Effect of DMARDs on differentially expressed genes in synovium of rheumatoid arthritis / 中华风湿病学杂志

Objective:To identify differentially expressed genes (DEGs) associated with the progression of synovitis in RA by using bioinformatics analysis and explore the effects of DMARDs such as methotrexate, tocilizumab and rituximab on the DEGs in RA synovium.Methods:RA expression profile microarray data GSE7307、GSE12021、GSE55457、GSE55235、GSE77298、GSE89408 were acquired from the public gene chip database (GEO), including 113 synovial tissue samples from RA and 70 healthy controls (HC). At the same time, synovial expression microarrays GSE45867, GSE24742 and GSE97165 after DMARDs treatment were obtained. These data included 8 samples treated with methotrexate, 12 treated with tocilizumab, 12 treated with rituximab and 19 treated with combined tDMARDs. R software was used to screen DEGs and Venn plots using gene ontology function enrichment and Kyoto encyclopedia of genes and genomes pathway enrichment analysis. Hub genes were selected by STRING online analysis tool and Cytoscape software.Results:Compared with HC, 797 DEGs were up-regulated and 434 DEGs were down-regulated in the synovial tissue of RA. These DEGs were mainly enriched in T cell activation, immune response-activating cell surface receptor signaling pathway. Using Cytoscape and cytoHubba to obtain 5 sets of DEGs based on the STRING database model, the degree algorithm screened out 10 hub genes: LCK, SYK, PTPRC, HLA-DRA, LYN, NCAPG, TOP2A, JUN, CXCR4, CCNB1. Methotrexate treatment significantly up-regulated 20 DEGs and down-regulated 30 DEGs. Rituximab treatment up-regulated 100 DEGs and down-regulated 55 DEGs. Tocilizumab treatment up-regulated 91 DEGs and down-regulated 317 DEGs. These altered DEGs were enriched in regulating cell adhesion, leukocyte-cell adhesion, leukocyte transfer, and insulin-like growth factor receptor signaling pathways. It was worth noting that after treatment, a total of 306 high-expressing DEGs were down-regulated, and 36 low-expressing DEGs were up-regulated.Conclusion:LCK, insulin-like growth factor receptor signaling pathway, etc. are the responsible molecular mechanisms and key pivot genes for the occurrence and development of RA, and the treatment of DMARDs, which are closely related to the response of RA to the treatment of DMARDs.

Management results of a cohort of rheumatoid arthritis patients in a specialized comprehensive healthcare institution in Colombia / Resultados de gestión en una cohorte de pacientes con artritis reumatoide en una institución de atención integral especializada en Colombia

ABSTRACT Objective: To determine the management results in a cohort of patients with rheumatoid arthritis in a specialized integral healthcare institution for this disease in Colombia. Materials and methods: Descriptive cross-sectional study based on a cohort of rheumatoid arthritis patients according to ACR/EULAR 2010 criteria. The information was analysed based on consolidated data from clinical records and national reports in the period 2015-2018. Administrative records related to medication authorizations and prescriptions were considered. Sociodemographic variables, outcome indicators related to disease activity status and medication use percentage were evaluated. Results: As of June 30th 2018, 698 patients were identified, of which the female sex represented 83.8%, the general average age was 55.47 years, and the highest number of cases were in the 60-64 year age group. Of the patients, 68.3% were between remission and low disease activity. Seventy-three point one percent were managed with conventional disease-modifying antirheumatic drugs and a reduction in the use of biological therapy was recorded from 27.2% in 2016 to 17.8% at the end of the period. Conclusions: This study presents the management results of a comprehensive care model for patients with rheumatoid arthritis in Colombia, which managed to maintain the highest proportion of patients in low activity and remission as they had a longer follow-up time, to decrease the percentage of biological DMARDs use, and establish conventional DMARDs as the main therapeutic alternative.

RESUMEN Objetivo: Conocer los resultados de gestión en una cohorte de pacientes con artritis reumatoide en una institución de atención integral especializada en esta enfermedad en Colombia. Materiales y métodos: Estudio descriptivo de corte transversal, a partir de una cohorte de pacientes de artritis reumatoide, según criterios ACR/EULAR 2010. La información se analizó con base en los datos consolidados de historia clínica y reportes nacionales en el periodo 2015-2018. Se tuvieron en cuenta los registros administrativos relacionados con autorizaciones y prescripciones de medicamentos. Se evaluaron variables sociodemográficas, indicadores de resultado relacionados con el estado de actividad de la enfermedad y porcentaje de uso de medicamentos. Resultados: A 30 de junio de 2018, se identificaron 698 pacientes, de los cuales el 83,8% correspondió a sexo femenino; el promedio general de edad fue de 55,47 años y el grupo de edad de 60 a 64 años concentró el mayor número de casos. El 68,3% se ubicó entre remisión y actividad baja de la enfermedad. El 73,1% se encontró manejado con fármacos antirreumáticos modificadores de enfermedad convencionales y se registró una reducción de uso de terapia biológica desde el 27,2% en 2016 al 17,8% al final del periodo. Conclusiones: Este estudio presenta los resultados de gestión de un modelo de atención integral para pacientes con artritis reumatoide en Colombia, que logró mantener la mayor proporción de pacientes en actividad baja y remisión a medida que estos contaban con mayor tiempo de seguimiento, también logró disminuir el porcentaje de uso de FARME biológicos y establecer los FARME convencionales como la principal alternativa terapéutica.

