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Purpose We assessed the efficacy and safety of biologic therapy in severe and refractory Peripheral Ulcerative Keratitis (PUK). Design Open-label multicenter study of biologic-treated patients with severe PUK refractory to conventional immunosuppressive drugs. Subjects We studied 34 patients (44 affected eyes) (24 women/10 men; mean age, 55.26±17.4 years). PUK was associated with a well-defined condition in 29 of them (rheumatoid arthritis [n = 20], psoriatic arthritis [n = 2], inflammatory bowel disease [n = 2], Behcet disease [n = 1], granulomatosis with polyangiitis [n = 1], microscopic polyangiitis [n = 1], systemic lupus erythematosus [n = 1] and axial spondyloarthritis [n = 1]). Besides topical and oral systemic glucocorticoids, patients had received: methylprednisolone pulses [n = 9], and conventional immunosuppressive drugs, mainly methotrexate [n = 18], and leflunomide [n = 7]. Eleven patients had required ocular surgery prior to biologic therapy. Methods Following biologic therapy, baseline main outcomes were compared with those found at 1st week, 1st and 6th months and 1st year. Main outcome measures Efficacy and safety of biologic therapy. Efficacy was analyzed by the assessment of corneal inflammation (corneal thinning, central keratolysis and ocular perforation); other causes of ocular surface inflammation (scleritis, episcleritis); intraocular inflammation (uveitis); visual acuity and glucocorticoid sparing effect. Results The first biologic agents used were anti-TNFα drugs (n = 25); adalimumab (n = 16), infliximab (n = 8), etanercept (n = 1), and non-TNFα agents (n = 9); rituximab (n = 7), tocilizumab (n = 1) belimumab (n = 1) and abatacept (n = 1). During the follow-up, switching to a second biologic agent was required in 12 of the 25 (48%) patients treated with anti-TNFα drugs. However, no switching was required in those undergoing biologic therapy different from anti-TNFα agents. The main outcome variables showed a rapid and maintained improvement after a mean follow-up of 23.7 ± 20 months. Major adverse effects were tachyphylaxis, relapsing respiratory infections, supraventricular tachycardia, pulmonary tuberculosis and death, one each. Conclusions Biologic therapy is effective and relatively safe in patients with severe and refractory PUK. Non-anti-TNFα agents appear to be effective in these patients.

[Abstract] Background: Treatment compliance with disease-modifying antirheumatic drugs (DMARD) is essential to achieve the therapeutic goals in rheumatoid arthritis (RA). However, despite the need for good compliance, there is evidence that patients with RA frequently fail to use DMARD for the control of RA. Thus, the main objective of the OBSERVAR study is to evaluate the reasons for the lack of therapeutic adherence to synthetic DMARD in these patients. Patients and methods: A Delphi process involving 18 randomly selected Spanish rheumatologists determined the level of agreement with 66 causes of noncompliance selected from the literature in relation to synthetic DMARD in RA. Results: The reasons for noncompliance were consistent in 75.7%, although 3 reasons (4.5%) were highly consistent: 1) not knowing what to do in the case of an adverse event with DMARD; 2) not having undergone adherence screening by health personnel for early detection of "noncompliant patients"; and 3) not having undergone interventions or strategies that improve adherence. Conclusion: In order to improve adherence to RA treatment with synthetic DMARD, the patient should be adequately informed of each new treatment introduced, the patient's compliance profile should be incorporated into the clinical routine and the patient's motivation for therapeutic compliance be reinforced through the methods available to us. [Resumen] Introducción. La cumplimentación del tratamiento modificador de la enfermedad es esencial para alcanzar los objetivos terapéuticos en la artritis reumatoide (AR). Sin embargo, y a pesar de la necesidad de una buena adherencia, existe evidencia de que muchos pacientes con AR no cumplen adecuadamente con la prescripción del tratamiento indicado con fármacos moduladores de la enfermedad de acción lenta (FAME) sintéticos o convencionales. Conscientes de la importancia de este hecho, el estudio sobre observancia terapéutica en AR (estudio OBSERVAR) tiene como objetivo principal valorar los motivos de la falta de adherencia terapéutica a los FAME sintéticos en estos pacientes. Pacientes y métodos. Mediante un proceso Delphi entre 18 reumatólogos españoles seleccionados aleatoriamente se determinó el grado de acuerdo con 66 causas de incumplimiento seleccionadas de la bibliografía, en relación con los FAME sintéticos en la AR. Resultados. Los motivos de incumplimiento fueron consistentes en el 75,7%, si bien 3 razones (4,5%) destacaron como muy consistentes: 1) desconocer qué hacer cuando se sufre un acontecimiento adverso con el FAME; 2) no llevar a cabo métodos de cribado de la adherencia por el personal sanitario para detectar a los «pacientes incumplidores» de forma temprana y 3) no aplicar intervenciones o estrategias que mejoren la adherencia terapéutica. Conclusión. Para mejorar la adherencia al tratamiento de la AR con FAME sintéticos se debe informar al paciente de cada tratamiento nuevo introducido, incorporar el perfil de cumplimiento del paciente en la rutina clínica, y reforzar la motivación del paciente al cumplimiento terapéutico mediante los métodos a nuestro alcance.

