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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:Interstitial lung disease (ILD) is one of the most significant comorbidities of rheumatoid arthritis (RA), increasing the mortality in these patients [1,2]. Although the pathogenesis of ILD associated to RA (RA-ILD+) remains poorly defined [1], it is known that vascular tissue plays a crucial role in lung physiology [3]. In this context, a population of cells termed endothelial progenitor cells (EPC) are involved in vasculogenesis and endothelial tissue repair [4]. Previous reports suggest the implication of EPC in different conditions such as RA and idiopathic pulmonary fibrosis (IPF), the most common and destructive ILD [5,6]. Nevertheless, little is known about their specific role in RA-ILD+.Objectives:The purpose of this study was to shed light on the potential role of EPC in endothelial damage in RA-ILD+.Methods:Peripheral venous blood was collected from a total of 68 individuals (18 with RA-ILD+, 17 with RA-ILD-, 19 with IPF and 14 healthy controls). All subjects were recruited from the Rheumatology and Pneumology departments of Hospital Universitario Marqués de Valdecilla, Santander, Spain. Quantification of EPC was analyzed by the expression of surface antigens by flow cytometry. The combination of antibodies against the stem cell marker CD34, the immature progenitor marker CD133, the endothelial marker VEGF receptor 2 (CD309) and the common leukocyte antigen CD45 was used. EPC were considered as CD34+, CD45Low, CD309+and CD133+. All statistical analyses were performed using Prism software 5 (GraphPad).Results:EPC frequency was significantly increased in patients with RA-ILD+, RA-ILD-and IPF compared to controls (p=0.001, p=0.002, p< 0.0001, respectively). Nevertheless, patients with RA, both RA-ILD+and RA-ILD-, showed a lower frequency of EPC than those with IPF (p= 0.048, p= 0.006, respectively).Conclusion:Our results provide evidence for a potential role of EPC as a reparative compensatory mechanism related to endothelial damage in RA-ILD+, RA-ILD-and IPF patients. Interestingly, EPC frequency may help to establish a differential diagnostic between patients with IPF and those who have an underlying autoimmune disease (RA-ILD+).References:[1] J Clin Med 2019; 8: 2038;[2] Arthritis Rheumatol 2015; 67: 28-38;[3] Nat Protoc 2015; 10: 1697-1708;[4] Science 1997; 275: 964-966;[5] Rheumatology (Oxford) 2012; 51: 1775-1784;[6] Angiogenesis 2013; 16: 147-157.Acknowledgments:Personal funds, VP-C: PREVAL18/01 (IDIVAL); SR-M: RD16/0012/0009 (ISCIII-ERDF); LL-G: PI18/00042 (ISCIII-ERDF); RL-M: Miguel Servet type I CP16/00033 (ISCIII-ESF).Disclosure of Interests:Verónica Pulito-Cueto: None declared, Sara Remuzgo-Martínez: None declared, Fernanda Genre: None declared, Victor Manuel Mora-Cuesta: None declared, David Iturbe Fernández: None declared, Sonia Fernández-Rozas: None declared, Leticia Lera-Gómez: None declared, Pilar Alonso Lecue: None declared, Javier Rodriguez Carrio: None declared, Belén Atienza-Mateo: None declared, Virginia Portilla: None declared, David Merino: None declared, Ricardo Blanco Grant/research support from: AbbVie, MSD, Roche, Consultant of: Abbvie, Eli Lilly, Pfizer, Roche, Bristol-Myers, Janssen, UCB Pharma and MSD, Speakers bureau: Abbvie, Eli Lilly, Pfizer, Roche, Bristol-Myers, Janssen, UCB Pharma. MSD, Alfonso Corrales Speakers bureau: Abbvie, Jose Manuel Cifrián-Martínez: None declared, Raquel López-Mejías: None declared, Miguel A González-Gay Grant/research support from: Pfizer, Abbvie, MSD, Speakers bureau: Pfizer, Abbvie, MSD

