Tuberculosis in children and adolescents with rheumatic diseases using biologic agents: an integrative review / Tuberculose em crianças e adolescentes com doenças reumáticas em uso de medicamentos biológicos: revisão integrativa

ABSTRACT Objective: To conduct a bibliographic review on tuberculosis (TB) disease in children and adolescents with rheumatic diseases, being managed with biologic therapy. Data source: An integrative review with a search in the U.S. National Library of Medicine and the National Institutes of Health (PubMed) using the following descriptors and Boolean operators: (["tuberculosis"] AND (["children"] OR ["adolescent"]) AND ["rheumatic diseases"] AND (["tumor necrosis factor-alpha"] OR ["etanercept"] OR ["adalimumab"] OR ["infliximab"] OR ["biological drugs"] OR ["rituximab"] OR ["belimumab"] OR ["tocilizumab"] OR ["canakinumab"] OR ["golimumab"] OR ["secukinumab"] OR ["ustekinumab"] OR ["tofacitinib"] OR ["baricitinib"] OR ["anakinra"] OR ["rilonacept"] OR ["abatacept"]), between January 2010 and October 2021. Data synthesis: Thirty-seven articles were included, with the total number of 36,198 patients. There were 81 cases of latent tuberculosis infection (LTBI), 80 cases of pulmonary tuberculosis (PTB), and four of extrapulmonary tuberculosis (EPTB). The main rheumatic disease was juvenile idiopathic arthritis. Among LTBI cases, most were diagnosed at screening and none progressed to TB disease during follow-up. Of the TB cases using biologics, most used tumor necrosis factor-alpha inhibitors (anti-TNFα) drugs. There was only one death. Conclusions: The study revealed a low rate of active TB in pediatric patients using biologic therapy. Screening for LTBI before initiating biologics should be done in all patients, and treatment, in cases of positive screening, plays a critical role in preventing progression to TB disease.

RESUMO Objetivo: Fazer um levantamento bibliográfico referente à tuberculose (TB) em crianças e adolescentes com doenças reumáticas, em uso de imunobiológicos. Fonte de dados: Revisão integrativa com busca na base United States National Library of Medicine (PubMed) utilizando os descritores e operadores booleanos: (["tuberculosis"] AND (["children"] OR ["adolescent"]) AND ["rheumatic diseases"] AND (["tumor necrosis fator-alpha"] OR ["etanercept"] OR ["adalimumab"] OR ["infliximab"] OR ["biological drugs"] OR ["rituximab"] OR ["belimumab"] OR ["tocilizumab"] OR ["canakinumab"] OR ["golimumab"] OR ["secukinumab"] OR ["ustekinumab"] OR ["tofacitinib"] OR ["baricitinib"] OR ["anakinra"] OR ["rilonacept"] OR ["abatacept"]), entre janeiro de 2010 e outubro de 2021. Síntese de dados: Trinta e sete artigos foram incluídos, com o total de 36.198 pacientes. Houve 81 casos de tuberculose latente (ILTB), 80 casos de tuberculose pulmonar (TBP) e quatro casos de tuberculose extrapulmonar (TBEP). A principal doença reumática foi a artrite idiopática juvenil. Entre os casos de ILTB, a maioria foi diagnosticada no rastreio e nenhum evoluiu para a TB. Dos casos de TB em uso de imunobiológicos, a maioria utilizava fármacos antiTNFα. Houve somente um caso de óbito. Conclusões: O estudo demonstrou baixa taxa de TB nos pacientes pediátricos em uso de imunobiológicos. O rastreio para ILTB antes do início da terapia com agentes biológicos deve ser realizado em todos os pacientes, e o tratamento, nos casos de rastreio positivo, é importante para evitar a progressão para TB doença.

Advances in application of biologic agents in pediatric Crohn′s disease / 国际儿科学杂志

The incidence of Crohn′s disease(CD) in children is increasing year by year.Compared with adults, children with CD face a more rapidly changing course, a larger range of intestinal involvement and growth and development problems.The advent of biological agents has broadened the treatment pathway for pediatric CD, among which the most widely used anti-TNF therapy, including Infliximab(IFX), Adalimumab(ADA), has been approved for the induction and remission therapy for pediatric CD.The efficacy and safety of biological agents from other pathways, such as the interleukin inhibitor Ustekinumab(UTK), the anti-integrin monoclonal antibody Vedolizumab(VDZ) and biosimilars have been progressively demonstrated in pediatric CD.Loss of response is a major problem in the treatment of biologic agents, and the development of more biologics as an alternative treatment is the direction that still needs to be worked on in the future.This article reviews the efficacy of biological agents in pediatric CD, aiming to provide recommendations for clinicians when making treatment decisions.