Perfil clínico e epidemiológico e comorbidades dos pacientes com artrite reumatoide atendidos no centro de especialidades médicas do centro universitário do Pará / Clinical and epidemiological and comorbidities of patients with rheumatoid arthritis assisted at the medical specialties center of Centro Universitário do Pará

Objetivos: Descrever as características clínico e epidemiológicas e a prevalência das comorbidades que acometem os pacientes com artrite reumatóide (AR) atendidos no ambulatório de reumatologia do Centro de Especialidades Médicas do Cesupa (CEMEC). Métodos: Estudo descritivo, observacional e retrospectivo realizado por meio da coleta de dados de prontuários médicos, no período de janeiro a novembro de 2020, de pacientes com artrite reumatoide, atendidos no Centro de Especialidades Médicas do Cesupa no período de 2012 a 2020. Resultados: Foram analisados 122 prontuários. A maioria dos pacientes foi do sexo feminino (88,52%). A raça predominante foi a não branca (90,88%) e a idade média dos participantes foi 54,09 anos (DP± 11,33). A maioria dos pacientes apresentavam fatores reumatoides positivo (56,55%). O tempo médio de doença foi de 9,7 anos (±8,57). As principais comorbidades não infecciosas encontradas foram: hipertensão arterial (40,16%), osteoporose (23,77%), dislipidemia (19,67%), diabetes (12,29%), obesidade (8,19%), depressão (4,09%), neoplasias (2,45%) e osteopenia (1,63%). Os medicamentos utilizados foram metotrexato (59,83%), prednisona (55,73%), leflunomida (36,06%), tocilizumabe (7,37%), anti-TNF (7,37%), anti-inflamatórios não hormonais (6,55%), tofacitinibe (2,45%), abatacepte (2,45%) e rituximabe (0%). Conclusão: As principais comorbidades que atingiram estes pacientes foram a hipertensão, osteoporose e dislipidemia. Assim, verifica-se a necessidade do controle de fatores de risco modificáveis dessas comorbidades assim como prezar pelo uso de doses baixas e pelo menor tempo possível, a fim de, apenas enquanto as drogas modificadoras de doença reumática (DMARDs) não estão fazendo efeito, reduzir a prevalência dessas comorbidades nestes pacientes.

Objectives: To describe the clinical and epidemiological characteristics and the prevalence of the main non ­ infectious comorbidities that affect patients with rheumatoid arthritis treated at the rheumatology outpatient clinic of the Centro de Especialidades Médicas do Cesupa (CEMEC). Methods: This is a descriptive, observational and retrospective study carried out by collecting data from medical records, from January to November 2020, of patients with rheumatoid arthritis, treated a Centro de Especialidades Médicas from 2012 to 2020. Results: In total, 122 medical records were analyzed, most of which corresponded to female patients (88.52%). The predominant race was non-white (90.88%) and the mean age of the participants was 54.09 years, with a standard deviation of 11.33 years. Regarding the rheumatoid factor, most of the sample is positive (56.55%). The mean disease duration was 9.7 years, with a standard deviation of 8.57 years. The main non-infectious comorbidities found were: arterial hypertension (40.16%), osteoporosis (23.77%), dyslipidemia (19.67%), diabetes (12.29%), obesity (8.19%) depression (4,09%), neoplasms (2.45%) and osteopenia (1.63%). The drugs used were methotrexate (59.83%), prednisone (55.73%), leflunomide (36.06%), tocilizumab (7.37%), anti-TNF (7.37%), non-steroidal anti-inflammatories. hormonal agents (6.55%), tofacitinib (2.45%), abatacept (2.45%) and rituximab (0%). Conclusion: The main comorbidities that affected these patients were hypertension, osteoporosis and dyslipidemia; and the most used drugs were prednisone, methotrexate and leflunomide, which are also related to the emergence of these pathologies. Thus, there is a need to encourage the practice of physical activity, as well as to value the use of low doses of corticosteroids, only while disease-modifying anti-rheumatic drugs (DMARDs) are ineffective, in order to reduce the prevalence of these Comorbidities in these patient

Uso de antirreumáticos en covid-19 desde la hidroxicloroquina hasta la anakinra pasando por tocilizumab y baricitinib: Una revisión de la literatura / Use of antirheumatic drugs in covid-19 from hydroxychloroquine to anakinra through tocilizumab and baricitinib: A review of the literature

RESUMEN Actualmente nos encontramos en una pandemia mundial causada por el coronavirus 2019 o COVID-19, presentando diferentes desafíos para el sistema de salud debido a que no se cuenta aún con alguna vacuna ni con un tratamiento que haya demostrado su eficacia en totalidad, siendo el manejo actual preventivo y de soporte. Por lo que, en esta revisión se estudiará a los fármacos antirreumáticos más resaltantes que tengan un probable efecto farmacológico, como son la hidroxicloroquina, el tocilizumab, el anakinra y el baricitinib, frente al COVID-19. Se espera que brinde apoyo para futuros tratamientos e investigaciones sobre la enfermedad.

ABSTRACT We are currently in a global pandemic caused by the coronavirus 2019 or COVID- 19, presenting different challenges for the health system due to the fact that there is still no vaccine or a treatment that has proven its effectiveness in its entirety, being the management current preventive and supportive. Therefore, this review will study the most prominent antirheumatic drugs that have a probable pharmacological effect, such as hydroxychloroquine, tocilizumab, anakinra and baricitinib, against COVID-19. It is expected that they will provide support for future treatments. and research on the disease.