Background:Infections are the most common adverse event of Tocilizumab (TCZ) in Giant Cell Arteritis (GCA). In GiACTA study(1),serious infections were observed in 7% (9.6/100 patient-years) of patients who received TCZ weekly. Randomized clinical trials (RCTs) are conducted under highly standardized design excluding some real-world patients. Therefore, adverse events may be underestimated in RCTs. In our series of real-life, serious infections occurred in 11.9% (10.6/100 patient-years)(2).Objectives:In a wide series of GCA of clinical practice treated with TCZ, we assess the frequency, type and predisposing factors of serious infections.Methods:Multicenter study of 134 patients diagnosed with GCA, all of them refractory to conventional therapy, treated with TCZ. Serious infection was considered when a life-threatening infection, fatal, or requiring hospitalization occurred, intravenous antibiotics were required, or the infectious process led to persistent or significant disability.Results:16 of 134 (11.9%, 10.6/100 patient-years) patients developed serious infections during follow-up. The most frequent infections were pneumonia (n=4), urinary tract infection (n=4), and facial herpes zoster (n=2). At TCZ onset, serious infections were more frequent in older patients (74.3±9.6 vs 72.9±8.7 years), with a longer GCA evolution (20 [4.3-45.6] vs 13 [5-29.3] months), with visual manifestations (43.75% vs 17.8%) and a higher dose of prednisone at TCZ onset (30.4±15.5 vs 21.1±16.1 mg/day) (TABLE). Presence of comorbidities were similar in both groups. 13 of the 16 patients who had infections received a dose of prednisone greater than 15 mg/day (16.3/100 patient-years) compared to 3 patients under treatment with less than 15 mg/day of prednisone (4.2/100 patient-years).Conclusion:The age, GCA duration, ocular involvement and the dose of glucocorticoids, at TCZ onset, seem to be predisposing factors related to an increased risk of developing serious infections in GCA patients.References:[1]Stone JH, et al. N Engl J Med. 2017; 377:317-28.[2]Calderón-Goercke M et al. Semin Arthritis Rheum 2019 Aug;49(1): 126-135.TABLESERIOUS INFECTIONS(n=16)WITHOUT SERIOUS INFECTIONS(n=118)pBASAL FEATURES AT TCZ ONSETGENERAL FEATURES Age, years, mean± SD74.3±9.672.9±8.70.552 Sex, female/male n(%)13/388/300.760 Time from GCA diagnosis to TCZ onset (months), median [IQR]20[4.3-45.6]13[5-29.3]0.604COMORBIDITIES Hypertension, n(%)9(56)86(73)0.551 Diabetes, n(%)3(19)39(33)0.677 Chronic kidney disease, n(%)3(19)27(23)0.512CLINICAL FEATURES OF GCA PMR, n(%)9(56.25)64(54.2)0.879 Aortitis, n(%)5(31.25)53(45)0.301 Visual manifestations, n(%)7(43.75)21(17.8)0.017CORTICOSTEROIDS AT TCZ ONSET Prednisone dose mg/d, mean (SD)30.4±15.521.1±16.10.031Disclosure of Interests:Monica Calderón-Goercke: None declared, D. Prieto-Peña: None declared, Santos Castañeda: None declared, Clara Moriano: None declared, Elena Becerra-Fernández: None declared, Marcelino Revenga: None declared, Noelia Alvarez-Rivas: None declared, Carles Galisteo: None declared, Águeda Prior-Español: None declared, E. Galindez: None declared, Cristina Hidalgo: None declared, Sara Manrique Arija: None declared, Eugenio de Miguel Grant/research support from: Yes (Abbvie, Novartis, Pfizer), Consultant of: Yes (Abbvie, Novartis, Pfizer), Paid instructor for: yes (AbbVie, Novartis, Pfizer, MSD, BMS, UCB, Roche, Grunental, Janssen, Sanofi), Speakers bureau: yes (AbbVie, Novartis, Pfizer, MSD, BMS, UCB, Roche, Grunental, Janssen, Sanofi), Eva Salgado-Pérez: None declared, Vicente Aldasoro Speakers bureau: Roche, Abbvie, MSD, UCB, Pfizer, Menarini, Grunenthal, Gebro, Novartis, Janssen, Ignacio Villa-Blanco Consultant of: UCB, Speakers bureau: Novartis, MSD, Lilly, Susana Romero-Yuste: None declared, J. Narváez: None declared, Catalina Gomez-Arango: None declared, Eva Perez-Pampín: None declared, Rafael Melero: None declared, Francisca Sivera: None declared, Carlos Fernández-Díaz Speakers bureau: Brystol Meyers Squibb, Alejandro Olive: None declared, María Álvarez del Buergo: None declared, Luisa Marena Rojas: None declared, Carlos Fernández-López: None declared, Francisco Navarro: None declared, Enrique Raya: None declared, Beatriz Arca: None declared, Roser Solans-Laqué: None declared, Arantxa Conesa: None declared, Carlos Vázquez: None declared, Jose Andrés Román-Ivorra: None declared, Pau Lluch: None declared, Paloma Vela-Casasempere: None declared, Carmen Torres-Martín: None declared, Juan Carlos Nieto Speakers bureau: Pfizer, Abbvie, MSD, Novartis, Janssen, Lilly, Nordic Pharma, BMS, Gebro, FAES Farma, Roche, Sanofi, Carmen Ordas-Calvo: None declared, Cristina Luna-Gomez: None declared, Francisco J. Toyos Sáenz de Miera: None declared, Nagore Fernández-Llanio: None declared, Antonio García: None declared, Carmen González-Vela: None declared, Javier García-Fernández: None declared, Patricia Vicente-Gómez: None declared, Ángel García-Manzanares: None declared, Norberto Ortego: None declared, Francisco Ortiz-Sanjuán: None declared, Montserrat Corteguera: None declared, J. Luis Hernández: 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

