with rheumatic diseases treated with biologics or targeted synthetic disease modifying anti-rheumatic drugs. For this analysis, all patients included in this registry since 2000 and diagnosed with RA, AS or PsA were included, and classified into four categories according to age at initiation of biologic treatment: young ( 75 years-old). Data collected included: 1) patient’s data 2) data on treatment and 3) data on AE. Proportions, means and standard deviations were used to describe the population. Poisson regression model was carried out to explore factors associated with the appearance of AEs. Crude and adjusted incidence rate ratios (IRRs) were calculated. Results A total of 2531 patients were included: 1154 RA (45.59%), 680 PsA (26.87%), and 697 AS (27.54%). Age groups: there were 64 young patients (2.52%), 2166 adults (85.57%), 243 elderly adults (9.6%), and 58 very elderly adults (2.29%). Comorbidities increased with age, while smoking rates decreased. Methotrexate use was similar in all age groups (53.99% in the total sample), but corticosteroid treatment increased with age (young 27.7%, adults 47%, elderly adults 64.36% and the very elderly 70.21%). 77.87% received anti-TNF treatment, and 22.13% other biological drugs. Poisson regression model showed an increased probability of suffering a first adverse event with increasing age regardless of the disease (IRR for AS: 1.04 (0.87-1.26); IRR for PsA: 1.08 (0.92-1.28)). Other factors associated with higher IRR were sex (being woman), type of biological treatment (TNF inhibitors), concomitant therapy (methotrexate), smoking, comorbidities (Charlson Index) and time of evolution of rheumatic disease. No differences were found between pathologies. Conclusion A mix of clinical and patient factors seem to explain the appearance of a first AE after biological therapy initiation, with age being one of those explanatory variables. Reference [1] Ishchenko A, Lories RJ. Safetyand Efficacy of Biological Disease-Modifying Antirheumatic Drugs in Older Rheumatoid Arthritis Patients: Staying the Distance. Drugs Aging2016; 33:387–398 Disclosure of Interests Paloma Vela-Casasempere Grant/research support from: UCB, Abbvie, Pfizer, Roche, Bristol-Myer-Squibb (another research, not BIOBADASER related), Consultant for: UCB, Lilly, Pfizer, Roche, Bristol-Myer-Squibb, Speakers bureau: Roche, UCB, MSD, Pfizer, GSK, BMS, Lilly, Carlos Sanchez-Piedra: None declared, Carolina Perez-Garcia: None declared, Sara Manrique Arija Speakers bureau: ABBvie, MSD, Janssen, Lillly, Roche, Pfyzer, Novartis., Maria del Carmen Castro Villegas Paid instructor for: MSD, Abbvie, Pfizer, Janssen, Lilly, Roche, Blanca Garcia-Magallon: None declared, Javier Manero: None declared, Silvia Gomez-Sabater: None declared, Rocio Cano-Alameda: None declared, Fernando Sanchez-Alonso: None declared, Federico Diaz-Gonzalez Grant/research support from: MSD, Abbvie, Roche, Novartis, Consultant for: Lilly, Novartis, Pfizer, Amgen, Biogen, Celgene, Speakers bureau: MSD, Lilly, Janssen, BMS, Roche, Juan Jesus Gomez-Reino: None declared