Biologic therapies of Takayasu arteritis in children / 国际儿科学杂志

Takayasu arteritis is a a rare, chronic large-vessel vasculitis that predominantly affects aorta, its major branches and the pulmonary arteries; it is the most common, granulomatous inflammation of large arteries in children.It induces a variety of nonspecific inflammatory symptoms and ischemic symptoms due to stenotic lesions.Recent advances in imaging modalities including magnetic resonance angiography, computed tomography(CT), sonography, and fluorodeoxy glucose positron emission tomography/CT(FDG-PET/CT)allow accurate diagnosis of Takayasu arteritis and shorter duration between onset of the disease and diagnosis.Medical treatment for Takayasu arteritis is also changing.In addition to the traditional glucocorticoids and immunosuppressants, many new biological agents such as TNF-α antagonists and tocilizumab are being applied to patients with Takayasu arteritis refractory to conventional treatment with favorable results.This review critically discusses recent advances in medical management of Takayasu arteritis, with a special focus on the rationale and evidence to support the use of biologic agents in this disease.

Vacinas COVID-19 e outros imunobiológicos ­ intervalos preconizados / COVID-19 vaccines and other immunobiological drugs ­ recommended intervals

Com o início do programa de vacinação contra a COVID-19 no Brasil, surgiu uma série de questionamentos relacionados ao uso dos imunizantes. Neste documento, o grupo de estudo da COVID-19 da Associação Brasileira de Alergia e Imunologia (ASBAI) avalia as evidências científicas e se posiciona em relação aos intervalos preconizados entre a administração das vacinas contra o SARS-CoV-2 e dos imunobiológicos.

With the beginning of the COVID-19 vaccination program in Brazil, a series of questions related to the use of vaccines arose. In this document, the COVID-19 study group of the Brazilian Association of Allergy and Immunology (ASBAI) assesses the scientific evidence and takes a stand for the recommended intervals between the administration of SARS-CoV-2 vaccines and that of immunobiological drugs.

Persistencia a largo plazo de agentes biológicos en el tratamiento de pacientes con Artritis Reumatoidea: una revisión sistemática de la literatura / Long-term persistence of biological agents in the treatment of patients with Rheumatoid Arthritis: a systematic literature review

La persistencia en el tratamiento es un marcador subrogante de éxito de tratamiento a largo plazo. Objetivo: Evaluar la persistencia de los agentes biológicos utilizados para el tratamiento de pacientes con artritis reumatoidea (AR) a un tiempo de 5 años y determinar las principales causas asociadas a persistencia o discontinuación. Material y métodos: Se realizó una revisión sistemática de la literatura (RSL), según las recomendaciones PRISMA, en las bases de datos Pubmed, Cochrane y Lilacs, y estudios presentados en los congresos ACR, EULAR, PANLAR (2018/2019) hasta Enero 2020. Dos revisoras independientes, evaluaron todas las publicaciones identificadas, por título y abstract y por full text, de acuerdo a la metodología PICO. Los criterios de elegibilidad fueron estudios de pacientes ≥ 18 años con diagnóstico de AR, en tratamiento con agentes biológicos, que midieran persistencia/discontinuación en un período de tiempo igual o superior a 5 años y que estuvieran en idioma inglés o español. En el caso de falta de acuerdo entre las dos revisoras, un tercer revisor fue consultado. La información extraída fue analizada mediante estadística descriptiva, se calculó el porcentaje promedio de persistencia de cada agente biológico a los 5 años. Resultados: Se seleccionaron 56 artículos luego de la remoción de los duplicados y de la exclusión por título/abstract, y por full text. De ellos 13, eran fase de extensión a largo plazo de estudios randomizados controlados, 15 cohortes retrospectivas, 18 cohortes prospectivas y 10 cohortes retro-prospectivas y correspondían a un total de 72177 (rango: 79-10396) pacientes con AR, con una edad media 53.8 años ± 12.1, 78.2% de sexo femenino y un tiempo promedio de evolución de la AR de 9.7 años ± 8.4. En 33.9% de los estudios, la terapia biológica estaba combinada con drogas modificadoras de la AR convencionales (DMARs-c), en 3.6% en monoterapia, 48.2% ambas modalidades y en 14.3% no informaba. Un estudio fue realizado en 1° línea (metotrexato näive), 29 estudios en 2° línea (respuesta inadecuada a MTX y/o DMARs-c), 5 en 3° línea (respuesta inadecuada a DMARs biológicas-b-), 12 en ≥2° línea terapéutica y en 9 no especificaban. En 30 estudios que evaluaron 2° línea terapéutica, la mayor persistencia correspondió a tocilizumab (TCZ) 66.41% (IC95% 57.8-79.94), abatacept (ABA) 57.91% (IC95% 50.96-64.87) y golimumab (GOL) 54.38% (IC95% 48.58-60.19). Y 10 estudios, en los cuales el DMAR-b había sido analizado en 3° línea terapéutica, las mayores tasas de retención correspondieron a rituximab (RTX) 61.19% (IC95% 57.53-66.22) y TCZ 61.1% (IC95% 58.81-63.32). Entre los estudios que evaluaron predictores, los más frecuentemente asociados a mayor sobrevida fueron: tratamiento combinado con DMAR-c, etanercept versus infliximab y adalimumab y 2° línea de tratamiento vs 3° o 4° línea y los asociados a menor sobrevida fueron: mayor uso de esteroides, mayor actividad basal de la enfermedad y sexo femenino. Conclusiones: En esta RSL, la persistencia de los DMAR-b a 5 años en pacientes con respuesta inadecuada a DMARs-c y DMARs-b fue numéricamente mayor para los agentes no TNFi. Y entre los TNFi, GOL presentó mayor retención en 2° línea terapéutica.

