Objectives:To analyze the risk of admission for COVID19 infection and outcome of patients treated with bDMARD or tsDMARD from our biologic therapy center, to compare with all patients admitted for COVID-19 infection in our hospital.Methods:Records of the patients from our center admitted for COVID-19 infection between March 8 and May 8, 2020 were analyzed retrospectively. Age, gender, and outcome of all patients admitted for COVID19 infection to our hospital on the same dates were collected. Chi-square, Student’s t and Man-Whitney U tests were used for comparisons when appropriate.Results:1,668 patients with inflammatory diseases treated with bDMARD or tsDMARD were included. Median age 53.0 years (range 17-91), 52.4% women. Diagnoses and DMARD distribution are shown in tables 1 and 2. 19/1668 (1.1%; 6.8 patient-years) were admitted for severe COVID19 infection. Mortality ratio: 4/19 (21.1%). Median age of the admitted patients was higher: 61.0y (SD 14.2) vs 53.0y (SD 15.0); p <0.009. Median age of deceased patients was also higher 69.5y (SD 20.3) vs 53.0y (SD 15.0); p: NS. Female gender had a worse prognosis trend: 52.4% of all group, 68.4% of those hospitalized, 75.0% of those who died. Females had a higher median age than men: 55.0y (SD 14.9) vs. 50.0y (SD 14.9); p <0.001.When comparing patients treated with DMARD admitted for COVID19 infection with all patients hospitalized for the same reason (4,601patients), no differences were found neither in age (61.0y [SD 14.2] vs 58.3y [SD 18.1]; NS) nor gender (female: 68.4% vs 54.7%; NS). However, DMARD group seemed to have higher mortality: 4/19 (21.1%) vs 551/4601 (12.0%); p: NS, at a younger age: 69.5y (SD 20.3) vs 82.4 (SD 11.4); p: NS.Rheumatoid arthritis patients were admitted more frequently: (9/392 (2.3%) vs 10/1276 (0.8%); p <0.025. And were older: median 62y (SD 13.5) vs 50.0y (SD 14.4); p <0.001.Patients treated with anti-TNF suffered less admissions: 6/1055 (0.6%) vs 13/613 (2.1%); p<0.001 and were younger: median 51.0y (SD 15.0) vs 55.0y (SD 14.7); p <0.001. Anti-TNF were less used in patients with rheumatoid arthritis 188/392 (48.0%) vs 867/1276 (67.9%); p<0.001.DiseaseN (%)AdmitteddeathsRheumatoid arthritisSpondylarthritisPsoriatic arthritisJIACTDVasculitisIBDPsoriasisOthers392 (23.5%)277 (16.6%)124 (7.4%)30 (1.8%)31 (1.9%)20 (1.2%)582 (34.9%)202 (12.1%)10 (0.6%)9/392 (2.3%)2/277 (0.7%)1/124 (0.8%)0/30 (0.0%)1/31 (3.2%)0/20 (0.0%)4/578 (0.7%)2/202 (1.0%)0/10 (0.0%)110010100TOTAL1,668 (100%)19/1668 (1.1%)4/19 (21.1%)JIA: Juvenile Idiopathic Arthritis; CTD: Connective Tissue Disease; IBD: Inflammatory Bowel DiseaseTreatmentN (%)AdmitteddeathsAnti-TNFAnti-CD20Anti-IL6CTLA4-IgAnti-IL17Anti-IL12/23Anti-integrinJAK inhibitorPDE4 inhibitorAnti-IL231055 (63.2%)79 (4.7%)96 (5.8%)44 (2.6%)92 (5.5%)143 (8.6%)79 (4.7%)34 (2.0%)32 (1.9%)14 (0.8%)6/1055 (0.6%)3/79 (3.8%)3/96 (3.1%)3/44 (6.8%)2/92 (2,2%)1/143 (0.7%)0/79 (0.0%)1/34 (2.9%)0/32 (0.0%)0/14 (0.0%)2101000000TOTAL1,668 (100%)19/1668 (1.1%)4/19 (21.1%)Conclusion:It seems reasonable that patients with inflammatory diseases treated with bDMARD or tsDMARD continue their treatment during the COVID19 epidemic. The different rates of hospitalization based on the diagnosis or DMARD may be due to comorbidity, confounding by indication