Objectives:To determine the incidence and risk factors implicated in the development of first cardiovascular (CV) event (CVE) in patients with chronic inflammatory rheumatic diseases (CIRD) attending Spanish rheumatology clinics after 5 years of follow-upMethods:Analysis of data of patients included in an observational prospective study [CARdiovascular in rheuMAtology (CARMA) project] after 5 years of follow-up. The study includes a cohort of 2234 patients with rheumatoid arthritis (RA), ankylosing spondylitis (AS) and psoriatic arthritis (PsA), and another cohort of matched individuals (n=677) without CIRD from 67 hospitals in Spain. Cumulative incidence per 1000 patients of CVE was estimated in both cohorts at 5 years from the start. Weibull proportional hazard model was used to calculate the Hazard Ratio (HR) and 95% confidence intervals (CI) of the risk factors involved in the development of CV events. Losses to follow-up and their causes were also analyzed.Results:The total number patient who completed the follow-up visit at 5 years was 2.382 (81.9%). Fifteen patients died due to CVE and sixty due to non-CVE. The patients with CIRD showed higher cardiovascular cumulative incidence (40.5; 95% CI: 36.2-44.8) than controls (28.3; 95% CI: 21.8-34.8). The higher risk of developing a first CVE during the 5 years of follow-up was seen in patients with AS (HR: 4.60; 95% CI: 1.32-15.99; p=0.02), those with older age (HR:1.09; 95% CI: 1.05-1.13; pConclusion:Patients with AS prospectively followed-up at rheumatology outpatient clinics showed higher risk of developing a first CVE than those without CIRD. Besides traditional CV disease risk factors, a longer time course of the disease is a risk factor for the development of CV disease in patients with CIRD.Acknowledgments:This project has been supported by an unrestricted grant from Abbvie, Spain. The design, analysis, interpretation of results and preparation of the manuscript has been done independently of Abbvie.Disclosure of Interests:Maria Auxiliadora Martin-Martinez: None declared, Santos Castañeda: None declared, Fernando Sánchez-Alonso: None declared, Carmen García Gomez: None declared, Carlos Gonzalez Juanatey: None declared, Maria Angeles Belmonte: None declared, Jesús Tornero: None declared, José Santos Rey: None declared, CARMEN OLGA SANCHEZ GONZALEZ: None declared, Estefanía Quesada-Masachs: None declared, MARIA DELPUERTO MORENO GIL: None declared, Tatiana Cobo-Ibáñez: None declared, Jose Antonio Pinto Tasende: None declared, Jesús Babío: None declared, Gemma Bonilla: None declared, Antonio Juan Mas: None declared, Javier Manero: None declared, Montserrat Romera: None declared, Javier Bachiller-Corral: None declared, Eugenio Chamizo Carmona: None declared, Javier Calvo: None declared, Raimon Sanmarti: None declared, Maria Celia Erausquin: None declared, Rosario Garcia de Vicuna Grant/research support from: BMS, Lilly, MSD, Novartis, Roche, Consultant of: Abbvie, Biogen, BMS, Celltrion, Gebro, Lilly, Mylan, Pfizer, Sandoz, Sanofi, Paid instructor for: Lilly, Speakers bureau: BMS, Lilly, Pfizer, Sandoz, Sanofi, Carmen Barbadillo: None declared, Sergio Ros Exposito: None declared, Javier del Pino Grant/research support from: Roche, Bristol, Consultant of: Gedeon, MARIA JOSE GONZALEZ: None declared, José Manuel Pina Salvador: None declared, Javier Llorca: None declared, Miguel A González-Gay Grant/research support from: Pfizer, Abbvie, MSD, Speakers bureau: Pfizer, Abbvie, MSD

Background Uveitis is the most common ocular manifestation in Behcet’s Disease (BD), which can cause irreversible blindness.1–2 Objectives To assess efficacy, safety and cost-effectiveness of adalimumab (ADA) therapy optimisation in a series of patients with uveitis due to BD. Methods Multicenter study of 74 ADA-treated patients with BD uveitis refractory to conventional immunosuppressants. Following remission, optimisation was performed by increasing the ADA dosing interval. Comparison between optimised and non-optimised group was performed. Results Ocular remission was achieved in 65 (86.6%) patients after a median ADA duration of 63–12 months. ADA was optimised in 23 cases. In the remaining 42 ADA was maintained at 40 mg/sc/2 weeks. No baseline differences were found at ADA onset between the optimised and non-optimised groups. Ocular outcomes were similar after a mean ±S.D. follow-up of 34.7±13.3 and 26±21.3 months in the both groups (table 1). Adverse effects were seen in non-optimised group (lymphoma, pneumonia, local reaction and bacteremia). Mean ADA treatment costs were lower in the optimised vs non-optimised group (6101.25 €/patient/year vs 12339.48). Conclusions ADA optimisation in BD uveitis refractory to conventional therapy is effective, safe and cost-effective. References [1] Calvo-Rio V, Blanco R, Beltran E, et al. Anti-TNF-alfa therapy in patients with refractory uveitis due to Behcet’s disease: a 1-year- follow-up study of 124 patients. Rheumatol. 2014; 53(12):2223–31 [2] Santos-Gomez M, Calvo-Rio V, Blanco R, et al. The effect of biologic therapy different from infliximab or adalimumab in patients with refractory uveitis due to Behcet’s disease: results of a multicentre open-label study. Clin Exp Rheumatol. 2016; 34 (6Suppl 102):S34-S40 Disclosure of Interest None declared

