Recomendaciones SER sobre la gestión de riesgo del tratamiento con FAME biológicos o sintéticos dirigidos en pacientes con artritis reumatoide / Recommendations by the Spanish Society of Rheumatology on risk management of biological treatment and JAK inhibitors in patients with rheumatoid arthritis

Objetivo: Elaborar recomendaciones basadas en la evidencia disponible y el consenso de expertos, para la gestión del riesgo del tratamiento biológico y los inhibidores de las JAK en pacientes con artritis reumatoide. Métodos: Se identificaron preguntas clínicas de investigación relevantes para el objetivo del documento. Estas preguntas fueron reformuladas en formato PICO (paciente, intervención, comparación, outcome o desenlace) por un panel de expertos, seleccionados en base a su experiencia en el área. Se realizó una revisión sistemática de la evidencia, graduándose de acuerdo a los criterios GRADE (Grading of Recommendations Assessment, Development, and Evaluation). A continuación, se formularon las recomendaciones específicas. Resultados: Se propusieron por el panel de expertos 6preguntas PICO en base a su relevancia clínica y a la existencia de información reciente referentes al riesgo de aparición de infecciones graves, el riesgo de reactivación del virus de la hepatitisB, el riesgo de reactivación del virus varicela-zoster, el riesgo de aparición de cáncer de piel (melanoma y no melanoma) o hematológico, el riesgo de aparición de enfermedad tromboembólica y el riesgo de progresión del virus del papiloma humano. Se formularon un total de 29 recomendaciones, estructuradas por pregunta, basadas en la evidencia encontrada y el consenso de los expertos. Conclusiones: Se presentan las recomendaciones SER sobre la gestión del riesgo del tratamiento con terapias biológicas e inhibidores de las JAK en la artritis reumatoide.(AU)

Objective: To present recommendations based on the available evidence and the consensus of experts, for risk management of biological treatment and JAK inhibitors in patients with rheumatoid arthritis. Methods: Clinical research questions relevant to the purpose of the document were identified. These questions were reformulated in PICO format (patient, intervention, comparison, outcome) by a panel of experts, selected based on their experience in the area. A systematic review of the evidence was carried out, grading according to the GRADE criteria (Grading of Recommendations Assessment, Development, and Evaluation). Specific recommendations were then formulated. Results: Six PICO questions were proposed by the panel of experts based on their clinical relevance and the existence of recent information regarding the risk of occurrence of serious infections, the risk of reactivation of the hepatitisB virus, the risk of reactivation of the virus varicella-zoster, the risk of appearance of skin (melanoma and non-melanoma) or hematological cancer, the risk of appearance of thromboembolic disease and the risk of progression of the human papilloma virus. A total of 29 recommendations were formulated, structured by question, based on the evidence found and the consensus of the experts. Conclusions: The SER recommendations on risk management of treatment with biologic therapies and JAK inhibitors in rheumatoid arthritis are presented.(AU)

Stress, Resilience, Burnout and Study Hours in Physical Education Pre-Service Teachers-An Explanatory Model about Gender.

The process of becoming a public teacher in Spain requires a long period of preparation. This long period of preparation has an impact on the psychosocial environment of the candidates. Differences have been observed in the psychosocial area according to gender in pre-service teachers. This research aims to study the relationship between the study hours per day, stress, burnout syndrome and resilience according to gender and to study the differences in the effects according to gender using multigroup equation modeling. A multigroup structural equation analysis has been proposed according to the gender of the participants. Parametric tests were used for the descriptive analysis of the results. The sample consists of 4117 participants, 1363 males and 2754 females. The instruments used to collect the data were a self-made questionnaire, Perceived Stress Questionnaire, Connor-Davidson Resilience Scale and Maslach Burnout Inventory. All the instruments have been validated and adapted to the sample. The data reveal that there are variations in the effects of the variables according to the gender of the participants. In conclusion, it is affirmed that gender is a very important factor in coping with the competitive examination process for state-public-teaching institutions, as well as in avoiding the appearance of disruptive states generated by this preparation process.

Safety and effectiveness of bDMARDs during pregnancy in patients with rheumatic diseases: Real-world data from the BIOBADASER registry.

