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This study aimed to calculate the healthcare resource utilization and direct medical costs in patients with 2 subtypes of axial spondyloarthritis (axSpA) in a rheumatic care center in Colombia.This is a retrospective cost-of-illness study. Patients with at least 1 medical consultation associated with an axSpA diagnosis between October 2018 and October 2019 were identified. Patients were classified as having radiographic (r-axSpA) or nonradiographic axSpA (nr-axSpA). Direct medical costs were calculated in Colombian pesos and expressed in American dollars using an exchange rate of 3263 Colombian pesos = 1 US dollar ($). Predictors of total direct costs were identified using a generalized linear model with gamma distribution and log-link.A total of 162 patients with a mean age of 49.6 years (± 13.7) were included in the study. Among these, 147 (90.7%) were considered as having r-axSpA and 15 (9.3%) nr-axSpA, with mean costs of $6600 (± 6203) and $843 (± 1135), respectively (P.001). The total direct mean cost was calculated at $6067 (± 6144) per patient. Medication costs were the main driver of total costs (97.6%, $5921), with biologic disease-modifying antirheumatic drugs accounting for nearly 92.0% ($5582) of these costs. Rheumatologist (100%) and physiatrist (64.2%) visits were the most frequently used medical service.The economic burden associated with axSpA in the Colombian setting is substantial. There is a significant difference in direct medical costs between the r-axSpA and the nr-axSpA. Health policies aimed at the comprehensive management of nr-axSpA would have an important role in the reduction of the associated direct medical costs.

Pedro Santos-Moreno,1 Susan Martinez,1 Linda Ibata,1 Laura Villarreal,1 Fernando Rodríguez-Florido,1 Manuel Rivero,1 Adriana Rojas-Villarraga,2 Claudio Galarza-Maldonado3 1Scientific Department, Biomab IPS SAS, Bogotá, Colombia; 2Research Institute, Fundación Universitaria de Ciencias de la Salud–FUCS, Bogotá, Colombia; 3Unit of Rheumatic and Autoimmune Diseases UNERA, Mont Sinai Hospital, Cuenca, EcuadorCorrespondence: Pedro Santos-Moreno, Scientific and Research Director, Rheumatology, Scientific department, Biomab IPS SAS, Calle 48 #13– 86, Bogotá, Colombia, Tel +57 320 8094232, Email pedrosantosmoreno@hotmail.comPurpose: Tofacitinib is recommended for treatment of rheumatoid arthritis (RA) in patients with moderate to severe disease activity, but there is not enough evidence on its effectiveness after conventional DMARDs vs its use after biologics. The aim was evaluating the effectiveness of tofacitinib in RA as first-line treatment (after conventional DMARDs) in a real-life setting in Colombian (Latin-American) patients.Patients and Methods: Retrospective cohort study conducted at a specialized center for RA management. A complete statistical analysis was performed to compare the values of the change in the DAS28 at months 3, 6, and 12 in both treatment groups.Results: A total of 152 RA patients who received tofacitinib: first-line 85 patients (55.9%) after failure on conventional DMARDs or second-line 67 patients (44.1%) after failure on biologic DMARDs. Comparative analysis of response to treatment showed a reduction in DAS28 at 3, 6, and 12 months in both study groups without statistical differences, but a higher proportion of first-line patients achieved remission (45% vs 23%). Nonresponse at three months were associated with no response at six months of follow-up. Baseline DAS28 was significantly associated with response at 12 months (OR: 1.87, 95%CI: 1.06– 3.30, p-value 0.028). In second-line patients, response to tofacitinib was not related to number of biologic DMARDs previously used.Conclusion: Tofacitinib is an effective treatment option for patients with RA, maybe better after conventional DMARDs than after biologic therapy failure. Further studies are required to determine the role of tofacitinib in different lines of RA treatment and in other groups of patients.Keywords: tofacitinib, rheumatoid arthritis, treatment, biologics

Supplementary Figures 1-20

Gene ontology description of the 301 G12V unique proteins shown in Figure 2B

It contains supplementary Experimental Procedures and Suppl. figures

Purpose:The study of the cancer secretome suggests that a fraction of the intracellular proteome could play unanticipated roles in the extracellular space during tumorigenesis. A project aimed at investigating the invasive secretome led us to study the alternative extracellular function of the nuclear protein high mobility group A1 (HMGA1) in breast cancer invasion and metastasis.Experimental Design:Antibodies against HMGA1 were tested in signaling, adhesion, migration, invasion, and metastasis assays using breast cancer cell lines and xenograft models. Fluorescence microscopy was used to determine the subcellular localization of HMGA1 in cell lines, xenograft, and patient-derived xenograft models. A cohort of triple-negative breast cancer (TNBC) patients was used to study the correlation between subcellular localization of HMGA1 and the incidence of metastasis.Results:Our data show that treatment of invasive cells with HMGA1-blocking antibodies in the extracellular space impairs their migration and invasion abilities. We also prove that extracellular HMGA1 (eHMGA1) becomes a ligand for the Advanced glycosylation end product-specific receptor (RAGE), inducing pERK signaling and increasing migration and invasion. Using the cytoplasmic localization of HMGA1 as a surrogate marker of secretion, we showed that eHMGA1 correlates with the incidence of metastasis in a cohort of TNBC patients. Furthermore, we show that HMGA1 is enriched in the cytoplasm of tumor cells at the invasive front of primary tumors and in metastatic lesions in xenograft models.Conclusions:Our results strongly suggest that eHMGA1 could become a novel drug target in metastatic TNBC and a biomarker predicting the onset of distant metastasis.

Introduction Surgical procedures in persons with haemophilia A or B with inhibitors (PwHABI) require the use of bypassing agents (BPA) and carry a high risk of complications. Historically, only two BPAs have been available; these are reported to have variable responses. Aim To prospectively evaluate the efficacy and safety of a new bypassing agent, human recombinant factor VIIa (eptacog beta) in elective surgical procedures in PwHABI in a phase 3 clinical trial, PERSEPT 3. Methods Subjects were administered 200 µg/kg (major procedures) or 75 µg/kg eptacog beta (minor procedures) immediately prior to the initial surgical incision; subsequent 75 µg/kg doses were administered to achieve postoperative haemostasis and wound healing. Efficacy was assessed on a 4-point haemostatic scale during the intra- and postoperative periods. Anti-drug antibodies, thrombotic events and changes in clinical/laboratory parameters were monitored throughout the perioperative period. Results Twelve subjects underwent six major and six minor procedures. The primary efficacy endpoint success proportion was 100% (95% CI: 47.8%-100%) for minor procedures and 66.7% (95% CI: 22.3%-95.7%) for major procedures; 81.8% (95% CI: 48.2%-97.7%) of the procedures were considered successful using eptacog beta. There was one death due to bleeding from a nonsurgical site; this was assessed as unlikely related to eptacog beta. No thrombotic events or anti-eptacog beta antibodies were reported. Conclusion Two eptacog beta dosing regimens in PwHABI undergoing major and minor surgical procedures were well-tolerated, and the majority of procedures were successful based on surgeon/investigator assessments. Eptacog beta offers clinicians a new potential therapeutic option for procedures in PwHABI.