Objectives In this retrospective study we assess the 1 to 3 year probability of persistence on golimumab in patients with spondyloarthritis (SpA), axial SpA or psoriatic arthritis (PsA) who started treatment with golimumab as second biological (after withdrawal of a first anti TNF-alpha drug) Methods GO-BEYOND was a retrospective study undergone in 20 Spanish rheumatology clinics. Information was collected on all axial SpA and PsA patients who initiated golimumab between January 2013 and December 2015 as second anti TNF-alpha (i.e. after discontinuation of a first anti TNF-alpha drug). Centres in which all the patients could not be included were excluded from the analysis. The probability of persistence was calculated with a Kaplan-Meier test and comparisons were done with the log-rank test. Results 210 patients were included (131 with axial SpA and 79 with PsA, mean age 49 years [SD=12], 40% women, median duration of disease at the initiation of golimumab 80.5 months). Reasons for discontinuation of the first anti TNF-alpha were loss of efficacy (71.4%), poor tolerability or adverse event (11.0%) and patient or physician preference (17.6%). During a median follow-up of 29.3 months, 72 of 210 patients (34.3%) discontinued golimumab, due to primary failure (n=21), disease reactivation or secondary failure (n=29), poor tolerability (n=4), adverse events (n=10), inactive disease or patient-physician agreement (n=8). The probability of persistence on golimumab since treatment initiation was 80% at year 1 (95% CI 75–86), 70% at year 264 – 77 and 65% at year 3 [59 – 72]. The figures were similar in patients with axial SpA or PsA, and in patients who discontinued the first anti TNF-alpha due to loss of efficacy or to other reasons (p=0.121 and p=0.835, table 1). n=number at risk, SpA=Spondyloarthritis; PsA=Psoriatic arthriitis Conclusions After discontinuation of a first anti TNF-alpha, patients with spondyloarthritis showed a high probability of persistence on golimumab. The probability of persistence was similarly high in patients with axial SpA or PsA, and in patients who discontinued the first anti TNF-alpha due to loss of efficacy vs other reasons. Real life effectiveness of golimumab as second anti TNF-alpha is high and durable in SpA patients. Acknowledgements This Study was funded by Merck Sharp and Dohme, Spain Disclosure of Interest None declared

Objectives In patients with spondyloarthritis (SpA: axial SpA or psoriatic arthritis [PsA]), treated with golimumab as second biological therapy (after failure or withdrawal of a first anti TNF-α drug), we describe patients’ insights with regard to their beliefs and their satisfaction with golimumab therapy. Methods Patients on golimumab from GO-BEYOND, a retrospective study undergone in 20 Spanish rheumatology clinics, were requested to respond to the Beliefs About Medicines Questionnaire (BMQ). Statements of the BMQ include a 5-item necessity and a 5-item concern scale with Likert response options from “strongly agree” to “strongly disagree”. Patients also responded to questions on their satisfaction and experience with golimumab self-injection. Descriptive data are displayed, and responses to the BMQ in axial SpA vs PsA patients were compared with the chi-square test. Results 123 patients on golimumab as second anti TNF-α responded (81 axial SpA and 42 PsA, mean age 49 years [SD=11], 40% women). Patients showed strong beliefs in the necessity of golimumab for the treatment of their SpA (percentages of “agree” or “strongly agree” to the necessity statements: 50%–80%), but also concerns: half the patients agreed/strongly agreed to be worried about long term effects of golimumab, and ≈30% about becoming too dependent on the drug (table 1). Responses were similar in axial SpA and PsA patients (table 1). 111 patients declared to self-inject golimumab. Of these, 22.7% considered the experience with self-injection as very positive, 66.4% as positive, 10.0% neutral and only 0.9% unfavourable, and the use of the device very easy (37.3%), easy (57.3%), neutral (3.6%) and only 1.8% difficult. Finally 36.4% and 49.1% were very satisfied or satisfied with the interval of administration of golimumab, 11.8% were neutral and only 1.8% and 0.9% declared to be dissatisfied or very dissatisfied. Conclusions Patients with SpA currently using golimumab as second anti TNF-alpha describe strong beliefs in the necessity of golimumab and good experience and satisfaction with self-administration. The BMQ also identified concerns that should be addressed in the clinic. The study is limited to the subset of patients still on golimumab at the study visit. Acknowledgements Funded by Merck Sharp and Dohme, Spain Disclosure of Interest None declared

