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

Effect of biological disease-modifying antirheumatic drugs on body composition in patients with rheumatoid arthritis: a systematic review and meta-analysis

Abstract Background: Rheumatoid arthritis (RA) generates an inflammatory profile that predisposes to total and visceral fatty accumulation and reduced fat free mass (FFM). This metabolic disorder contributes to poor functionality, increased cardiovascular risk and higher mortality. This study aimed to address a systematic review with meta-analysis to determine the effect of biological and targeted synthetic disease-modifying antirheumatic drugs (bDMARDs and tsDMARDs) on body composition (BC) of patients with RA. Methods: The search was conducted at the electronic databases PubMed, Cochrane Library, Embase, Lilacs and grey literature. This investigation was carried until July 2021. Outcomes of interest were total weight, body mass index (BMI), fat mass (FM) and FFM. A meta-analysis comparing these outcomes in RA patients under bDMARD treatment versus controls was performed. Results: Out of 137 studies reviewed, 18 were selected: fifteen prospective cohorts, two retrospective cohorts, and one cross-sectional study. The studies comprised 1221 patients, 778 on bDMARD treatment and 443 controls, which included RA patients under conventional synthetic DMARD (csDMARD). No study addressing BC analysis in patients using tsDMARD was found. The mean age and duration of the disease was 56.7 years and 6.77 years, respectively. Ten studies demonstrated a significant increase of total weight in 88.2% of patients and 42.3% for BMI. In studies that analyzed BC by double X-ray absorptiometry (DXA), the increase in total weight and BMI correlated positively to the increase in FFM. The meta-analysis carried out in five studies showed no significant difference of the mean difference for total weight 0.12 kg (95% CI − 5.58, 5.82), BMI 0.08 kg/m2 (95% CI − 1.76, 1.92), FM − 0.08 kg (95% IC − 5.31, 5.14), and FFM − 2.08 kg (95% CI − 7.37, 3.21). Conclusion: This systematic review suggests a possible impact of bDMARDs on BC of RA patients, even though, the meta-analysis carried out in a small part of these studies was not able to confirm significant variation in BC components. Trial registration: PROSPERO code: CRD42020206949.

Clinical application and prospect of novel markers of rheumatoid arthritis / 中华检验医学杂志

Rheumatoid arthritis (RA) is a chronic erosive arthritis. Early diagnosis, standardized treatment and regular monitoring of the disease will effectively mitigate disease progression and reduce the disability rate. Currently, traditional synthetic disease-modifying antirheumatic drugs (DMARDs) are used alone or in combination with new biological DMARDs or targeted synthetic DMARDS in the treatment of RA, resulting in effective remission in some refractory patients. However, the efficacy and toxicities of different treatments varies. With the development of proteomic and epigenetic technologies, some proteins, non-coding RNAs, and anti-drug antibodies (ADA) have been identified as potential markers for early diagnosis, concomitant diagnosis and disease assessment of RA. We summarized and analyzed the application prospects of novel RA diagnosis markers, including serum proteins, cell membrane proteins, non-coding RNAs, and ADA, with the aim of promoting the application of new markers that allow more precise diagnosis and treatment of RA.

Desarrollo de artritis reumatoide refractaria al tratamiento convencional / Development of rheumatoid arthritis refractory to conventional treatment

