The mRNA levels of TGF-ß Type II receptor splice variants in monocytes are associated with disease activity in patients with rheumatoid arthritis.

OBJECTIVES: In rheumatoid arthritis (RA) patients, TGF-ß exerts a singular effect on lymphocytes, macrophages, and polymorphonuclear leukocytes. Moreover, evidences indicate that TGF-ß1 stimulation affects the expression levels of TGF-ß receptors. Therefore, we analysed in different leukocyte subpopulations, whether the mRNA abundance of TGFBR2 splice variants might be related to RA. METHODS: We isolated different leukocyte subpopulations from peripheral blood from 9 healthy control volunteers and 9 RA patients, matched by gender and age (cohort 1), and 8 additional RA patients (cohort 2). Then we quantified, by RT-qPCR, the mRNA relative abundance of TGFBR2 splice variants (namely TGFBR2A and TGFBR2B) in PMNs, and PBMCs (monocytes and non-monocytes). We first checked whether the TGFBR2-splice variant mRNA profile could be associated with any particular blood cell type both, in healthy control volunteers and in RA patients. In addition, PBMC and PMN mRNA levels were correlated, using Spearman's rank-order correlation test, with clinical and biochemical determinations of RA patients. RESULTS: We have shown that TGFBR2 exhibits an alternative splicing pattern in different subpopulations of human leucocytes from healthy controls, and the lack of it in the same cell type from RA samples. Furthermore, our study yields initial evidence that TGFBR2 mRNA expression levels in monocytes might mirror RA disease activity. CONCLUSIONS: mRNA abundance of TGFBR2 splice variants in monocytes shows changes linked to RA disease activity.

Efficacy, Safety, and Immunogenicity of Biosimilar Etanercept (Enerceptan) Versus Its Original Form in Combination With Methotrexate in Patients With Rheumatoid Arthritis: A Randomized, Multicenter, Evaluator-Blinded, Noninferiority Study.

BACKGROUND: Enerceptan (EtaBS) has been developed as a proposed biosimilar of etanercept. METHODS: This randomized, multicenter, evaluator-blinded, noninferiority study conducted in Argentina included adults with active, moderate, and severe rheumatoid arthritis with inadequate response to methotrexate. Subjects were randomly assigned to 32 weeks treatment with EtaBS (n = 99) or etanercept (n = 51) at a weekly 50-mg dose administered subcutaneously. Patients were categorized according to prior use of biologic disease-modifying antirheumatic drugs and concomitant use of steroids. The primary efficacy endpoint was ACR20 response rate at week 32. Safety, immunogenicity, and steady-state concentration of both drugs were evaluated. The noninferiority margin for ACR20 was estimated at 12%. RESULTS: In the per-protocol population, 85 subjects (92.4%) treated with EtaBS and 44 subjects (93.6%) treated with etanercept achieved ACR20 (difference, -1.2%; 95% confidence interval, -10.1% to 7.6%). Frequent adverse drug reactions occurred in 34.3% and 38% of subjects treated with EtaBS and etanercept, respectively. The most common reaction was upper respiratory tract infection. Six and 3 serious adverse events occurred in 4 and 3 subjects treated with EtaBS and etanercept, respectively. Injection site reactions occurred in 67.7% and 66.0% of subjects treated with EtaBS and etanercept, respectively. Two subjects treated with EtaBS and 1 subject treated with etanercept developed antibodies by week 32. CONCLUSIONS: Efficacy outcomes for EtaBS were noninferior to original etanercept in patients with moderate-to-severe rheumatoid arthritis with inadequate response to methotrexate. Safety and immunogenicity results were comparable between the two. This study is a major step toward improving access to biologics in Latin America.