INTRODUCTION: Inflammatory rheumatic diseases usually affect women of childbearing age treated with biologic drugs. However, there is a lack of literature on the efficacy and toxicity of biologic disease-modifying drugs during pregnancy. The aim of this study was to determine the presence of pregnant patients treated with bDMARDs in a real-world dataset and to examine the impact of pregnancy and lactation on the evolution of rheumatic disease in a registry of Spanish patients. METHOD: This was a multicentre prospective study with a real-world setting. Information was obtained from BIOBADASER registry. Patients included are women who got pregnant until November 2020 from 19 rheumatology units. We conducted proportions, means, and standard deviations (SD) to describe the study population and the use of treatments. T-test and Chi-square test were applied to assess differences between groups. RESULT: Ninety cases of pregnancy were registered (n=68 full-term pregnancies; n=22 spontaneous miscarriages). Most of the cases discontinued bDMARDs during pregnancy (78.9%) but 13 cases continued treatment during pregnancy, mainly using certolizumab pegol. These cases were obtaining better management of rheumatic disease, although the differences were not statistically significant [DAS28-CRP, 2.9 (SD: 1.6) vs. 2.0 (1.2), p=.255; DAS28-ESR, 2.2 (1.0) vs. 1.7 (.5), p=.266]. No serious adverse events were reported during pregnancy and lactation. CONCLUSION: Being pregnant is still an uncommon condition in patients with rheumatic diseases and using bDMARDs. Our results show that rheumatic disease tended to progress better during pregnancy in patients who continued to take bDMARDs.

Recommendations by the Spanish Society of Rheumatology on risk management of biological treatment and JAK inhibitors in patients with rheumatoid arthritis.

OBJECTIVE: To present recommendations based on the available evidence and the consensus of experts, for risk management of biological treatment and JAK inhibitors in patients with rheumatoid arthritis. METHODS: Clinical research questions relevant to the purpose of the document were identified. These questions were reformulated in PICO format (patient, intervention, comparison, outcome or outcome) by a panel of experts, selected based on their experience in the area. A systematic review of the evidence was carried out, grading according to the GRADE criteria (Grading of Recommendations Assessment, Development, and Evaluation). Specific recommendations were then formulated. RESULTS: 6 PICO questions were proposed by the panel of experts based on their clinical relevance and the existence of recent information regarding the risk of occurrence of serious infections, the risk of reactivation of the hepatitis B virus, the risk of reactivation of the virus varicella-zoster, the risk of appearance of skin (melanoma and non-melanoma) or haematological cancer, the risk of appearance of thromboembolic disease and the risk of progression of the human papilloma virus. A total of 28 recommendations were formulated, structured by question, based on the evidence found and the consensus of the experts. CONCLUSIONS: The SER recommendations on risk management of treatment with biologic therapies and JAK inhibitors in rheumatoid arthritis are presented.

Safety and effectiveness of bDMARDs during pregnancy in patients with rheumatic diseases: Real-world data from the BIOBADASER registry / Seguridad y efectividad de los FAME biológicos durante el embarazo en pacientes con enfermedades reumáticas: datos del mundo real procedentes del registro BIOBADASER

Introduction: Inflammatory rheumatic diseases usually affect women of childbearing age treated with biologic drugs. However, there is a lack of literature on the efficacy and toxicity of biologic disease-modifying drugs during pregnancy. The aim of this study was to determine the presence of pregnant patients treated with bDMARDs in a real-world dataset and to examine the impact of pregnancy and lactation on the evolution of rheumatic disease in a registry of Spanish patients.Method: This was a multicentre prospective study with a real-world setting. Information was obtained from BIOBADASER registry. Patients included are women who got pregnant until November 2020 from 19 rheumatology units. We conducted proportions, means, and standard deviations (SD) to describe the study population and the use of treatments. T-test and Chi-square test were applied to assess differences between groups.Result: Ninety cases of pregnancy were registered (n=68 full-term pregnancies; n=22 spontaneous miscarriages). Most of the cases discontinued bDMARDs during pregnancy (78.9%) but 13 cases continued treatment during pregnancy, mainly using certolizumab pegol. These cases were obtaining better management of rheumatic disease, although the differences were not statistically significant [DAS28-CRP, 2.9 (SD: 1.6) vs. 2.0 (1.2), p=.255; DAS28-ESR, 2.2 (1.0) vs. 1.7 (.5), p=.266]. No serious adverse events were reported during pregnancy and lactation.Conclusion: Being pregnant is still an uncommon condition in patients with rheumatic diseases and using bDMARDs. Our results show that rheumatic disease tended to progress better during pregnancy in patients who continued to take bDMARDs.(AU)