To determine the ability of Coronary Artery Calcification Score (CACS) and carotid ultrasonography in detecting subclinical atherosclerosis in rheumatoid arthritis (RA).A set of 104 consecutive RA patients without history of cardiovascular (CV) events were studied to determine CACS, carotid intima-media thickness (cIMT) and plaques. Systematic Coronary Risk Evaluation (SCORE) modified according to the EULAR recommendations (mSCORE) was also assessed.The mean disease duration was 10.8 years, 72.1% had rheumatoid factor and/or anti-CCP positivity and 16.4% extra-articular manifestations. Nine were excluded because they had type 2 diabetes mellitus or chronic kidney disease. CV risk was categorised in the remaining 95 RA patients according to the mSCORE as follows: low (n=21), moderate (n=60) and high/very high risk (n=14). Most patients with low mSCORE (16/21; 76.2%) had normal CACS (zero), and none of them CACS100. However, a high number of patients with carotid plaques was disclosed in the groups with CACS 0 (23/40; 57.5%) or CACS 1-100 (29/38; 76.3%). 72 (75.8%) of the 95 patients fulfilled definitions for high/very high CV as they had an mSCORE ≥5% or mSCORE5% plus one of the following findings: severe carotid ultrasonography findings (cIMT0.9 mm and/or plaques) or CACS100. A CACS100 showed sensitivity similar to mSCORE (23.6% vs 19.4%). In contrast, the presence of severe carotid ultrasonography findings allowed identifying most patients who met definitions for high/very high CV risk (70/72; sensitivity 97.2% (95% CI 90.3 to 99.7)).Carotid ultrasonography is more sensitive than CACS for the detection of subclinical atherosclerosis in RA.

ObjectiveTo evaluate whether the systemic sclerosis (SSc)-associated IRAK1 non-synonymous single-nucleotide polymorphism rs1059702 is responsible for the Xq28 association with SSc or whether there are other independent signals in the nearby methyl-CpG-binding protein 2 gene (MECP2).MethodsWe analysed a total of 3065 women with SSc and 2630 unaffected controls from five independent Caucasian cohorts. Four tag single-nucleotide polymorphisms of MECP2 (rs3027935, rs17435, rs5987201 and rs5945175) and the IRAK1 variant rs1059702 were genotyped using TaqMan predesigned assays. A meta-analysis including all cohorts was performed to test the overall effect of these Xq28 polymorphisms on SSc.ResultsIRAK1 rs1059702 and MECP2 rs17435 were associated specifically with diffuse cutaneous SSc (PFDR=4.12×10−3, OR=1.27, 95% CI 1.09 to 1.47, and PFDR=5.26×10−4, OR=1.30, 95% CI 1.14 to 1.48, respectively), but conditional logistic regression analysis showed that the association of IRAK1 rs1059702 with this subtype was explained by that of MECP2 rs17435. On the other hand, IRAK1 rs1059702 was consistently associated with presence of pulmonary fibrosis (PF), because statistical significance was observed when comparing SSc patients PF+ versus controls (PFDR=0.039, OR=1.30, 95% CI 1.07 to 1.58) and SSc patients PF+ versus SSc patients PF− (p=0.025, OR=1.26, 95% CI 1.03 to 1.55).ConclusionsOur data clearly suggest the existence of two independent signals within the Xq28 region, one located in IRAK1 related to PF and another in MECP2 related to diffuse cutaneous SSc, indicating that both genes may have an impact on the clinical outcome of the disease.