Background Blocking of the Tumor Necrosis Factor (TNF) activity is a successful therapeutic approach for 50–60% of rheumatoid arthritis (RA) patients. However, there are yet no biomarkers to stratify patients for anti-TNF therapy. Rheumatoid factor (RF) and anti-cyclic-citrullinated antibodies (anti-CCP) have been evaluated as biomarkers of response but the results have shown limited consistency. Anti-carbamylated protein (anti-CarP) and anti-peptidylarginine deiminase type 4 (anti-PAD4) antibodies have been much less studied. Despite being linked to common immune processes, the interaction between these markers has not been evaluated yet. Our aim was to analyze the interaction between these four antibodies in relation to the response to anti-TNF therapy. Methods For this objective, a prospective cohort of n = 80 RA patients starting anti-TNF therapy was recruited. Serum determinations at baseline were performed for RF, anti-CCP, anti-CarP and anti-PAD4 antibodies using enzyme-linked immunosorbent assays (ELISA). The clinical response to anti-TNF therapy was determined at week 12 using the change in DAS28 score. Association was performed using multivariate linear regression adjusting for baseline DAS28, sex and age. Results The interaction between pairs of antibodies was tested by the addition of an interaction term. We found two highly significant antibody interactions associated with treatment response: anti-CarP with anti-PAD4 (p = 0.0062), and anti-CCP with RF (p = 0.00068). The latter antibody interaction was replicated in an independent retrospective cohort of RA patients (n = 199, p = 0.04). Conclusions The results of this study suggest that antibody interaction effects are important factors in the response to anti-TNF therapy in RA., This project was supported by UCB Pharma. The funders had no role in the study design, data analysis, data interpretation or writing the manuscript.

Objective To assess the efficacy of abatacept (ABA) in RA patients with interstitial lung disease (ILD) (RA-ILD). Methods This was an observational, multicentre study of RA-ILD patients treated with at least one dose of ABA. ILD was diagnosed by high-resolution CT (HRCT). We analysed the following variables at baseline (ABA initiation), 12 months and at the end of the follow-up: Modified Medical Research Council (MMRC) scale (1-point change), forced vital capacity (FVC) or diffusion lung capacity for carbon monoxide (DLCO) (improvement or worsening ≥10%), HRCT, DAS on 28 joints evaluated using the ESR (DAS28ESR) and CS-sparing effect. Results We studied 263 RA-ILD patients [150 women/113 men; mean (s.d.) age 64.6 (10) years]. At baseline, they had a median duration of ILD of 1 (interquartile range 0.25–3.44) years, moderate or severe degree of dyspnoea (MMRC grade 2, 3 or 4) (40.3%), FVC (% of the predicted) mean (s.d.) 85.9 (21.8)%, DLCO (% of the predicted) 65.7 (18.3) and DAS28ESR 4.5 (1.5). The ILD patterns were: usual interstitial pneumonia (UIP) (40.3%), non-specific interstitial pneumonia (NSIP) (31.9%) and others (27.8%). ABA was prescribed at standard dose, i.v. (25.5%) or s.c. (74.5%). After a median follow-up of 12 (6–36) months the following variables did not show worsening: dyspnoea (MMRC) (91.9%); FVC (87.7%); DLCO (90.6%); and chest HRCT (76.6%). A significant improvement of DAS28ESR from 4.5 (1.5) to 3.1 (1.3) at the end of follow-up (P Conclusion ABA may be an effective and safe treatment for patients with RA-ILD.

Background Rheumatoid arthritis (RA) may associate with Interstitial Lung Disease (ILD). Disease-modifying anti-rheumatic drug (DMARD) or TNF alfa inhibitors (iTNF), had been involved in the ILD development as well as exacerbation of an existing one. Nowadays there is no consensus related to treatment. Objectives The aimed of this study is to evaluate efficacy and safety of Abatacept (ABA) treatment in patients with AR and ILD. Methods Multicentre study in patients with RA and ILD associated were treated with ABA. ILD was diagnosed by High Resolution Computed Tomography (HRCT). ABA was used at dose of 10 mg/kg/4 weeks iv or 125 mg/week sc. Its efficacy was evaluated according to the following measures: a) Dyspnea classified by the Modified Medical Research Council (MMRC); Significant variability of 1 point and asymptomatic MMRC=0; b) Pulmonary function test (PFT); Significant oscillations >10% in Forced Vital Capacity (FVC) and diffusing capacity of the lung for carbon monoxide (DLCO) >10%; c) Imaging technique (HRCT); d) Joint assessment (DAS28). Quantitative variables were expressed as mean ± SD or as median (interquartile range) and compared with (Wilcoxon test) (Test Fisher) between the baseline and 3, 6 and 12 months. Results 34 individuals were included (19 women /15 men), patients with ILD associated to RA, with a mean age of 61,4 ± 9,8 years. The median duration of RA before ADA was initiated was 4,8 [0,86–13,12] (0–25) years, and had previously received an average 1,29±0,90 DMARDs. RA was seropositive in 24 cases (71%). ILD was associated with a DMARD: MTX (n=3), Etanercept (n=3), Adalimumab (n=3) y Certolizumab (n=1). ABA was used in monotherapy in 14 patients and combined with other immunosuppressors in 20 patients: Leflunomide (LFD) (n=7), LFD and cyclosporine (n=1), Sulfasalazine (n=1), MTX (n=2), MTX with LFD (n=1), hydroxychloroquine (n=5), Hydroxychloroquine with LFD (n=2), Azathioprine (n=1). A significant improvement of dyspnea was observed; patients who didn9t have dyspnea, kept asymptomatic. FVC and HRCT showed a significant improvement during 6 to 12 months period. DLCO remained stable in the majority of the patients. RA (DAS28) activity also improved. After follow up of 12,82±7,48 months, the most significant adverse effects were: pulmonary Infection (n=2), urinary infections (n=1), infusion reactions (n=1). ABA was discontinued due to: Serious infections (n=2); join inefficacy (n=2), pulmonary inefficacy (n=1), infusion reaction (n=1). Conclusions ABA seems to be an effective and relatively safe treatment in patients with RA and associated ILD. This data should be verified again in prospective and randomized studies. Disclosure of Interest None declared