Introducción: Las enfermedades reumáticas inflamatorias afectan normalmente a mujeres en edad fértil tratadas con fármacos biológicos. Sin embargo, escasea la literatura sobre la eficacia y la toxicidad de los fármacos modificadores de la enfermedad (FAME) biológicos durante el embarazo. El objetivo de este estudio fue determinar la presencia de pacientes embarazadas tratadas con FAME biológicos en un conjunto de datos del mundo real y examinar el impacto del embarazo y la lactancia en la evolución de la enfermedad reumática en un registro de pacientes españoles.Método: Estudio prospectivo multicéntrico en un entorno del mundo real. La información se obtuvo del registro BIOBADASER. Los pacientes fueron mujeres embarazadas hasta el mes de noviembre del 2020, de 19 unidades de Rreumatología. Obtuvimos proporciones, medias y desviaciones estándar (DE) para describir la población de estudio y el uso de tratamientos. Se realizaron las pruebas t y χ2 para evaluar las diferencias entre grupos.Resultado:Se registraron 90 casos de embarazo (n=68 embarazos a término; n=22 abortos espontáneos). La mayoría de los casos suspendieron el tratamiento con FAME biológicos durante el embarazo (78,9%), pero 13 casos prosiguieron el tratamiento durante el embarazo, utilizando principalmente certolizumab pegol. Dichos casos obtuvieron un mejor manejo de la enfermedad reumática, aunque las diferencias no fueron estadísticamente significativas (DAS28-CRP, 2,9 [DE 1,6] vs. 2 [1,2], p=0,255; DAS28-ESR, 2,2 [1] vs. 1,7 [0,5], p=0,266). No se reportaron episodios adversos graves durante el embarazo y la lactancia.Conclusión: La situación de embarazo sigue siendo infrecuente en las pacientes con enfermedades reumáticas que utilizan FAME biológicos. Nuestros resultados reflejan que la enfermedad reumática tendió a progresar mejor durante el embarazo en las mujeres tratadas con FAME biológicos.(AU)

Relationship between Physical Activity, Mediterranean Diet and Emotional Intelligence in Spanish Primary Education Students.

There is an international social concern about the low levels of physical activity among young people. It is essential to know what factors influence the practice of physical activity in order to design effective proposals for health promotion. The study aims to: (1) classify primary school students according to their levels of out-of-school physical activity, Mediterranean diet, emotional attention, emotional clarity and emotional repair; (2) analyse descriptively and correlationally the adolescents' profiles of out-of-school physical activity, Mediterranean diet and emotional attention, clarity and repair. The study design was cross-sectional and descriptive-correlational. The sample consisted of 293 children aged 10-12 years in Granada (Spain). An ad hoc socio-academic questionnaire, the KIDMED test and the Trait Meta-Mood Scale (TMMS-24) were used for data collection. Four clusters were identified by the Ward's method and participants were classified using the K-means method. Subsequently, cluster classification was validated through the MANOVA test (F (861) = 106.12; p ≤ 0.001; f = 1.95). The strongest correlation was obtained in cluster 1 between emotional clarity and emotional repair (r = 0.56; p ≤ 0.01). In conclusion, the mean values of time spent in out-of-school physical activity, Mediterranean diet, emotional attention, emotional clarity and emotional repair of students are adequate and vary according to sex. There are significant differences among the physical activity levels of all clusters, as well as among the emotional variables of attention, clarity and repair. In addition, the correlations between the variables studied vary in each cluster.

Programas de prevención de lesiones en la clase de Educación Física. Una revisión sistemática / Injury prevention programmes in the physical education classroom. A systematic review

Las lesiones musculoesqueléticas están relacionadas en gran medida con la práctica de actividad físico-deportiva. En el caso de los niños y adolescentes se vinculan al ejercicio que realizan en el transcurso de las clases de Educación Física o las actividades deportivas extraescolares. En esta revisión sistemática, el objetivo de investigación es conocer la tipología lesional existente en el contexto escolar educativo y los programas de prevención vinculados a la descripción de las lesiones que se producen en él y conocer los programas de prevención que se implementan por docentes de Educación Física en el transcurso de sus clases. Se realizó una búsqueda de literatura científica durante los meses de enero y febrero del año 2023 en las bases de datos Web of Science, SCOPUS y PubMed. Como motores de búsqueda se utilizaron las siguientes palabras clave: "injur*", "prevent*”, “program*" y "physical education"; empleándose el operador boleano “and”. Como conclusión destaca la necesidad de continuar investigando y desarrollando programas efectivos de prevención de lesiones en el ámbito escolar y deportivo con el fin de proteger la salud y seguridad de los estudiantes. (AU)

Musculoskeletal injuries are largely related to the practice of physical-sporting activity. In the case of children and adolescents, they are linked to the exercise they carry out during Physical Education classes or extracurricular sports activities. In this systematic review, the aim of the research is to find out about the types of injuries that exist in the educational school context and the prevention programmes linked to the description of the injuries that occur in it and to find out about the prevention programmes that are implemented by Physical Education teachers in the course of their classes. A search of scientific literature was carried out during the months of January and February 2023 in the Web of Science, SCOPUS and PubMed databases. The following keywords were used as search engines: "injur*", "prevent*", "program*" and "physical education", using the Boolean operator "and". In conclusion, it highlights the need to continue researching and developing effective injury prevention programmes in schools and sports in order to protect the health and safety of students. (AU)