Several pieces of evidence indicate that rheumatoid arthritis (RA) is a proatherogenic disease associated with increased cardiovascular (CV) mortality.1 ,2 Besides genetic and traditional CV risk factors,3 ,4 chronic inflammation has emerged as a pivotal component implicated in the development of this process. A chronic inflammatory burden, determined by the mean values of C-reactive protein (CRP) over the extended follow-up of patients with RA, was associated with subclinical atherosclerosis and increased risk of CV events.5 ,6 In keeping with these observations, in a large retrospective cohort study, CV disease-related mortality was increased in RA patients with elevated measures of inflammation markers.7 These findings are in accordance with data from the general population that showed that CRP could be an independent predictor of CV disease with CRP values ≥3 mg/L defining high CV-risk individuals.8 With respect to this, levels of the proinflammatory cytokine interleukin-6, the main inducer of CRP, also predict outcome following hospitalisation for unstable angina.9 Despite some similarities, there are also some differences between patients with chronic inflammatory diseases and the general population. While the risk to develop atherosclerosis increases progressively with increasing low-density lipoprotein (LDL) cholesterol levels and declines with increasing levels of high-density lipoprotein (HDL) cholesterol in healthy individuals,10 the presence of a proinflammatory state leads to a decrease of total cholesterol, HDL cholesterol and LDL cholesterol in patients with RA.11 Paradoxically, anti-inflammatory therapies increase total cholesterol, HDL cholesterol and LDL cholesterol to variable degrees in patients with RA.11 ,12 This lipid increase is not associated with a rise in the number of CV events in these patients. On the contrary, probably due to the anti-inflammatory effect, conventional disease-modifying antirheumatic drugs, such as methotrexate, and different biological agents have demonstrated a reduction of the CV …

Objectives: Recent results have shown that the IL23R gene, coding for a subunit of the interleukin-23 receptor, is strongly associated with autoimmunity. The aim of the current study was to investigate, for the first time, the possible involvement of the IL23R gene in genetic susceptibility to ankylosing spondylitis (AS). Methods: We carried out a case–control association study in which 365 patients with AS and 500 blood bank donors were included. Eight single nucleotide polymorphisms (SNPs) spanning the IL23R gene were selected as genetic markers for our association study and were genotyped using a Taqman 5′ allelic discrimination assay. Results: Interestingly, we observed association of two of eight IL23R genotyped SNPs. The strongest effect was conferred by the non-synonymous rs11209026 (Arg381Gln) SNP (odds ratio 0.46 95% confidence interval 0.2 to 0.7 p = 0.001). Similarly, the IL23R rs1343151 SNP showed association with AS genetic susceptibility (odds ratio 0.68 95% confidence interval 0.55 to 0.83 p = 0.0002). After a conditional case–control test we observed that the effect of these two genetic variants was independent of linkage disequilibrium. Conclusions: These results suggest that the IL23R gene seems to be involved in AS genetic predisposition.