Identifying the scope of surgical mentoring at Pontificia Universidad Javeriana and compare the perceptions of teachers and students to recognize characteristics and competences of such practice and future needs.Two surveys were designed to evaluate the existence and importance of mentoring and inquire about the characteristics, qualities and skills expected on mentors.Both groups agree on the importance of having a mentor. 84.2% of teachers consider themselves mentors, however, only 38.6% of students considered them as such. The most relevant quality of the mentor recognized by students was the willingness and ability to teach, while for teachers it was respect. For the students, the most important competence was the ability to explain and teach about the procedures to be performed, while for teachers it was the ability to provide confidence and security.There is a paradoxical behavior, most students consider they do not have a mentor while most teachers consider to be such. The need to expand the literature regarding mentoring in Colombia specifically in the surgical field was identified.Identificar el alcance del mentoring quirúrgico en la Facultad de Medicina de la Pontificia Universidad Javeriana y comparar las percepciones de docentes y estudiantes, con el fin de reconocer características y competencias de dicha práctica y necesidades a futuro.Se diseñaron dos encuestas para evaluar la existencia y la importancia del proceso de mentoring e indagar acerca de las características, las cualidades y las competencias esperadas de los mentores.Ambos grupos coinciden en la importancia de contar con un mentor. El 84.2% de los docentes consideran ser mentores, pero solo el 38.6% de los estudiantes los consideraron a ellos como tales. Las cualidad más relevantes del mentor reconocidas por los estudiantes fueron la disposición y la habilidad para enseñar, mientras que para los docentes fue el respeto. Para los estudiantes, la competencia más importante fue la capacidad de explicar y enseñar sobre los procedimientos a realizar, mientras que para los docentes fue la capacidad de brindar confianza y seguridad.Existe un comportamiento paradójico, pues los estudiantes no consideraron contar con un mentor mientras que los docentes sí estimaron serlo. Se identificó la necesidad de ampliar la literatura respecto al mentoring en Colombia, específicamente en el ámbito quirúrgico.

Pedro Santos-Moreno,1 Gabriel-Santiago Rodríguez-Vargas,1 Susan Martínez,2 Linda Ibatá,2 Laura Villarreal-Peralta,1 Anggie Aza-Cañon,1 Manuel Rivero,1 Pedro Rodriguez,1 Adriana Rojas-Villarraga3 1Rheumatology Department, Biomab IPS, Bogotá, Colombia; 2Epidemiology Department, Epithink Health Consulting, Bogotá, Colombia; 3Research Institute, Fundación Universitaria de Ciencias de la Salud–FUCS, Bogotá, ColombiaCorrespondence: Pedro Santos-Moreno, Rheumatology Department, Biomab IPS, Calle 48 # 13-86, Bogotá, Colombia, Tel +57 320 8094232, Email pedrosantosmoreno@hotmail.comPurpose: To describe clinical characteristics and effectiveness of health care in patients with rheumatoid arthritis (RA) as part of a multidisciplinary care model (MCM) in a specialized rheumatology center, compared with the results of a national registry of RA (NARRA) as evidence of real-world management.Patients and Methods: We conducted a real-world study (July 1, 2018 to June 30, 2019) based on an analysis of electronic health records of a cohort of RA patients managed with the “Treat-to-Target” strategy in a specialized rheumatology center in Colombia with an MCM, compared with the NARRA that includes different models of usual care.Results: We have analyzed 7053 subjects with RA treated at a specialized rheumatology center and 81,492 patients from the NARRA. Cohorts were similar in their baseline characteristics, with women in predominance and diagnosis age close to 50 years. At the time of diagnosis, a higher proportion of clinical diagnostic test use and rheumatology consultation access was observed in the specialized rheumatology center than in the national registry (4– 6 per year versus three or less). In addition, higher proportions of patients in remission and low disease activity were reported for the specialized rheumatology center, with a > 40% amount of data lost in the national registry. Pharmacological management was similar regarding the analgesic use. In the specialized center, Certolizumab was more frequently used than in the NARRA registry; also, there were significant differences in methotrexate, leflunomide, and sulfasalazine use, being higher in the specialized rheumatology center.Conclusion: The MCM of a specialized center in RA can guarantee comprehensive care, with better access to all the services required to manage the disease. It ensures specialist management and evidence-based care that facilitates the achievement of therapeutic objectives. In addition, better patient records and follow-ups are available to evaluate health outcomes.Keywords: rheumatoid arthritis, therapeutics, multidisciplinary healthcare, real-world data

Sticky Platelet Syndrome (SPS) is a disorder characterized by platelet hyperaggregability, diagnosed by studying in vitro platelet aggregation with ADP and epinephrine. It is the second most common cause of thrombophilia in Mexican Mestizos and manifests as an autosomal dominant trait which, combined with other coagulopathies, contributes significantly to the morbidity and mortality of patients with primary thrombophilia. It is easily treatable with antiplatelet drugs; however, the methods for diagnosis are not readily available in all clinical laboratories and the disorder is often overlooked by most clinicians. Herein, we present the results of more than 20 years of Mexican experience with the study of SPS in a Mestizo population.

Pedro Santos-Moreno,1 Nelson J Alvis-Zakzuk,2 Edwin Castillo,1 Laura Villarreal,1 Carlos Pineda,3 Hugo Sandoval,4 Omaira Valencia1,5 1Center of Rheumatoid Arthritis, BIOMAB, Bogota, Colombia; 2Universidad de la Costa-CUC, Departamento de Ciencias Económicas, Barranquilla, Colombia; 3Sociomedical Research Unit, Instituto Nacional de Rehabilitación Luis Guillermo Ibarra Ibarra, Ciudad de México, Mexico; 4Sociomedical Research Unit, Instituto Nacional de Rehabilitación Luis Guillermo Ibarra Ibarra, Ciudad de México, México; 5Fundación Santa Fé de Bogotá, Bogotá, ColombiaCorrespondence: Omaira ValenciaFundación Santa Fé de Bogotá, Carrera 7B # 123-90, Bogotá, ColombiaEmail o.valencia10@uniandes.edu.coBackground: Seronegative rheumatoid arthritis (SRA) is a condition that is not well understood and difficult to confirm by a conventional diagnostic process. We aimed to quantify the potential cost-savings of an alternative diagnostic process (ADP) imaging-based, for patients with presumptive SRA from everyday clinical practice.Methods: We performed a retrospective analysis for patients with presumptive SRA who tested negative for both rheumatoid factor and anti-cyclic citrullinated peptide antibodies, through an ADP imaging-based, that is a standard clinical practice in our center. After we confirmed the diagnosis of SRA or reclassified patients in terms of another proper diagnosis, we estimate direct costs in two scenarios: a conventional and ADP. We compared the cost of RA treatment during the first year against the cost of the most misdiagnosed treatment (osteoarthritis) found after applying the ADP to determine potential cost-savings.Results: We included 440 patients with a presumptive diagnosis of SRA. According to the imaging-based ADP, SRA was confirmed in 106/440 (24.1%), unspecified RA in 9/440 (2.0%), and osteoarthritis in 325/440 (73.9%) of those patients. Although the costs of conventional diagnosis per patient is lower than those of ADP ($59,20 USD vs $269,57 USD), we found a potential drug cost-savings of $1,570,775.20 US Dollars after 1 year of correct treatment.Conclusion: An alternative diagnosis process, including X-rays, US and MRI imaging, and clinical and blood-test assessment, not only increased diagnostic certainty in patients referred for evaluation of presumptive SRA but also suggested a potential cost-savings in pharmacological treatments avoided in misdiagnosed patients.Keywords: cost-savings, seronegative rheumatoid arthritis, diagnosis, imaging