Adherencia al tratamiento en pacientes con artritis reumatoidea / Adherence to treatment in patients with rheumatoid arthritis

Objetivo: Este estudio se propone evaluar el cumplimiento del tratamiento farmacológico en pacientes con AR e identificar los factores que pueden afectar al mismo. Materiales y métodos: Estudio observacional, analítico, transversal. Se realizaron encuestas a 176 pacientes de la base de datos, seleccionados al azar de un centro privado especializado en Reumatología ubicado en el conurbano sur de la provincia de Buenos Aires (Instituto Médico CER - Quilmes). Entre septiembre de 2015 y julio de 2016 fueron realizadas de manera telefónica por voluntarios no médicos de la Fundación Articular entrenados a tal fin. Se utilizaron los cuestionarios BAM, CQR19 y se indagó la percepción del paciente sobre su grado de adhesión al tratamiento dividiéndolo en dos grupos: cumplimiento total o cumplimiento parcial/nulo. Se recabaron datos sociodemográficos, estado de enfermedad, tratamiento, comorbilidades y hábitos. Se utilizaron las siguientes pruebas estadísticas: ANOVA de un factor para evaluar diferencias en niveles medios de CQR19 y variables cualitativas; prueba de Brown-Forsythe para determinar asociación entre CRQ y diversas variables, correlación no paramétrica Rho de Spearman entre CQR19 y variables cuantitativas y regresión logística para explicar adherencia al tratamiento (CQR19 agrupada). Los datos fueron analizados usando el programa SPSS (versión 19.0). Resultados: El 85,8% eran mujeres y la edad promedio fue de 55,1 años. El 51,1% de los pacientes considera que su salud es buena con relación a la AR y el 40,9% considera que es regular. El tratamiento más frecuente fue MTX oral (79%). La monoterapia fue la modalidad terapéutica más referida (79,5%) y el tiempo medio de tratamiento es de 4,4 años. La actitud de los pacientes hacia los medicamentos mostró acuerdo en los 5 ítems que corresponden a la dimensión necesidad del BAM. El nivel de acuerdo-desacuerdo resultó más heterogéneo en los ítems de la dimensión preocupación. CQR19 mostró alto nivel de acuerdo en la mayor parte de los ítems positivos y alto nivel de desacuerdo en la mayor parte de los ítems negativos. Las únicas variables que se asociaron a mayor CQR fueron la presencia de comorbilidades (Brown-Forsythe=7,960; p=0,005) y medicación concomitante (Brown-Forsythe=7,529; p=0,007). También se encontró asociación significativa entre CRQ19 y tabaquismo (F=0,019; p=0,981). Se observó correlación significativa entre CQR y BAM Específico-Necesidad (Rho=0,379; p <0,001) y entre CQR y BAM Específico-Preocupación (Rho=-0,188; p=0,012). Se observó mayor adherencia cuando el paciente siente la necesidad de cumplir con la medicación (O.R.=1,342; p=0,012) y cuando menos preocupado está por la misma (O.R.=0,870; p=0,047). Detectamos menor cumplimiento del tratamiento en pacientes casados o que viven en pareja (Chi²=7,448; p=0,024) y con mayor nivel educativo (Chi²=6,313; p=0,043). Cuando se evalúa el cumplimiento de la medicación prescrita por indagación directa a los pacientes, el nivel de cumplimiento es más elevado. Conclusión: Se trata de una población con nivel moderado de adherencia. Mayor conciencia de necesidad de medicación y menor nivel de preocupación acerca de la misma generan mayor adherencia. Los pacientes sobreestiman el cumplimiento de la medicación cuando se los interroga de manera directa por lo cual es mandatorio utilizar otro método de evaluación. El mayor conocimiento de la adherencia de los pacientes con AR nos permitirá desarrollar herramientas que mejoren este aspecto a largo plazo.

