Informe diário de evidências COVID-19: busca realizada em 17 de julho de 2020 / COVID-19 daily evidence report: search conducted on July 17, 2020

O Informe Diário de Evidências é uma produção do Ministério da Saúde que tem como objetivo acompanhar diariamente as publicações científicas sobre tratamento farmacológico e vacinas para a COVID-19. Dessa forma, são realizadas buscas estruturadas em bases de dados biomédicas, referentes ao dia anterior desse informe. Não são incluídos estudos pré-clínicos (in vitro, in vivo, in silico). A frequência dos estudos é demonstrada de acordo com a sua classificação metodológica (revisões sistemáticas, ensaios clínicos randomizados, coortes, entre outros). Para cada estudo é apresentado um resumo com avaliação da qualidade metodológica. Essa avaliação tem por finalidade identificar o grau de certeza/confiança ou o risco de viés de cada estudo. Para tal, são utilizadas ferramentas já validadas e consagradas na literatura científica, na área de saúde baseada em evidências. Cabe ressaltar que o documento tem caráter informativo e não representa uma recomendação oficial do Ministério da Saúde sobre a temática. Foram encontrados 14 artigos e 13 protocolos.

Evaluation of the effect of intraperitoneal etanercept administration on oxidative stress and inflammation indicators in the kidney and blood of experimental sepsis-induced rats

Abstract INTRODUCTION: Sepsis is an important cause of mortality and morbidity, and inflammatory response and oxidative stress play major roles underlying its pathophysiology. Here, we evaluated the effect of intraperitoneal etanercept administration on oxidative stress and inflammation indicators in the kidney and blood of experimental sepsis-induced rats. METHODS: Twenty-eight adult Sprague Dawley rats were classified into Control (Group 1), Sepsis (Group 2), Sepsis+Cefazolin (Group 3), and Sepsis+Cefazolin+Etanercept (Group 4) groups. Kidney tissue and serum samples were obtained for biochemical and histopathological investigations and examined for the C reactive protein (CRP), tumor necrosis factor-alpha (TNF-α), triggering receptor expressed on myeloid cells (TREM), and malondialdehyde (MDA) levels. RESULTS: The levels of TNF-α, TREM, and MDA in serum and kidney samples were significantly higher in rats from sepsis group than in rats from control group (p < 0.05). Group 3 showed a significant reduction in serum levels of TNF-α, CRP, and TREM as compared with Group 2 (p < 0.05). Serum TNF-α, CRP, TREM, and MDA levels and kidney TNF-α and TREM levels were significantly lower in Group 4 than in Group 2 (p < 0.05). Serum TNF-α and TREM levels in Group 4 were significantly lower than those in Group 3, and histopathological scores were significantly lower in Group 3 and Group 4 than in Group 2 (p < 0.05). Histopathological scores of Group 4 were significantly lower than those of Group 3 (p < 0.05). CONCLUSIONS: Etanercept, a TNF-α inhibitor, may ameliorate sepsis-induced oxidative stress, inflammation, and histopathological damage.

Safety and tolerability of a single dose T0001 in Chinese healthy adult volunteers: a first-in-human ascending dose study

T0001 is the first mutant of etanercept with a higher affinity to tumor necrosis factor α (TNF-α) than etanercept. In order to investigate the safety and tolerability of T0001, a study was carried out in healthy Chinese subjects. A first-in-human, dose escalation study was conducted in healthy Chinese subjects. Fifty-six subjects were divided into six dose cohorts (10 mg, 20 mg, 35 mg, 50 mg, 65 mg and 75 mg) to receive a single subcutaneous injection of T0001. Safety and tolerability assessment were based on the records of vital signs, physical examinations, clinical laboratory tests, 12-lead electrocardiograms and adverse events (AEs). All subjects were in good compliance and none withdraw due to AEs. No serious AEs occurred. A total of twenty-three AEs in sixteen subjects were recorded, and eighteen of these AEs were believed to be related to T0001. The most frequently reported AEs were injection site reactions and white blood cell count increase. All these AEs were of mild to moderate intensity and most of them recovered spontaneously within 14 days. In this study, no dose-limiting toxicity was observed, and the maximum tolerated dose was identified as 75 mg. T0001 was considered safe and generally well tolerated at doses up to 75 mg in healthy Chinese volunteers

