Abstract: The mortality in Systemic Lupus Erythematosus (SLE) varies largely across different countries most probably due to social, healthcare and ethnic differences. Objectives: To analyze the causes and identify predictive factors of mortality of SLE in Spain in the present century. Methods: We performed a cross-sectional and retrospective study analyzing data from the RELESSER cohort (Spanish Registry of Systemic Lupus Erythematosus of the Spanish Society of Rheumatology). We included all patients diagnosed with SLE since the year 2000 and recorded sociodemographic, clinical and serological variables, comorbidities and treatments, as well as indicators of disease activity, damage and severity. The characteristics of the deceased patients were compared with those of the survivors, and variables with clinical significance or statistical significance were grouped into multivariate models to determine which ones were independently associated with the outcome of the disease. Results: A total of 2004 patients were included, 88.6% female, the mean age at diagnosis was 38.3 (± 15.3) years, with a mean delay in diagnosis of 28.9 (± 52.6) months. Up to 2.84% of the individuals had died. The leading cause of death was SLE activity (n=16), followed by infections (n=14), vascular events (n=7) and cancer (n=6). The mean age of death was 54.68 (± 20.13) years, and neither age, sex nor delay in diagnosis was independently associated with mortality. The presence of nephritis, depression, severe infections, organ damage (SLICC/ACR DI) or disease activity (SLEDAI), as well as the use of cyclophosphamide, rituximab or high doses of corticosteroids, were predictors of mortality in our cohort. Antimalarial treatment and skin manifestations were linked to improved survival. Conclusion: In the RELESSER cohort, clinical factors, co-morbidities, as well as therapeutic attitudes were associated with a significant increase in mortality in SLE. Interestingly, depression was independently associated to mortality. The activity of the disease and infections continue to be the main causes of death at the beginning of the 21st century amongst our patients. Disclosure of Interests: Clara Moriano: None declared, Jaime Calvo Grant/research support from: Lilly, UCB, Consultant of: Abbvie, Jansen, Celgene, Iñigo Rua-Figueroa: None declared, Elvira Diez Alvarez: None declared, Cristina Bermúdez: None declared, Francisco J López-Longo Grant/research support from: AbbVie and GSK, Speakers bureau: AbbVie, Actelion, Bristol Myers Squibb, GSK, MSD, Pfizer, Roche, and UCB Pharma, María Galindo-Izquierdo: None declared, Alejandro Olive: None declared, Eva Tomero Muriel: None declared, Antonio Fernandez-Nebro: None declared, Mercedes Freire González: None declared, Olaia Fernández- Berrizbeitia: None declared, Ana Pérez Gómez: None declared, Esther Uriarte Isacelaya: None declared, Carlos Marras Fernandez Cid: None declared, Carlos A. Montilla-Morales: None declared, Gregorio Santos Soler: None declared, Ricardo Blanco Grant/research support from: AbbVie, MSD, and Roche, Speakers bureau: AbbVie, Pfizer, Roche, Bristol-Myers, Janssen, and MSD, M. Rodíguez-Gómez: None declared, Paloma Vela-Casasempere: None declared, Alina Boteanu: None declared, J. Narváez: None declared, Victor Martinez Taboada: None declared, Blanca Hernández-Cruz Speakers bureau: Abbvie, Lilly, Sanofi, BMS, STADA, José Luis Andreu: None declared, José A Hernandez Beriain: None declared, Lorena Expósito: None declared, Raúl Menor-Almagro: None declared, Mónica Ibañez Barceló: None declared, Ivan Castellví Consultant of: Boehringer Ingelheim, Actelion, Kern Pharma, Speakers bureau: Boehringer Ingelheim, Actelion, Bristol-Myers Squibb, Roche, Carles Galisteo: None declared, Enrique Raya: None declared, Víctor Quevedo Vila: None declared, Tomas Vazquez Rodriguez: None declared, Jesus Ibañez: None declared, Jose M Pego-Reigosa: None declared