Hyperoxia−hypoxia exposure is a proposed cause of alveolar developmental arrest in bronchopulmonary dysplasia in preterm infants, where mitochondrial reactive oxygen species and oxidative stress vulnerability are increased. The aryl hydrocarbon receptor (AhR) is one of the main activators of the antioxidant enzyme system that protects tissues and systems from damage. The present study aimed to determine if the activation of the AhR signaling pathway by prenatal administration of indole-3-carbinol (I3C) protects rat pups from hyperoxia–hypoxia-induced lung injury. To assess the activation of protein-encoding genes related to the AhR signaling pathway ( Cyp1a1, Cyp1b1, Ugt1a6, Nqo1, and Gsta1), pup lungs were excised at 0, 24, and 72 h after birth, and mRNA expression levels were quantified by reverse transcription-quantitative polymerase chain reaction assays (RT-qPCR). An adapted Ratner's method was used in rats to evaluate radial alveolar counts (RACs) and the degree of fibrosis. The results reveal that the relative expression of AhR-related genes in rat pups of prenatally I3C-treated dams was significantly different from that of untreated dams. The RAC was significantly lower in the hyperoxia–hypoxia group (4.0 ± 1.0) than that in the unexposed control group (8.0 ± 2.0; P < 0.01). When rat pups of prenatally I3C-treated dams were exposed to hyperoxia–hypoxia, an RAC recovery was observed, and the fibrosis index was similar to that of the unexposed control group. A cytokine antibody array revealed an increase in the NF-κB signaling cascade in I3C-treated pups, suggesting that the pathway could regulate the inflammatory process under the stimulus of this compound. In conclusion, the present study demonstrates that I3C prenatal treatment activates AhR-responsive genes in pup’s lungs and hence attenuates lung damage caused by hyperoxia–hypoxia exposure in newborns.

INTRODUCTION: Eptacog beta is a new recombinant activated human factor VII bypassing agent approved in the United States for the treatment and control of bleeding in patients with haemophilia A or B with inhibitors 12 years of age or older. AIM: To prospectively assess in a phase 3 clinical trial (PERSEPT 2) eptacog beta efficacy and safety for treatment of bleeding in children

Pedro Santos-Moreno,1 Susan Martinez,2 Linda Ibatá,2 Laura Villarreal,1 Manuel Rivero,3 Adriana Rojas-Villarraga4 1Rheumatology, Biomab IPS, Bogotá, DC, Colombia; 2Epidemiology, Biomab IPS, Bogotá, DC, Colombia; 3Pharmacy, Biomab IPS, Bogotá, DC, Colombia; 4Rheumatology, Research División, Fundación Universitaria de Ciencias de la Salud – FUCS, Bogotá, DC, ColombiaCorrespondence: Pedro Santos-MorenoRheumatology, Biomab IPS, Calle 48 # 13-86, Bogotá, ColombiaEmail pedrosantosmoreno@hotmail.comObjective: Although it is known that methotrexate (MTX) increases the effectiveness of biological drugs (mainly anti-TNFs) in patients with rheumatoid arthritis (RA), in real life, it is known that many patients using anti-TNFs are on monotherapy due to many causes. This article compares the effectiveness of certolizumab as monotherapy as combined with MTX or leflunomide (LFN) in RA patients with failure to conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) in a real-world setting.Methods: A retrospective observational cohort study was conducted at a specialized centre for RA management in Colombia. Patients treated with certolizumab as monotherapy or in combination with MTX, LFN, or MTX+LFN, between 2011 and 2020 with a minimum 3-month follow-up were included. Demographics and RA clinical characteristics were recorded; effectiveness was assessed as the improvement in Disease Activity Score (DAS28) getting remission or low disease activity at 3, 6, and 12 months of treatment.Results: A total of 181 patients were included, 24 received certolizumab as monotherapy, 62 certolizumab plus MTX, 47 certolizumab plus LFN and 48 certolizumab plus MTX+LFN. At 3 months of follow-up, 80% of the patients showed decreased disease activity, with no significant differences between groups; at 12 months of treatment, response in certolizumab monotherapy group was 94.4% compared to 81.8% in combination with MTX, 80.5% in combination with LFN and 51.4% in combination with MTX+LFN. Response at 3 months (OR 4.04; 95% CI 1.28– 12.69) and positive anti-CCP (OR 3.83; 95% CI 1.11– 13.21) were associated with 12-month response.Conclusion: Certolizumab seems to be effective as monotherapy in the treatment of RA patients with failure to csDMARDs.Keywords: rheumatoid arthritis, treatment, anti-TNFs, certolizumab, monotherapy

Menkes disease (MD) is a rare and often lethal X-linked recessive syndrome, characterized by generalized alterations in copper transport and metabolism, linked to mutations in the ATPase copper transporting α (ATP7A) gene. Our objective was to identify genomic alterations and circulating proteomic profiles related to MD assessing their potential roles in the clinical features of the disease. We describe the case of a male patient of 8 months of age with silvery hair, tan skin color, hypotonia, alterations in neurodevelopment, presence of seizures, and low values of plasma ceruloplasmin. Trio-whole-exome sequencing (Trio-WES) analysis, plasma proteome screening, and blood cell migration assays were carried out. Trio-WES revealed a hemizygous change c.4190C &gt, T (p.S1397F) in exon 22 of the ATP7A gene. Compared with his parents and with child controls, 11 plasma proteins were upregulated and 59 downregulated in the patient. According to their biological processes, 42 (71.2%) of downregulated proteins had a participation in cellular transport. The immune system process was represented by 35 (59.3%) downregulated proteins (p = 9.44 × 10–11). Additional studies are necessary to validate these findings as hallmarks of MD.

Objective: To describe sustainability of low disease activity levels in patients with rheumatoid arthritis (RA) who were followed-up in a specialized center based on a healthcare model maintaining adherence to appointments and treatment.Material and methods: As part of a comprehensive RA healthcare model, services related to care like rheumatology, physiatry, physiotherapy, occupational therapy, nutrition, and psychology can be found in the specialized center. Patients with RA are followed-up at least six times a year to ensure retention in care model and adherence to the treatment. Using this approach, a cohort of RA patients were followed-up during 2018. Demographical and clinical data were extracted retrospectively from the electronic health records. The association between clinical and demographic variables was studied by means of the Chi-square test and analyzed using the McNemar test for changes in disease activity levels. Results: 2,239 RA patients were followed-up, 82.76% were women. The average disease duration was eight years (IQR: 3-18 years). During the follow-up year, 91.62% of patients with conventional therapy had at least six rheumatology appointments, while for those who received biological therapy 81.51%. For the ones treated with biological therapy, there were no significant changes for each level of disease activity during study period; nevertheless, in patients who received conventional therapy there was a significant increase of patients in remission (p-value = 0.004).Conclusions: The results evidence that the model used guarantees high levels of adherence for medical appointments and keeps remission levels for RA under control.