Objective To evaluate the responsiveness in terms of correlation of the Hospital Universitario La Princesa Index (HUPI) comparatively to the traditional composite indices used to assess disease activity in rheumatoid arthritis (RA), and to compare the performance of HUPI-based response criteria with that of the EULAR response criteria. Methods Secondary data analysis from the following studies: ACT-RAY (clinical trial), PROAR (early RA cohort) and EMECAR (pre-biologic era long term RA cohort). Responsiveness was evaluated by: 1) comparing change from baseline (Delta) of HUPI with Delta in other scores by calculating correlation coefficients; 2) calculating standardised effect sizes. The accuracy of response by HUPI and by EULAR criteria was analyzed using linear regressions in which the dependent variable was change in global assessment by physician (Delta GDA-Phy). Results Delta HUPI correlation with change in all other indices ranged from 0.387 to 0.791); HUPI's standardized effect size was larger than those from the other indices in each database used. In ACT-RAY, depending on visit, between 65 and 80% of patients were equally classified by HUPI and EULAR response criteria. However, HUPI criteria were slightly more stringent, with higher percentage of patients classified as non-responder, especially at early visits. HUPI response criteria showed a slightly higher accuracy than EULAR response criteria when using Delta GDA-Phy as gold standard. Conclusion HUPI shows good responsiveness in terms of correlation in each studied scenario (clinical trial, early RA cohort, and established RA cohort). Response criteria by HUPI seem more stringent than EULAR's., Our study was supported by grants RD16/0012/0011 and PI14/00442 from the Ministerio de Economia y Competitividad (Instituto de Salud Carlos III; Spain) and cofunded by the Fondo Europeo de Desarrollo Regional (FEDER). Data from ACT-RAY clinical trial were kindly provided by Hoffmann-La Roche Ltd. No financial support was received from Hoffmann-La Roche Ltd Data from EMECAR and PROAR cohorts were provided by the Spanish Society of Rheumatology. No financial support was received from the Spanish Society of Rheumatology. None of these institutions played any role in the analysis or interpretation of data, nor were they involved in the writing of the manuscript. Roche and Sociedad Espanola de Reumatologia were involved in the collection of data from ACT-RAY, and EMECAR and PROAR, respectively. However, these funders had no role in study design, analysis, decision to publish, or preparation of the manuscript.

Background:Interstitial Lung Disease (ILD) is an extra-articular complication of rheumatoid arthritis (RA) that is associated with increased morbidity and mortality. Conventional disease-modifying drugs (DMARDs) such as methotrexate (MTX) have been implicated in the development and exacerbation of a pre-existing ILD.Objectives:The aim of our study was to check the influence of combined MTX treatment in patients with RA-ILD treated with abatacept (ABA).Methods:National multicentre retrospective registry of 263 patients with RA-ILD treated with ABA. RA was diagnosed according to the ACR classification criteria of 1987 or by the EULAR/ACR criteria of 2010. ILD was diagnosed by high resolution computed tomography (HRCT). In this study we have done a subanalysis of the 46 patients treated with ABA in combination with MTX (ABA+MTX) vs. 217 patients treated with ABA in monotherapy or in combination with other synthetic DMARDs. Efficacy was evaluated according to the following parameters: a) Dyspnoea (MMRC) considering variations ≥ 1; b) Lung function test (LFT) considering variations ≥ 10% in FVC and a variation of DLCO ≥ 10%; c) Imaging test (HRCT) d) DAS28 score e) prednisone dose. Variables were collected at the beginning of the study and at months 3, 6, 12 and then every 12 months until a maximum of 60 months.Results:263 patients with ILD associated with RA were included in the study with mean age 64.64±10 years. RF or CCPA were positive in 235 (89.4%) and 233 (88.6%) cases, respectively, with a mean follow-up of 22.7±19.7 months. Baseline characteristics of both groups are shown in table 1, while data obtained during evolution of this complication are presented in Figure 1.Conclusion:Despite the baseline differences of both groups, the good evolution in the ABA+MTX subgroup suggests that this therapeutic strategy can be a safe combination for patients with RA-ILD.ABA with MTX (n=46)ABA w/t MTX (n=217)PSex (F/M)28/18122/950.625Age (years)65.11±10.216.2±9.80.202RF/CCPA + (%)91.3/91.389.8/90.10.810Smoking or past smoking (%)47.855.10.417Follow-up (months)22.73±18.0022.3±20.850.916DAS28 at baseline4.08±1.514.61±1.470.056DAS28 at last visit3.00±1.463.13±1.310.642Prednisone at baseline, median (IQR) (mg)5 (5-7.5)7.75 (5-15)0.008*Prednisone at the end of study, median (IQR) (mg)5 (1-5)5 (5-7.5)0.032*DLCO at baseline (%)66.85±19.0465.43±18.210.823DLCO at the end of study (%)66.05±20.9565.17±19.720.831FVC at baseline (%)90.06±17.7785.40±21.560.164FVC at the end of study (%)90.58±15,4584.21±21.490.038*Disclosure of Interests:Carlos Fernández-Díaz Speakers bureau: Brystol Meyers Squibb, Santos Castañeda: None declared, Rafael Melero: None declared, J. Loricera: None declared, Francisco Ortiz-Sanjuán: None declared, A. Juan-Mas: None declared, Carmen Carrasco-Cubero Speakers bureau: Janssen, MSD, AbbVie, Novartis, Bristol Myers Squibb, and Celgene, S, Rodriguéz-Muguruza: None declared, S. Rodrigez -Garcia: None declared, R. Castellanos-Moreira: None declared, RAQUEL ALMODOVAR Speakers bureau: Abbvie, Celgene, Janssen, Lilly, Novartis, Pfizer., CLARA AGUILERA CROS: None declared, Ignacio Villa-Blanco Consultant of: UCB, Speakers bureau: Novartis, MSD, Lilly, Sergi Ordoñez: None declared, Susana Romero-Yuste: None declared, C. Ojeda-Garcia: None declared, Manuel Moreno: None declared, Gemma Bonilla: None declared, I. Hernández-Rodriguez: None declared, Mireia Lopez Corbeto: None declared, José Luis Andréu Sánchez: None declared, Trinidad Pérez Sandoval: None declared, Alejandra López Robles: None declared, Patricia Carreira Grant/research support from: Actelion, Roche, MSD, Consultant of: GlaxoSmithKline, VivaCell Biotechnology, Emerald Health Pharmaceuticals, Boehringer Ingelheim, Roche, Speakers bureau: Actelion, GlaxoSmithKline, Roche, Natalia Mena-Vázquez: None declared, C. Peralta-Ginés: None declared, ANA URRUTICOECHEA-ARANA: None declared, Luis Marcelino Arboleya Rodríguez: None declared, J. Narváez: None declared, DESEADA PALMA SANCHEZ: None declared, Olga Maiz-Alonso: None declared, J. Fernández-Leroy: None declared, I. Cabezas-Rodriguez: None declared, Ivan Castellví Consultant of: Boehringer Ingelheim, Actelion, Kern Pharma, Speakers bureau: Boehringer Ingelheim, Actelion, Bristol-Myers Squibb, Roche, A. Ruibal-Escribano: None declared, JR De Dios-Jiménez Aberásturi: None declared, Paloma Vela-Casasempere: None declared, C. González-Montagut Gómez: None declared, J M Blanco: None declared, Noelia Alvarez-Rivas: None declared, N. Del-Val: None declared, M. Rodíguez-Gómez: None declared, Eva Salgado-Pérez: None declared, Carlos Fernández-López: None declared, E.C. Cervantes Pérez: None declared, A. Devicente-DelMas: None declared, Blanca Garcia-Magallon Consultant of: MSD, Speakers bureau: Pfizer, Amgen, Celgene, MSD, Cristina Hidalgo: None declared, Sabela Fernández: None declared, Edilia García-Fernández: None declared, R. López-Sánchez: None declared, S. Castro: None declared, P. Morales-Garrido: None declared, Andrea García-Valle: None declared, Rosa Expósito: None declared, L. Exposito-Perez: None declared, Lorena Pérez Albaladejo: None declared, Ángel García-Aparicio: None declared, Ricardo Blanco Grant/research support from: AbbVie, MSD, and Roche, Speakers bureau: AbbVie, Pfizer, Roche, Bristol-Myers, Janssen, and MSD, Miguel A González-Gay Grant/research support from: Pfizer, Abbvie, MSD, Speakers bureau: Pfizer, Abbvie, MSD