Latent tuberculosis infection in patients with autoimmune diseases treated with Infliximab and Etanercept / Infección latente por tuberculosis en pacientes con enfermedades autoinmunes que reciben tratamiento con Infliximab y Etanercept

Introduction: Latent tuberculosis infection (LTI) in patients receiving biological therapies is a reality, but this has not been studied in depth in Colombia. Objective: To determine the prevalence of LTI in patients with autoimmune diseases receiving treatment with Infliximab / Etanercept in a referral health center in Cali, Colombia, between the years 2011-2017. Methodology: A retrospective observational study was conducted. We reviewed the 'Registry of patients exposed to tumor necrosis factor-alpha (TNF-α) antagonist drugs in Fundación Valle del Lili'. Patients diagnosed with a chronic inflammatory disease were included who received treatment with Infliximab, Etanercept, or both and followed at least two years. Design: Retrospective observational study. We reviewed the 'Registry of patients exposed to tumor necrosis factor alpha (TNF-α) antagonist drugs in Fundación Valle del Lili'. Patients diagnosed with a chronic inflammatory disease were included who received treatment with Infliximab, Etanercept or both and followed at least a period of 2 years. Results: We included 82 patients; the median age was 47.5 years (IQR=28-60 years), 76% were female, 2% had intimate contact with tuberculosis, 15% were older than 65 years. The 56% had a diagnosis of rheumatoid arthritis as an indication of therapy, and 2% presented infection by hepatitis C virus. The median PPD was 12 mm (IQR=10-17 mm). The prevalence was 3.8% for LTI. Conclusion: The conversion to LTI shows an important prevalence, so it is convenient to perform a routine follow-up of patients receiving therapies with Infliximab and Etanercept.

Introducción: La infección latente por tuberculosis (ILTB) en pacientes que reciben terapias biológicas es una realidad, pero esto no ha sido estudiado a profundidad en Colombia. Objectivo: Determinar la prevalencia de ILTB en pacientes con enfermedades autoinmunes que reciben tratamiento con Infliximab/Etanercept en una institución de salud de referencia de Cali, Colombia, entre los años 2011-2017. Metodología: Se realizó un estudio observacional retrospectivo. Se revisó el 'Registro de pacientes expuestos a fármacos antagonistas del factor de necrosis tumoral alfa (anti TNF-α) en la Fundación Valle del Lili entre los años 2011 y 2017'. Se incluyeron pacientes con diagnóstico de una enfermedad inflamatoria crónica quienes recibieron tratamiento con Infliximab, Etanercept o ambos y con seguimiento al menos un periodo de 2 años. Resultados: Se incluyeron 82 pacientes; la mediana de edad fue 47,5 años RIC (28-60 años), el 76% fue de sexo femenino, el 2% tuvo contacto íntimo con TB, el 15% era mayor de 65 años. El 56% tenía diagnóstico de artritis reumatoide como indicación de terapia y el 2% presentaba infección por HCV. La mediana de PPD fue 12 mm RIC (10-17 mm). La prevalencia fue del 3,8% para ILTB. Conclusiones: La conversión a ILTB muestra una prevalencia importante, por lo que resulta conveniente la realización de un seguimiento rutinario a los pacientes que reciben terapias con Infliximab y Etanercept.

Psoriasis in moderate grave plaque - immunobiological treatment

The Guidelines Project, an initiative of the Brazilian Medical Association, aims to combine information from the medical field in order to standardize producers to assist the reasoning and decision-making of doctors. The information provided through this project must be assessed and criticized by the physician responsible for the conduct that will be adopted, depending on the conditions and the clinical status of each patient.