Pedro Santos-Moreno,1 Nelson J Alvis-Zakzuk,2 Laura Villarreal-Peralta,1 Maria Carrasquilla-Sotomayor,3 Fernando de la Hoz-Restrepo,4 Nelson Alvis-Guzmán5,6 1Rheumatology, Biomab IPS, Bogotá, Colombia; 2Department of Health Sciences, Universidad de la Costa -CUC, Barranquilla, Colombia; 3Department of Health Technology Assessment, ALZAK Foundation, Cartagena, Colombia; 4Department of Public Health, Universidad Nacional de Colombia, Bogotá, DC, Colombia; 5Department of Health Sciences, Universidad de la Costa – CUC, Barranquilla, Colombia; 6Department of Economic Sciences, Universidad de Cartagena, Cartagena, ColombiaCorrespondence: Pedro Santos-MorenoRheumatology, Biomab IPS, Calle 48 # 13-86, Bogotá, ColombiaEmail pedrosantosmoreno@hotmail.comBackground: Health systems need to optimize the use of resources, especially in high-cost diseases as rheumatoid arthritis (RA). We aimed to evaluate the efficiency of using centers of excellence (CoE) as a strategy for improving RA treatment in Colombia.Methods: A cost description analysis was carried out using the standard costing technique. We estimated the costs of medical consultations, laboratories, images, and medications for RA. Categories of care standards stratified by severity were defined using the disease activity score in 28 joints (DAS28). We evaluated the impact, in terms of costs (US dollars), for providing RA clinical care for a previously described cohort using the CoE approach. Statistical analyses were performed in Microsoft Excel®, and R.Results: Expenditure on therapeutic drugs increases as the severity of RA increases. Drugs represent 53.6% of the total cost for the low disease activity (LDA) stage, 75.2% for moderate disease activity (MDA), 88.5% for severe disease activity (SDA) and 97% for SDA with biologic treatment (SDA+Biologic). Treating 968 patients would cost US$612,639 (US$487,978– 1,220,160) at baseline, per year. After a year of follow-up at the CoE, treating the same patients would cost US$388,765 (US$321,710– 708,476), which implies potential cost-savings of up to US$223,874 per year.Conclusion: The strategy of providing clinical care for RA through CoE can save US$231.3 per patient-per year. The results of our study show that CoE could greatly impact the public policies dealing with treatment of RA in Colombia. Applying the CoE model in our country would both improve health outcomes, as well as being more efficient in terms of costs.Keywords: rheumatoid arthritis, treat to target, cost-savings, cost-analysis

Background: Rheumatoid arthritis (RA) is an autoimmune chronic pathology, present in between 0.5% and 1% of adults. This disease is accompanied by comorbidities such as sleep disorders (SD) that occur in between 54% and 70% of the population with RA. The objective of this study was to identify the associated risk factors and the prevalence of sleep disorders in a group of patients with rheumatoid arthritis in a referral center for the management of autoimmune diseases in Bogotá, Colombia.Methods: An analytical cross-sectional study was carried out on a population of patients with Rheumatoid Arthritis (RA) evaluated with the DSM-V. The factors related to sleep disorders and disease activity of were explored. The prevalence of sleep disorders was determined, and a multivariate logistic regression analysis was conducted.Results: the study analyzed a total of 1436 patients, with a median age of 56 years. The prevalence of sleep disorders was 31.1%. There was an association between the presence of sleep disorders and Disease Activity Score 28 (DAS28) (OR: 3.8 CI 95%: 3-5), Health Assessment Questionnaire (HAQ) (OR: 3.2 CI 95%: 2.5-4.1), self-care activities (OR: 0.6 CI 95%: 0.4-0.9), and somatic symptom disorder (OR: 1.8, CI 95%: 1.3-2.6). Conclusions: An association (p-value

Hemophilia is a hereditary disorder that can be life-threatening in individuals who have severe spontaneous bleeding resulting from minor trauma or surgery. Although replacement therapy of the missing exogenous factor has improved patients' quality of life, it has not been possible to establish a long-term treatment. Due to the severity of the disease and the need for repetitive doses throughout the patient's life, replacement therapy has become a high-cost treatment option; therefore, the development of self-sustainable long-term therapies is critical. Hemophilia is a good candidate for gene therapy because it is a monogenic disease that can be counteracted by expression of the missing factor. In this article, we review some of the most relevant advances in gene therapy for this illness.

Hemophilia is a hereditary disorder that can be life-threatening in individuals who have severe spontaneous bleeding resulting from minor trauma or surgery. Although replacement therapy of the missing exogenous factor has improved patients' quality of life, it has not been possible to establish a long-term treatment. Due to the severity of the disease and the need for repetitive doses throughout the patient's life, replacement therapy has become a high-cost treatment option; therefore, the development of self-sustainable long-term therapies is critical. Hemophilia is a good candidate for gene therapy because it is a monogenic disease that can be counteracted by expression of the missing factor. In this article, we review some of the most relevant advances in gene therapy for this illness.

We have read with interest the work of Bozzalla-Cassione et al1 published recently in your journal regarding the implementation of a telemedicine programme for patients with lupus in northern Italy. It is logical to suppose that the risk of patients with rheumatic diseases of having a more severe clinical course if they become infected with the COVID-19 infection is very high; however, although some of the reports show that there seems to be a low incidence of COVID-19 infection in patients with rheumatic disease, collaborative work with large cohorts is needed, which could show us the real incidence of COVID-19 infection in these patients and what happens with the establishment of telemedicine programmes.2–6 We show an experience in a specialised centre in Bogota, Colombia; currently, we have a cohort of 5597 patients with rheumatoid arthritis (RA) in exclusively ambulatory care. On 12 March 2020, in Colombia, the health emergency by COVID-19 was established and a week later the Ministry of Health ordered the outpatient care procedure for the population in isolation. From that moment on, our institution, carrying out the proper logistical and legal processes, proceeded to convert its ambulatory care services into care through telemedicine.

We read with interest the paper of Graef et al recently published in your journal about the situation resulting from the massive use of antimalarials for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2/COVID-19), despite the fact that the evidence is controversial and there are concerns about its possible cardiotoxicity, leaving rheumatic patients who use them in a position of vulnerability due to medication shortages.1 In the past few weeks, several papers have been published about the efficacy and safety of the antimalarials chloroquine (CLQ) and hydroxychloroquine (HCLQ) for the treatment of the different phases of infection by SARS-CoV-2/COVID-19, and the data are controversial. However, it is striking that some studies report high rates of cardiovascular events (CVEs) associated mainly with cardiac arrhythmias.2 . These findings of adverse CVEs reported in the aforementioned studies have unfortunately led to the emergency in this group of patients around fear of chronic use of antimalarials, and many users are abandoning these medications, which implies great clinical risk due to relapses that may appear.3 On the other hand, the massive use of antimalarials for COVID-19 has resulted in medication shortages in some settings with potential consequences to patients users. Antimalarials have been used for several decades for the treatment of malaria and some autoimmune diseases, mainly rheumatoid arthritis (RA) and lupus, with great utility and efficacy, and also great safety at conventional doses (250mg per day of CLQ and 200–400mg per day of HCLQ).