Background:Interstitial Lung Disease (ILD) is a severe complication of Rheumatoid Arthritis (RA). Several conventional disease-modifying anti-rheumatic drugs (cDMARDs) and biologic (b) DMARDs may induce or impaired ILD-RA. Abatacept (ABA) may be useful in ILD-RA (1).Objectives:To assess the efficacy and safety of ABA in a large series of ILD-RA for a long-term follow-up.Methods:Multicenter open-level study of ILD-RA treated with at least 1 dose of ABA. ILD was diagnosed by high-resolution computed tomography (HRTC). We study these outcomes: a) 1-point change Modied Medical Research Council (MMRC); b) forced vital capacity (FVC) and/or DLCO improvement or decline ≥10%; c) change in HRCT, d) change in DAS28. e) Prednisone dose. Values were collected at 0, 3, 6, 12 and then every 12 months.Results:We studied 263 patients (150 women/113 men) (mean age;64.6±10 years), with ILD-RA. At ABA-onset they were smokers or exsmoker (53.8%), positive APCC (88.6%), median [IQR] duration of ILD of 12 [3-41.25] months, mean DLCO (65.7±18.3) and FVC (85.9±21.8).The ILD-pattern were usual interstitial pneumonia (UIP) (40.3%), non-specific interstitial pneumonia (NSIP) (31.9%) and others (27.8%).ABA was prescribed at standard subcutaneous (125 mg/w) in 196 (74.5%) or intravenously (10 mg/kg/4 w) in 67 (25.5%); in monotherapy (n=111) or combined with cDMARDs (n=152); especially leflunomide (n=55), MTX (n=46), or antimarials (n=21).After a mean follow-up of 22.7±19.7 months most outcomes remain stable (Figure). Moreover, DAS28 improved from 4.5±1.5 to 3.1±1.3; prednisone dose reduced from a median 7.5 [5-10] to 5 mg [5-7.5] and retention rate was 76.4%. The main adverse effects were serious infections (n=28), neoplasia (n=3), serious infusion reaction (n=1) and myocardial infarction (n=1).Conclusion:ABA seems effective and relatively safe in ILD-RA.References:[1]Fernández-Díaz C et al. Semin Arthritis Rheum. 2018; 48:22-27Disclosure of Interests:Carlos Fernández-Díaz Speakers bureau: Brystol Meyers Squibb, Santos Castañeda: None declared, Rafael Melero: None declared, J. Loricera: None declared, Francisco Ortiz-Sanjuán: None declared, A. Juan-Mas: None declared, Carmen Carrasco-Cubero Speakers bureau: Janssen, MSD, AbbVie, Novartis, Bristol Myers Squibb, and Celgene, S, Rodriguéz-Muguruza: None declared, S. Rodrigez -Garcia: None declared, R. Castellanos-Moreira: None declared, RAQUEL ALMODOVAR Speakers bureau: Abbvie, Celgene, Janssen, Lilly, Novartis, Pfizer.CLARA AGUILERA CROS: None declared, Ignacio Villa-Blanco Consultant of: UCB, Speakers bureau: Novartis, MSD, Lilly, Sergi Ordoñez: None declared, Susana Romero-Yuste: None declared, C. Ojeda-Garcia: None declared, Manuel Moreno: None declared, Gemma Bonilla: None declared, I. Hernández-Rodriguez: None declared, Mireia Lopez Corbeto: None declared, José Luis Andréu Sánchez: None declared, Trinidad Pérez Sandoval: None declared, Alejandra López Robles: None declared, Patricia Carreira Grant/research support from: Actelion, Roche, MSD, Consultant of: GlaxoSmithKline, VivaCell Biotechnology, Emerald Health Pharmaceuticals, Boehringer Ingelheim, Roche, Speakers bureau: Actelion, GlaxoSmithKline, Roche, Natalia Mena-Vázquez: None declared, C. Peralta-Ginés: None declared, ANA URRUTICOECHEA-ARANA: None declared, Luis Marcelino Arboleya Rodríguez: None declared, J. Narváez: None declared, DESEADA PALMA SANCHEZ: None declared, Olga Maiz-Alonso: None declared, J. Fernández-Leroy: None declared, I. Cabezas-Rodriguez: None declared, Ivan Castellví Consultant of: Boehringer Ingelheim, Actelion, Kern Pharma, Speakers bureau: Boehringer Ingelheim, Actelion, Bristol-Myers Squibb, Roche, A. Ruibal-Escribano: None declared, JR De Dios-Jiménez Aberásturi: None declared, Paloma Vela-Casasempere: None declared, C. González-Montagut Gómez: None declared, J M Blanco: None declared, Noelia Alvarez-Rivas: None declared, N. Del-Val: None declared, M. Rodíguez-Gómez: None declared, Eva Salgado-Pérez: None declared, Carlos Fernández-López: None declared, E.C. Cervantes Pérez: None declared, A. Devicente-DelMas: None declared, Blanca Garcia-Magallon Consultant of: MSD, Speakers bureau: Pfizer, Amgen, Celgene, MSD, Cristina Hidalgo: None declared, Sabela Fernández: None declared, Edilia García-Fernández: None declared, R. López-Sánchez: None declared, S. Castro: None declared, P. Morales-Garrido: None declared, Andrea García-Valle: None declared, Rosa Expósito: None declared, L. Exposito-Perez: None declared, Lorena Pérez Albaladejo: None declared, Ángel García-Aparicio: None declared, Miguel A González-Gay Grant/research support from: Pfizer, Abbvie, MSD, Speakers bureau: Pfizer, Abbvie, MSD, Ricardo Blanco Grant/research support from: AbbVie, MSD, and Roche, Speakers bureau: AbbVie, Pfizer, Roche, Bristol-Myers, Janssen, and MSD