Increased cardiovascular (CV) mortality due to accelerated atherosclerosis occurs in ankylosing spondylitis (AS) patients.1 ,2 Beneficial effects of antitumour necrosis factor (anti-TNF)-α agents on disease activity and endothelial cell activation were reported in AS.3 ,4 Dramatic reduction of insulin resistance (IR) and improvement of insulin sensitivity after infliximab administration were also described in non-diabetic AS patients.5 We aimed to assess, for the first time, whether infliximab administration in AS patients may alter levels of retinol-binding protein 4 (RBP-4), a protein released from adipocytes, considered as an emerging cardiometabolic risk factor, which correlates with IR in individuals with obesity, impaired glucose tolerance or type 2 diabetes, and in non-obese subjects with or without family history of type 2 diabetes.6–⇓8 RBP-4 serum levels were measured by ELISA (Phoenix Pharmaceuticals, EK-028-28) in 30 consecutive non-diabetic and mostly non-obese AS patients without history of CV events before and after an infliximab infusion. Local institutional committee approval and patients’ informed consent were obtained. Information on blood sample determinations in this cohort was previously reported.9 Infliximab was given as an intravenous infusion in saline solution over 120 min.5 Measurements were made in …

We read with great interest the extended report by Lilleker et al 1 on the EuroMyositis registry. Our attention was particularly addressed to antisynthetase syndrome (ASSD) because in the last years we and all members of the AENEAS (American and European Network of Antisynthetase Syndrome) collaborative group strongly contributed2–7 to increase the knowledge on this peculiar disease. We think that a comparison between our cohorts could be of interest and useful for clinicians, even if the lack of some data in the EuroMyositis paper does not allow us to perform statistical analysis. Both groups collected a very large number of patients (AENEAS collaborative group 813 cases, EuroMyositis 512 cases). The comparison of available …

Cumulative evidence indicates that the BCL2-antagonist/killer 1 ( BAK1 ) gene could be involved in several autoimmune diseases.1 2 The proapoptotic BCL2 family members BAX and BAK are essential for regulating the number of B and T cells.2,–,4 A recent study in a Colombian population suggested that the BAK1 rs513349 and rs5745582 single nucleotide polymorphisms (SNPs) as well as the haplotype rs513349G-rs561276C-rs5745582A are significantly associated with autoimmune rheumatic diseases.1 The aim of the present study was to evaluate the influence …

Background: Asporin belongs to a family of proteins associated with the cartilage matrix. Objective: To investigate the role of the functional polymorphism consisting of an aspartic acid (D) repeat polymorphism located in the ASPN gene in the susceptibility to and clinical outcome of rheumatoid arthritis. Methods: A total of 803 Spanish Caucasian patients with rheumatoid arthritis and 904 controls of the same ethnic origin and matched for age and sex were included in the study. The asporin D repeat polymorphism was genotyped using polymerase chain reaction with a fluorescent primer. Results: No significant differences were detected in the distribution of the 10 alleles found in our population on comparing patients with rheumatoid arthritis with control groups. Nevertheless, individuals bearing D14 produced rheumatoid factor more often than the rest (85.7% v 72.1%, p = 0.006, odds ratio (OR) = 2.35, 95% confidence interval 1.21 to 4.50), and the mean (SD) onset age was higher in the group of individuals bearing D13 (50.09 (13.94)) compared with the rest (47.21 (14.31)), although the difference did not reach significance (p = 0.06). Conclusion: The results do not support a major role for asporin D repeat polymorphism in the susceptibility to rheumatoid arthritis. Nevertheless, they support the influence of this gene on the outcome of the disease.

We read with great interest the elegant systematic review on cardiovascular (CV) comorbidities by Jamnitski et al , in patients with psoriatic arthritis (PsA) published in the February 2013 issue of ARD .1 Overall, we agree that there is an increased CV risk in patients with PsA similar to that observed in patients with rheumatoid arthritis (RA).2 Therefore, adequate CV risk stratification is also required in PsA patients. The authors confirmed that subclinical atherosclerosis and CV risk factors are increased in patients with PsA when compared with controls.1 It is well known that inflammation promotes endothelial cell activation in patients with chronic inflammatory rheumatic diseases like RA.3 The presence of a chronic inflammatory state is responsible for the development of subclinical atherosclerosis and increased incidence of CV events …