Introduction Following treatment with a bypassing agent, parents or caregivers often face difficulties in determining bleeding episode (BE) resolution in children with hemophilia A or B and inhibitors (CwHABI), potentially contributing to a longer treatment duration in children as compared to adults (Valentino et al, Haemophilia 2012; 18:554-60. Gruppo et al, Haemophilia 2013; 19:524-32). Eptacog beta is a new recombinant activated human factor VII proven to be safe and effective for the treatment and control of BEs in patients with hemophilia A or B with inhibitors (≥12 years of age). The pivotal phase 3 trial (PERSEPT 1; NCT02020369) included subjects from ages 12 to Aims The study objective is to evaluate and compare the clinical response to eptacog beta for BEs in CwHABI at 12 and 24 hours after initial dose of eptacog beta in 3 pediatric age subgroups ( Methods PERSEPT 1 and PERSEPT 2 were prospective, global, open-label trials of eptacog beta using two initial dose regimens (IDRs) of 75 and 225 µg/kg in a randomized, non-blinded, crossover design. Subjects received initial doses of 75 or 225 µg/kg eptacog beta followed by 75 µg/kg dosing at predefined intervals (determined by clinical response) to treat BEs (Figure 1). Treatment success for mild or moderate BEs was defined as obtaining a hemostasis evaluation of "excellent" or "good" with no use of additional eptacog beta, alternative hemostatic agents or blood products, and no increase in pain following the first "excellent" or "good" assessment. Evaluations were provided by the parent/caregiver in conjunction with the study participant when possible, depending upon subject age and verbal capacity. Written informed consent from the participants' parents/legal guardians were obtained at enrollment. Results Thirty subjects were assessed (25 from PERSEPT 2 [13 subjects, 0 to Conclusions Eptacog beta treatment of BEs in this pediatric population yielded remarkable (>95%) treatment success proportions in both IDRs by 24 hours after initial eptacog beta infusion of 75 or 225 µg/kg. Differing age group pharmacokinetics could contribute to the observed increase in treatment efficacy at 12 hours with increasing subject age. In addition, when taken together with the wide CIs associated with treatment success point estimates at 12 hours for the 0 to Figure 1 Figure 1. Disclosures Young: Apcintex, BioMarin, Genentech/Roche, Grifols, Novo Nordisk, Pfizer, Rani, Sanofi Genzyme, Spark, Takeda, and UniQure: Consultancy; Genentech/Roche, Grifols, and Takeda: Research Funding. Pipe: Catalyst Biosciences: Consultancy; CSL Behring: Consultancy; HEMA Biologics: Consultancy; Freeline: Consultancy, Other: Clinical trial investigator; Novo Nordisk: Consultancy; Pfizer: Consultancy; Roche/Genentech: Consultancy, Other; Sangamo Therapeutics: Consultancy; Sanofi: Consultancy, Other; Takeda: Consultancy; Spark Therapeutics: Consultancy; uniQure: Consultancy, Other; Regeneron/ Intellia: Consultancy; Genventiv: Consultancy; Grifols: Consultancy; Biomarin: Consultancy, Other: Clinical trial investigator; Bayer: Consultancy; ASC Therapeutics: Consultancy; Apcintex: Consultancy; Octapharma: Consultancy; Shire: Consultancy. Carcao: Bayer, Bioverativ/Sanofi, CSL Behring, Novo Nordisk, Octapharma, Pfizer, Roche, and Shire/Takeda: Research Funding; Bayer, Bioverativ/Sanofi, CSL Behring, Grifols, LFB, Novo Nordisk, Pfizer, Roche, and Shire/Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees. Castaman: Uniqure: Honoraria; Bayer: Honoraria; Sobi: Honoraria; CSL Behring: Honoraria; Novo Nordisk: Honoraria; Kedrion: Honoraria; LFB: Honoraria; Grifols: Honoraria; Werfen: Honoraria; Biomarin: Honoraria; Sanofi: Honoraria; F Hoffmann-La Roche Ltd: Honoraria. Davis: Genentech, Spark Therapeutics, BioMarin, Bayer: Consultancy; Takeda, Sanofi: Honoraria; Genentech, Sanofi, Novo Nordisk: Membership on an entity's Board of Directors or advisory committees. Ducore: Octapharma: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; HEMA Biologics: Consultancy, Honoraria; Bayer: Consultancy, Honoraria, Speakers Bureau; Shire: Consultancy, Honoraria. Dunn: Sanofi, Takeda, Freeline, BioMarin, ATHN, Novo Nordisk: Research Funding; Genentech, Kedrion, CSL Behring, BioMarin: Consultancy; UniQure, CSL Behring, World Federation of Hemophilia USA: Membership on an entity's Board of Directors or advisory committees; Roche/Genentech: Honoraria. Journeycake: HEMA Biologics: Honoraria; LFB: Honoraria. Khan: Genentech, Octapharma, BioMarin, CSL Behring, HEMA Biologics, Kedrion, and Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees. Mahlangu: Bayer, Biogen, BioMarin, CSL, Novo Nordisk, Sobi, Roche, and UniQure: Research Funding; Amgen, Bayer, Biotest, Biogen, Baxalta, CSL Behring, Catalyst Biosciences, Novo Nordisk, Roche, and Spark: Membership on an entity's Board of Directors or advisory committees; Alnylam, Bayer, Biotest, Biogen, Novo Nordisk, Pfizer, Sobi, Shire, Roche, ISTH, and WFH: Speakers Bureau. Meeks: Sangamo Therapeutics: Consultancy; Spark Therapeutics: Consultancy; National Hemophilia Foundation: Research Funding; Pfizer: Consultancy; Sanofi: Consultancy; CSL Behring: Consultancy; Genentech: Consultancy; Takeda: Consultancy; Hemophilia of Georgia: Research Funding; National Institutes of Health: Research Funding. Négrier: UniQure: Membership on an entity's Board of Directors or advisory committees; CSL Behring: Membership on an entity's Board of Directors or advisory committees; Biomarin: Consultancy, Membership on an entity's Board of Directors or advisory committees; Novo Nordisk: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche-Chugai: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Sanofi-Sobi: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees; Spark: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bayer: Honoraria, Membership on an entity's Board of Directors or advisory committees. Recht: Foundation for Women and Girls with Blood Disorders, Partners in Bleeding Disorders: Speakers Bureau; uniQure: Consultancy; Takeda: Consultancy; Sanofi: Consultancy; Pfizer: Consultancy; Octapharma: Consultancy; Novo Nordisk: Consultancy; Kedrion: Consultancy; Hema Biologics: Consultancy; Genentech: Consultancy; CSL Behring: Consultancy; Catalyst Biosciences: Consultancy; American Thrombosis and Hemostasis Network: Current Employment; Oregon Health & Science University: Current Employment. Chrisentery-Singleton: Biomarin: Speakers Bureau; Spark: Consultancy, Research Funding; Takeda: Consultancy, Speakers Bureau; Kedrion: Consultancy; Octapharma: Consultancy; Pfizer: Consultancy, Research Funding, Speakers Bureau; Sanofi: Consultancy; Hema Biologics: Consultancy; Grifols: Consultancy; CSL Behring: Consultancy, Speakers Bureau; Genentech: Consultancy, Speakers Bureau; Novo Nordisk: Consultancy, Speakers Bureau. Stasyshyn: CSL Behring: Consultancy, Research Funding; Novo Nordisk: Consultancy, Research Funding, Speakers Bureau; Octapharma: Consultancy, Research Funding, Speakers Bureau; Pfizer: Consultancy, Research Funding, Speakers Bureau; Takeda: Consultancy, Research Funding, Speakers Bureau; Grifols: Consultancy, Speakers Bureau; Shire: Consultancy. Wang: Octapharma: Other; Pfizer/Spark: Other: clinical trial investigator; uniQure: Consultancy, Other: Clinical trial investigator; Hema Biologics: Consultancy, Other: Clinical trial investigator; Takeda: Consultancy, Other: Clinical trial investigator; Genentech: Consultancy, Other: Clinical trial investigator; Novo Nordisk: Consultancy, Other: Clinical trial investigator; CSL Behring: Consultancy, Other: Clinical trial investigator; Bioverativ: Consultancy, Other: Clinical trial investigator; Bayer: Consultancy, Other: Clinical trial investigator; BioMarin: Consultancy, Other: Clinical trial investigator. Windyga: Alnylam Pharmaceuticals: Research Funding; Novo Nordisk: Research Funding, Speakers Bureau; Octapharma: Research Funding, Speakers Bureau; Rigel: Research Funding; Roche: Research Funding, Speakers Bureau; Sanofi/Genzyme: Research Funding, Speakers Bureau; Shire/takeda: Research Funding, Speakers Bureau; Sobi: Research Funding, Speakers Bureau; Alexion: Speakers Bureau; CSL Behring: Speakers Bureau; Werfen: Speakers Bureau. Alexander: HEMA Biologics: Consultancy, Ended employment in the past 24 months. Al-Sabbagh: LFB: Current Employment. Bonzo: LFB: Current Employment. Macie: HEMA Biologics: Current Employment. Mitchell: HEMA Biologics: Consultancy, Current Employment. Wilkinson: GLOVAL, LLC: Consultancy. Shapiro: Genentech: Other: Advisory board fees, Research Funding, Speakers Bureau; Glover Blood Therapeutics: Research Funding; Kedrion Biopharma: Research Funding; Daiichi Sankyo: Research Funding; Bioverativ (a Sanofi company): Other: Advisory board fees, Research Funding; Takeda: Research Funding; Novo Nordisk: Other: Advisory board fees, Research Funding, Speakers Bureau; Octapharma: Research Funding; OPKO: Research Funding; Sangamo: Other: Advisory board fees, Research Funding; Prometric BioTherapeutics: Research Funding; Pfizer: Research Funding; Sigilon Therapeutics: Other: Advisory board fees, Research Funding; Novartis: Research Funding; BioMarin: Research Funding; Agios: Research Funding.