Drug prices in Latin American countries: the case of rheumatoid arthritis Biosimilars

Abstract Background: The objective of this paper is to analyze the prices of biological drugs in the treatment of Rheumatoid Arthritis (RA) in three Latin American countries (Brazil, Colombia and Mexico), as well as in Spain and the United States of America (US), from the point of market entry of biosimilars. Methods: We analyzed products authorized for commercialization in the last 20 years, in Brazil, Colombia, and Mexico, comparing them to the United States of America (USA) and Spain. For this analysis, we sought the prices and registries of drugs marketed between 1999 and October 1, 2019, in the regulatory agencies' databases. The pricing between countries was based on purchasing power parity (PPP). Results: The US authorized the commercialization of 13 distinct biologicals and four biosimilars in the period. Spain and Brazil marketed 14 biopharmaceuticals for RA, ten original, four biosimilars. Colombia and Mexico have authorized three biosimilars in addition to the ten biological ones. For biological drug prices, the US is the most expensive country. Spain's price behavior seems intermediate when compared to the three LA countries. Brazil has the highest LA prices, followed by Mexico and Colombia, which has the lowest prices. Spain has the lowest values in PPP, compared to LA countries, while the US has the highest prices. Conclusions: The economic effort that LA countries make to access these medicines is much higher than the US and Spain. The use of the PPP ensured a better understanding of the actual access to these inputs in the countries analyzed.(AU)

COVID-19 and patients with immune-mediated inflammatory diseases undergoing pharmacological treatments: a rapid living systematic review

ABSTRACT BACKGROUND: Patients with immune-mediated inflammatory diseases (IMID) are at increased risk of infection. OBJECTIVE: To assess whether patients undergoing pharmacological treatment for IMID present higher risk of worse outcomes when diagnosed with COVID-19. DESIGN AND SETTING: Rapid systematic review conducted in the medical school of the Federal University of São Paulo (SP), Brazil. METHODS: We searched CENTRAL, MEDLINE, EMBASE, LILACS, SCOPUS, Web of Science, L·OVE, ClinicalTrials.gov and WHO-ICTRP for studies evaluating patients diagnosed with COVID-19 who were undergoing pharmacological treatment for IMID. Two authors selected studies, extracted data and assessed risk of bias and certainty of evidence, following the Cochrane recommendations. RESULTS: We identified 1,498 references, from which one cohort study was included. This compared patients with and without rheumatic diseases (RD) who all had been diagnosed with COVID-19. Those with RD seemed to have higher chances of hospitalization and mortality, but no statistical difference was detected between the groups: hospitalization: odds ratio (OR) 1.17; 95% confidence interval (CI) 0.6 to 2.29; mortality rate: OR 1.53; 95% CI 0.33 to 7.11 (very low certainty of evidence). Patients with RD were three times more likely to require admission to intensive care units (ICUs), with invasive mechanical ventilation (IMV), than those without RD: OR 3.72; 95% CI 1.35 to 10.26 (for both outcomes; very low certainty of evidence). CONCLUSION: Patients undergoing pharmacological treatment for IMID seem to present higher chances of requiring admission to ICUs, with IMV. Additional high-quality studies are needed to analyze the effects of different treatments for IMID.

Caracterización de pacientes con artritis indiferenciada y evolución a otras enfermedades inflamatorias en una cohorte del noroccidente colombiano: Estudio observacional / Characterization of patients with undifferentiated arthritis and evolution to other inflammatory diseases in a Colombian northwestern cohort: An observational study

RESUMEN Objetivo: La artritis indiferenciada es una artropatía inflamatoria que no cumple con los criterios de enfermedades reumatológicas específicas y cuyos síntomas persisten durante un año. Estos individuos pueden remitir espontáneamente o evolucionar a otra artropatía definida, especialmente artritis reumatoide. El objetivo de este estudio fue describir las características clínicas y de laboratorio, tanto basales como de seguimiento, de pacientes con artritis indiferenciada en un centro de referencia. Materiales y métodos: Se realizó un estudio descriptivo retrospectivo con pacientes con artritis indiferenciada por criterio de reumatólogo. Se analizaron variables sociodemográficas, clínicas y terapéuticas. Las variables cualitativas se expresaron como frecuencias absolutas y relativas, y las cuantitativas con mediana y rango intercuartílico. Resultados: Se incluyeron 66 pacientes; la mediana de edad fue 46,3 años (RIC: 37,5-51,8); diez (15,2 %) sujetos tenían antecedente familiar de artritis reumatoide. Cuarenta (60,6 %) individuos tuvieron compromiso articular en interfalángicas proximales; el principal síntoma fue la rigidez matinal en 29 pacientes (44 %). El compromiso extraarticular más frecuente fue el cutáneo (n=14; 21,2 %). Los antiinflamatorios no esteroideos (n=18; 27,2 %) y los esteroides (n=15; 22,7 %) fueron los tratamientos más frecuentes. De 43 pacientes, 22 (51,2 %) permanecieron con diagnóstico de artritis indiferenciada, 18 (41,9 %) progresaron a otras enfermedades, siendo la más frecuente artritis reumatoide, y en tres (7 %) hubo remisión. Conclusiones: En una cohorte de pacientes con artritis indiferenciada del noroccidente colombiano, luego de 12 meses, la mayoría, persiste con este diagnóstico; fue llamativa la frecuencia importante de antecedente familiar de artritis reumatoide y de baja remisión espontánea.