To determine if the use of carotid ultrasonography (US) may improve the stratification of the cardiovascular (CV) risk in rheumatoid arthritis (RA).A set of 370 consecutive patients without history of CV events were studied to assess carotid intima-media thickness (cIMT) and plaques. As previously proposed, CV risk was calculated according to the modified EULAR systematic coronary risk evaluation (mSCORE) for RA that was adapted by the application of a multiplier factor of 1.5 in those patients fulfilling ≥ 2 of 3 specific criteria.The mean disease duration was 9.8 years, 250 (68%) had rheumatoid factor/anticyclic citrullinated peptide positivity and 61 (17%) extra-articular manifestations. 43 were excluded because they had type 2 diabetes mellitus or severe chronic kidney disease. CV risk was categorised in the remaining 327 RA patients according to the mSCORE: mild (96 cases; 29.3%), moderate (201; 61.5%) and high/very high risk (30; 9.2%). Only five patients were reclassified as having high/very high CV risk when the mSCORE was applied. Severe carotid US abnormalities (cIMT0.90 mm and/or plaques) were uncommon in patients with low mSCORE (13%). Nevertheless, in patients with moderate mSCORE, severe carotid US abnormalities were observed in 63% of cases. A model that included a chart mSCORE risk ≥ 5% plus the presence of severe carotid US findings in patients with moderate mSCORE risk (≥ 1% and5%) yielded high sensitivity for high/very high CV risk (93 (95% CI 88 to 96)).Our results support the use of carotid US in the assessment of CV risk in patients with RA.

Ankylosing spondylitis (AS) has been associated with increased cardiovascular (CV) mortality1 ,2 and accelerated atherosclerosis.3 Traditional CV risk factors and inflammation contribute to increased CV morbidity in AS.2 Antitumour necrosis factor (anti-TNF)-α therapy has been found to be effective in patients with AS and other spondyloarthropathies.4 We have observed that non-diabetic AS patients treated with infliximab experienced a dramatic reduction in serum insulin levels and improvement of insulin sensitivity after administration of this drug.5 It is plausible to think that TNF-α blockade may account for some other biological changes that slow the progression of atherosclerosis in AS. Therefore, it may be important to establish potential changes in biomarkers of endothelial cell activation following the administration of anti-TNF-α drugs in AS patients. Angiopoietin-2 (Angpt-2) is a marker of endothelial cell activation, involved in angiogenesis, which makes the endothelium responsive to inflammatory cytokines.6 Angpt-2 levels have been found increased in rheumatoid arthritis (RA) patients with CV disease (CVD) when compared with those without CVD.6 However, to our knowledge, there are no studies assessing Angpt-2 …

We have read with great interest the European League Against Rheumatism (EULAR) initiative on comorbidities in chronic inflammatory rheumatic diseases (CIRDs) that was recently published online in ARD .1 This initiative focuses primarily on the most prevalent and important comorbidities in patients with CIRDs, mainly rheumatoid arthritis (RA), spondyloarthritis, connective tissue disorders and crystal arthropathies but the authors indicate that they may be also applied to cases of severe osteoarthritis.1 Comorbidity has high impact in the prognosis and health outcome. It is applicable to patients with CIRDs. In this regard, the existence of several comorbidities increases the patient's disability in CIRDs. For example, in RA, the disability measured by the Health Assessment Questionnaire (HAQ), increases depending on …

Adequate stratification of cardiovascular (CV) risk is one of the major points of interest in the management of patients with rheumatoid arthritis (RA). A task force of the European League Against Rheumatism has proposed to adapt CV risk management calculated in RA patients according to the systematic coronary risk evaluation (SCORE) function by application of a multiplier factor of 1.5 in those patients with two of the following three criteria: disease duration >10 years, rheumatoid factor (RF) or anticyclic citrullinated peptide (anti-CCP) antibody positivity, and presence of severe extra-articular manifestations. However, a major concern when using the modified SCORE is to know whether the effect of chronic inflammation on the CV risk of RA patients can be fully determined using this tool. As increased carotid intima-media thickness (IMT) and carotid plaques have been proved to predict the development of CV events in RA, the authors suggest performing carotid ultrasound when SCORE does not yield results indicating high CV risk in RA patients with extra-articular manifestations, RF or anti-CCP positivity as well as in patients with 10 years disease duration or longer. The presence of abnormal carotid IMT (>0.90 mm) or carotid plaques would lead to these patients being considered as having high CV risk regardless of the results derived from the modified SCORE.