Aim: Management of osteoarthritis (OA) is basically symptomatic. Recently, stem cells (SC) have been used in the search for an optimum treatment. We decided to conduct a controlled clinical trial to determine if a single intra-articular injection of in vivo stimulated bone marrow SC could lead to an improvement in pain management and quality of life in patients with knee OA. Method: This was a prospective, open-label, phase I/II clinical trial to assess the safety and efficacy of a single intra-articular injection of autologous stimulated bone marrow stem cells (BM-SC) in patients with knee OA. Individuals of both genders older than 30 years with confirmed diagnosis of OA who signed informed consent were included in two groups: SC group received in vivo BM stimulation with subcutaneous administration of granulocyte colony stimulating factor (G-CSF). SC were obtained by BM aspiration and administered in a single intra-articular injection. The control group received exclusively oral acetaminophen. Visual analogue scale and Western Ontario and McMaster Universities Osteoarthritis Index scores were performed at 1 week, 1 month and 6 months in both groups. This trial was registered in ClinialTrials.gov NCT01485198. Results: A total of 61 patients were included. Socio-demographic characteristics, OA grades and initial scores were similar in both groups. The BM-SC group showed significant improvement in knee pain and quality of life during the 6-month follow-up. Conclusion: The study demonstrates feasibility and supports efficacy of a completely ambulatory procedure in treatment of knee OA. Key words: bone marrow, knee osteoarthritis, stem cells.

Osteoarthritis (OA), also known as osteoarthrosis, is the most prevalent form of joint pathology. It is attributed to diverse causes like joint injury, obesity, aging, and genetic predisposition. The result is the degeneration of the articular cartilage, the subchondral bone, and the entire joint organ. The articular cartilage destruction, typical of OA, is associated with joint space narrowing and periarticular hypertrophic changes. Chronic knee pain significantly affects quality of life (1). People suffering from OA are often confused about the management of their condition. Healthcare professionals must provide support and clear advice on the possible ways to regulate symptoms like pain and decreased physical function, which have an impact on self-efficacy and social engagement.

B-cell precursor acute lymphoblastic leukemia (BCP-ALL) is a hematological malignancy of immature B-cell precursors, affecting children more often than adults. The etiology of BCP-ALL is still unknown, but environmental factors, sex, race or ethnicity, and genomic alterations influence the development of the disease. Tools based on protein detection, such as flow cytometry, mass spectrometry, mass cytometry and reverse phase protein array, represent an opportunity to investigate BCP-ALL pathogenesis and to identify new biomarkers of disease. This review aims to document the recent advancements with respect to applications of proteomic technologies to study mechanisms of leukemogenesis, how this information could be used in the discovery of biological targets, and finally we describe the challenges of application of proteomic tools for the approach of BCP-ALL.

Drosophila l(3)mbt malignant brain tumors present sexual dimorphism., The notable male predominance across many human cancer types remains unexplained. Here, we show that Drosophila l(3)mbt brain tumors are more invasive and develop as malignant neoplasms more often in males than in females. By quantitative proteomics, we have identified a signature of proteins that are differentially expressed between male and female tumor samples. Prominent among them is the conserved chromatin reader PHD finger protein 7 (Phf7). We show that Phf7 depletion reduces sex-dependent differences in gene expression and suppresses the enhanced malignant traits of male tumors. Our results identify potential regulators of sex-linked tumor dimorphism and show that these genes may serve as targets to suppress sex-linked malignant traits.

Background Rheumatoid arthritis (RA) is a chronic, disease that affects more than 1% of global population, it is a long term condition that causes pain and disability. Evidence had shown that most of the patients are moderately disabled, which brings the necessity of a caregiver to become the patients companion due to its chronic disease. The caregiving role can have an impact in the psychological and physical spheres of the caregivers life. Objectives The aim of this study was to explore demographical characteristics and caregiver burden through the Zarit Scale. Methods We conducted a cross sectional study in a meeting where caregivers in a rheumatoid arthritis specialized setting. We collected sociodemographic information, and applied the Zarit caregiver burden interview (ZBI) adapted to Spanish. The ZBI includes 22 questions which has 5 responses from 0 (never) to 4 (nearly always), where scores lower than 47 indicated little to no burden, 47 to 55 low burden and >55 intense burden. We calculated means, and standard deviations for continuous variables and categorical variables were presented as rates. Results We applied a survey to 132 caregivers. Mean age was 52 years SD 19 and 72% were women, 78% of them were taking care of a patient with rheumatoid arthritis, 12% osteoarthrosis 2% lupus, 2% osteoporosis the remaining 6% were caregivers of patients with ankylosing spondylitis, fibromyalgia, Sjogren syndrome. Regarding the time as caregiver 48% of them had been carrying the task for less than a year, 16% between two and three years, 18% for more than three years, and 13% for more than four years 5% of them were temporarily caregivers. In our study 85% of caregivers were a family member while15% was a nurse or a non-related person. Zarit mean score was 38.2913, additionally 35% had a score higher than 41 points. See table 1. Conclusion In our study 93% of our patients reported to have moderate to severe burden; thus, it is important to develop strategies and explore the factors related to burden in caregivers in patient with rheumatoid arthritis. Disclosure of Interests: Diana Buitrago-Garcia: None declared, Laura Villarreal: None declared, Michael Cabrera: None declared, Pedro Santos-Moreno Grant/research support from: Dr Santos has received research grants from Janssen, Abbvie and UCB, Speakers bureau: Dr Santos has received speaker fees from Sanofi, Lilly, Bristol, Pfizer, Abbvie, Janssen and UCB, Fernando Rodriguez: None declared