Impacto del confinamiento en el desarrollo curricular de Educación Física en Educación primaria y Secundaria / Impact of confinement on the development of the physical education in primary and secondary education

Debido a la pandemia por el COVID-19, el estado de alarma y el confinamiento domiciliario, la docencia pasó a ser virtual en cuestión de unos pocos días y los docentes tuvieron que adaptar todo su trabajo de manera inexorable. Ante esta situación totalmente inédita en la historia de nuestro sistema educativo mediante esta investigación se ha indagado y descrito el impacto del periodo de confinamiento en el currículo escolar de educación física en Educación Primaria (EP) y Educación Secundaria obligatoria (ES). El instrumento utilizado ha sido un cuestionario realizado en Google Forms mediante la técnica Delphi. La muestra está́ compuesta por 100 docentes de las etapas de Educación Primaria y Educación Secundaria en España, en concreto en la comunidad autónoma Andaluza. Entre las principales conclusiones destacamos que el profesorado ha considerado que los objetivos de salud y los de condición física, fueron los objetivos más trabajados del área. Los docentes consideran que no se consiguieron llevar a cabo los tiempos motrices establecidos, ni la programación, pero si se consiguió que el alumnado realizara una tarea semanal con una implicación de aproximadamente una hora. Se concluyo que el impacto en el aprendizaje fue grande pues no se consiguieron trabajar todos los contenidos y las tareas planteadas no eran evaluables. (AU)

Due to the COVID-19 pandemic, the state of alarm and home confinement, teaching became virtual in a matter of a few days and teachers had to adapt all their work inexorably. Faced with this totally unprecedented situation in the history of our educational system, this research has been used to investigate and describe the impact of the period of confinement on the school curriculum of physical education in primary and compulsory secondary education. The instrument used was a questionnaire made in Google Forms using the Delphi technique. The sample consisted of 100 teachers of the Primary Education (PE) and Secondary Education (SE) stages in Spain, specifically in the autonomous community of Andalusia. Among the main conclusions we highlight that the teachers considered that the objectives of health and physical condition were the most worked objectives in the area. The teachers consider that they did not manage to carry out the established motor times, nor the programming, but they did get the students to carry out a weekly task with an involvement of approximately one hour. It was concluded that the impact on learning was great because not all the contents were worked on and the tasks set were not evaluable. (AU)

Effects of COVID-19 vaccination on disease activity in patients with rheumatoid arthritis and psoriatic arthritis on targeted therapy in the COVIDSER study.

OBJECTIVE: To investigate the influence of COVID-19 vaccination on disease activity in rheumatoid arthritis (RA) and psoriatic arthritis (PsA) patients under targeted therapies. PATIENTS AND METHODS: 1765 vaccinated patients COVID-19, 1178 (66.7%) with RA and 587 (33.3%) with PsA from the COVID-19 registry in patients with rheumatic diseases (COVIDSER) project, were included. Demographics, disease characteristics, Disease Activity Score in 28 joints (DAS28) and targeted treatments were collected. DAS28-based flare rates and categorised disease activity distribution prevaccination and post vaccination were analysed by log-linear regression and contingency analyses, respectively. The influence of vaccination on DAS28 variation as a continuous measure was evaluated using a random coefficient model. RESULTS: The distribution of categorised disease activity and flare rates was not significantly modified by vaccination. Log-linear regression showed no significant changes in the rate of flares in the 6-month period after vaccination compared with the same period prior to vaccination in neither patients with RA nor patients with PsA. When DAS28 variations were analysed using random coefficient models, no significant variations in disease activity were detected after vaccination for both groups of patients. However, patients with RA treated with Janus kinase inhibitors (JAK-i) (1) and interleukin-6 inhibitor (IL-6-i) experienced a worsening of disease activity (1.436±0.531, p=0.007, and 1.201±0.550, p=0.029, respectively) in comparison with those treated with tumour necrosis factor inhibitor (TNF-i). Similarly, patients with PsA treated with interleukin-12/23 inhibitor (IL-12/23-i) showed a worsening of disease activity (4.476±1.906, p=0.019) compared with those treated with TNF-i. CONCLUSION: COVID-19 vaccination was not associated with increased rate of flares in patients with RA and PsA. However, a potential increase in disease activity in patients with RA treated with JAK-i and IL-6-i and in patients with PsA treated with IL-12/23-i warrants further investigation.

High-sensitivity cardiac troponin I is a biomarker for increased arterial stiffness in systemic lupus erythematous women with normal kidney function.