Objectives To compare the efficacy of infliximab (IFX) versus adalimumab (ADA) as first biologic drug in refractory uveitis with cystoid macular oedema (CME) associated to BD. Methods Multicenter study of 40 patients with BD-associated uveitis with CME refractory or intolerant to standard treatment (corticosteroids and at least one conventional immunosuppressive agent). CME was considered if macular thickness was greater than 300 µm. Comparative outcome measures were macular thickness, improvement of visual acuity (VA), activity of anterior chamber inflammation and vitritis. Results were expressed as mean ±SD for variables with a normal distribution, or as median [25th-75th interquartile range- IQR] when not normally distributed. The comparison of continuous variables among time-periods was performed with the Wilcoxon signed rank test. Results We selected patients with CME from a cohort of 177 patients with refractory BD-related uveitis (n=40). IFX was used in 15 cases and ADA in 25. No significant differences at baseline were observed between IFX vs ADA groups in sex (♂/♀ 8/7 vs 13/12, p=0.93), mean age (38±9 vs 41±10 years, p=0.53), HLA-B51 + (10 vs 19, p=0.87), uveitis pattern (panuveitis 67% vs 80%, posterior uveitis 33% vs 20%, p=0.34), previous conventional treatment (intravenous pulses of methylprednisolone 60% vs 52%, p=0.62, oral corticosteroids 93% vs 72%, p=0.1, methotrexate 53% vs 52%, p=0.93, cyclosporin A 73% vs 88%, p=0.23, azathioprine 53% vs 56%, p=0.86, other drugs 47% vs 68%, p=0.18), and combined treatment (67% vs 64%, p=0.86). After 1 year of therapy, ocular remission was achieved in 60% of cases with IFX and in 76% of cases with ADA (p=0.28). Regarding CME, 65% of patients with IFX reached a macular thickness Conclusions IFX and ADA show a similar efficacy in the treatment of CME in BD-related refractory uveitis. Reference [1] Calvo-Rio V, Blanco R, Beltran E, Sanchez-Burson J, Mesquida M, Adan A, et al. Anti-TNF- therapy in patients with refractory uveitis due to Behcet’s disease: a 1-year follow-up study of 124 patients. Rheumatology (Oxford)2014;53(12):2223–31. Disclosure of Interest None declared

Background Juvenile idiopathic arthritis (JIA) is the most frequent chronic rheumatic disease in childhood. The early disease recognition and treatment is critical to prevent long-term complications and disability in childhood. During the last decade the arrivals of biologics has dramatically changed the prognosis of these patients. A number of well-designed clinical trials, as well as cohort studies have demonstrated that biologics are an effective option for JIA patients who do not respond or cannot tolerate treatment with synthetic disease modifying drugs (DMARDs). JIA is not confined to childhood, and a 41% had active disease are on medication after 30 years and 28% had a high symptom state. Objectives The aim of this work was to study the pattern of use, drug survival and adverse events of biologic therapy in JIA patients during the transition period from the diagnostic to the adulthood. Methods Information was obtained from BIOBADASER, a safety multicenter prospective registry. All patients included in the registry diagnosed of JIA between 2000 and 2015 were analysed. Proportions, means and standard deviations (SD) were used to describe population. Incidence rates and 95% confidence intervals were calculated to assess adverse events. Kaplan-Meier analysis was used to compare the drug survival. Results 469 patients, 46.1% women were included in this study. Age at diagnosis was 9.4 (SD=5.3) and years of disease evolution 24.1 (SD=14.1). The age at biological treatment initiation was 23.9 years (SD=13.9). The pattern of use of biologics in JIA patients in the paediatric age shows a linear increase from 24% in 2000 to 65% in 2014. Interestingly, the biologic suspension for disease remission was higher in patients who initiated its use under 16 years (25.7%) than in those who began at 16 years or later (7.9%, p Conclusions The biologic survival and suspension by remission was higher when the biologic therapy started before 16 years old in JIA patients. The incidence rate severe adverse events in the childhood and adulthood in JIA patients treated with biologics was similar, however, a significant increment of infection was observed in patients under 16 years old. Disclosure of Interest None declared