Background:Interstitial Lung Disease (ILD) is a severe extraarticular manifestation of rheumatoid arthritis (RA). In this line, several radiological patterns of RA-ILD have been described: i) usual interstitial pneumonia (UIP), ii) nonspecific interstitial pneumonia (NSIP), iii) obliterating bronchiolitis, iv) organized pneumonia and mixed patterns. Abatacept (ABA) could be an effective and safe option for patients with RA-ILD, although the response in the different radiological patterns is not well defined.Objectives:Our aim was to assess the response to ABA in different radiological patterns of ILD.Methods:Observational retrospective multicenter study of RA-ILD treated with ABA. ILD was diagnosed by HRCT and classified by radiological patterns in 3 different subgroups of RA-ILD: a) UIP, b) NSIP and c) “other”. ABA was used sc. or iv. at standard dose. We assessed: a) Dyspnoea (MMRC scale; significant variation ≥1); b) Respiratory function tests (significant changes ≥10% in FVC and DLCO); c) HRCT imaging; d) DAS28 e)prednisone dose.Variables were collected at months 0, 3, 6, 12 months and subsequently every 12 months until a maximum of 60 months.Results:We included 263 patients: 106 UIP, 84 NSIP and 73 others (150 women / 113 men), mean age 64.64±10 years. Total patients positive for RF or CCPA were 235 (89.4%) and 233 (88.6%), respectively. In 26 out of 263 patients, the development of ILD was closely related to the administration of sDMARDs (MTX n = 11 and LFN n = 1) or bDMARDs (ETN n = 5, ADA n = 4, CZP n = 2 and IFX n = 3). Patient characteristics are shown in table 1. Figure 1 shows the evolution of the cases with available data after a mean follow-up of 22.7±19.7 months. Mean DLCO and FVC remained stable in the 3 groups without statistically significant changes, and all the groups showed a statistically significant reduction in DAS28 and prednisone dose.Conclusion:ABA could be a good choice of treatment in patients with RA-ILD independently of the radiological pattern of ILD.Disclosure of Interests:Carlos Fernández-Díaz Speakers bureau: Brystol Meyers Squibb, Santos Castañeda: None declared, Rafael Melero: None declared, J. Loricera: None declared, Francisco Ortiz-Sanjuán: None declared, A. Juan-Mas: None declared, Carmen Carrasco-Cubero Speakers bureau: Janssen, MSD, AbbVie, Novartis, Bristol Myers Squibb, and Celgene, S, Rodriguéz-Muguruza: None declared, S. Rodrigez -Garcia: None declared, R. Castellanos-Moreira: None declared, RAQUEL ALMODOVAR Speakers bureau: Abbvie, Celgene, Janssen, Lilly, Novartis, Pfizer., CLARA AGUILERA CROS: None declared, Ignacio Villa-Blanco Consultant of: UCB, Speakers bureau: Novartis, MSD, Lilly, Sergi Ordoñez: None declared, Susana Romero-Yuste: None declared, C. Ojeda-Garcia: None declared, Manuel Moreno: None declared, Gemma Bonilla: None declared, I. Hernández-Rodriguez: None declared, Mireia Lopez Corbeto: None declared, José Luis Andréu Sánchez: None declared, Trinidad Pérez Sandoval: None declared, Alejandra López Robles: None declared, Patricia Carreira Grant/research support from: Actelion, Roche, MSD, Consultant of: GlaxoSmithKline, VivaCell Biotechnology, Emerald Health Pharmaceuticals, Boehringer Ingelheim, Roche, Speakers bureau: Actelion, GlaxoSmithKline, Roche, Natalia Mena-Vázquez: None declared, C. Peralta-Ginés: None declared, ANA URRUTICOECHEA-ARANA: None declared, Luis Marcelino Arboleya Rodríguez: None declared, J. Narváez: None declared, DESEADA PALMA SANCHEZ: None declared, Olga Maiz-Alonso: None declared, J. Fernández-Leroy: None declared, I. Cabezas-Rodriguez: None declared, Ivan Castellví Consultant of: Boehringer Ingelheim, Actelion, Kern Pharma, Speakers bureau: Boehringer Ingelheim, Actelion, Bristol-Myers Squibb, Roche, A. Ruibal-Escribano: None declared, JR De Dios-Jiménez Aberásturi: None declared, Paloma Vela-Casasempere: None declared, C. González-Montagut Gómez: None declared, J M Blanco: None declared, Noelia Alvarez-Rivas: None declared, N. Del-Val: None declared, M. Rodíguez-Gómez: None declared, Eva Salgado-Pérez: None declared, Carlos Fernández-López: None declared, E.C. Cervantes Pérez: None declared, A. Devicente-DelMas: None declared, Blanca Garcia-Magallon Consultant of: MSD, Speakers bureau: Pfizer, Amgen, Celgene, MSD, Cristina Hidalgo: None declared, Sabela Fernández: None declared, R. López-Sánchez: None declared, Edilia García-Fernández: None declared, S. Castro: None declared, P. Morales-Garrido: None declared, Andrea García-Valle: None declared, Rosa Expósito: None declared, L. Exposito-Perez: None declared, Lorena Pérez Albaladejo: None declared, Ángel García-Aparicio: None declared, Miguel A González-Gay Grant/research support from: Pfizer, Abbvie, MSD, Speakers bureau: Pfizer, Abbvie, MSD, Ricardo Blanco Grant/research support from: AbbVie, MSD, and Roche, Speakers bureau: AbbVie, Pfizer, Roche, Bristol-Myers, Janssen, and MSD