Long Term Safety and Efficacy of Etanercept in Juvenile Idiopathic Arthritis in a Single Center

OBJECTIVE: Our aim was to investigate the long term safety and efficacy of etanercept in children with juvenile idiopathic arthritis (JIA). METHODS: The study subjects were the 90 JIA patients treated with etanercept in the Department of Pediatrics, Hallym University Medical Center between January 2004 and December 2017. We retrospectively reviewed their medical records for age at diagnosis, duration of etanercept treatment, number of active joints, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and adverse events during treatment. RESULTS: Among the 90 patients, 38 (42.0%) were male and 52 (58.0%) were female; 15 (16.7%) had systemic onset, 41 (45.6%) had extended oligoarticular, 14 (15.6%) had rheumatoid factor-positive polyarticular, 18 (20.0%) had rheumatoid factor-negative polyarticular, and 2 (2.1%) had enthesitis-related arthritis. The median age at the start of etanercept treatment was 9 years (range, 3~18 years), and the median duration of etanercept treatment was 6 years (range, 0.5~13 years). The median number of active joints decreased from 9 to 0 after 6 months of etanercept treatment. The median CRP and ESR were within normal range after 3 months of treatment. Six patients experienced recurrence, 9 switched to other medications and 3 discontinued etanercept. Of the 14 reported adverse events, 1 was serious, and there were no tuberculosis infections or malignancies. CONCLUSION: Long-term treatment with etanercept is efficacious and safe for children with JIA. However, those with the systemic onset subtype appear to have low drug survival rate compared to those with other types of JIA.

Pustulotic Arthro-osteitis Improved with Anti TNF-α Inhibitor / 대한피부과학회지

Pustulotic arthro-osteitis (PAO) is a rare chronic inflammatory disorder characterized by inflammatory osteitis of the sternoclavicular joint and palmoplantar pustulosis. Here, we report a case of PAO that was successfully treated with a TNF-α inhibitor. A 45-year-old man presented with a 3-month history of pustular eruption on the palms and soles. Physical examination showed multiple erythematous papulopustules on the palms, back, and left shin, accompanied by sternoclavicular joint swelling and tenderness. Skin biopsy showed intraepidermal pustules filled with neutrophils on the palm. Bone scintigraphy revealed increased uptake in the bilateral sternoclavicular and other axial joints. Based on these findings, we made the diagnosis of PAO. Even after 6-month treatment of oral steroids and cyclosporine, skin manifestations insufficiently improved, so etanercept therapy was started. Complete clearance of skin lesions and joint pain were achieved after 3 months of etanercept therapy.

The Effects of Systemic Psoriasis Therapies on the C-Reactive Protein and the Neutrophil-Lymphocyte Ratio

BACKGROUND: Currently, no generally accepted laboratory marker for monitorizing the disease activity and therapy response of psoriasis is known. OBJECTIVE: The aim of the study is to evaluate the effects of systemic therapies on C-reactive protein (CRP) and the neutrophil-lymphocyte ratio (NLR) in psoriasis. METHODS: One hundred patients with psoriasis treated with narrow band ultraviolet B, acitretin, cyclosporine, methotrexate, adalimumab, etanercept, and ustekinumab were prospectively evaluated. At baseline and at week 12, CRP, NLR, and Psoriasis Area and Severity Index (PASI) were evaluated. RESULTS: A statistically significant decrease was observed in PASI scores, CRP, and NLR values from the baseline to the 12-week visit (p=0.001, p=0.001, p=0.001, respectively). The reduction in PASI scores and NLR values was positively correlated (r=0.460, p=0.001). The comparisons between treatment groups revealed that the median decrease in NLR values was statistically higher in the adalimumab group than in the methotrexate group (p=0.007). And the median decrease in PASI scores was significantly higher in the adalimumab group compared with the methotrexate and acitretin therapy group (p=0.007, p=0.042, respectively). CONCLUSION: In the present study, systemic therapy of psoriasis was demonstrated to decrease the levels of CRP and NLR, which are known to be indicators of systemic inflammation and cardiovascular comorbidities.