Objective: This study aims to evaluate the compliance of pharmacological treatment in patients with RA and identify the factors that may affect it. Materials and methods: Observational, analytical and cross-sectional study. Surveys were conducted on 176 randomly selected patients from a private center specialized in Rheumatology located in the southern suburbs of the province of Buenos Aires (CER Medical Institute - Quilmes), between September 2015 and July 2016, by telephone by trained non-medical volunteers of the Articular Foundation. The BAM, CQR19 questionnaires were used and the patient's perception of their degree of adherence to the treatment was investigated, dividing it into two groups: total compliance or partial/no compliance. Sociodemographic data, disease status, treatment, comorbidities and habits were collected. The following statistical tests were used: one-way ANOVA to evaluate differences in mean levels of CQR19 and qualitative variables; Brown-Forsythe test to determine the association between CRQ and various variables, non-parametric Spearman's Rho correlation between CQR19 and quantitative variables and logistic regression to explain adherence to treatment (CQR19 grouped). The data was analyzed using the SPSS program (version 19.0). Results: 85.8% were women and the average age was 55.1 years. 51.1% of patients consider that their health is good in relation to RA and 40.9% consider it to be fair. The most frequent treatment was oral MTX (79%). Monotherapy was the most referred therapeutic modality (79.5%) and the mean treatment time is 4.4 years. The attitude of the patients towards the medicines showed agreement in the 5 items that correspond to the dimension of necessity of the BAM. The level of agreement-disagreement was more heterogeneous in the items of the concern dimension. CQR19 showed a high level of agreement in most of the positive items and a high level of disagreement in most of the negative items. The only variables that were associated with higher CQR were the presence of comorbidities (Brown-Forsythe=7.960, p=0.005) and concomitant medication (Brown-Forsythe=7.529, p=0.007). There was also a significant association between CRQ19 and smoking (F=0.019, p=0.981). Significant correlation was observed between CQR and BAM Specific-Necessity (Rho=0.379, p <0.001) and between CQR and BAM Specific-Concern (Rho=-0.188; p=0.012). Greater adherence was observed when the patient felt the need to comply with the medication (O.R.=1.342, p=0.012) and when least concerned about it (O.R.=0.870, p=0.047). We detected less compliance with treatment in married patients or those living with a partner (Chi²=7.448, p=0.024) and with a higher educational level (Chi²=6.313, p=0.043). When the compliance of the prescribed medication is evaluated by direct inquiry to the patients, the level of compliance is higher. Conclusion: It is a population with a moderate level of adherence. Greater awareness of the need for medication and a lower level of concern about it generate greater adherence. Patients overestimate medication compliance when they are interrogated directly, which is why it is mandatory to use another evaluation method. The greater knowledge of the adherence of patients with RA will allow us to develop tools that improve this aspect in the long term.

Work disability in Argentinian patients with systemic lupus erythematosus is prevalent and it is due to ethnic, socioeconomic and disease-related factors.

OBJECTIVE: To study the prevalence and the associated factors of work disability (WD) in systemic lupus erythematosus (SLE) patients. METHODS: A sample of 419 SLE patients from an observational cross-sectional multicenter study was included. Sociodemographic features, disease characteristics, comorbidities, quality of life, unhealthy behaviors, and work-related factors were measured in a standardized interview. Work disability was defined by patient self-report of not being able to work because of SLE. To identify variables associated with work disability, two different multivariate regression models using a stepwise backward method were performed. RESULTS: Prevalence of WD due to SLE was 24.3%. Eighty-nine percent were female and 51% were Caucasians. Mean disease duration was 8.9 ± 7.2 years, and median System Lupus International Collaborating Clinics/American College of Rheumatology damage index SLICC-SDI was 1.5 (range 0-17). In stepwise multivariate logistic regression, living below the poverty line (odds ratio [OR] = 4.65), less than 12 years of education (OR = 2.84), Mestizo ethnicity (OR = 1.94) and SLICC-SDI (OR = 1.25) were predictors of WD. A second model was performed including patient-derived measures; in this model sedentary lifestyle (OR = 2.69) and lower emotional health domain score of the Lupus Quality of Life (LupusQoL) questionnaire (OR = 1.03) were found to be associated to WD and a higher score in LupusQoL physical health domain (OR = 0.93) was protective. CONCLUSION: The prevalence of WD in Argentinian SLE patients was 24.3%. WD was associated with ethnic (Mestizo), socioeconomic (poverty) and disease-related factors. Patient-related outcomes such us sedentary lifestyle and poor emotional quality of life were also associated with WD.