Background:Blocking of the Tumor Necrosis Factor (TNF) activity is a successful therapeutic approach for 2 out of 3 Rheumatoid Arthritis patients. Identifying the patients that will not respond to this therapeutic approach is a major translational goal in RA. Association of seropositivity to rheumatoid factor (RF) or anti-cyclic-citrullinated antibodies (anti-CCP) with anti-TNF response has proven inconclusive, suggesting that other yet unexplored biomarkers could be more informative for this goal.Objectives:We tested the association of two recently introduced biomarkers in RA: anti-carbamylated protein antibodies (anti-CarP) and anti-peptidylarginine deiminase type 4 (anti-PAD4).Methods:A prospective cohort of n=80 RA patients starting anti-TNF therapy was recruited and levels for all four autoantibodies -RF, anti-CCP, anti-CarP and anti-PAD4- were measured at baseline. The change in DAS28 score between baseline and week 12 of therapy was used as the clinical endpoint.Results:Single marker-analysis showed no significant association with drug response. However, when testing for interactions between autoantibodies, we found highly significant associations with drug response. Anti-CCP and RF showed a positive interaction with the response to anti-TNF therapy (P=0.00068), and anti-PAD4 and antiCarP titers showed a negative interaction with the clinical response at week 12 (P=0.0062). Using an independent retrospective sample (n=199 patients), we validated the interaction between anti-CCP and RF with the clinical response to anti-TNF agents. (P=0.044).Conclusion:The results of this study show that interactions between antibodies are important in the response to anti-TNF therapy and suggest potential pathogenic relationships.Acknowledgments :We would like to thank the clinical researchers and patients participating in the IMID Consortium for their collaborationDisclosure of Interests:Antonio Julià: None declared, Maria Lopez Lasanta: None declared, Francisco Blanco: None declared, Antonio Gómez: None declared, Isabel Haro: None declared, Antonio Juan Mas: None declared, Alba Erra: None declared, Mª Luz García Vivar: None declared, Jordi Monfort: None declared, Simon Sánchez Fernandez: None declared, Isidoro González-Álvaro Grant/research support from: Roche Laboratories, Consultant of: Lilly, Sanofi, Paid instructor for: Lilly, Speakers bureau: Abbvie, MSD, Roche, Lilly, Mercedes Alperi-López: None declared, Raúl Castellanos: None declared, Antonio Fernandez-Nebro: None declared, Cesar Diaz Torne: None declared, Núria Palau: None declared, Raquel M Lastra: None declared, Jordi Lladós: None declared, Raimon Sanmarti: None declared, Sara Marsal: None declared

Objective To determine the incidence and risk factors of first cardiovascular event (CVE) in patients with chronic inflammatory rheumatic diseases (CIRD). Methods Analysis of data after 2.5 years of follow-up from the prospective study CARMA project, that includes patients with CIRD [rheumatoid arthritis (RA), ankylosing spondylitis (AS), and psoriatic arthritis (PsA)] and matched individuals without CIRD from 67 hospitals in Spain. CVE cumulative incidence per 1000 patients was calculated after 2.5 years from the start of the project. Weibull proportional hazard model was used to calculate hazard ratio (HR) and 95% confidence interval (95% CI) of the risk factors. Results 2595 (89.1%) patients completed the 2.5 years of follow-up visit. Cumulative incidence of CVE in patients with CIRD was 15.30 cases per 1000 patients (95% CI: 12.93-17.67), being higher in the subgroup with AS; 22.03 (95% CI: 11.01-33.04). Patients with AS (HR: 4.11; 95% CI: 1.07-15.79), those with older age (HR: 1.09; 95% CI: 1.05-1.13), systolic hypertension (HR: 1.02; 95% CI: 1.00-1.04) and long duration of the disease (HR: 1.07; 95% CI: 1.03-1.12) were at higher risk of first CVE during the 2.5 years of follow-up. In contrast, female gender was a protective factor (HR: 0.43; 95% CI: 0.18-1.00). Conclusion Among CIRD patients prospectively followed-up at rheumatology outpatient clinics, those with AS show higher risk of first CVE. Besides cardiovascular risk factors, such as hypertension, being a man and older