Purpose: To assess efficacy, safety, and cost-effectiveness of adalimumab (ADA) therapy optimization in a large series of patients with uveitis due to Behcet disease (BD) who achieved remission after the use of this biologic agent. Design: Open-label multicenter study of ADA-treated patients with BD uveitis refractory to conventional immunosuppressants. Subjects: Sixty-five of 74 patients with uveitis due to BD, who achieved remission after a median ADA duration of 6 (range, 3-12) months. ADA was optimized in 23 (35.4%) of them. This biologic agent was maintained at a dose of 40 mg/subcutaneously/2 weeks in the remaining 42 patients. Methods: After remission, based on a shared decision between the patient and the treating physician, ADA was optimized. When agreement between patient and physician was reached, optimization was performed by prolonging the ADA dosing interval progressively. Comparison between optimized and nonoptimized patients was performed. Main Outcome Measures: Efficacy, safety, and cost-effectiveness in optimized and nonoptimized groups. To determine efficacy, intraocular inflammation (anterior chamber cells, vitritis, and retinal vasculitis), macular thickness, visual acuity, and the sparing effect of glucocorticoids were assessed. Results: No demographic or ocular differences were found at the time of ADA onset between the optimized and the nonoptimized groups. Most ocular outcomes were similar after a mean +/- standard deviation follow-up of 34.7+/-13.3 and 26+/-21.3 months in the optimized and nonoptimized groups, respectively. However, relevant adverse effects were only seen in the nonoptimized group (lymphoma, pneumonia, severe local reaction at the injection site, and bacteremia by Escherichia coli, 1 each). Moreover, the mean ADA treatment costs were lower in the optimized group than in the nonoptimized group (6101.25 euros/patient/year vs. 12 339.48; P < 0.01). Conclusion: ADA optimization in BD uveitis refractory to conventional therapy is effective, safe, and costeffective. (C) 2018 by the American Academy of Ophthalmology

Objectives To evaluate the efficacy of adalimumab (ADA) in short and long term follow-up in refractory uveitis of Behcet9s disease (BD) Methods Multicenter study. Ocular inflammation was evaluated according to “SUN working Group” (Am J Ophthalmol 2005;140:509–516), and the macular thickening with OCT. A comparison was carried out between baseline, and follow-up visits. Results are expressed as mean±SD or median [IQR]. Continuous variables were compared with Wilcoxon test. Results We studied 74 patients/132 affected eyes (39M/35W); mean age 38.7±11.3. The ocular pattern was panuveitis (n=45), posterior uveitis (n=14), anterior uveitis (n=14) and intermediate uveitis (n=1). Before ADA, systemic treatment with corticosteroids, iv metilprednisolone (n=23), Cyclosporin A (58), azathioprine (33), metotrexate (31) and other drugs (28) was used. The dose of ADA was 40 mg/2 weeks/ sc in monotherapy (n=22) or combined (n=52). Most patients showed a rapid and progressive improvement (TABLE). The 24 patients (37 affected eyes) with CME showed a significant improvement. ADA was optimized in 23 (31.1%) that were in remission for 15.3±9 months. Interval of administration was increased to 3 (n=6), 4 (13), 5 (1), 6 (1) and 8 weeks. After a mean follow-up of 13.0±9.7 months after optimization, 21 patients were stable and 2 had a severe flare. In 4 patients ADA was stopped after 35.2±9.3 months in remission. The main adverse effects observed were lymphoma (n=1), pneumonia (1), and 2° bacteriemia by E. Coli (1) Conclusions ADA was effective in short and long-term follow-up in refractory uveitis associated to BD. Optimization or even suspension of ADA is possible. Disclosure of Interest None declared

Describe the objectives, methods and results of the first year of the new version of the Spanish registry of adverse events involving biological therapies and synthetic drugs with an identifiable target in rheumatic diseases (BIOBADASER III).Multicenter prospective registry of patients with rheumatic inflammatory diseases being treated with biological drugs or synthetic drugs with an identifiable target in rheumatology departments in Spain. The main objective of BIOBADASER Phase III is the registry and analysis of adverse events; moreover, a secondary objective was added consisting of assessing the effectiveness by means of the registry of activity indexes. Patients in the registry are evaluated at least once every year and whenever they experience an adverse event or a change in treatment. The collection of data for phase iii began on 17 December 2015.During the first year, 35 centers participated. The number of patients included in this new phase in December 2016 was 2,664. The mean age was 53.7 years and the median duration of treatment was 8.1 years. In all, 40.4% of the patients were diagnosed with rheumatoid arthritis. The most frequent adverse events were infections and infestations.BIOBADASER Phase III has been launched to adapt to a changing pharmacological environment, with the introduction of biosimilars and small molecules in the treatment of rheumatic diseases. This new stage is adapted to the changes in the reporting of adverse events and now includes information related to activity scores.