Correlation of ultrasonography synovitis with disease activity and clinical response to etanercept treatment in juvenile idiopathic arthritis patients

This study aimed to investigate the correlation of ultrasonography (US) of synovitis with disease activity and clinical response to etanercept (ETN) in juvenile idiopathic arthritis (JIA) patients. Eighty-two JIA patients who underwent ETN treatment for 24 weeks were consecutively enrolled. US evaluations of 28 joints (shoulder, elbow, wrist, metacarpophalangeal, and proximal interphalangeal of hands and knee) at baseline were performed using grey-scale US and power doppler (PD) US, and US synovitis was defined as grey-scale abnormalities or PD abnormalities. Clinical response was assessed according to the ACRpedi 50 response criteria. In total, 2296 joints were scanned and 608 (26.5%) joints presented US synovitis, which was numerically higher than clinical synovitis (513 (22.3%)). The mean number of joints showing synovitis on US was 7.42±3.35, which was also numerically higher than that of clinical synovitis (6.26±2.70). The number of joints showing synovitis on US was positively correlated with C-reactive protein, erythrocyte sedimentation rate, number of joints with active disease, number of joints with limited range of motion, physician's global assessment of disease activity, parent/patient global assessment of overall well-being, and childhood health assessment questionnaire score. Most interestingly, the baseline number of joints showing synovitis on US was increased in ACRpedi 50 response JIA patients compared to non-response JIA patients, and it serves as an independent predictive factor for higher clinical response to ETN treatment. In conclusion, US is a more sensitive test to evaluate subclinical synovitis and disease activity in JIA patients, and US synovitis might serve as a marker for predicting increased clinical response rate to ETN treatment.

The Effect of Tumor Necrosis Factor-Alpha Inhibitors on Uveitis in Patients with Ankylosing Spondylitis

BACKGROUND: Tumor necrosis factor-alpha (TNF-α) inhibitors (TNFis), which are the main treatment for ankylosing spondylitis (AS), have been reported not only to reduce the incidence of anterior uveitis (AU) but also to induce it, and these effects differ among the various types of TNFis in clinical use. The present study investigated the effect of TNFis on uveitis by analyzing the long-term clinical course of AU in AS patients treated with TNFi therapy. METHODS: Patients treated with at least one TNFi between January 2007 and July 2017 were reviewed, and 54 patients with at least one episode of AU were included in this study. The TNFis included anti-TNF-α antibodies (adalimumab, infliximab, and golimumab), and a soluble TNF receptor molecule (etanercept). The effect of prevention of AU, the likelihood of new-onset uveitis after the initiation of TNFi therapy, and the effects of drug switching and dose escalation were assessed. RESULTS: The first uveitis flare was observed before TNFi therapy in 39 patients and after TNFi therapy in 15 patients. Anti-TNF-α antibodies were more efficacious in decreasing the recurrence of AU than etanercept. Among patients in which uveitis first occurred after beginning TNFi therapy, patients on etanercept tended to first develop AU less than 1 year after starting the drug, and their AS tended to be well-controlled at the time of uveitis flares. Patients with a uveitis flare before their medication was switched did not recur afterwards, and five of eight patients showed no relapse after dose escalation. CONCLUSION: TNFis have various effects on AU. TNFis, particularly anti-TNF-α antibodies, should be considered in patients with AS and frequent AU relapse. Additionally, clinicians should consider whether AU is due to an absence of a therapeutic response of AS to TNFi treatment or to TNFi treatment itself, and appropriate treatment changes should be made accordingly.

Perfil de gastos com o tratamento da Artrite Reumatoide para pacientes do Sistema Único de Saúde em Minas Gerais, Brasil, de 2008 a 2013 / Profile of spending on the treatment of rheumatoid arthritis for patients of the Unified Health System in the state of Minas Gerais - 2008-2013