Background The Patient Activation Measure (PAM) is a 13-item measure that assesses patient knowledge, skill, and confidence for self-management. The measure was developed using Rasch analyses and is an interval level, unidimensional, Guttman-like measure. The current analysis is aimed at reducing the number of items in the measure while maintaining adequate precision(1). A Spanish adaptation of the scale was performed in 2017. Objectives To determine the level of activation, knowledge and skills for self-management in patients with Rheumatoid Arthritis Methods We performed a quantitative, observational, cross-sectional, and questionnaire-based study, convenience sampling was used. Participants were recruited in a specialized RA center, during a patients meeting. We applied the PAM-13 scale validated in Spanish. The scale has a score from 1 to 4 divided in four levels where level 1 represents a disengaged patient and suggests that the doctor is in charge of their health; level 2: the patient becomes aware but struggling; level 3: The patient is taking action and considers himself as a part of the healthcare team, and level 4 represents a patient that maintains behaviors and pushes forward. The maximum score is 52 points. Results 322 patients participated, 23 patients generated incomplete PAM scores (response rate 92%) and were excluded. From total 93% of patients were women. Mean age was 60 years 10; mean PAM-13 Was 19.83 6.16. In our study 68% of patients were in level 2 according to PAM-13 scale which means that they are becoming aware of their knowledge, skills and self-management but are still struggling. See table 1. In average 80% of patients answered each question to be in level 1 or 2, 15% in level 3 and only 5% in level 4. Conclusion This is the first study in our country where the Patient Activation Measure is applied in patients with rheumatoid arthritis. Thus, it might be useful to implement patient activation monitoring, since the level of activation is low in patients with RA. Disclosure of Interests Laura Villarreal: None declared, Fernando Rodriguez: None declared, Pedro Santos-Moreno Grant/research support from: Dr Santos has received research grants from Janssen, Abbvie and UCB, Speakers bureau: Dr Santos has received speaker fees from Sanofi, Lilly, Bristol, Pfizer, Abbvie, Janssen and UCB, Diana Buitrago-Garcia: None declared

Background Rheumatoid arthritis (RA) is an inflammatory, chronic disease of unknown etiology. Usually it leads to deformity and destruction of joints through the erosion of cartilage and bone. Over 90% of patients with RA report to suffer symptoms in hands and joints, swelling, loss of motion, muscle weakness among others. These symptoms affect all aspects in a patients life. Therefore, management of a patient with RA should not only include evaluate outcomes related to the rheumatology specialty, on the contrary, aspects such as physical disability, nutrition, mental health, among others should be taken into account. Centers of excellence in rheumatoid arthritis have proposed a multidisciplinary model of care with an initial diagnosis, treatment prescription and follow-up with a rheumatologist, periodic consultations with a physiatrist, psychologist, physiotherapist, occupational therapy nutrition, and, a patient focused program. With a multidisciplinary model of care the patient is seen as a whole, and the expectation is to achieve the best results in the management of RA. Objectives The aim of this research was to define adherence/attendance to a multidisciplinary model of care for patients with RA that attend to a RA specialized center in Colombia. Methods We implemented the center of excellence model program proposed by REAL-PANLAR group in 2015 (3). In order to define adherence to the multiapproach model the authors performed an informal expert consensus to propose a method to measure adherence to the model. The authors proposed three levels of adherence. We proposed three levels of adherence as follows: High adherence: For rheumatology patients had to attend between 6 and 12 consultations in one year. For physical therapy, physiatry, psychology, occupational therapy and nutrition patients had to attend to 3 or more consultations during one year per each specialty. Moderate adherence: For rheumatology patients had to attend between 3 and 5 consultations in one year. For physical therapy, physiatry, psychology, occupational therapy and nutrition patients had to attend between 2 or 4 consultations during one year per each specialty. Low adherence: For rheumatology patients had to attend between 1 and 2 consultations. For physical therapy, physiatry, psychology, occupational therapy and nutrition patients achieved only 1 consultation or less during one year per each specialty. We performed a descriptive analysis and compared the level of adherence and disease activity. Results During 2018 we reviewed the medical charts of 6851 patients diagnosed with rheumatoid arthritis; 82% were female and 18% were male. Mean age was 59 years 13 years old. Regarding disease activity mean DAS28 was 2.69 0.84. Most of patients that were considered as Moderate or High adherent achieve remission or LDA. See table 1. Levels of Adherence in Patients with RA Conclusion This is an initial approach in order to evaluate patients adherence and attendance to a new implemented multidisciplinary disease management model of attention for patients with RA in Colombia. Our descriptive study demonstrated that patients with moderate or high adherence can achieve better clinical outcomes compared to those who arent adherent to the model. Disclosure of Interests Laura Villarreal: None declared, Fernando Rodriguez: None declared, Michael Cabrera: None declared, Pedro Santos-Moreno Grant/research support from: Dr Santos has received research grants from Janssen, Abbvie and UCB, Speakers bureau: Dr Santos has received speaker fees from Sanofi, Lilly, Bristol, Pfizer, Abbvie, Janssen and UCB

Background:The Covid-19 pandemic has generated restrictions in the mobility of people, affecting the face-to-face care of patients with chronic diseases, including autoimmune. The health emergency has created the need to establish follow-up alternatives, giving rise to telemedicine.Objectives:To evaluate the level of attendance to teleconsultation and the face-to-face usual care in patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) who underwent to a developed innovative telemedicine program after the declaration of quarantine due to the Covid-19 pandemic.Methods:The present cross-sectional descriptive study reports retrospective data collected from patients with RA and SLE from March to June, 2020;. Since the beginning of March 2020 when Covid-19 was declared in Colombia as a health emergency establishing specific standards for outpatient care, our center has made the necessary legal and technical adjustments to develop an innovative telemedicine service to prevent the epidemiological risk. To all contacted patients were offered the option of teleconsultation or face-to-face consultation; a standardized protocol was set with clinimetry measures evaluated in both groups. Continuous variables were described using mean and standard deviation, and categorical variables were described using numbers and percentages. We performed chi-square tests of independence to determine differences between teleconsulting and conventional face-to-face consultation.Results:A total of 5745 RA patients were followed-up, 5292 (92.1%) by teleconsulting and 453 (7.9%) by conventional face-to-face consultation; among the group of SLE patients, a total of 646 were assessed, of which there were 386 (60%) by teleconsultation and 260 (40%) by face-to-face consultation; this highlights an important difference in the level of acceptance of the teleconsultation between patients with RA and SLE, being much lower in patients with SLE (p value< 0.0001). Regarding gender differences, in men, there were 33 (12.7%) SLE and 89 (19.6%) RA face-to-face consultations, while in women there were 227 (87.3%) SLE and 364 (80.4%) RA in a face-to-face consultation. Regarding patients who were attended through telemedicine, 45 (11.7%) SLE and 966 (18.3%) RA were men, while 341 (88.3%) SLE and 4326 (81.7%) RA were women; that means, in the RA cohort, a greater number of men prefer the face-to-face consultation than in the SLE cohort (p value< 0.0185). 10 RA patients were diagnosed with the Covid-19 in teleconsultation; in all cases, close contact with infected relatives was verified as the probable cause.Table 1.Differences by gender in the level of teleconsultation acceptance and face-to-face assistance in patients with SLE and RARA PatientsGenderTeleconsulting (%a)Face-to-face consultation (%a)Male105596691,57%898,43%Female4690432692,23%3647,77%SLE PatientsGenderTeleconsulting (%a)Face-to-face consultation (%a)Male784557,69%3342,31%Female56834160,03%22739,97%a Total percentage of patients by gender. RA: Rheumatoid arthritis; SLE: Systemic lupus erythematosus.Conclusion:Telemedicine may provide a viable option for the follow-up of patients with rheumatological diseases even beyond the pandemic. But unexpectedly, data showed an important difference in the acceptance of teleconsultation between patients with RA and SLE, being much higher in older and/or male patients with RA compared to patients with SLE; however, further studies are needed to support this conclusion.Disclosure of Interests:None declared