and other bias. The study is not powerful enough to study these confounders.Disclosure of Interests:Carlos Gonzalez Consultant of: Gilead, Janssen, Novartis, Speakers bureau: Abbvie, Celgene, Gilead, Janssen, Novartis, Pfizer, Roche, Luis Alberto Menchén Viso Grant/research support from: Abbvie, Janssen, MSD, Takeda, Consultant of: Abbvie, Janssen, Takeda, MSD, Medtronic, Tillotts, Pfizer, Dr. Falk Pharma, Speakers bureau: Abbvie, Janssen, Takeda, MSD, General Electric, Tillotts, Pfizer, Ferring, General Electric, Fresenius, Ofelia Baniandrés Rodríguez: None declared, Ana Herranz Alonso: None declared, Carmen Lobo Rodríguez: None declared, Juan Carlos Nieto Speakers bureau: Pfizer, Abbvie, MSD, Novartis, Janssen, Lilly, Nordic Pharma, BMS, Gebro, FAES Farma, Roche, Sanofi, Indalecio Monteagudo Sáez: None declared, Ignacio Marín Jiménez: None declared, Amparo López: None declared, Ana López: None declared, Arantza Ais Larisgoitia: None declared, Esther Chamorro de Vega: None declared, Paloma Morales de los Ríos: None declared, Maria Jesus Lizcano: None declared, Jose Maria Alvaro Gracia: None declared, Sonia García de San José: None declared

Background Colon immune dysregulation results in a chronic inflammatory response typical of IBD and mainly driven by T-cell response to microbial antigens. Interestingly, stress can trigger or modulate inflammation and even modify the clinical course of IBD. Sphingosine 1-phosphate (S1P) increase in tissues is involved in T-cell recruitment and different compounds acting on S1P signaling are currently under clinical trials to test their ability to impact IBD progression, including sphingosine kinase 2 (Sphk2) inhibitors. Methods Male C57BL/6NJ and Sphk2-/- mice were randomly assigned to 4 experimental groups: Control WT (n=5), Control Sphk2-/- (n=5), Stress WT (n=8), and Stress Sphk2-/- (n=8). A sub-chronic stress mixed model based on immobilization and ultrasound exposure for 2h during 4 days was used. A set of tissue and biochemical assays was performed to evaluate stress and immune responses, S1P pathways, and epithelial barrier integrity. Results Stress caused weight loss and corticosterone upregulation regardless of the genotype. S1P was increased in the colon of stressed mice due to a decrease in its degradation enzymes and Sphk2, leading to an immune dysregulation reflected by an upregulation of TLR4 pathway, an inhibition of anti-inflammatory mechanisms – 15-lipoxygenase, N-formyl-peptide receptor 2 and Liver X Receptor – a decrease in IgA+ and a decrease in IgM+ B-cells and plasmablasts, and a Th17 polarization. Sphk2 deletion did not affect inflammatory processes but could interfere with Th17 response. Moreover, Sphk2-/- mice showed lower expression levels of claudins 3, 4, 5, 7, and 8 that could be related to structural abnormalities relevant to IBD. Stress exposure also decreased some of these claudins and increased intestinal permeability, but a synergistic effect between stress and genotype for permeability was not detected. Conclusion Sub-chronic stress induced colon S1P increase, immune dysregulation and increased intestinal permeability. Sphk2 deletion is involved in structural abnormalities and Th17 response but did not aggravate the inflammatory processes exerted by stress.