ABSTRACT Introduction: Undifferentiated arthritis is an inflammatory arthropathy that does not meet the criteria of specific rheumatological diseases and whose symptoms persist for one year. These individuals may spontaneously remit or evolve to another defined arthropathy, especially rheumatoid arthritis. The aim of this study was to describe the clinical and laboratory characteristics, both baseline and follow-up, of patients with undifferentiated arthritis in a reference center. Materials and methods: A retrospective descriptive study was conducted with patients with undifferentiated arthritis defined by rheumatologist criteria. Sociodemographic, clinical and therapeutic variables were analyzed. The qualitative variables were expressed as absolute and relative frequencies and the quantitative variables with median and interquartile range. Results: 66 patients were included; the median age was 46.3 years (IQR: 37.5-51.8); 10 subjects (15.2 %) had a family history of rheumatoid arthritis. Forty individuals (60.6 %) had involvement in proximal interphalangeal joints; the main symptom was morning stiffness in 29 patients (44 %). The most frequent extra-articular involvement was cutaneous (n = 14, 21.2 %). Non-steroidal anti-inflammatory drugs (n=18; 27.2%) and steroids (n=15; 22.7 %) were the most frequent treatments. Of 43 patients, 22 (51.2 %) remained with a diagnosis of undifferentiated arthritis, 18 (41.9 %) progressed to other diseases, the most frequent being rheumatoid arthritis, and in three (7 %) there was disease remission. Conclusions: In a cohort of patients with undifferentiated arthritis from northwestern Colombia, after 12 months, most of them persist with this diagnosis; it was striking the important frequency of a family history of rheumatoid arthritis and a low spontaneous remission.

Epidemiología, uso de recursos y costos de la artritis reumatoidea en Argentina / Epidemiology, resource use and costs of rheumatoid arthritis in Argentina

RESUMEN La presente revisión tiene como objetivo identificar información sobre parámetros epidemiológicos y estimar el costo de la artritis reumatoidea (AR) moderada a severa. Se llevó a cabo una búsqueda de la literatura en las principales bases de datos. Se recurrió a un consenso de expertos locales en reumatología para encontrar los parámetros más realistas, utilizando un método Delphi modificado. Se estimaron los costos médicos directos, utilizando información recopilada en la base de datos de costos unitarios del Instituto de Efectividad Clínica y Sanitaria de Argentina. Los costos indirectos se estimaron a través del enfoque del capital humano. Los costos se expresaron en dólares estadounidenses (USD) a noviembre de 2017. La prevalencia reportada de AR en Argentina fue 0,94% (IC95%: 0,86 a 1,02), con una tasa de incidencia anual de 19 cada 100 000 personas (IC95%: 17 a 20). El costo anual de las drogas modificadoras de la enfermedad fue de USD 33 936,10 por paciente. El costo atribuido a las infecciones serias fue de USD 2474,6. El costo del reemplazo bilateral de rodillas por paciente fue de USD 5276,8, y el del reemplazo total de cadera, de USD 9196,4. El costo por paciente por año de días de hospitalización y los costos indirectos de la AR se acrecentaron al aumentar el puntaje de discapacidad. La revisión reporta información útil acerca de parámetros epidemiológicos y de costos de la AR moderada a severa en la era de los agentes biológicos, con el fin de resultar de utilidad para la conducción de evaluaciones económicas de salud en Argentina.

ABSTRACT This review aims to identify information on epidemiological parameters and estimate the cost of moderate to severe rheumatoid arthritis (RA). A search for related literature was carried out in major databases. A consensus of local rheumatology experts was used to find the most realistic parameters, using a modified Delphi method. Direct medical costs were estimated, using information collected from the cost per unit database of the Instituto de Efectividad Clínica y Sanitaria de Argentina. Indirect costs were estimated using the human resources approach. Costs were expressed in US dollars (USD) as of November 2017. The reported prevalence of RA in Argentina was 0.94% (95%CI: 0.86 to 1.02), with an annual incidence rate of 19 per 100,000 people (95%CI: 17 to 20). The annual cost of disease-modifying drugs was 33,936.10 USD per patient. The cost attributed to serious infections was 2,474.6 USD. The cost of bilateral knee replacement per patient was $5,276.8 USD; and the cost for total hip replacement was $9,196.4. Both, the cost of hospitalization days per patient per year, and the indirect costs of RA increased as the disability score increased. This review reports useful information on epidemiological and cost parameters of moderate to severe RA, in the era of biological agents, in order to be useful for conducting economic evaluations regarding health in Argentina.

Respuesta a medicamentos biológicos en pacientes con artritis reumatoide según nivel de actividad al inicio / Response to biological agents in patients with rheumatoid arthritis according to disease activity state at the beginning of treatmen

Introducción: la Ley Ricarte Soto (LRS) permite a pacientes con artritis reumatoide refractaria acceder a medicamentos biológicos. Sin embargo con esta regulación los pacientes inician éstos con actividad alta de enfermedad por un período prolongado, luego de recibir al menos 3 fármacos sintéticos. Previo a la implementación de esta ley no era necesario cumplir estos requisitos. Objetivos:comparar la respuesta a tratamiento lograda con el uso de medicamentos biológicos según niveles de actividad al inicio mediante la comparación de pacientes con biológicos antes y después de la LRS. Métodos: tomando datos del Programa de atención de pacientes con artritis reumatoide de la Red de Salud UC-Christus se compraró grupos de pacientes que accedieron a biológicos pre y post implementación de la LRS. Se analizó el cambio en DAS28 y la categorización de actividad de enfermedad según DAS28. Se realizó una regresión lineal evaluando edad, seropositividad y DAS28 pre tratamiento. Resultados: se encontró una diferencia significativa en el cambio de DAS28 a los 6 meses de tratamiento (p=0,02) y en la regresión solo con el DAS28 pre tratamiento (p=0,00). Dentro del grupo de pacientes que requirió cambio de biológico, los pacientes post ley iniciaron la terapia más activos y presentaban mayor persistencia de actividad severa a los 6 meses de tratamiento (11% vs 25%).Conclusiones: si bien el nivel de actividad al inicio no influyó en la respuesta a los 6 meses de tratamiento, si influyó en la persistencia de actividad severa en quienes requirieron cambio de biológico.