Abstract: 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) P Sex (F/M) 28/18 122/95 0.625 Age (years) 65.11±10.21 6.2±9.8 0.202 RF/CCPA + (%) 91.3/91.3 89.8/90.1 0.810 Smoking or past smoking (%) 47.8 55.1 0.417 Follow-up (months) 22.73±18.00 22.3±20.85 0.916 DAS28 at baseline 4.08±1.51 4.61±1.47 0.056 DAS28 at last visit 3.00±1.46 3.13±1.31 0.642 Prednisone 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±19.04 65.43±18.21 0.823 DLCO at the end of study (%) 66.05±20.95 65.17±19.72 0.831 FVC at baseline (%) 90.06±17.77 85.40±21.56 0.164 FVC at the end of study (%) 90.58±15,45 84.21±21.49 0.038* 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

Abstract: 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; 48:22-27 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, 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

Abstract: 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

Abstract: There are several metabolic pathways involved in cell metabolism, including glycolysis, tricarboxylic acid (TCA) cycle and fatty acid (FA) oxidation. Metabolic flexibility has previously described as the ability to respond or adapt to changes in metabolic demand; assessed by the ability to switch from fat to carbohydrate oxidation. In the last years there is a growing interest to assess the influence of metabolic flexibility, as a mechanism to explain how lipids can accumulate in the tissue. During OA, it has been established a relationship between mitochondrial dysfunction and cellular damage due to impairments in mitochondrial function and metabolic flexibility. Several studies have suggested that fatty acids may play an important role in OA development and progression. Objectives: The aim of this work was to examine the differences in glucose and fatty acid metabolism, with special focus on metabolic flexibility, in cybrids from healthy (N) or OA donors. Methods: Cybrids were developed using 143B.TK - Rho-0 cell line (nuclear donor) and platelets (mitochondrial donors) from healthy (N) and OA donors. Glucose and FA metabolism were measured using D-[ 14 C(U)]glucose and [1- 14 C]oleic acid respectively. Metabolic flexibility was evaluated by co-culturing with glucose and oleic acid acutely by using inhibitors against glucose and FA oxidation, 20µM UK5099 and 10µM etomoxir, respectively. Incorporation of FA into lipid droplet (LD) was evaluated by thin layer chro matography and LD were stained by LD540 and analyzed by confocal microscope and flow cytometry. Mitochondrial dynamics was measured by real-time PCR method. Percentage of mitochondrial Anion Superoxide (O 2 - ) production was evaluated incubating cells with MitoSox® using Flow Cytometer. Appropriate statistical analyses were performed with GraphPad Prism v6. Results: There were no changes in basal glucose metabolism between cybrids. N cybrids had higher acid-soluble metabolites, reflecting incomplete FA β-oxidation than OA cybrids. Comparing glucose and FA metabolism showed that both types of cybrids preferred to oxidize glucose. Co-culturing with glucose and Oleic acid, increased total cellular uptake and oxidation of glucose in N compared to basal condition (Figure-1) and in this condition the OA cybrids showed an increase in mitochondrial O 2 - production. Inhibition of FA oxidation by etomoxir increased complete glucose oxidation of N cybrids but not in OA cybrids that had a preference to oxidize oleic acid compared to basal condition. Gene expression of mitofusin-2 ( MFN2 ) was higher in N than OA cybrids under inhibiting conditions. Combine these data indicate that N cybrids are more metabolically flexible and have better adaptative response than OA. Cybrids presented different lipid distribution patterns. Lipid droplet (LD) formation increased in both groups incubated in presence of FA. Furthermore, N cybrids showed less LD formation than OA. Conclusion: The results indicated that cybrids from OA patients had reduced metabolic flexibility compared to N cybrids. These results enhance our understanding of the mitochondria metabolism in OA, suggesting a mitochondrial dysfunction and impairment of metabolic flexibility during the OA process. Disclosure of Interests: Andrea Dalmao-Fernandez: None declared, Jenny Lund: None declared, Tamara Hermida Gómez: None declared, Maria Eugenia Vazquez Mosquera: None declared, Ignacio Rego-Perez: None declared, Francisco J. Blanco Grant/research support from: Sanofi-Aventis, Lilly, Bristol MS, Amgen, Pfizer, Abbvie, TRB Chemedica International, Glaxo SmithKline, Archigen Biotech Limited, Novartis, Nichi-iko pharmaceutical Co, Genentech, Jannsen Research & Development, UCB Biopharma, Centrexion Theurapeutics, Celgene, Roche, Regeneron Pharmaceuticals Inc, Biohope, Corbus Pharmaceutical, Tedec Meiji Pharma, Kiniksa Pharmaceuticals, Ltd, Gilead Sciences Inc, Consultant of: Lilly, Bristol MS, Pfizer, Mercedes Fernandez-Moreno: None declared