La artritis reumatoide es una enfermedad inflamatoria crónica sistémica que afecta del 0,4 por ciento de América Latina. Sus manifestaciones consisten en dolor crónico, destrucción articular y muerte prematura, afectando principalmente a mujeres. Mediante el puntaje del Health Assesment Questionnaire, se puede realizar un conteo de articulaciones tumefactas, presencia de nódulos reumatoides, factor reumatoide, velocidad de sedimentación globular, proteína C reactiva y erosiones en radiografía, los cuales estaban asociados con la elección del primer tratamiento con medicamentos antirreumáticos modificadores de la enfermedad (DMARD). El propósito de este estudio es determinar los principales estudios sobre el desarrollo de la artritis reumatoide refractaria al tratamiento convencional. Se realizó la búsqueda de literatura mediante una exploración de artículos en PubMed y SciELO; se consideraron artículos originales y de revisión, publicados en idioma inglés y español, haciendo uso de los descriptores. Se realizó una lectura preliminar de los artículos con el objetivo de seleccionar los que se ajustaban a nuestro propósito. Los documentos que tenían información con los aspectos formales se incluyeron en nuestra revisión, es decir, se seleccionó un total de 24 artículos. Es en este punto la observación clínica ha permitido describir que no todos los pacientes tienen el mismo curso de evolución de la enfermedad, incluso con tratamientos estandarizados a nivel mundial, y al evaluar los desenlaces de la enfermedad se sugiere que debe haber características de cada paciente que hacen que su enfermedad cause más daño en su evolución en comparación con otros pacientes(AU)

Rheumatoid arthritis is a systemic chronic inflammatory disease that affects 0.4 percent to 1 percent of Latin America, manifested by chronic pain, joint destruction and premature death, affecting mainly women. Using the Health Assessment Questionnaire score, a count of swollen joints, presence of rheumatoid nodules, rheumatoid factor, erythrocyte sedimentation rate, C-reactive protein and erosions in radiography, were associated with the choice of the first treatment with disease-modifying antirheumatic drugs (DMARDs). To determine the main studies that ensure efficacy towards the development of rheumatoid arthritis refractory to conventional treatment. The literature search was carried out by means of an exploration of articles in PubMed and SciELO; Original and review articles were considered, published in English and Spanish, making use of the descriptors, a preliminary reading of the articles was carried out with the aim ofSelect those that fit our purpose, the documents that had information with the formal aspects, were included in our review, that is, a rigorous reading, which selected a total of 24 articles. It is at this point that clinical observation has made it possible to describe that not all patients have the same course of evolution of the disease, even with standardized treatments worldwide, and when evaluating the outcomes of the disease it is suggested that there must be characteristics of each patients who cause their disease to cause more damage in their evolution compared to other patients(AU)

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)

Attitudes of patients with a rheumatic disease on drug use in the COVID-19 pandemic

Abstract Background: Anti-rheumatic drugs can increase the predisposition to infection, and patients may be unaware of continuing their treatment during the COVID-19 pandemic. Objective: This study aimed to assess whether patients maintain their treatment for rheumatic conditions during the pandemic period and determine the factors responsible for discontinuation. Methods: Patients were randomly selected from the prospectively collected database of our tertiary referral center. The patients were interviewed by telephone through a standardized closed-ended questionnaire, which is targeting the continuity of the treatment plan and the considerations related to the individual choice. The patients were asked whether they hesitated to visit the hospital for follow-up or intravenous drug administration. Results: A total of 278 patients completed the questionnaire. While 62 of the patients (22.3%) had reduced or interrupted the treatment, only 11 patients (3.9%) stopped the treatment completely. A significant difference was observed between the duration of illness and the discontinuation of treatment. (p = 0.023) There was a significant difference in disease activity between the group that stopped treatment and continued treatment. (p = 0.001) There was no statistically significant difference in other demographic characteristics. One hundred thirty-five patients (48.6%) made the treatment decision by themselves, and 80% continued the treatment. Reasons for stopping the treatment were anxiety (48.4%), not being able to go to the hospital for intravenous treatment (45.1%), and not being able to find the drug (6.5%). Conclusion: Since patients with long-term illnesses were found to be significantly more likely to stop their treatment, this group of patients should be monitored.