Joan Miquel Nolla,1 Esperanza Martín,2 Pilar Llamas,3 Javier Manero,4 Arturo Rodríguez de la Serna,5 Manuel Francisco Fernández-Miera,6 Mercedes Rodríguez,6 José Manuel López,7 Alexandra Ivanova,8 Belén Aragón9 1Rheumatology Department, IDIBELL-Hospital Universitari de Bellvitge, Barcelona, 2Hospital Universitario de Getafe, Madrid, 3Hospital Universitario Fundación Jiménez Díaz, Madrid, 4Hospital Universitario Miguel Servet, Zaragoza, 5Hospital de la Santa Creu i Sant Pau, Barcelona, 6Hospital Universitario Marqués de Valdecilla, Santander, 7Hospital Universitario Virgen del Rocío, Sevilla, 8Max Weber Institute, Madrid, 9MSD, Madrid, Spain Objective: To estimate the unit costs of administering intravenous (IV) biological agents in day hospitals (DHs) in the Spanish National Health System.Patients and methods: Data were obtained from 188 patients with rheumatoid arthritis, collected from nine DHs, receiving one of the following IV therapies: infliximab (n=48), rituximab (n=38), abatacept (n=41), or tocilizumab (n=61). The fieldwork was carried out between March 2013 and March 2014. The following three groups of costs were considered: 1) structural costs, 2) material costs, and 3) staff costs. Staff costs were considered a fixed cost and were estimated according to the DH theoretical level of activity, which includes, as well as personal care of each patient, the DH general activities (complete imputation method, CIM). In addition, an alternative calculation was performed, in which the staff costs were considered a variable cost imputed according to the time spent on direct care (partial imputation method, PIM). All costs were expressed in euros for the reference year 2014.Results: The average total cost was €146.12 per infusion (standard deviation [SD] ±87.11; CIM) and €29.70 per infusion (SD ±11.42; PIM). The structure-related costs per infusion varied between €2.23 and €62.35 per patient and DH; the cost of consumables oscillated between €3.48 and €20.34 per patient and DH. In terms of the care process, the average difference between the shortest and the longest time taken by different hospitals to administer an IV biological therapy was 113minutes.Conclusion: The average total cost of infusion was less than that normally used in models of economic evaluation coming from secondary sources. This cost is even less when the staff costs are imputed according to the PIM. A high degree of variability was observed between different DHs in the cost of the consumables, in the structure-related costs, and in those of the care process. Keywords: day hospitals, rheumatoid arthritis, intravenous biological agents, unit cost of infusion, variability, care process&nbsp

OBJECTIVE: The aim of this study was to assess the efficacy of anti-TNF-α therapy in refractory uveitis due to Behcet's disease (BD). METHODS: We performed a multicentre study of 124 patients with BD uveitis refractory to conventional treatment including high-dose corticosteroids and at least one standard immunosuppressive agent. Patients were treated for at least 12 months with infliximab (IFX) (3-5 mg/kg at 0, 2 and 6 weeks and then every 4-8 weeks) or adalimumab (ADA) (usually 40 mg every 2 weeks). The main outcome measures were degree of anterior and posterior chamber inflammation, visual acuity, macular thickness and immunosuppression load. RESULTS: Sixty-eight men and 56 women (221 affected eyes) were studied. The mean age was 38.6 years (s.d. 10.4). HLA-B51 was positive in 66.1% of patients and uveitis was bilateral in 78.2%. IFX was the first biologic agent in 77 cases (62%) and ADA was first in 47 (38%). In most cases anti-TNF-α drugs were used in combination with conventional immunosuppressive drugs. At the onset of anti-TNF-α therapy, anterior chamber and vitreous inflammation was observed in 57% and 64.4% of patients, respectively. In both conditions the damage decreased significantly after 1 year. At baseline, 50 patients (80 eyes) had macular thickening [optical coherence tomography (OCT) >250 μm] and 35 (49 eyes) had cystoid macular oedema (OCT>300 μm) that improved from 420 μm (s.d. 119.5) at baseline to 271 μm (s.d. 45.6) at month 12 (P < 0.01). The best-corrected visual acuity and the suppression load also showed significant improvement. After 1 year of follow-up, 67.7% of patients were inactive. Biologic therapy was well tolerated in most cases. CONCLUSION: Anti-TNF-α therapy is effective and relatively safe in refractory BD uveitis.