Cardiovascular disease (CVD) is a main cause of death in patients with systemic lupus erythematous (SLE). Algorithms for cardiovascular risk stratification in general population underestimate the risk for CVD in SLE. Our study aimed to determine whether serum high-sensitivity cardiac troponin I (hs-cTnI) might help to identify SLE patients with subclinical atherosclerosis. Arterial stiffness was assessed measuring the carotid-femoral pulse wave velocity (PWV) in 68 SLE women with a normal or almost normal kidney function and in 71 controls of similar characteristics. None of the participants had a history of an overt CVD. Serum hs-cTnI level was measured using the chemiluminescence method. Factors associated with an increased PWV (iPWV) were identified and multivariate analysis was performed. When detectable, patients tended to have had higher hs-cTnI levels than controls [2.9 (2.3-4.0) vs 2.4 (2.2-4.1); p = 0.098] and were more likely to have detectable hs-cTnI [50% vs 28%, odds ratio (OR) 7.0; 95% confidence interval (CI) 0.008-0.013]. Also, patients with iPWV were more likely to have detectable hs-cTnI than those with normal PWV (OR 6.4; 95% CI 0.019-0.026). In the multivariate analysis, the age at SLE diagnosis (OR 1.24; 95% CI 1.04-1.48), systolic blood pressure (OR 1.28; 95% CI 1.10-1.48) and detectable hs-cTnI level (OR 2.04; 95% CI 1.18-3.50) were independently associated with an iPWV. The negative predictive value of having an iPWV with undetectable hs-cTnI levels was 88%. Hs-cTnI may be a useful biomarker for the identification of SLE patients with iPWV as a surrogated marker of subclinical atherosclerosis. Specifically targeted prospective studies are needed to confirm this hypothesis.

Physical Activity Time, Alcohol Consumption, Mediterranean Diet, and Anxiety in Education Science Students.

Student lifestyles change during university. This research aimed to classify university students according to their levels of physical activity, alcohol consumption, adherence to the Mediterranean diet, and anxiety and studied the relationships between the variables using a multigroup equation model according to gender. The sample was composed of 549 participants (M = 23.06; S.D. = 6.22), of whom 409 were women and 140 were men. Validated and adapted instruments such as the Beck Anxiety Inventory, the PREDIMED Questionnaire, and the Alcohol Use Disorder Identification Test were used. The data revealed four clusters through Ward's method and the k-means method. Regarding the exploratory model, differences were found in the effects of the variables according to sex. In conclusion, alcohol consumption was positively associated with the Mediterranean diet, and physical activity was negatively associated with the Mediterranean diet and anxiety.

Sclerostin as a biomarker of cardiovascular risk in women with systemic lupus erythematosus.

Cardiovascular disease is one of the main causes of death in patients with systemic lupus erythematosus (SLE). On the other hand, sclerostin is a reliable and early biomarker of vascular calcification. This study aimed to estimate the association between sclerostin and two markers of cardiovascular risk, carotid atherosclerotic plaque (CP) and carotid-femoral pulse wave velocity (PWV), in women with SLE. The presence of CP (determined by carotid artery ultrasound) and PWV were measured in 68 women with SLE and preserved renal function. None of the participants had a history of cardiovascular disease. Serum levels of sclerostin were determined using the ELISA method. Other factors associated with increased cardiovascular risk were also measured. The association between sclerostin, CP and PWV was assessed using Receiver Operating Characteristic (ROC) curves and multivariate regression models. The area under the ROC curve was 0.785 (95% confidence interval [CI] 0.662-0.871) for CP and 0.834 (95% CI 0.729-0.916) for dichotomized PWV. After adjusting for other cardiovascular risk factors, it was found that a 10-units increase in sclerostin values was associated with a 44% increase in the odds of CP (95% CI 1-105), but no adjusted association was observed between sclerostin and PWV. Predictive models included age (for both outcomes), hypertension, Framingham risk score and C-reactive protein (for PWV), but not sclerostin. Sclerostin is associated with the presence of CP in women with SLE. Further research should confirm its possible role as a biomarker of cardiovascular risk in these patients.

Real-World Effectiveness and Treatment Retention of Secukinumab in Patients with Psoriatic Arthritis and Axial Spondyloarthritis: A Descriptive Observational Analysis of the Spanish BIOBADASER Registry.