Risk factors for losing hepatitis B virus surface antibody in patients with HBV surface antigen negative/surface antibody positive serostatus receiving biologic disease-modifying anti-rheumatic drugs: a nested case-control study

Abstract Background: Hepatitis B virus (HBV) reactivation consequent to immunosuppressive therapy is an increasingly prevalent problem with serious clinical implications. Treatment with biologic agents conduces to the loss of protective antibody to HBV surface antigen (anti-HBs), which significantly increases the risk of HBV reactivation. Hence, we investigated the risk factors for losing anti-HBs in patients with rheumatic diseases and HBV surface antigen negative/anti-HBs positive (HBsAg-/anti-HBs+) serostatus during treatment with biologic disease-modifying anti-rheumatic drugs (DMARDs). Methods: Using a nested case-control design, we prospectively enrolled patients with rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis/psoriasis, or juvenile idiopathic arthritis, who were treated with biologic DMARDs at Changhua Christian Hospital, Taiwan, from January 2013 to June 2019 and had HBsAg-/anti-HBs+ serostatus; the analytic sample excluded all patients with HBsAg+ or anti-HBs- serostatus. Anti-HBs titers were monitored 6-monthly and cases were defined as anti-HBs < 10 mIU/ml during follow-up. Cases were matched one- to-all with controls with anti-HBs ≥ 10 mIU/ml on the same ascertainment date and equivalent durations of biologic DMARDs treatment (control patients could be resampled and could also become cases during follow-up). Between-group characteristics were compared and risk factors for anti-HBs loss were investigated by conditional logistic regression analyses. Results: Among 294 eligible patients, 23 cases were matched with 311 controls. The incidence of anti-HBs loss was ∼ 2.7%/person-year during biologic DMARDs treatment. Besides lower baseline anti-HBs titer (risk ratio 0.93, 95% CI 0.89-0.97), cases were significantly more likely than controls to have diabetes mellitus (risk ratio 4.76, 95% CI 1.48-15.30) and chronic kidney disease (risk ratio 14.00, 95% CI 2.22-88.23) in univariate analysis. Risk factors remaining significantly associated with anti-HBs loss in multivariate analysis were lower baseline anti-HBs titer (adjusted risk ratio 0.93, 95% CI 0.88-0.97) and chronic kidney disease (adjusted risk ratio 45.68, 95% CI 2.39-871.5). Conclusions: Besides lower baseline anti-HBs titer, chronic kidney disease also strongly predicts future anti-HBs negativity in patients with HBsAg-/anti-HBs+ serostatus who receive biologic DMARDs to treat rheumatic diseases. Patients with low anti-HBs titer (≤ 100 mIU/ml) and/or chronic kidney disease should be monitored during biologic DMARDs therapy, to enable timely prophylaxis to preempt potential HBV reactivation.

Intravenous tocilizumab in the management of rheumatoid arthritis: Clinical practice findings from a 6-month international, multicentre, observational study in Central America and the Caribbean / El tocilizumab intravenoso en el tratamiento de la artritis reumatoide: resultados de la práctica clínica de un estudio internacional, multicéntrico y observacional de 6 meses de duración en América Central y el Caribe

ABSTRACT Tocilizumab (TCZ), an 1interieukin-6 receptor-α Inhibitor, is Indicated in patients with moderate to severe rheumatoid arthritis with inadequate response to disease modifying drugs. ACT UP is a multinational project co11ecting information from severa1 post-marketing TCZ studies. Aim: To determine the proportion of patients in the routine clinical care setting receiving intravenous TCZ after 6 months treatment. Identification of TCZ treatment patterns, efficacy, and safety were also recorded. Method: This prospective non-interventional 6-month study, collected real-world information from 169 Central American and Caribbean patients. No interventional procedures or additional visits outside routine clinical care practice were performed. Statistical analysis was essentially descriptive. Results: Adherence rate was 74.0%, with 97% of patients receiving TCZ as first biological therapy line and there were no deviations from the local label. Almost 85% of patients started with combination therapy, and the majority remained under this scheme throughout the study. A significant decrease in disease activity assessments and acute phase reactants values were detected during TCZ treatment. The percentage of patients that achieved improvement according to the different levels of the American College of Rheumatology (ACR) increased during the study, and relevant enhancements in quality of life were also accomplished. Adverse events (AEs) occurred in 35 patients, with metabolic and nutritional disorders being the most common. Serious AEs were reported in 3% of patients, and special interest AEs occurred in 6 patients. Conclusion: Treatment adherence was mainly determined by follow-up and compliance with the administration schedule. Efficacy analysis showed better results than those reported in international literature. The incidence of AEs was also lower than in previously published data.