Background:Tumour necrosis factor-a (TNFa) inhibitors are one of the most used biological therapy for rheumatoid arthritis (RA) patients without response to conventional disease-modifying antirheumatic drugs (cDMARDs). There is scarce information about biological DMARDs (bDMARDs) effectiveness as monotherapy in real life.Objectives:To assess the effectiveness of Certolizumab pegol in real-life clinical practice in a cohort of patients with RA and previous failure to cDMARDs who received certolizumab as monotherapy, combined with Methotrexate (MTX), combined with leflunomide (LFN), or both MTX and LFN.Methods:A retrospective cohort study was conducted at a specialized center for RA management in Colombia. Patients treated with Certolizumab as monotherapy or in combination with MTX, or LFN, or both MTX plus LFN, (2012 – 2020) were included. The indication of certolizumab was a independent decision based on disease activity. Patients could be taking adjuvant medications for pain and/or corticosteroids. Certolizumab was administered 400 mg SC monthly after three induction doses at weeks 0, 2 y 4, as monotherapy or in combination with MTX (until 25 mg/week), LFN (20 mg/day) or both as a first-line treatment after failure with cDMARDs or as a second-line treatment after failure with one or more bDMARDs. Effectiveness was assessed at three, six, and twelve months according to the change in DAS28. Exploratory comparisons of numeric variable data between groups were done (ANOVA). Chi-square test and Fisher’s exact test were used for categorical variables. Multivariate analyses (logistic regressions) were performed to analyse factors related to the response at 6 and 12 months.Results:Of 181 enrolled patients, 24 received certolizumab as monotherapy, 62 combined with MTX, 47 in combination with LFN and 48 in combination with MTX and LFN. 55.2% of patients were first-line treatment, without significant differences between groups. Mean age of subjects included was 57.87 ± 12.33 with a mean age of around 60 years in patients treated with CERTO+MTX and CERTO+LFN (p=0,014). Women predominated in all groups (84% of the total) (p=0,275). The duration of arthritis on average was 8.27 ± 8.73 years, without significant differences between treatment groups (p=0,871). In terms of disease activity, 78.5% of patients were in moderate or high disease activity, according to DAS28, without significant differences between the groups (p=0,787). Differences in the number of biologicals and corticoid use were observed, patients in the combination groups had used in a higher proportion two or more biological (p=0,046) than in the monotherapy group and had used corticosteroids (p=0,042) more frequently. Overall, there were decreased disease activity, at 3 and 6 months with no significant differences between groups (p=0,08). At 12 months of treatment, there was a higher maintenance in mild activity/remission response in monotherapy group compared to the others (p=0,01). In the multivariate analysis, no differences were observed in the response at 6 and 12 months between the treatment groups. The response at three months was the only variable associated with the 6-month response (OR 5.46; CI 95% 2.08 – 14.32). The response at three months (OR 4.04; CI 95% 1.28-12.69) and positive anti-CCP (OR 3.83; CI 95% 1.11-13.21) were associated with 12-month response.Conclusion:These exploratory results show a clear trend of Certolizumab being effective as monotherapy in patients previously treated with cDMARDs and even after being treated with one bDMARD. Although results are not statistically different, it seems that certolizumab in monotherapy could be as least as effective as combination therapy. Prospective studies with larger sample size and with a structured follow-up are needed to confirm these findings.Disclosure of Interests:Paola Osorio: None declared, Laura Villarreal: None declared, Wilberto Rivero: None declared, Linda Ibata: None declared, Susan Martinez: None declared, Adriana Rojas-Villarraga: None declared, Pedro Santos-Moreno Speakers bureau: has received fees for conferences from: Abbvie, Abbott, Biopas-UCB, Bristol, Janssen, Pfizer, Roche, Sanofi, Consultant of: has received fees for counseling, advisory boards from: Abbvie, Abbott, Biopas-UCB, Bristol, Janssen, Pfizer, Roche, Sanofi, Grant/research support from: has received fees for research grants from: Abbvie, Abbott, Biopas-UCB, Bristol, Janssen, Pfizer, Roche, Sanofi

Objective: Most adipose tissue programming is realized in early life. Also, the postnatal three months, rather than the later phases of infancy, may be more relevant in the development of an adverse cardiometabolic risk profile. The adipokines phenotype, as a predictor of early-life weight gain, has been recently explored in cord blood. To determine whether in addition to leptin levels in cord samples, adiponectin, interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), resistin, plasminogen activator inhibitor-1 (PAI-1), and tumor necrosis factor alpha (TNF-α) levels improve weight gain prediction during the first three months of life. Methods: Adiponectin, IL-6, MCP-1, leptin, resistin, PAI-1, and TNF-α were measured by multiplex immunoassay in a subsample of 86 healthy term newborns. Results: Leptin levels significantly predicted weight gain at 3 months of follow-up (r2=0.09, p=0.006). In the multivariate analysis, including additional adipokines in the model, stepwise or all at once, did not increase the prediction of weight gain after the first three months of life. Conclusion: Adding adiponectin, IL-6, MCP-1, resistin, PAI-1, and TNF-α to the prediction model of weight gain in healthy newborns did not prove to be useful. It is probable that their relative contribution to weight gain is not important. Only leptin was relevant as a predictor of weight gain at the 3-month endpoint.

Background:Several medicines are prescribed for chronic disease management of rheumatoid arthritis (RA) including biologics; however, adherence to long-term therapy remains poor because many causes; the latter results in worsening clinical results.Objectives:To analyze the relationship between adherence to treatment and the achievement of remission or low disease activity in patients with RA treated with three anti-TNF molecules of subcutaneous use.Methods:In patients treated with 3 subcutaneous anti-TNFs, with at least one year of follow-up previously, adherence was measured with Compliance Questionnaire for Rheumatology (CQR19) applied by psychologist; the CQR19 is a 19 item, self-administered questionnaire that was developed with the aim of correctly identify rheumatology patients that were classified as “low” adherers (taking Results:112 patients diagnosed with RA were included, 34.8% (39/112) treated with adalimumab, 38.4% (43/112) etanercept and 26.8% (30/112) golimumab; The results of CQR19 at BL, M6 and M12 were greater than 80%, with no statistically significant differences between the three molecules. The MPR was higher than 80% in the three periods, being very similar between the three molecules, but in M12 period the difference in MPR between adalimumab 86% and golimumab 92.1% was statistically significant (p CQR19MPRBLM6M12BLM6M12ADALIMUMAB89,789,390,198,590,586,1ETANERCEPT87,489,789,797,989,690,9GOLIMUMAB88,287,691,597,196,192,1No statistical differences in adherence between biologics were found depending on sex, type of concomitant conventional treatment for RA or presence of comorbidities.RELATION BETWEEN Rem/LDA AND COMPLIANCE WITH APPOINTMENTSRemLDAMDAHDAADALIMUMAB63%60%53%29%PETANERCEPT66%62%73%--GOLIMUMAB68%73%55%-PConclusion:There seems to be a higher MPR with the monthly golimumab compared to the biweekly adalimumab and weekly etanercept; however, it does not necessarily imply greater effectiveness. Longer term studies are needed to confirm if there is better adherence and clinical results with monthly anti-TNFs than to other dosing regimens. Patients with remission and low disease activity had greater assistance to scheduled consultations with the interdisciplinary group, regardless of the type of molecule used. This study confirms the relation between adherence to medications and care model with clinical results.Disclosure of Interests:Paola Osorio: None declared, Laura Villarreal: None declared, Michael Cabrera: None declared, Omaira Valencia: None declared, Pedro Santos-Moreno Grant/research support from: I have received research grants from Abbvie, Biopas-UCB, Janssen, Novartis, Pfizer., Speakers bureau: I have been a speaker for Abbvie, Biopas-UCB, Janssen, Lilly, Novartis, Pfizer, Roche, Sanofi.