Introduction: Chilean regulations (Ley Ricarte Soto (RS) allow patients with refractory rheumatoid arthritis to have access to biological agents, but because of the requirements of the law, they spend a long period with active disease. Objectives: To compare the effective-ness of treatment with biological agents according to baseline disease activity by comparing subjects initiating biologics previous to and after ley RS. Methods: Using data from the rheumatoid arthritis clinic at Red Salud UC-Christus, we compared groups of patients who had access to biological agents before and after the implementation of the RS law. Change in DAS 28 was analyzed as well as disease activity categories according to DAS 28. We performed linear regression evaluating age, seropositivity, and baseline DAS28. Results: We found a significant difference in the DAS28 score delta at six months of treatment (p=0.02). In linear statistically significant association in the treatment response with the pre-treatment DAS28 (p=0.00), but in the group of patients that required more than one biological agent, the post-LRS group had a higher pre-treatment DAS28 and a higher rate of high disease activity (11% vs. 25%) after six months of treatment. Discussion: Although the baseline disease activity level did not influence the final response to treatment, it had an impact on the persistence of severe activity in patients that required more than one biologic agent

Doença de Still do adulto: um desafio diagnóstico / Adult-onset Still's disease: a diagnostic challenge

A doença de Still do adulto é uma rara condição inflamatória, cujo diagnóstico é um desafio, por se tratar de diagnóstico de exclusão, após vasta investigação. Manifesta-se com febre alta diária, amigdalite não supurativa, artrite, rash evanescente, leucocitose e hiperferritinemia. O presente caso demonstra a doença de Still do adulto e sua vasta investigação, motivando a realização de revisão bibliográfica sobre inovações na fisiopatologia, no diagnóstico e no tratamento.

Adult onset Still's disease is a rare inflammatory condition, the diagnosis of which is a challenge, because it is a diagnosis of exclusion, and demands extensive investigation. It manifests with high daily fever, nonsuppurative tonsillitis, arthritis, evanescent rash, leukocytosis, and hyperferritinemia. The present case de­monstrates adult-onset Still's disease and its extensive inves­tigation, motivating literature review on innovations of its pathophysiology, diagnosis, and treatment.

Sequential therapy with etanercept and conventional synthesis disease-modifying anti-rheumatic drugs in treating ankylosing spondylitis patients with hip involvement: an evaluation of therapeutic effect / 第二军医大学学报

Objective To evaluate the efficacy of sequential therapy with tumor necrosis factor inhibitor (TNFi) and conventional synthesis disease-modifying anti-rheumatic drugs (csDMARDs) in delaying imaging progress and maintaining function of the affected hip in ankylosing spondylitis (AS) patients. Methods AS patients with hip pain and limited activity were enrolled in this study. C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) were measured regularly, and ankylosing spondylitis disease activity score based on C-reactive protein (ASDASCRP) was performed to evaluate the disease activity. Etanercept (a TNFi) and csDMARDs were used sequentially according to the disease activity. Before sequential therapy and 3, 6 and 12 months after sequential therapy, the subjective symptoms were assessed by visual analogue scale, the condition was assessed using ASDASCRP and Bath ankylosing spondylitis disease activity index (BASDAI), the body function was assessed using Bath ankylosing spondylitis function index (BASFI), and the imaging changes of hip joint lesions were assessed using Bath ankylosing spondylitis radiology index-hip (BASRI-hip) and minimum joint space width (mJSW). Results A total of 51 patients (38 males [74.5%] and 13 females [25.5%]) aged from 10-56 years were enrolled, and the onset age was 9-40 years. No hip arthroplasty was performed due to limited hip function or further damage of hip joint structure. Based on assessments in ankylosing spondylitis (ASAS) Work Group criteria, 70.59% (36/51), 84.31% (43/51) and 96.08% (49/51) patients met the ASAS20 criteria and 58.82% (30/51), 78.43% (40/51) and 86.27% (44/51) patients met the ASAS40 criteria 3, 6 and 12 months after sequential therapy, respectively. At the follow-up points of 3, 6 and 12 months, the overall trends of CRP level and ESR, patient global assessment score, ASDASCRP, BASDAI score and BASFI score were significantly decreased (all P0.05). Conclusion Sequential therapy with etanercept (a TNFi) and csDMARDs can effectively inhibit inflammation, avoid further damage of hip joint, improve joint function, and keep the hip joint space width in AS patients.

Access to high-cost medications for psoriatic arthritis in the National Health System in Brazil: the long path up to dispensation

Abstract Background: Pharmaceutical Assistance (PA) is a dynamic and multidisciplinary process that aims to supply health systems, programs or services with quality medicines, enabling access and health care, in an efficient and timely manner. The objective of the study was to evaluate the profile of administrative processes for the treatment of PsA, identify the time elapsed in the flow of processes and its associated factors. Methods: A cross-sectional study of medication requests for the treatment of PsA was carried out between November 2014 and December 2016. Linear regression was used to verify the factors associated with time to delivery. Results: A total of 218 cases containing 250 drugs were analyzed. The median time between the medical appointment and the first dispensation was 66 days (interquartile range, 44-90). The State proceedings, which includes requesting the drug until the authorization of treatment, was the stage that most contributed to the total time spent. The factors associated with the longer time to delivery of medications were prescriptions coming from clinics and specialty centers, from dermatologists, non-authorized processes and non-persistent patients in the treatment in 12 months. Conclusion: The median time to receive medicines for the PsA treatment in Belo Horizonte health region after a medical prescription was higher than 2 months. The time between the solicitation of the medicines and the authorization of the treatment in the SUS (State administrative procedure) was the main component of the total time spent.