The IL-23R region is associated with a number of non-infectious inflammatory conditions including inflammatory bowel disease, ankylosing spondylitis and psoriasis,1,–,3 and albeit with less consistent evidence, rheumatoid arthritis (RA).4,–,6 Association of rs1343151 (G→A) with RA, but not rs1004819/rs10489629/rs2201841 , has been reported in European and New Zealand sample sets;5 none of rs3212227/rs6887695/rs7530511 was associated in European and North American sample sets,6 and rs7517847 was not associated in meta-analysed European and New Zealand sample sets.4 Given the immunological evidence pointing to the importance of the Th17–IL-23 axis in inflammation and autoimmunity,7 and the unresolved question of whether or not IL-23R is associated with RA, we further investigated association of IL-23R with RA in white European Caucasian case–control sample sets (cases ascertained …

Several pieces of evidence indicate that rheumatoid arthritis (RA) is a proatherogenic disease associated with increased cardiovascular (CV) death rate.1 The mechanisms leading to that are complex, including traditional CV risk factors and also the presence of a chronic inflammatory state.1 Dyslipidemia with reduction in total cholesterol and its fractions and qualitative impairment in the high density lipoprotein (HDL)-cholesterol has been observed in RA patients with active disease.2 Chronic inflammation promotes oxidative changes that alter HDL structure and reduce apolipoprotein-A-I in patients with active RA. Decreased levels of the antioxidant HDL-associated enzyme paraoxonase (PON1) have been observed in these patients.3 Improvement of inflammation, as shown in patients undergoing biologic therapy, is associated with increases of PON1 activities.4 RA is a polygenic disease. Previous studies have emphasised the implication of a genetic component in the risk of CV disease in RA.5 ,6 A functional, genetic T/C amino acid variant found within the PON1 gene (rs662) confers an amino acid change (Q192R) influential in determining PON1 activity values. …

Behcet disease (BD) is a multifactorial disorder with a highest prevalence among people with Mediterranean or Asian ancestry having association with HLA-B51 and other HLA and non-HLA loci.1–4 Very recently, one genome-wide association study (GWAS) identified the GIMAP locus, which encoded proteins involved in development of the T and B lymphocytes, as associated with the disease in the Asian populations.5 To investigate whether this association is replicated in Europeans, a total of 1086 (326 patients and 760 controls) Spanish individuals of European origin were genotyped after obtaining written informed consent and approval from the local ethical committees of all the institutions involved. Patients fulfilled the 1990 International Study Group classification criteria for Behcet’s disease,6 and the group was composed of 44.5% men with the following clinical features: 100% had oral ulcers, 63.6% genital ulcers, 58.7% uveitis, 48% arthritis, 20.2% vascular, 21.9% neurological and 19.2% gastrointestinal involvement. Regarding HLA association, in addition to B*51 (p

Polymyalgia rheumatica (PMR) is a relatively common inflammatory condition characterised by pain, aching and morning stiffness involving the shoulder and hip girdles and the neck.1 2 Patients are generally older than 50 years and the erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) are usually elevated.1 PMR may occur as an isolated disease or it may be observed in the setting of giant cell arteritis (GCA).3 Arthroscopic studies have confirmed the presence of synovitis in proximal joints of patients with PMR.4 However, the cause of musculoskeletal symptoms in these patients is not clearly defined because joint synovitis may only partially explain the diffuse discomfort along with involvement of periarticular structures. Interestingly, MRI and ultrasonography (US) studies disclosed bilateral inflammation of subacromial and subdeltoid bursae in association with synovitis of the glenohumeral joints and tenosynovitis of the biceps in patients with PMR.5 6 More recently, using MRI and US, Cantini et al also confirmed the presence of trochanteric bursitis and, less commonly, iliopsoas and ischiogluteal bursitis in PMR patients.7 These studies support the pivotal role of the involvement of extraarticular synovial structures, in particular bursae, in PMR. Shoulder pain is the most common and the presenting feature in patients with PMR.1 2 By contrast, pelvic and cervical involvement is less commonly observed.2 In this regard, in a population-based study from Northwest Spain, the frequency of shoulder girdle involvement was almost 100% in patients with isolated PMR and PMR associated with GCA.8 However, neck involvement was observed in 74% of individuals with isolated PMR and 67% of those with PMR associated with GCA.8 Population-based studies have confirmed …