RESUMEN El tocilizumab (TCZ) está indicado en la artritis reumatoide moderada a severa, principalmente en respuestas inadecuadas a fármacos convencionales. ACT UP es un proyecto multinacional que recopila información relacionada con varios estudios de poscomercialización. Objetivo: Determinar la proporción de pacientes en la atención clínica de rutina que continúan en tratamiento con TCZ intravenoso después de 6 meses. Se llevó a cabo la identificación de patrones de administración, eficacia y seguridad. Método: Este estudio observacional prospectivo recopiló información de la vida real de 169 pacientes de América Central y el Caribe. No se hicieron intervenciones ni visitas adicionales fuera de la práctica clínica habitual. El análisis estadístico fue esencialmente descriptivo. Resultados: La tasa de adherencia al tratamiento fue del 74,0%, el 97% de los pacientes reci bieron TCZ como primera línea biológica y no existieron desviaciones en las indicaciones de administración según el inserto local. Aproximadamente el 85% de los pacientes inició TCZ como terapia combinada, y la mayoría permaneció bajo este esquema. Se evidenció una dis minución en la actividad de la enfermedad y un aumento en el porcentaje de pacientes que lograron respuesta según los diferentes grados del Colegio Americano de Reumatología. En 35 pacientes se presentaron eventos adversos (EA), siendo los relacionados con metabolismo y nutrición los más comunes. Se informaron EA graves en el 3% de los pacientes y de interés especial en 6 casos. Conclusión: El seguimiento de los pacientes y el cumplimiento del programa fueron los prin cipales determinantes en la adherencia. El análisis de eficacia mostró mejores resultados que los reportados previamente y la incidencia de EA fue menor que en otros estudios.

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.

Combination of Methotrexate and Leflunomide for Adult-onset Still's Disease: A Case Report and Literature Review

The treatment of adult-onset Still's disease (AOSD) aims to control systemic inflammation and prevent organ damage. Systemic inflammation can be controlled with corticosteroid (CS) monotherapy in most cases. However, symptoms often flare as CS is tapered, often requiring long-term CS treatment, with its associated risks of infection, cardiovascular disease, and osteoporosis. Disease-modifying antirheumatic drugs (DMARDs) are often used as CS-sparing agents; however, the choice of DMARD has been largely empirical. Methotrexate (MTX) is recommended as the first-line steroid-sparing drug due to its well-known efficacy and safety in rheumatoid arthritis (RA). When MTX treatment is unsuccessful in AOSD, the choice of a second-line drug has not been established. In RA, leflunomide (LEF) has been used as an alternative to or in combination with MTX. To date, there has been no adequate assessment of the combination of LEF and MTX in AOSD. Here, we report a case of refractory chronic AOSD successfully treated with the MTX-LEF combination.

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.

Colombian Association of Rheumatology. Consensus on recommendations to decrease and discontinue biological therapy in patients with rheumatoid arthritis, ankylosing spondylitis, and psoriatic arthritis / Asociación Colombiana de Reumatología. Consenso sobre recomendaciones para disminución y descontinuación de la terapia biológica en pacientes con artritis reumatoide, espondilitis anquilosante y artritis psoriásica