Time to and factors associated with initiation of biological therapy in patients with rheumatoid arthritis in Colombia / Tiempo y factores asociados con el inicio de terapia biológica con antirreumáticos modificadores de enfermedad en pacientes con Artritis Reumatoide en Colombia

ABSTRACT Aims: To determine the time Colombian patients with rheumatoid arthritis (RA) are treated with non-biological disease-modifying antirheumatic drugs (DMARDs) before changing to biological therapy. Methods: A retrospective cohort study that collected information about the start of antirheumatic treatment in patients of all ages with a diagnosis of RA until the change to biological DMARD therapy. Survival analysis using Kaplan-Meier curves, from 1 January 2007 until 31 December 2013 by SPSS 23.0 for Windows, was made. Results: A total of 3880 patients (75.3% women) with a mean age of 51.3 years started non-biological DMARDs. After 5 years, 234 patients (6.0%) initiated biological DMARD therapy in 17.5 ± 13.9 months. The use of glucocorticoids (OR: 2.49; 95% CI: 1.658-3.732), having any comedication (OR: 1.83; 95%CI: 1.135-2.966) and being treated in the city of Bogota (OR: 2.30; 95%CI: 1.585-3.355) or in the cities of the Colombian Atlantic coast (OR: 2.848; 95%CI: 1.468-5.524) were associated with a higher likelihood of biological DMARD initiation. Whereas the initiation of therapy with methotrexate (OR: 0.04; 95% CI: 0.014-0.108; p < 0.001) or chloroquine (OR: 0.13; 95% CI: 0.092-0.187; p < 0.001) or receiving antihypertensive medication (OR: 0.64; 95% CI: 0.421-0.960; p = 0.031) was associated with a significant reduce in likelihood. Conclusion: After 5 years of non-biological DMARD therapy, 6.0% of people with RA started biological DMARDs. Receiving glucocorticoids, having any comedication, being treated in Bogota City or cities of the Colombian Atlantic coast affected the probability of switching to biological therapy in these patients.

RESUMEN Objetivo: Determinar el tiempo transcurrido desde que pacientes de Colombia con artritis reumatoide (AR) en tratamiento con fármacos antirreumáticos modificadores de enfermedad no biológicos (FAMEs) cambian a terapia con biológicos. Materiales y métodos: Estudio de cohorte retrospectiva que recogió información sobre inicio de tratamiento antirreumático en pacientes de todas las edades con diagnóstico de AR hasta que pasaron a terapia con FAMEs biológicos. Se hizo un análisis de sobrevida, utilizando curvas de Kaplan-Meier, desde el 1 de enero de 2007 hasta el 31 de diciembre de 2013 mediante SPSS 23.0 para Windows. Resultados: Un total de 3880 pacientes iniciaron terapia con FAMEs no biológicos, (75,3% fueron mujeres) con una edad media de 51,3 anos. Tras cinco años de seguimiento, 234 pacientes (6,0%) iniciaron FAMEs biológicos en promedio a los 17,5 ± 13,9 meses. El uso de corticoides (OR: 2,49; IC95%: 1,658-3,732; p<0,001), recibir alguna comedicación (OR: 1,83; IC95%: 1,135-2,966), ser tratado en Bogotá (OR: 2,30; IC95%: 1,585-3,355), en las ciudades de la costa Atlántica (OR: 2,848; IC95%: 1,468-5,524) estuvieron asociados con una mayor probabilidad de inicio de biológicos mientras que el uso de metotrexate (OR: 0,04; IC95%: 0,014-0,108) o cloroquina (OR: 0,13; IC95%: 0,092-0,187) o recibir medicación antihipertensiva (OR: 0,64; IC95%: 0,421-0,960) redujeron la posibilidad. Conclusiones: Después de cinco años de terapia antirreumática convencional, un 6,0% de pacientes con AR inició terapia con FAMEs biológicos. Recibir corticoides, recibir comedicación, ser tratado en Bogotá o la costa Atlántica afectan la probabilidad de cambiar a terapia biológica.

Transaminase Changes in Korean Rheumatoid Arthritis Patients with Chronic Hepatitis C after Biologic Therapy

OBJECTIVE: Coexisting chronic hepatitis C can be problematic when treating rheumatoid arthritis (RA). This study examined the changes in the transaminase and viral load in hepatitis C virus (HCV)-infected RA patients after initiating biologic agents. METHODS: A multicenter retrospective study was conducted at 12 University Hospitals in Korea between November 2014 and November 2015, and 78 RA patients, who met the 2010 American College of Rheumatology and European League Against Rheumatism classification criteria for RA and were concomitantly infected with HCV, were identified. The baseline and longitudinal clinical data, changes in liver function, and viral RNA titers were evaluated. RESULTS: Seventeen (21.8%) patients were treated with biologic agents, including etanercept (n=8), adalimumab (n=8), infliximab (n=2), tocilizumab (n=2), abatacept (n=1), and golimumab (n=1) (median 1.5 patient-years). Four patients experienced marked increases in transaminase during treatment with adalimumab (n=2) and tocilizumab (n=2). Two patients (one using adalimumab, the other using tocilizumab) were treated with anti-viral agents and showed dramatic improvement in both the viral RNA and transaminase. One patient discontinued adalimumab due to the repeated elevated transaminase levels along with a twofold increase in the viral RNA titer, and the transaminase level subsequently normalized. No case of overt viral reactivation was identified. CONCLUSION: The data support that changes in transaminase and/or viral load associated with biologic agents in HCV-infected RA patients are possible. Therefore, the liver function and viral RNA titer should be followed regularly during biologic therapy.