Ankylosing spondylitis (AS) is a common chronic rheumatic disease whose aetiology arises as a result of the contribution of environmental factors and a strong genetic component.1 One crucial point in the pathogenesis of the disease is the regulation of T cell response.2 Recently, it has been shown that the functional 1858 C/T polymorphism of PTPN22 , the gene that encodes a lymphoid-specific protein tyrosine phosphatase (LYP), is associated with several autoimmune diseases (ADs), supporting the hypothesis that common aetiopathological pathways are shared by different ADs.3 LYP has a key role as a negative regulator of T cell activation.4 It seems that the single nucleotide polymorphism (SNP) 1858 C/T disrupts the interaction …

Background Tofacitinib is a novel, oral Janus kinase inhibitor being investigated as a targeted immunomodulator and disease-modifying therapy in rheumatoid arthritis (RA). Objectives To evaluate the cardiovascular (CV) event rates and changes in blood pressure (BP) in the tofacitinib Phase 3 (P3) and long-term open-label extension (LTE) studies. Methods Five P3 studies in patients (pts) with inadequate response to nonbiologic/biologic disease-modifying anti-rheumatic drugs (DMARDs) and 2 LTE studies were included. Tofacitinib was administered as monotherapy or with background nonbiologic DMARDs, predominantly methotrexate. One P3 study included adalimumab (ADA) as active control. An independent CV Safety Endpoint Adjudication Committee performed blinded adjudication of deaths, potential major adverse CV events (MACE), and events of congestive heart failure (CHF). MACE was defined as CV death and non-fatal CV events. Results: MACE IRs (per 100 pt-y) in placebo (PBO) and tofacitinib groups in P3 were low. IR in the LTE studies in the tofacitinib All Dose group (0.19) was lower than in P3 (0.57). IRs of CHF in tofacitinib were low. In P3, mean changes from baseline at Month 3 for systolic and diastolic BP, respectively, were -0.1 mmHg and -0.8 mmHg for PBO and -0.2 and 0.3 mmHg for tofacitinib. Mean BP changes at Months 6 and 12 and in the LTE studies remained stable. Conclusions Incidence rates of MACE were similar across groups in P3 with lower rates in LTE, suggesting no increased risk over 3 years of follow up. Tofacitinib was not associated with clinically meaningful increases in BP. Although the number of events have been fewand longer observation periods are warranted, CV risk does not appear to be increased with tofacitinib treatment and rates of CV events are consistent with those observed among patients with RA of similar disease severity.1-3 References Solomon DH et al. Circulation 2003; 107: 1303-1307; Solomon DH et al. Ann Rheum Dis 2006; 65: 1608-1612; 3. Nicola PJ et al. Arthritis Rheum 2006; 54: 60-67. Disclosure of Interest C. Charles-Schoeman Grant/Research support from: Pfizer Inc., Consultant for: Pfizer Inc., P. Wicker Consultant for: Pfizer Inc., U. Sechtem Consultant for: Pfizer Inc., M. Gonzalez-Gay Consultant for: Pfizer Inc., S. Wood Shareholder of: Pfizer Inc., Employee of: Pfizer Inc., M. Boy Shareholder of: Pfizer Inc., Employee of: Pfizer Inc., J. Geier Shareholder of: Pfizer Inc., Employee of: Pfizer Inc., D. Gruben Shareholder of: Pfizer Inc., Employee of: Pfizer Inc., K. Soma Shareholder of: Pfizer Inc., Employee of: Pfizer Inc., R. Riese Shareholder of: Pfizer Inc., Employee of: Pfizer Inc., J. Bradley Shareholder of: Pfizer Inc., Employee of: Pfizer Inc.

Salvarani et al recently studied 39 patients with giant cell arteritis (GCA) and found no association with HLA-DRB1*04.1 In contrast, previous immunogenetic studies did show an association between HLA-DRB1*04 and GCA.2 3Rauzy et al , also, reported a significant increase in DRB1*04 frequency in GCA. HLA-DRB1*04 was present in 20 of their 41 patients with …