Background:Patients with immunity mediated inflammatory diseases (IMID) often have clinical manifestations and comorbidity in the field of various medical specialties. A center has been created in our hospital for the comprehensive care of patients with IMID who are being treated with biological therapies (BT) or targeted synthetic molecules (TSM). It is an innovative healthcare model, that incorporate patients into its governance. Physicians, pharmacists and advanced practice nurses (APN), collaborates in consultation or in the day hospital (DH).Objectives:To analyze the activity developed during the first year of operation of the center, with special attention to effectiveness, efficiency, interdisciplinary relationships and patient satisfaction.Methods:Observational analysis with indicators of management and monitoring of patients, care activity, effectiveness, adverse effects, resource consumption and patient satisfaction using the hospital’s own information systems.Results:Center staff during 2019: two admission assistants, one nursing assistant, six nurses, seven part-time doctors and three pharmacists. 1,490 patients were included: 694 (46.6%) Rheumatology (Rheu), 585 (39.3%) Digestive (Dig) and 211 (14.1%) Dermatology (Der) generated 11,363 medical consultations, 14,850 APN consultations and 3,920 treatment sessions in the DH. IV treatment 529/1490 (35.5%) patients (45.0% Reu, 53.9% Dig, 1.1% Der). Patients with rheumatic diseases: rheumatoid arthritis: 339/694, 48.8%; Spondyloarthritis: 226/694, 32.6%; psoriatic arthritis: 117/694, 16.9%; and juvenile idiopathic arthritis: 12/694, 1.7%. 217/1490 (14.6%) patients needed multidisciplinary consultations.Table 1. shows the most relevant indicators and table 2 shows the patient satisfaction survey for 2019.Table 1.relevant indicatorsRHEUDIGDEROn demand consultations 2019 %21.0%34.2%14.3%Teleconsultations 2019 %17.8%41.9%0.0%BT, TSM tapering. %201931.9%0.2%45,5%201818.9%0.2%13.4%BT, TSM intensification. %20195.8%35.2%0.5%20182.6%36.5%0.5%Biosimilars %201943.1%48.5%15.9%201830.4%4.0%12.1%Adherence>90% 2019 %89.4%91.7%86.4%Remission 2019 %47.8%67.3%78.5%hospital admission, any cause pat-years20191.41.70.120181.51.50.04emergency admission, any cause pat-years20192.12.11.620182.12.01.5Table 2.patient satisfaction surveyCategoríaMean and (DS) 1-5General aspects of the center4.3 (0.9)Physicians4.5 (1.1)DH and APN4.5 (1.2)Pharmacy4.6 (0.9)Health proffesional coordinaton4.4 (0.9)Hospital global satisfaction4.3 (0.8)Conclusion:From previous situation there is an increase in interdisciplinary consultations and HD activity maintenance without an increase in human resources. Efficiency (tapering, biosimilars) and patient and staff satisfaction have improved. However, no improvement in adverse effects has been observed, which is an area of improvement. Effectiveness is good, waiting to compare with the previous year. Nutrition and preventive medicine consultations has not been evaluated because have been recently established. Other indicators are being analyzed at the end of the submission deadline.The impact of this pioneering management model, with a holistic approach and incorporating patients into its governance, is difficult to measure until its implementation is completed. Uveitis and psychology consultations and patient school starting in 2020 will improve the quality of IMID patient care, as well as their satisfaction and that of their relatives.Disclosure of Interests:Carlos Gonzalez Consultant of: Gilead, Janssen, Novartis,, Speakers bureau: Abbvie, Celgene, Gilead, Janssen, Novartis, Pfizer, Roche, Luis Alberto Menchén Viso Grant/research support from: Abbvie, Janssen, MSD, Takeda, Consultant of: Abbvie, Janssen, Takeda, MSD, Medtronic, Tillotts, Pfizer, Dr. Falk Pharma, Speakers bureau: Abbvie, Janssen, Takeda, MSD, General Electric, Tillotts, Pfizer, Ferring, General Electric, Fresenius, Ofelia Baniandrés Rodríguez: None declared, Ignacio Marín-Jiménez Consultant of: AbbVie,Chiesi,FAES Farma,Falk-Pharma,Ferring,Gebro Pharma, Hospira,Janssen,MSD,Otsuka Pharmaceutical,Pfizer,Shire,Takeda,Tillots and UCB Pharma, Speakers bureau: AbbVie,Chiesi,FAES Farma,FalkPharma,Ferring,Gebro Pharma,Hospira,Janssen,MSD,Otsuka Pharmaceutical,Pfizer,Shire,Takeda,Tillots and UCB Pharma, Juan Carlos Nieto Speakers bureau: Pfizer, Abbvie, MSD, Novartis, Janssen, Lilly, Nordic Pharma, BMS, Gebro, FAES Farma, Roche, Sanofi, Indalecio Monteagudo: None declared, Arantza Ais Larisgoitia: None declared, Esther Chamorro de Vega: None declared, Elena Lobato Matilla: None declared, Rosa Romero Jiménez: None declared, Ana Herranz Alonso: None declared, Carmen Lobo Rodríguez: None declared, María Prado Simón Moreno: None declared, Jose-Maria Alvaro-Gracia Grant/research support from: Abbvie, Elli-Lilly, MSD, Novartis, Pfizer, Consultant of: Abbvie, BMS, Janssen-Cilag, Elli-Lilly, MSD, Novartis, Pfizer, Sanofi, Tigenix, Roche, UCB, Paid instructor for: Elli-Lilly, Pfizer, Roche, Speakers bureau: Abbvie, BMS, Janssen-Cilag, Elli-Lilly, Gedeon Richter, MSD, Novartis, Pfizer, Sanofi, Tigenix, Roche, UCB, Sonia García de San José: None declared