Comparative efficacy of biological agents in methotrexate-refractory rheumatoid arthritis patients: a Bayesian mixed treatment comparison

BACKGROUND/AIMS: Biological agents (biologics) targeting proinflammatory signaling have emerged as an important treatment option in rheumatoid arthritis (RA). Despite the clinical effectiveness of biologics for patients with RA who do not respond to ‘traditional’ disease-modifying anti-rheumatic drugs (DMARDs), there are concerns regarding their cost and long-term safety. In this study, we aimed to compare the efficacy of various biologics and traditional DMARDs in RA patients refractory to methotrexate (MTX). METHODS: Four DMARDs (hydroxychloroquine, sulfasalazine, MTX, leflunomide) and five anti-tumor necrosis factor drugs (adalimumab, etanercept, golimumab, infliximab, and certolizumab) were selected. A systematic search of published studies was performed from inception through July 2013. Randomized trials of adults with MTX-refractory RA comparing two or more of the selected medications were included. Among 7,938 titles identified, in total, 16 head-to-head trials were selected. Two reviewers independently abstracted the study data and assessed methodological quality using the Cochrane Risk of Bias. Comparative efficacy was analyzed using a Bayesian mixed treatment comparison (MTC). RESULTS: In total, 9, 4, and 11 studies were included for the outcome measures of the Health Assessment Questionnaire (HAQ), Disease Activity Score 28-erythrocyte sedimentation rate (DAS28-ESR) < 2.6 (remission), and American College of Rheumatology (ACR) 70 response, respectively. The treatments with the highest efficacy for each outcome measure were certolizumab combined with MTX, golimumab combined with MTX, and certolizumab combined with MTX, respectively. CONCLUSIONS: Based on MTC analysis, using data from published randomized controlled trials, certolizumab and golimumab combined with MTX showed the highest efficacy in the three outcome measures (HAQ, DAS28-ESR < 2.6, and ACR 70 response) in MTX-refractory RA patients.

Comparative efficacy of biological agents in methotrexate-refractory rheumatoid arthritis patients: a Bayesian mixed treatment comparison

BACKGROUND/AIMS: Biological agents (biologics) targeting proinflammatory signaling have emerged as an important treatment option in rheumatoid arthritis (RA). Despite the clinical effectiveness of biologics for patients with RA who do not respond to ‘traditional’ disease-modifying anti-rheumatic drugs (DMARDs), there are concerns regarding their cost and long-term safety. In this study, we aimed to compare the efficacy of various biologics and traditional DMARDs in RA patients refractory to methotrexate (MTX). METHODS: Four DMARDs (hydroxychloroquine, sulfasalazine, MTX, leflunomide) and five anti-tumor necrosis factor drugs (adalimumab, etanercept, golimumab, infliximab, and certolizumab) were selected. A systematic search of published studies was performed from inception through July 2013. Randomized trials of adults with MTX-refractory RA comparing two or more of the selected medications were included. Among 7,938 titles identified, in total, 16 head-to-head trials were selected. Two reviewers independently abstracted the study data and assessed methodological quality using the Cochrane Risk of Bias. Comparative efficacy was analyzed using a Bayesian mixed treatment comparison (MTC). RESULTS: In total, 9, 4, and 11 studies were included for the outcome measures of the Health Assessment Questionnaire (HAQ), Disease Activity Score 28-erythrocyte sedimentation rate (DAS28-ESR) < 2.6 (remission), and American College of Rheumatology (ACR) 70 response, respectively. The treatments with the highest efficacy for each outcome measure were certolizumab combined with MTX, golimumab combined with MTX, and certolizumab combined with MTX, respectively. CONCLUSIONS: Based on MTC analysis, using data from published randomized controlled trials, certolizumab and golimumab combined with MTX showed the highest efficacy in the three outcome measures (HAQ, DAS28-ESR < 2.6, and ACR 70 response) in MTX-refractory RA patients.

Pharmacologic treatment of rheumatoid arthritis

Rheumatoid arthritis (RA) is a systemic inflammatory disease that affects the joints. This chronic inflammatory condition causes joint destruction and functional disability, and reduces the quality of life of patients. Therefore, the aims of RA treatment are to control a patient's symptoms by decreasing the inflammation, to prevent joint damage, and to maintain the patient's quality of life while minimizing the progress of the disease. In recent years, the early initiation of disease-modifying anti-rheumatic drugs (DMARDs) has been emphasized because a window of opportunity is thought to exist in early RA, when the disease is more responsive to treatment. Recently, the treat-to-target strategy for RA treatment has also been suggested. This strategy involves setting a goal such as remission or low disease state, implementing strict monitoring, and switching the medication regimen promptly as needed. Currently, several DMARDs are available to manage RA. DMARDs form two major classes: synthetic chemical compounds (sDMARDs) and biological agents (bDMARDs), which target specific pro-inflammatory cytokines to prevent inflammation. This review summarizes the effectiveness and safety of the current DMARDs available for RA treatment. Tumor necrosis factor inhibitors, T cell costimulation inhibitor, an anti-B cell agent, and the interleukin 6 receptor-blocking monoclonal antibody are classified as bDMARDs. Tofacitinib, a new sDMARD specifically designed to target janus kinases, is also discussed in this article.