A B S T R A C T Objective: The objective of this study was to establish recommendations for the reduction and discontinuation of biological disease-modifying antirheumatic drugs, with the aim of becoming a guide document for health professionals involved in the management of patients with rheumatoid arthritis, ankylosing spondylitis, and psoriatic arthritis. Materials and methods: The recommendations were established through consensus by a panel of experts in rheumatology, and based on the analysis of available scientific evidence obtained from systematic reviews and the clinical experience of the panellists. Results: A total of 33 rheumatoid arthritis related studies were included, with 6 psoriatic arthritis related, and 9 ankylosing Spondylitis related. The recommendations for the reduction of biological therapies were made by establishing a plan to determine when and how to reduce the biological disease-modifying antirheumatic drugs in patients with these 3 diseases, and in some cases lead to the discontinuation of these treatments. Conclusion: The recommendations established in this document will serve as a guide to improve the efficiency of biological therapy in these diseases, reduce the variability in clinical practice, and establish an adequate risk/benefit ratio.

RESUMEN Objetivo: El objetivo de este estudio fue establecer recomendaciones para la disminución y descontinuación de la terapia biológica con el fin de que se convierta en un documento guía para los profesionales de la salud involucrados en el manejo de pacientes con artritis reumatoide, espondilitis anquilosante y artritis psoriásica. Materiales y métodos: Las recomendaciones fueron establecidas mediante consenso desarrollado a través de un panel de expertos en reumatología, basado en el análisis de la evidencia científica disponible obtenida de revisiones sistemáticas y sobre la experiencia clínica de los panelistas. Resultados: Se incluyeron 33 estudios relacionados con artritis reumatoide, 6 de artritis psoriásica y 9 de espondilitis anquilosante. Las recomendaciones para la disminución de las terapias biológicas se realizaron estableciendo un plan para determinar cuándo y cómo reducir los fármacos biológicos modificadores de enfermedades reumáticas en pacientes con estas 3 enfermedades y en algunos casos conducir a la descontinuación de estos tratamientos. Conclusión: Las recomendaciones establecidas en este documento servirán de guía para mejorar la eficiencia de la terapia biológica en estas enfermedades, reducir la variabilidad en la práctica clínica y establecer de manera adecuada una relación riesgo/beneficio.

Prescribing pattern and adverse drug effects monitoring of anti-rheumatoid drugs in rheumatoid arthritis patients in a tertiary care hospital

Background: Rheumatoid arthritis (RA) is a common disease that causes substantial morbidity in most patients and premature mortality in many. All the drugs used in the treatment of rheumatoid arthritis show significant toxicity and hence it is important to monitor the drugs for adverse drug reaction. This study will estimate the prescribing pattern and bring out the possible adverse drug reactions in patients with rheumatoid arthritis.Methods: This study included 200 patients with rheumatoid arthritis who fulfilled the study criteria were observed for three months. Their prescriptions were collected and analysed. The symptoms of adverse drug reaction were documented through questionnaire. The causality assessment was done by WHO-UMC assessment scale and severity by using modified Hartwig-Seigel severity assessment scale.Results: This study showed most of the patients were female (86%). Majority of them were in age group of 51-60 years. Average number of drugs per prescription was 10.57. Out of 200 patients, 2% were on single DMARD and 50.5% were on two DMARDs. 40% and 7.5% were taking three and four DMARDs respectively. A total of 450 adverse drug reactions were reported, out of which 68.4% due to steroid,12.5% due to DMARDs and 19.1 due to use of NSAIDs, DMARDs and glucocortisteroids. Chloroquine maculopathy occurred in 3 patients and elevated liver enzymes due to methotrexate in 3 patients, which necessitated DMARD withdrawal. Most patients had 1-3 ADRs. 6% of ADRs were severe and 54% belongs to probable category of causality assessment.Conclusions: Treatment of rheumatoid arthritis is mainly based on DMARDs, glucocorticosteroids and NSAIDs. So, occurrence of ADR is much common. Proper monitoring of therapy and timely modification of drugs and lifestyle can reduce the ADR occurrence.

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.