Rheumatic diseases are extensively managed with biological disease-modifying antirheumatic drugs (bDMARDs), but a notable proportion of patients withdraw in the long term because of lack of effectiveness, adverse events, or the patient's decision. The present real-world analysis showed the effectiveness, retention, and safety data collected in the Spanish BIOBADASER registry for patients with psoriatic arthritis (PsA) and axial spondyloarthritis (axSpA, including ankylosing spondylitis (AS) and non-radiographic axSpA) treated with secukinumab, a human antibody against interleukin-17A (IL-17A), for more than 12 months. Six hundred and thirty-nine patients were analysed (350, 262, and 27 PsA, AS, and nr-axSpA patients, respectively). The results showed an improvement in the disease activity after 1 year of treatment, in terms of decreases of the mean Disease Activity Score 28 using C-reactive protein (DAS28-CRP), the mean Disease Activity Psoriatic Arthritis (DAPSA) score, swollen joint counts (SJC), and tender joint counts (TJC) in PsA patients and decreases in the mean Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and the mean Ankylosing Spondylitis Disease Activity Score (ASDAS) in axSpA patients. This improvement was maintained or increased after 2 and 3 years of treatment, indicating that secukinumab is effective in both naïve and non-responder patients. Retention rates were higher when secukinumab was used as the first-line biological treatment, although they were also adequate in the second and third lines of treatment. Collected safety data were consistent with previous reports.

Multidisciplinary models for pregnancy care in patients with rheumatic diseases: Clinical experiences and experts opinion.

OBJECTIVES: To describe different models of multidisciplinary pregnancy care for patients with inflammatory and autoimmune rheumatic diseases, and the steps to follow concerning their implementation. METHODS: A qualitative study was conducted including: (1) a comprehensive literature search in PUBMED focused on multidisciplinary care models; (2) structured interviews with seven rheumatologists from multidisciplinary pregnancy clinics for patients with inflammatory and autoimmune rheumatic diseases. Data were collected related to the hospitals, medical departments, populations cared for, and multidisciplinary care models (type, material, and human resources, professional requirements, objectives, referral criteria, agendas, protocols, responsibilities, decision-making, research and educational activities, multidisciplinary clinical sessions, initiation/start, planning, advantages/disadvantages, and barriers/facilitators for implementation); (3) a nominal meeting group in which the results of searches and interviews were analyzed and the recommendations for the implementation of the multidisciplinary care models defined. RESULTS: We analyzed seven models of multidisciplinary care in pregnancy, implemented 3-10 years ago, which can all be summarized by two different subtypes: parallel (patients are assessed the same day in the involved medical services) and preferential (patients are assessed on different days in the involved medical services) circuits. The implementation of a specific model results rather from an adaptation to the hospital's and professionals' circumstances. Correct planning and good harmony among professionals are key points to implementing a model. CONCLUSION: Different multidisciplinary care models have been implemented for patients with inflammatory and autoimmune rheumatic diseases during pregnancy. They pretend to improve care, system efficiency, and collaboration among specialists and should be carefully implemented.

Validation of GWAS-Identified Variants for Anti-TNF Drug Response in Rheumatoid Arthritis: A Meta-Analysis of Two Large Cohorts.

We aimed to validate the association of 28 GWAS-identified genetic variants for response to TNF inhibitors (TNFi) in a discovery cohort of 1361 rheumatoid arthritis (RA) patients monitored in routine care and ascertained through the REPAIR consortium and DANBIO registry. We genotyped selected markers and evaluated their association with response to TNFi after 6 months of treatment according to the change in disease activity score 28 (ΔDAS28). Next, we confirmed the most interesting results through meta-analysis of our data with those from the DREAM cohort that included 706 RA patients treated with TNFi. The meta-analysis of the discovery cohort and DREAM registry including 2067 RA patients revealed an overall association of the LINC02549rs7767069 SNP with a lower improvement in DAS28 that remained significant after correction for multiple testing (per-allele ORMeta=0.83, PMeta=0.000077; PHet=0.61). In addition, we found that each copy of the LRRC55rs717117G allele was significantly associated with lower improvement in DAS28 in rheumatoid factor (RF)-positive patients (per-allele ORMeta=0.67, P=0.00058; PHet=0.06) whereas an opposite but not significant effect was detected in RF-negative subjects (per-allele ORMeta=1.38, P=0.10; PHet=0.45; PInteraction=0.00028). Interestingly, although the identified associations did not survive multiple testing correction, the meta-analysis also showed overall and RF-specific associations for the MAFBrs6071980 and CNTN5rs1813443 SNPs with decreased changes in DAS28 (per-allele ORMeta_rs6071980 = 0.85, P=0.0059; PHet=0.63 and ORMeta_rs1813443_RF+=0.81, P=0.0059; PHet=0.69 and ORMeta_rs1813443_RF-=1.00, P=0.99; PHet=0.12; PInteraction=0.032). Mechanistically, we found that subjects carrying the LINC02549rs7767069T allele had significantly increased numbers of CD45RO+CD45RA+ T cells (P=0.000025) whereas carriers of the LINC02549rs7767069T/T genotype showed significantly increased levels of soluble scavengers CD5 and CD6 in serum (P=0.00037 and P=0.00041). In addition, carriers of the LRRC55rs717117G allele showed decreased production of IL6 after stimulation of PBMCs with B burgdorferi and E coli bacteria (P=0.00046 and P=0.00044), which suggested a reduced IL6-mediated anti-inflammatory effect of this marker to worsen the response to TNFi. In conclusion, this study confirmed the influence of the LINC02549 and LRRC55 loci to determine the response to TNFi in RA patients and suggested a weak effect of the MAFB and CNTN5 loci that need to be further investigated.