Risk of Herpes Zoster in Patients with Rheumatoid Arthritis Undergoing Biologic Disease-Modifying Therapy

OBJECTIVE: Rheumatoid arthritis (RA) patients suffer from an increased risk of herpes zoster (HZ) partially due to immunosuppressant medications. This study investigated HZ in RA patients treated with biologic disease-modifying antirheumatic drugs (bDMARDs), as compared with conventional DMARDs (cDMARDs). METHODS: This retrospective case series study assembled record information of 277 RA patients who received bDMARDs after failure of at least one cDMARDs at Seoul National University Hospital between August 2003 and February 2015. Following capture of baseline information and identification of HZ episodes, crude HZ incidence rates per 100 patient-years (95% confidence intervals) were calculated. RESULTS: For 718 treatment courses, 277 (38.6%) comprised cDMARDs, 66 (9.2%) infliximab, 175 (24.4%) etanercept, 95 (13.2%) adalimumab, 9 (1.3%) golimumab, 41 (5.7%) rituximab, 31 (4.3%) abatacept, and 24 (3.3%) tocilizumab. There were 37 HZ episodes, 16 during cDMARD treatment courses, and 21 accompanying bDMARDs, two with infliximab, eight with etanercept, five with adalimumab, and three each with rituximab and abatacept. The crude HZ incidence rate per 100 patient-years was 2.4 (1.4∼3.9) for cDMARDs, 2.2 (0.3∼7.9) for infliximab, 1.8 (0.8∼3.6) for etanercept, 3.7 (1.2∼8.4) for adalimumab, 3.9 (0.8∼11.0) for rituximab, and 8.5 (1.8∼23.1) for abatacept. CONCLUSION: We conclude that bDMARDs do not always increase the risk of HZs in RA patients, although HZ rates vary for different bDMARDs.

Effects of avocado/soybean unsaponifiables (ASU) on the treatment of ligature-induced periodontitis in rats

Abstract The purpose of this study is to evaluate the effect of the avocado/soybean unsaponifiables (ASU) on the treatment of induced periodontitis in rats. Periodontitis was induced in 84 rats via ligature placement around the second upper molar, which was removed after 7 days, and scaling and root planning (SRP) was performed at this time. Subsequently, the rats were randomly allocated to four groups with 21 animals each: One SRP group in which saline solution was administered (SS), and three groups in which ASU was administered (0.6 g/kg/day), beginning either 7 days before the induction of periodontitis (SRP/ASU-7), on the day of periodontitis induction (SRP/ASU0), or on the day of treatment (SRP/ASU+7). ASU and SS were administered daily by gavage until the sacrifice of the animals (7, 15, and 30 days after SRP). The % bone in the furcation area was evaluated by histomorphometry and micro-CT. The expression of proteins (TRAP, RANKL, and alkaline phosphatase) and mRNA (IL-1β, TNF-α, IL-6, RANKL, and alkaline phosphatase) were evaluated by immunohistochemistry and qPCR. The SRP/ASU+7 group presented a higher percentage of bone fill in the furcation area and higher expression of alkaline phosphatase than in the SRP group (at 7 and 30 days, respectively). The SRP/ASU0 and SRP/ASU+7 groups presented lower expression levels of RANKL mRNA than the SRP and SRP/ASU-7 groups at 15 days. ASU administration on the day of the SRP treatment of the ligature-induced periodontitis promoted subtle beneficial effects on periodontal repair following the treatment of induced periodontitis within the experimental period of 7 days.

Adherencia al tratamiento en artritis reumatoide: condición indispensable para el control de la enfermedad / Adherence to treatment in rheumatoid arthritis: an essential condition for disease control

Introducción: la artritis reumatoide es la poliartritis inflamatoria más frecuente en el adulto y generalmente lleva a discapacidad funcional, lo cual impacta de manera dramática en la vida diaria de los individuos que la padecen. El tratamiento de esta entidad tiene como objetivo disminuir la actividad inflamatoria y la progresión de la enfermedad, sin embargo, la terapia farmacológica se fundamenta en medicamentos antireumáticos con múltiples efectos adversos y esquemas de dosificación difíciles de comprender, situaciones que pueden asociarse a bajos índices de adherencia. Objetivo: abarcar aspectos generales sobre el tratamiento de la artritis reumatoide y el impacto de la adherencia al mismo. Métodos: se utilizaron artículos de reciente publicación y de relevancia en el tema; las bases de datos usadas fueron PubMed, Scielo y LILACS. Conclusiones: la mayoría de publicaciones analizadas en la literatura evidenciaron un bajo cumplimiento de los esquemas terapéuticos en pacientes con artritis reumatoide, esto se asoció a mayor progresión de la enfermedad y desenlaces clínicos desfavorables; por lo tanto, es fundamental diseñar estrategias, que tengan como propósito incrementar la adherencia a los esquemas de tratamiento recomendados(AU)

Introduction: Rheumatoid arthritis is the most common inflammatory arthritis in adults and in many cases leads to work disability, which has a dramatic impact on the daily lives of the individuals suffering this disease. The main objective of the treatment is to reduce inflammatory activity and progression of the disease, however, the therapy is based on antirheumatic agents with many side effects and dosing schedules difficult to understand; this circumstances may be associated low adhesion to therapy. Objective: To cover general aspects of the treatment of rheumatoid arthritis and the impact of adherence to it. Methods: Recently published and relevant articles were used for this review; the databases used were PubMed, Scielo and LILACS. Conclusions: Most publications available in the literature showed low compliance with treatment regimens in patients with rheumatoid arthritis, this was associated with greater progression of disease and adverse clinical outcomes; therefore, it is essential to design strategies that aim to increase adherence to recommended treatment schemes(AU)