Resumo A artrite reumatoide (AR) é uma doença crônica que afeta cerca de 1% da população adulta. No estudo de coorte histórica de pacientes de Minas Gerais, registrados no Sistema de Informações Ambulatoriais (SIA), em 2008-2013, foram identificados 11.573 indivíduos. A perspectiva foi a do financiador público e os valores observados como gastos do Sistema Único de Saúde (SUS) foram ajustados pelo Índice Nacional de Preços ao Consumidor Amplo (IPCA), de dezembro de 2015. O Etanercept foi o tratamento mais caro. A análise múltipla mostrou uma relação negativa entre o aumento das despesas e idade, sexo feminino e diagnóstico de entrada na coorte, e relação positiva para as variáveis Índice de Desenvolvimento Humano Municipal (IDH-M) e o uso de medicamentos bloqueadores do fator de necrose tumoral (ANTI-TNF). Este estudo identificou os fatores que têm impacto sobre o gasto com o tratamento medicamentoso da AR. Também apontou que métodos que permitem extrair dados demográficos e de gastos de sistemas de informação administrativos podem ser ferramentas importantes na construção de estudos econômicos capazes de subsidiar as avaliações econômicas de saúde, especialmente do ponto de vista da gestão.

Abstract Rheumatoid arthritis (RA) is a chronic condition that affects about 1% of the adult population. In a historical cohort of Minas Gerais State, 11,573 RA patients registered in the Outpatient Information System (SIA) between 2008 and 2013 were identified. For this study we adopted the public funding body's perspective and the values were adjusted by the national inflation index (IPCA) of December 2015. Etanercept was the most expensive treatment. The mean cohort age was 52 years old and most of the patients were women. Multiple regression analysis indicated a negative association between higher expenditure and age, female sex, and diagnosis at entry in the cohort and positive association between high expenditure and the Human Development Index (HDI) of the municipality and use of tumor necrosis factor agents. This study identified the factors that have an impact on RA drug treatment expenditure. Also, we showed that methods that enable extracting demographic and expenditure data of administrative information systems may represent important tools in the construction of economic studies to subsidize economic health evaluations, especially from the standpoint of the managers.

Farmacogenómica de etanercept, infliximab, adalimumab y metotrexato en artritis reumatoide. Revisión estructurada / Pharmacogenomics of etanercept, infliximab, adalimumab and methotrexate in rheumatoid arthritis. A structured review

RESUMEN Introducción: La variabilidad genética individual favorece que la capacidad de respuesta y toxicidad a los fármacos sea diferente en cada persona. En la artritis reumatoide se reportan índices de respuesta a los medicamentos etanercept, infliximab, adalimumab y metotrexato cercanos al 60%. Esta variabilidad puede explicarse por polimorfismos genéticos característicos de cada paciente. Objetivo: Identificar polimorfismos genéticos reportados en artículos científicos que pueden afectar la farmacocinética y la farmacodinámica de etanercept, infliximab, adalimumab y metotrexato, y su respuesta en pacientes con artritis reumatoide. Materiales y método: Se realizó una búsqueda sistemática en PubMed/Medline, con los términos clave: «rheumatoid arthritis¼ and «pharmacogenomic¼ and «polymorphisms¼ and «metotrexato¼ and «infliximab¼ and «adalimumab¼ and «etanercept¼ obteniendo 164 artículos, 117 no duplicados y 19 artículos que cumplieron los criterios de inclusión. Resultados: De los 19 artículos, 2 reportaron polimorfismos que afectan la farmacocinética de infliximab, adalimumab, etanercept y metotrexato, y 17, la farmacodinámica. En los 19 artículos se identificaron 23 polimorfismos de relevancia clínica en población europea, japonesa, jordana e india. Conclusiones: Se identifican 23 polimorfismos de relevancia clínica, los cuales podrían ser el soporte para el diseño de un test de secuenciación específica en pacientes con artritis reumatoide, en los que se considere la utilización de infliximab, adalimumab, etanercept o metotrexato. La utilidad práctica de este tipo de estrategia requiere ser evidencia en estudios clínicos específicos, relacionados con una prescripción orientada por test genéticos y personalizada, y su efecto sobre la efectividad y seguridad de la farmacoterapia con estos medicamentos.