Resumen Objetivo Estudiar la posibilidad de inducir endometriosis interna/externa en rata wistar, a traves de un nuevo modelo microquirurgico, que denominamos PGR 1. Sujetos y metodos Se han utilizado 11 ratas Wistar, a las que se ha realizado un autotransplante de fragmento uterino, sobre la cicatriz resultante de la cirugia necesaria para su obtencion. Despues de 8 semanas se les practico una nueva intervencion, para la inspeccion de la cavidad abdominal y la toma de muestras relevantes para su estudio anatomopatologico. Resultados Macroscopicos: adherencias que afectaban fundamentalmente a la zona del implante; vesiculas amarillentas. Microscopicos: vesiculas/quistes; fenomenos inflamatorios; neovascularizacion; endometriosis interna en un animal. Conclusiones Este nuevo modelo de implante nos puede ayudar a comprender mejor los mecanismos involucrados en la aparicion de endometriosis, tanto interna como externa.

Resumen Fundamento y objetivo El conocimiento de las posibles diferencias de efectividad de los 3 inhibidores del factor de necrosis tumoral alfa (anti-TNF-α) en la artritis reumatoide (AR) tiene importantes implicaciones en la practica clinica. El objetivo del estudio fue determinar la efectividad de los 3 anti-TNF-α en la AR y estudiar posibles diferencias de resultados entre ellos. Pacientes y metodo Se incluyo a todos los pacientes con AR atendidos en consultas del Sector Sanitario II de Zaragoza entre mayo de 2000 y diciembre de 2006 que completaron un ano de tratamiento con anti-TNF-α. Se analizaron diferentes parametros demograficos y clinicos al inicio y al ano de tratamiento, y se compararon entre los 3 grupos. Resultados Un total de 119 pacientes completaron un ano de tratamiento con los anti-TNF-α: 38 pacientes con infliximab, 44 pacientes con etanercept y 37 pacientes con adalimumab. Despues de un ano de tratamiento hubo un descenso medio (desviacion estandar) del Disease Activity Score 28 (DAS 28) de 1,82 puntos (1,42) y de 0,3 puntos (0,58) del Health Assessment Questionnaire (HAQ) (p Conclusiones Los anti-TNF-α son farmacos efectivos para el tratamiento de la AR y se observa una efectividad similar para todos ellos.

Objectives Cystic macular edema (CME) is the most serious complication of uveitis and the most common cause of blindness. Our objective was to compare the efficacy and safety of adalimumab (ADA) vs infliximab (IFX) as the first biological drug in uveitic cystoid macular edema (CME) due to Behcet9s disease (BD) during 1 year follow-up. Methods In a multicentre study of 175 patients with BD and uveitis refractory to conventional therapy, 34 patients had CME, defined by (OCT >300μ) at baseline. IFX (3–5 mg/kg 0,2, and 6 weeks and then every 4–8 weeks) was used in 12 cases and ADA (40 mg/2 weeks) in 22 cases. The main objective was the absence of CME. Secondary objectives: improvement in visual acuity (VA) (increased AV >20% in at least one of two eyes), inactive anterior chamber inflammation, vitritis, retinitis and retinal vasculitis. A bivariate analysis was performed to compare the response to biological therapy (ADA and IFX). Results We studied 34 patients (63 affected eyes). No statistically significant baseline differences were observed between both groups (IFX vs ADA) sex (men/women 4/6 vs 11/11; p=0.35), mean age (37.3±10.1 vs 41.5±8.3; p=0.2) HLAB51 positive (70% vs 80.9%; p=0.5), duration of uveitis before anti TNF alpha treatment [median (IQR]; 36 [10–82] vs 33 months [15.5 to 83]; p=0.8), VA (0.4 ± 0.33 vs 0.46±0.29; p=0.44); retinal vasculitis (75% vs 77%; p=0.87); retinitis (46% vs 30%; p=0.2); macular thickening (140.9±410.13 vs 409.46±138.55; p=0.98); combined treatment (58.33% vs 59.1%; p=0.96). We found differences in the presence of cells in the anterior chamber (Median [IQR]; 1 [0–1.2] vs 1 [0–3]; p=0.02) and vitritis (median [IQR], 1 [0–2] vs. 3 [0.5 -3]; p=0.002). Regarding the main objective, the improvement of CME is higher in patients treated with ADA during first month of treatment maintained at a year, although the difference is not statistically significant (table). With IFX we observed an improvement during the first month of treatment in vitritis, that became inactive, in the disappearance of the anterior chamber cells, and in retinitis and vasculitis that also became inactive. In no case statistically significant differences are reached. When adjusting for duration of illness, age and sex these differences remain. After a year of treatment all patients with retinitis and vasculitis in its baseline improve (ADA and IFX). Conclusions Our study suggests that ADA and IFX don9t show statistically significant differences in treatment of CME due to refractory uveitis in BD after 1 year follow-up. Disclosure of Interest None declared