Aim: To describe the methodology of the EPISER 2016 (study of the prevalence of rheumatic diseases in adult population in Spain), as well its strengths and limitations. The aim of this study is to estimate the prevalence of rheumatoid arthritis (RA), psoriatic arthritis (PsA), ankylosing spondylitis (AS), systemic lupus erythematosus (SLE), Sjogren's syndrome (SS), osteoarthritis (knee, hip, hands, and cervical and lumbar spine), fibromyalgia, gout and clinical osteoporotic fracture. Material and method: Population-based, multicenter, cross-sectional study, with the participation of 45 municipalities in the 17 Spanish autonomous communities. The reference population will consist of adults aged 20 years and over residing in Spain. A computer-assisted telephone interview (CATI) system will be used for data collection. Diagnostic suspicions and diagnoses received by the participants will be studied by rheumatologists in the referral hospitals in the selected municipalities. Statistical analysis: the prevalence of the rheumatic diseases will be calculated using estimators and their 95% confidence intervals. Weights will be calculated in each of the sampling stages in accordance with the probability of selection. The distribution of the population in Spain will be obtained from the Spanish Statistics Institute. Conclusions: Sociodemographic and lifestyle changes over the last 16 years justify EPISER 2016. This study will provide current data about the prevalences of RA, AS, PsA, SLE, SS, osteoarthritis, fibromyalgia, gout and clinical osteoporotic fracture. The results will allow comparisons with studies from other countries and EPISER 2000. (C) 2017 Elsevier Espana, S.L.U. and Sociedad Espanola de Reumatologia y Colegio Mexicano de Reumatologia. All rights reserved.

Background This study shows that treatment with biologic drugs, including ant-TNF drugs, in NION associated to IMIDs, refractory to conventional treatment, seems to be effective. These results must be confirmed in prospective and randomised trials. Objectives Our aim was to compare anti-TNFα vs Rituximab (RTX) in refractory PUK. Methods Multicenter study of 24 patients with PUK. All of them presented inadequate response to corticosteroids and at least 1 systemic traditional immunosuppressive drug. Anti-TNFα were used in 17 patients: Adalimumab (n=9) 40 mg/sc every 1–2 weeks, infliximab (IFX) (n=7) 3–5 mg/kg iv/4–6 weeks, etanercept (n=1) 50 mg/week. RTX was used in 7 patients 1–2 g i.v. every 6 or 12 months. The main outcomes were Best Corrected Visual Acuity (BCVA), signs of inflammation (scleritis and episcleritis), progression to corneal thinning, central keratolysis and ocular perforation. Results We studied 24 patients/32 affected eyes. The underlying diseases in the anti-TNFα group were Rheumatoid Arthritis (RA) (n=14), Psoriatic Arthritis (n=2) and Behcet Disease (n=1); and in the RTX group: RA (n=5), granulomatous polyangiitis (n=1) and microscopic polyangiitis (n=1). At baseline there were no significant differences between both groups in general features or in ocular involvement (table 1). Before biologic therapy they had received the following systemic drugs (anti-TNFα vs RTX) i.v. methylprednisolone (2 vs 4), doxycycline (7 vs 1), ascorbic acid (2 vs 0), MTX (11 vs 4), AZA (1 vs 2) and others (7 vs 3). In addition,10 patients, in both groups, had required surgery: amniotic membrane (n=5), penetrating keratoplasty (n=2), conjunctival resection (n=2), tissue adhesives (n=2), conjunctival flap (n=1) and lamellar keratoplasty (n=1). Once the treatment was initiated the ocular outcome was similar (table 1). After a mean follow-up of 22.53±22.60 (anti-TNFα) and 22.28±8.28 months with RTX the following severe side effects were observed: supraventricular tachycardia (n=1) with RTX and pulmonary tuberculosis (n=1) with IFX. Conclusions In this study, anti-TNFα therapy and RTX were equally effective for the treatment of peripheral ulcerative keratitis associated to rheumatic diseases refractory to conventional treatment. Disclosure of Interest None declared