ABSTRACT Introduction: Individual genetic variability favours the capacity of response and toxicity to the drugs is different in each person. Rheumatoid arthritis reported rates of response to the drugs etanercept, infliximab, adalimumab and methotrexate is close to 60%. This variability can be explained by genetic polymorphisms characteristic of each patient. Objective: To identify genetic polymorphisms reported in scientific articles that may affect the pharmacokinetics and pharmacodynamics of etanercept, infliximab, adalimumab, and methotrexate, and their response in patients with rheumatoid arthritis. Materials and method: A systematic search was performed in PubMed and Medline, with the key terms: "rheumatoid arthritis" and "pharmacogenomic" and "polymorphisms" and "methotrexate" and "infliximab" and "adalimumab" and "etanercept", obtaining 164 articles, 117 non-duplicates, and 19 articles that met the inclusion criteria. Results: Of the 19 articles, 2 reported polymorphisms affecting the pharmacokinetics of infliximab, adalimumab, etanercept, methotrexate, and 17, pharmacodynamics. In the 19 articles, 23 polymorphisms of clinical relevance were identified in European, Japanese, Jordanian, and Indian populations. Conclusions: A total of 23 polymorphisms with clinical relevance were identified, which could be the basis for the design of a specific test sequencing in rheumatoid arthritis patients being considered for treatment with infliximab, adalimumab, etanercept, or methotrexate. The practical usefulness of this strategy requires evidence in specific clinical studies, associated with a targeted and personalised genetic test, and its effect on the effectiveness and safety of drug therapy with these drugs prescription.

TNF-α/TNFR1 Signaling is Required for the Full Expression of Acute and Chronic Itch in Mice via Peripheral and Central Mechanisms / 神经科学通报·英文版

Increasing evidence suggests that cytokines and chemokines play crucial roles in chronic itch. In the present study, we evaluated the roles of tumor necrosis factor-alpha (TNF-α) and its receptors TNF receptor subtype-1 (TNFR1) and TNFR2 in acute and chronic itch in mice. Compared to wild-type (WT) mice, TNFR1-knockout (TNFR1-KO) and TNFR1/R2 double-KO (DKO), but not TNFR2-KO mice, exhibited reduced acute itch induced by compound 48/80 and chloroquine (CQ). Application of the TNF-synthesis inhibitor thalidomide and the TNF-α antagonist etanercept dose-dependently suppressed acute itch. Intradermal injection of TNF-α was not sufficient to evoke scratching, but potentiated itch induced by compound 48/80, but not CQ. In addition, compound 48/80 induced TNF-α mRNA expression in the skin, while CQ induced its expression in the dorsal root ganglia (DRG) and spinal cord. Furthermore, chronic itch induced by dry skin was reduced by administration of thalidomide and etanercept and in TNFR1/R2 DKO mice. Dry skin induced TNF-α expression in the skin, DRG, and spinal cord and TNFR1 expression only in the spinal cord. Thus, our findings suggest that TNF-α/TNFR1 signaling is required for the full expression of acute and chronic itch via peripheral and central mechanisms, and targeting TNFR1 may be beneficial for chronic itch treatment.

Anti-Tumor Necrosis Factor Therapy in Intestinal Behçet's Disease

Intestinal Behçet's disease is a rare, immune-mediated chronic intestinal inflammatory disease; therefore, clinical trials to optimize the management and treatment of patients are scarce. Moreover, intestinal Behçet's disease is difficult to treat and often requires surgery because of the failure of conventional medical treatment. Administration of anti-tumor necrosis factor–α, a potential therapeutic strategy, is currently under active clinical investigation, and evidence of its effectiveness for both intestinal Behçet's disease and inflammatory bowel diseases has been accumulating. Here, we review updated data on current experiences and outcomes after the administration of anti-tumor necrosis factor–α for the treatment of intestinal Behçet's disease. In addition to infliximab and adalimumab, which are the most commonly used agents, we describe agents such as golimumab, etanercept, and certolizumab pegol, which have recently been shown to be effective in refractory intestinal Behçet's disease. This review also discusses safety issues associated with anti-tumor necrosis factor–α, including vulnerability to infections and malignancy.