A cost-consequence analysis of the preferential use of secukinumab versus adalimumab for the treatment of psoriatic arthritis.

OBJECTIVES: To assess the efficiency of secukinumab compared to adalimumab as first biologic treatment for psoriatic arthritis (PsA) from the Spanish National Health System (SNHS) perspective. METHODS: A cost-consequence analysis of the cost and clinical response of two treatment strategies was conducted over a 2-year time horizon. A hypothetical cohort of 10 patients with PsA initiated treatment with secukinumab 150mg (cohort A) or adalimumab 40mg (cohort B), respectively. Patients achieving clinical response (ACR20/50/70) at week 24 continued the initial treatment, while patients with inadequate response switched to secukinumab 300mg. Pharmacological costs were calculated based on SmPC (notified ex-factory price). The lowest cost of adalimumab biosimilar was considered. Data on clinical response were extracted from the two matching-adjusted indirect comparison (MAIC) published comparing secukinumab vs adalimumab. Results were expressed as the cost difference between the two cohorts (€, 2019) and were calculated for each clinical response criteria (ACR20/50/70) and for each MAIC. Sensitivity analysis assessed the impact of potential discounts on the cost of adalimumab while maintaining the cost of secukinumab unchanged. RESULTS: Depending on the MAIC used, the cost of initiating biologic treatment for PsA with secukinumab 150mg was 18-33% lower than the one estimated for adalimumab 40mg, for ACR20, 18-28% for ACR50, and 16-23% for ACR70 response rate. Sensitivity analysis showed that it would be necessary a discount of 40-60%, 40-65% and 50-75% over the adalimumab cost to compensate for the differences in efficacy observed for ACR20/50/70, respectively, depending on the MAIC used. CONCLUSION: In patients with PsA, secukinumab could be considered a more efficient first-line biologic treatment compared to adalimumab, from the SNHS perspective.

A cost-consequence analysis of the preferential use of secukinumab versus adalimumab for the treatment of psoriatic arthritis / Análisis de las consecuencias en materia de costos del uso preferencial del secukinumab en comparación con el adalimumab para el tratamiento de la artritis psoriásica

Objectives: To assess the efficiency of secukinumab compared to adalimumab as first biologic treatment for psoriatic arthritis (PsA) from the Spanish National Health System (SNHS) perspective. Methods: A cost-consequence analysis of the cost and clinical response of two treatment strategies was conducted over a 2-year time horizon. A hypothetical cohort of 10 patients with PsA initiated treatment with secukinumab 150mg (cohort A) or adalimumab 40mg (cohort B), respectively. Patients achieving clinical response (ACR20/50/70) at week 24 continued the initial treatment, while patients with inadequate response switched to secukinumab 300mg. Pharmacological costs were calculated based on SmPC (notified ex-factory price). The lowest cost of adalimumab biosimilar was considered. Data on clinical response were extracted from the two matching-adjusted indirect comparison (MAIC) published comparing secukinumab vs adalimumab. Results were expressed as the cost difference between the two cohorts (€, 2019) and were calculated for each clinical response criteria (ACR20/50/70) and for each MAIC. Sensitivity analysis assessed the impact of potential discounts on the cost of adalimumab while maintaining the cost of secukinumab unchanged. Results: Depending on the MAIC used, the cost of initiating biologic treatment for PsA with secukinumab 150mg was 18–33% lower than the one estimated for adalimumab 40mg, for ACR20, 18–28% for ACR50, and 16–23% for ACR70 response rate. Sensitivity analysis showed that it would be necessary a discount of 40–60%, 40–65% and 50–75% over the adalimumab cost to compensate for the differences in efficacy observed for ACR20/50/70, respectively, depending on the MAIC used. Conclusion: In patients with PsA, secukinumab could be considered a more efficient first-line biologic treatment compared to adalimumab, from the SNHS perspective.(AU)