Background Peripheric Ulcerative Keratitis (PUK) is a severe inflammation that may lead to ocular perforation. PUK may be primary or associated with systemic conditions. Treatment is based on corticosteroids and conventional systemic immunosuppressive drugs. Objectives To evaluate biologic therapy in cases with severe and refractory PUK. Methods Multicenter study from 9 hospitals. Patients presented inadequate response or intolerance to conventional therapy with corticosteroids and at least 1 systemic traditional immunosuppressive drug. The main outcome measures were visual acuity, signs of inflammation, progression to corneal thinning, central keratolysis and ocular perforation. Comparisons were made between baseline and 1st week, 1st month, 6th month and 1st year. Statistical analysis was performed using the software STATISTICA (StatSoft). Results were expressed as mean±SD for variables with a normal distribution, or as median [IQR] when they were not normally distributed. The comparison of continuous variables was performed using the Wilcoxon test and categorical variables with chi-square test. Results We studied 27 patients/35 affected eyes (7 men/20 women), mean age, 57.2±16.3 years (range 28–89). PUK was primary in 1 case whereas in the 26 remaining cases, the underlying diseases were Rheumatoid Arthritis (RA) (n=19), Psoriasic Arthritis (n=2), RA+Felty syndrome+common variable immunodeficiency (n=1), Behcet Disease (n=1), Type I diabetes mellitus (n=1), granulomatous polyangiitis (n=1) and microscopic polyangiitis (n=1). They received the following topical therapy: corticosteroids (n=18), antibiotics (n=17), lubricants (n=18), autologous serum (n=11), topical cyclosporin 2% (n=11) and topical tacrolimus 0.03% (n=1). Besides oral corticosteroids and before the onset of the biologic therapy they had received iv pulses of methylprednisolone (n=8), methotrexate (16), oral doxycycline (9), azathioprine (3) and ascorbic acid (2). Moreover, 10 patients required surgery: amniotic membrane (n=7), penetrating keratoplasty (n=4), conjunctival resection (n=3), tissue adhesives (n=2), conjunctival flap (n=1) and lamellar keratoplasty (n=1). Anti-TNFα drugs were the most common biologic agents used in these cases (n=19): Adalimumab (ADA) (n=10; 37%), Infliximab (IFX) (n=8; 29.6%) and etanercept (n=1; 3.7%). In the remaining 8 cases the biologic agents were rituximab (n=7; 25.9%) and tocilizumab (n=1; 3.7%). The main outcome measures are summarized in the Table. After a mean follow-up of 23.7±20 months, all objective outcomes had improved with a reduction of the median prednisone dose from 33.7 [17.5–52.5] mg at baseline to 0 [0–2.5] mg (p=0.028). The main observed adverse effects were supraventricular tachycardia (n=1) and pulmonary Tuberculosis (n=1). Conclusions In our series, biological therapy, especially IFX and ADA, is effective and relatively safe in patients with PUK refractory to standard systemic treatment. Disclosure of Interest None declared

Background The WHO defines health as the state of physical, psychic and social well-being. In contrast, patients with rheumatoid arthritis (RA) frequently report that treatment is directed mainly at combating physical affection and hardly anything to emotional and social aspects. Objectives To assess the emotional impact and degree of satisfaction with the medical care received in the patient with poor prognosis RA. Methods National, structured and anonymous survey of 26 questions conducted between March and July 2016. Responses were counted as percentages or as means/medians of the score given on a Likert scale from 1 to 10 (minimum and maximum, respectively). Analyzes were performed using Microsoft 2012: mean (m), standard deviation (SD), median (M), interquartile range (IQR) and statistical significance of differences (Student t test). The study was approved by the National Coordinator ConArtritis and the CEIC of the reference hospital. Results The survey was completed by 100 of 122 enrollees, 75 by telephone and 25 via email; 83 women and 17 men, with a mean age of 49.4 years (SD 12.1); from all the Spanish Autonomous Communities. 52% were considered of poor prognosis (participant9s own perception). 66.7% of self-perceived high-activity RA by patients exceeded the physician9s impression; and 31.03% of the intermediate-activity. The degree of knowledge and the importance given to certain aspects of the disease in relation to the poor prognosis ranged from 8 to 9/10 in the different items analyzed. The awareness of their seropositivity against FR and ACPA was 77% and 17%, respectively. 63% consider the physical aspect more disabling, but 52% gave more value to feeling good emotionally. The mean treatment score for physical aspects was 7.07 (SD 2.52), whereas for emotional aspects was 3.39 (SD 2.57). 51.9% of self-considered poor prognosis patients believed that biological treatment was delayed and 50% related that to poorer outcome. 97% wanted to participate in the doctor9s decisions, but 38% declared they had no choice. There were no statistically significant differences between the prognostic groups. Conclusions More than half of the patients self-reported poor prognosis. Two-thirds estimated poorer health status than physicians if their RA was of high activity; 1/3 if it was intermediate. Patients considered all assessed aspects as determinants of poor prognosis (m>8). The degree of knowledge of their condition was high, being lower for joint damage and activity and prognostic markers. The beginning of treatment with biologicals was perceived as delayed in more than half of those who declared themselves with poor prognosis and half of them related it to a worse evolution. A high percentage of patients showed low satisfaction with the emotional attention received. Most claim to be more involved in medical decisions, although more than 1/3 does not seem to be able to do so. Acknowledgements Coordinadora Nacional de Artritis (ConArtritis) Disclosure of Interest None declared

Objective To investigate the validity, reproducibility, and responsiveness of a simplified power Doppler ultrasound (PDUS) assessment of joint inflammation compared with a comprehensive 44-joint PDUS assessment in patients with rheumatoid arthritis (RA) who started therapy with a biologic agent. Methods A total of 160 patients with active RA who started a biologic agent were prospectively recruited in 18 Spanish centers. The patients underwent clinical and laboratory assessment and blinded PDUS examination at baseline and 6 months. A PDUS examination of 128 synovial sites in 44 joints was performed. US synovitis and PD signal were semiquantitatively graded from 1 to 3 in all synovial sites. US count and index for synovitis and PD signal were obtained. PDUS intraobserver and interobserver reliability were evaluated. A process of data reduction based on the frequency of involvement of synovial sites by both synovitis and PD signal was conducted. Construct and discriminant validity of a simplified PDUS assessment was investigated. Results A PDUS simplified assessment including 24 synovial sites from 12 joints detected 100% of patients with synovitis and 91% of patients with PD signal. There was a highly significant correlation between the 44-joint count and index for synovitis and PD signal and the 12-joint count and index for synovitis and PD signal at baseline and 6 months (r = 0.84–0.90, P < 0.0005). The smallest detectable difference was lower than the mean change in simplified PDUS variables. Conclusion A 12-joint PDUS assessment of RA joint inflammation may be a valid, feasible method for multicenter monitoring of therapeutic response to biologic agents.