IgA nephropathy in a patient with ankylosing spondylitis well controlled with etanercept / 고신대학교의과대학학술지

Ankylosing spondylitis (AS) can involve the eye, gastrointestinal system, cardiopulmonary system, skin, kidneys, and spinal and peripheral joints. It is rarely accompanied by immunoglobulin A (IgA) nephropathy. Although IgA is involved in both AS and IgA nephropathy, the relationship between these diseases remains unclear. We detected hematuria and proteinuria in a 32-year-old male patient with ankylosing spondylitis that remained stable for 4 years through treatment with etanercept, a tumor necrosis factor-α (TNF-α) inhibitor, and diagnosed IgA nephropathy through a renal biopsy. IgA nephropathy seems to be less commonly associated with AS disease activity or specific treatment such as TNF-α inhibitor use.

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.

Drug survival of tumor necrosis factor α inhibitors in patients with ankylosing spondylitis in Korea

BACKGROUND/AIMS: To evaluate drug survival of the tumor necrosis factor α inhibitors (TNFi) and risk factors for the drug discontinuation in patients with ankylosing spondylitis (AS). METHODS: We retrospectively evaluated 487 AS patients at a single tertiary hospital. Among the TNFi users, drug survival and risk factors of TNFi discontinuation were investigated. RESULTS: Among 487 patients, 128 AS patients were treated with at least one TNFi. Patients who were treated with TNFi were younger at disease onset, had more peripheral manifestations, and had higher level of acute phase reactants and body mass index than those of TNFi non-users at baseline. Of 128 patients, 28 patients (21.9%) discontinued first TNFi therapy during the follow-up period of 65.1 ± 27.9 months. In the multivariable analysis, female (hazard ratio [HR], 6.08; 95% confidence interval [CI], 2.27 to 16.27; p = 0.003), hip involvement (HR, 2.52; 95% CI, 1.08 to 5.87; p = 0.033) and a high C-reactive protein (CRP; HR, 1.10; 95% CI, 1.00 to 1.21; p = 0.044) were risk factors for drug discontinuation. Etanercept showed better survival rate than infliximab. The main reason for discontinuation of TNFi was inefficacy. CONCLUSIONS: TNFi discontinuation rate of Korean patients with AS seems to be similar to those with the European patients. Female sex, hip involvement, CRP, and the type of TNFi were associated with TNFi discontinuation.

Eficacia de medicamentos biológicos aprobados por ley 20850, para pacientes con artritis reumatoide refractaria a tratamiento / Efficacy of biological drugs approved by law N°20. 850, for patients with rheumatoid arthritis refractory to treatment

INTRODUCCIÓN: La artritis reumatoide es una enfermedad crónica, sistémica, de origen autoinmune, caracterizada por compromiso articular simétrico. Dentro de su tratamiento destacan fármacos antirreumáticos, modificadores de la enfermedad, glucocorticoides y agentes biológicos. Estos últimos, han llegado a revolucionar la progresión de la enfermedad, otorgando una mejor calidad de vida a los pacientes. CUERPO DE LA REVISIÓN: En Chile, los fármacos biológicos están asegurados para personas con artritis reumatoide refractaria a tratamiento por la ley 20.850 "Ley Ricarte Soto", que incluye los fármacos adalimumab, etanercept, abatacept y rituximab. Por lo tanto, el objetivo de esta investigación fue resumir los principales estudios que aseguran la eficacia de estos medicamentos. CONCLUSIÓN: Se ha demostrado la eficacia de los medicamentos biológicos, con clara superioridad en relación con la progresión radiológica, síntomas, alteración funcional y nivel de actividad de la enfermedad comparativamente con los placebos.

INTRODUCTION: Rheumatoid arthritis is a chronic, systemic disease of autoimmune origin, characterized by symmetrical joint involvement. Its treatment includes antirheumatic drugs, disease modifiers, glucocorticoids and biological agents. The latter have come to revolutionize the progression of the disease, giving a better quality of life to patients. REVIEW BODY: In Chile, biological drugs are insured for people with rheumatoid arthritis refractory to treatment by the 20.850 "Ricarte Soto Law", which includes the drugs adalimumab, etanercept, abatacept and rituximab. Therefore, the objective of this research was to summarize the main studies that ensure the efficacy of these medications. CONCLUSION: The efficacy of biological drugs has been demonstrated, with clear superiority in relation to radiological progression, symptoms, functional alteration and level of disease activity compared to placebos.