Objetivos: Evaluar la eficiencia de secukinumab comparado con adalimumab como primer tratamiento biológico para la artritis psoriásica desde la perspectiva del Sistema Nacional de Salud español. Métodos: Se realizó un análisis de coste-consecuencia considerando el coste y la respuesta clínica a dos estrategias de tratamiento, en un horizonte temporal de 2 años. Una cohorte hipotética de 10 pacientes con artritis psoriásica inició el tratamiento con secukinumab 150mg (cohorte A) o adalimumab 40mg (cohorte B), respectivamente. Los pacientes con respuesta clínica (ACR20/50/70) en la semana 24 continuaron el tratamiento inicial, mientras que los pacientes con respuesta inadecuada recibieron 300mg de secukinumab. Los costes farmacológicos se calcularon en base a la ficha técnica (precio notificado). Se consideró el coste más bajo de adalimumab biosimilar. Los datos de respuesta clínica se extrajeron de los dos estudios publicados de comparación indirecta ajustada entre secukinumab y adalimumab. Se calculó la diferencia de coste entre las dos cohortes (€, 2019) para cada criterio de respuesta (ACR20/50/70) y para cada estudio. El análisis de sensibilidad evaluó los resultados aplicando posibles descuentos sobre el coste de adalimumab, manteniendo constante el coste de secukinumab. Resultados: Dependiendo del estudio utilizado, el coste de iniciar el tratamiento biológico con secukinumab 150mg fue un 18-33% menor que el estimado para adalimumab 40mg, para ACR20, 18-28% para ACR50, y 16-23% para ACR70. El análisis de sensibilidad mostró que sería necesario un descuento del 40-60%, 40-65% y 50-75% sobre el coste del adalimumab para compensar las diferencias de eficacia observadas para ACR20/50/70, respectivamente.Conclusión: En pacientes con artritis psoriásica, la elección de secukinumab como terapia biológica inicial podría considerarse una opción más eficiente comparado con adalimumab desde la perspectiva del Sistema Nacional de Salud español.(AU)

Genetic Polymorphisms of GGH and ABCC2 Are Associated with Methotrexate Intolerance in Patients with Rheumatoid Arthritis.

OBJECTIVE: to identify new single-nucleotide polymorphisms (SNPs) in genes encoding proteins involved in methotrexate (MTX) metabolism and to evaluate the associations of these SNPs with MTX toxicity or intolerance in a southern Spanish cohort of patients with rheumatoid arthritis (RA). METHODS: An observational, retrospective, and multicenter study was conducted at three participating hospitals in southern Spain. The main variable was intolerance to MTX (i.e., bDMARD monotherapy), defined as an interruption of treatment due to adverse events or toxicity. Patients being treated with MTX and bDMARDs (combined treatment) at the time of the study visit were considered "tolerant" of MTX. Ten polymorphisms were selected for sequencing in our patients according to a literature review. Each polymorphism was classified according to three possible genotypes (e.g., two homozygous (AA or GG) and one heterozygous (AG)), and the association of these combinations with MTX intolerance was evaluated. RESULTS: A total of 227 patients were included in the final analysis (107 intolerant of MTX and 120 tolerant). A significant association was observed between MTX intolerance and the GGH-T401C AA/AG genotype (OR 2.13, 95% CI 1.06-4.29) in comparison with the GG genotype. On the other hand, an inverse association was observed between the ABCC2-C24T TT/TC genotype and intolerance to MTX (OR 0.59, 95% CI 0.35-1.00) in comparison with the CC genotype. CONCLUSION: This study provides new data on the association between genetic polymorphisms and MTX intolerance, which may contribute to the development of new biomarkers and personalized medicine in patients with RA.

Tocilizumab in COVID-19: Factors Associated With Mortality Before and After Treatment.

Tocilizumab (TCZ) has been administered in SARS-CoV-2 pneumonia but the factors associated with mortality before and after treatment remain unclear. Cox regression models were used to estimate the predictors of time to death in a cohort of hospitalized patients with COVID-19 receiving TCZ. In addition, the mean differences between discharged and deceased patients in laboratory parameters measured before and 3, 6 and 9 days after TCZ administration were estimated with weighted generalized estimation equations. The variables associated with time to death were immunosuppression (Hazard Ratio-HR 3.15; 95% confidence interval-CI 1.17, 8.51), diabetes mellitus (HR 2.63; 95% CI 1.23-5.64), age (HR 1.05; 95% CI 1.02-1.09), days since diagnosis until TCZ administration (HR 1.05, 95% CI 1.00-1.09), and platelets (HR 0.27; 95% CI: 0.11, 0.69). In the post-TCZ analysis and compared to discharged patients, deceased patients had more lactate dehydrogenase (p = 0.013), troponin I (p = 0.013), C-reactive protein (p = 0.013), neutrophils (p = 0.024), and fewer platelets (p = 0.013) and lymphocytes (p = 0.013) as well as a lower average PaO2/FiO2 ratio. In conclusion, in COVID-19 diagnosed patients receiving TCZ, early treatment decreased the risk of death, while age, some comorbidities and baseline lower platelet counts increased that risk. After TCZ administration, lower platelet levels were again associated with mortality, together with other laboratory parameters.