Percepción de la AR en una población fuera del ámbito sanitario / Perception of RA in a population outside health services

Objetivos: El acceso temprano a la población de pacientes con artritis reumatoidea (AR) a la asistencia especializada es un predictor de buen pronóstico. Sin embargo, la demora en la consulta es una constante; fueron identificados factores tales como los vinculados al paciente, el médico generalista o al sistema de salud. El objeto del estudio fue el de explorar la percepción de la población fuera del ámbito asistencial en un escenario potencial de sintomatología compatible con AR. Material y métodos: Se realizó un muestreo aleatorio de 1073 individuos mayores de 18 años, se realizó en la vía pública de los partidos de Quilmes y Berazategui. La encuesta fue efectuada por voluntarias entrenadas a tal fin las que indagaron acerca de a qué profesional consultaría si tuviera dolor e inflamación de los nudillos y muñecas de ambas manos, si cree padecer estos síntomas y si conoce la diferencia entre artritis y artrosis. Resultados: Frente a la posibilidad de padecer síntomas que remedan AR, la población encuestada eligió a los siguientes especialistas: traumatólogo (61%), clínico (17%), reumatólogo (15%), otros (7%). Un tercio de los encuestados refirió padecer esos síntomas y la mayoría (61%) referían no conocer la diferencia entre artritis y artrosis. Quienes más eligieron al reumatólogo como opción (56%) fueron del sexo femenino de entre 51 y 80 años y que conocían la diferencia entre AR y OA. Conclusiones: La ausencia relativa del reumatólogo en la preferencia de la población encuestada, así como la confusión respecto de la presencia de sintomatología compatible con la enfermedad o de la diferencia entre artritis y artrosis señalan la necesidad de ejecutar campañas de concientización pública dirigidas a la reafirmación de la especialidad frente a la patología articular inflamatoria.

Objectives: Early access to specialized care is a predictor of goodprognosis in patients recently diagnosed rheumatoid arthritis (RA).However, the delay in the consultation is a constant; they wereidentified factors such as those related to the patient, the generalpractitioner or the health system. The purpose of the study wasto explore the perception of the population outside the healthcaresetting in a potential scenario of symptoms compatible with RA.Material and methods: A random sample of 1073 individualsaged 18 and over was conducted. It was held in public matches ofQuilmes and Berazategui. The survey was conducted by volunteerstrained for this purpose which were asked which professional (interms of specialty) would consult if they had pain and swellingof the knuckles and wrists of both hands, and "if you know thedifference between arthritis and osteoarthritis".Results: Facing the possibility of having symptoms that mimic RA,the population surveyed chose the following specialists: orthopedicsurgeons (61%), clinicians (17%), rheumatologists (15%), others(7%). A third of respondents have referred these symptoms and most(61%) reported not knowing the difference between arthritis andosteoarthritis. People who chose rheumatologist an option (56%)were female between 51 and 80 years and knew the differencebetween RA and OA.Conclusions: The relative absence of rheumatologist in thepreference of the surveyed population, as well as confusion aboutthe presence of symptoms compatible with the disease or thedifference between arthritis and osteoarthritis indicate the needto implement public awareness campaigns aimed at reaffirmingspecialty against inflammatory joint disease.

La cama y la mesada: gestión tecnológica de la investigación traslacional

La mayoría de los resultados de la investigación cientifica nunca ve la luz de la realidad en la que habita. Paradojicamente, la brecha entre estos hallazagos y sus implicancias sociales en salud no deja ampliarse frente a cada nuevo descubrimiento.