Abstract: Metotrexate (MTX) is the first-line treatment for rheumatoid arthritis (RA) both in monotherapy and in combination with biologic disease-modifying antirheumatic drugs (bDMARDs), it usually well tolerated but AEs may appear that causing toxicity that requires suspension of the treatment Objectives: Determine the prevalence of certain polymorphisms among patients that receive bDMARD in monotherapy or in combination with MTX to confirm its relevance as biomarkers of intolerance. Evaluate the influence of certain polymorphisms in the effectiveness of monotherapy or combined treatment in patients, through “Disease Activity Score 28” (DAS28), SDAI Simple disease activity index (SDAI), Clinical disease activity index (CDAI) and each one of its components Methods: Retrospective observational multicentric study (University Hospital Complex, Granada, Carlos de Haya Hospital, Malaga and University Hospital Reina Sofia, Cordoba), of cases-control of 227 patients with RA (criteria ACR/EULAR), of which 120 received MTX and bDMARD combined therapy (cases) and other with only bDMARD (controls). All of them had been or were currently treated with MTX, remained with stable doses of bDMARD, and had a DNA sample stored before the inclusion in the study DNA was isolated from total peripheral blood and by fluorescent probe HybProbe and/ or Taqman, 10 polymorphisms of 10 protein coding genes were determined involved in the metabolism and toxicity of MTX according to current evidence Besides the type of polymorphism, data on the activity of the disease were analysed (DAS28VSG, DAS28PCR, SDAI, CDAI, at the start of the MTX income, of the BT, and in the inclusion visit A descriptive and comparative study was carried out on all that and afterwards an assessment was made through a multiple logistic regression analysis (MLR) on the risk of intolerance to MTX Results: An analysis was carried out on 227 patients (120 cases and 107 controls) with an average age of 60 (12,1) being women 78,4%, with a time of evolution since diagnosis of 14,84 (7,78) years 48,9% registered adverse events (AE) MTX related, mainly gastrointestinal, hepatobiliary and skin-subcutaneous tissue. The percentage of AE appearance was superior in the monotherapy group than in the group with combined therapy The most prevalent polymorphism (84,6% (IC95%: 84,09%-85,11%) and in cases (86,0% (IC95%: 79,43%-92,57%) was homozygous CC (ITPase-c94a ); in controls homozygous GG (GGH-T401C ) (87,5% (IC95%:81,58%-93,42%) There were no significant differences in the parameters of activity between groups, in both, patients were best basally controlled than at the start of the MTX income and/or bDMARD Being homozygous-AA for the DHFR gene was significantly associated (p 〈 0.05) with the appearance of AE (none of the 4 homozygous AA patients for that gene had AE) In MLR, homozygous GG (ref. heterozygous AG) in polymorphism GGH-T401C, being homozygous CC (ref. heterozygous TC) in polymorphism ABCC2-C24T and PCR (mg/dL) at the start of bDMARD resulted independent predictive factors of MTX intolerance Conclusion: Polymorphisms T401C for the GGH gene and C24T for the ABCC2 gene and PCR at the start of the bDMARD resulted independent predictive factors of MTX intolerance . Polymorphism homozygous AA for DHFR gene was related to significant protection against appearance of AE Disclosure of Interests: Alejandro Escudero Contreras: None declared, Rafaela Ortega Castro: None declared, Jerusalem Calvo Gutierrez: None declared, Natalia Mena-Vázquez: None declared, Rafael Cáliz Cáliz: None declared, Eduardo Collantes Estevez Grant/research support from: ROCHE and Pfizer, Speakers bureau: ROCHE, Lilly, Bristol and Celgene, Antonio Fernandez-Nebro: None declared, Maria del Carmen Abalos-Aguilera: None declared, Chary Lopez-Pedrera Grant/research support from: ROCHE and Pfizer., Mª Teresa Ruiz Jimenez Employee of: Roche Farma, SPAIN, Font Ugalde Pilar: None declared