Structure of N,N′-(Phenoxathiine-4,6-dicarbonyl)bis(proline methyl ester) - Conformation in the Crystal, in Solution, and According to Semiempirical Methods The title compound 1 is synthesized by coupling phenoxathiine-4,6 -dicarboxylic acid (2) with proline methyl ester. An improved synthesis of 2 is presented. The conformation of 1 in the crystal structure and in solution is discussed. The geometry of the product is investigated by semiempirical methods.The conformative hypersurfaces (Ramachandran diagrams) of N-acetylproline methyl ester and N-acetylproline methylamide are calculated with PM3.

Starting from tert-Butyloxycarbonyl(BOC)-Anthranilic-Acid(Abz) (1), BOC-Abz-Proline-Methyl-Ester (2) is synthesized. The crystal structure of both compounds are discussed. The conformational features of the crystal structures of 2 are compared with the conformation in solution. The whole conformational area (Φ and Ψ) of the amino acid part of 2 was investigated with the semi-empirical quantummechanical method AM 1, in order to check the general availability of the influence of ester functions to depsipeptide conformations. Cyclo-anthranoyl-prolinyl (3), which had already been described in the literature, forms crystals with a high density. Two independent molecules are found in the crystal structure; these molecules have very similar conformations.

The objective of this work is to analyze the survival of infliximab, etanercept and adalimumab in patients who have switched among tumor necrosis factor (TNF) antagonists for the treatment of chronic arthritis. BIOBADASER is a national registry of patients with different forms of chronic arthritis who are treated with biologics. Using this registry, we have analyzed patient switching of TNF antagonists. The cumulative discontinuation rate was calculated using the actuarial method. The log-rank test was used to compare survival curves, and Cox regression models were used to assess independent factors associated with discontinuing medication. Between February 2000 and September 2004, 4,706 patients were registered in BIOBADASER, of whom 68% had rheumatoid arthritis, 11% ankylosing spondylitis, 10% psoriatic arthritis, and 11% other forms of chronic arthritis. One- and two-year drug survival rates of the TNF antagonist were 0.83 and 0.75, respectively. There were 488 patients treated with more than one TNF antagonist. In this situation, survival of the second TNF antagonist decreased to 0.68 and 0.60 at 1 and 2 years, respectively. Survival was better in patients replacing the first TNF antagonist because of adverse events (hazard ratio (HR) for discontinuation 0.55 (95% confidence interval (CI), 0.34-0.84)), and worse in patients older than 60 years (HR 1.10 (95% CI 0.97-2.49)) or who were treated with infliximab (HR 3.22 (95% CI 2.13-4.87)). In summary, in patients who require continuous therapy and have failed to respond to a TNF antagonist, replacement with a different TNF antagonist may be of use under certain situations. This issue will deserve continuous reassessment with the arrival of new medications. © 2006 Gomez-Reino and Loreto Carmona; licensee BioMed Central Ltd.

Two different molecules are observed in the asymmetric unit of the crystal structure of tert-butyloxycarbonyl-anthranilic-acid-glycin-methyl-ester (1). The whole conformational area (φ and ψ) of the amino acid part of 1 was investigated with the semi-empirical quantenmechanical method AM 1. The structures of 1 in the crystal are well described by the calculations. Rules are derived for the conformational space of peptides containing esters and anthranilic acids.

Zusammenfassung Using silylated alkenyl phosphonium salts, (n,n+3)-alkadienes were synthesized via desilylation/Wittig reaction. Among them, three Lepidoptera pheromones were prepared.

The crystal structure of 2-(chloromethyl)-5-(phthalimidomethyl)thiophene (1), as an example of a 2,5-disubstituted thiophene, together with data from semi-empirical and ab initio calculations provide strong evidence against an intramolecular S ⋯ N attraction in 2-formylthiophene semicarbazone (2), as well as in other five-membered heterocycles.