Treatment persistence is a surrogate marker for long-term treatment success. Objective: To assess the persistence of the biological agents used for treatment of patients with rheumatoid arthritis (RA) over 5 years period and to determine the main causes associated with persistence or discontinuation. Material and methods: A systematic literature review (SLR) was carried out, according to PRISMA recommendations, including Pubmed, Cochrane and Lilacs databases, and studies presented at the ACR, EULAR, PANLAR congresses (2018/2019) until January 2020. Two independent reviewers evaluated the identified publications, by title and abstract and full text, according to PICO methodology. Eligibility criteria were: studies including RA patients ≥ 18 years, treated with biological agents, which measured persistence/ discontinuation for a period of time equal to or greater than 5 years and who were in English or Spanish language. In the case of lack of agreement between the two reviewers, a third reviewer was consulted. The extracted information was analyzed using descriptive statistics, an average percentage of persistence for each biological agent at 5 years was calculated. Results: 56 articles were selected after removal of duplicates and exclusion by title/abstract, and by full text. Long-term extension phase of randomized controlled studies were 13, another 15 retrospective cohorts, 18 prospective cohorts and 10 retro-prospective cohorts and corresponded to a total of 72177 (range: 79-10396) patients with RA, with a mean age of 53.8 years ± 12.1, 78.2% female and an average RA disease duration of 9.7 years ± 8.4. In 33.9% of the studies, biological therapy was combined with conventional disease modifying anti-rheumatic drugs (c-DMARDs), in 3.6% monotherapy, 48.2% both modalities, and in 14.3% not reported. One study was in the 1st line (methotrexate näive), 29 studies in 2nd line (inadequate response to MTX and/or c-DMARDs), 5 in 3rd line (inadequate response to biological b-DMARDs), 12 in ≥2nd therapeutic line and in 9 studies did not specify this condition. In 30 studies which evaluated the 2nd therapeutic line, the highest persistence corresponded to tocilizumab (TCZ) 66.41% (95% CI 57.8-79.94), abatacept (ABA) 57.91% (95% CI 50.96-64.87) and golimumab (GOL) 54.38% (95% CI 48.58-60.19). In 10 studies, in which b-DMARD had been analyzed in 3rd therapeutic line, highest retention rates corresponded to rituximab (RTX) 61.19% (95% CI 57.53-66.22) and TCZ 61.1% (95% CI 58.81-63.32). Among studies that evaluated predictors, the most frequently associated with higher survival were: combined treatment with c-DMARD, etanercept versus infliximab and adalimumab and 2nd line of treatment vs. 3rd or 4th line whereas those associated with lower survival rates were: greater use of steroids, higher baseline disease activity, and female gender. Conclusions: In this SLR, the 5-year persistence of b-DMARD in patients with inadequate response to DMARs-c and DMARs-b was numerically greater for non-TNFi agents. And among TNFi, GOL presented a higher retention in 2nd therapeutic line.

The Risk of Cardiovascular Disease and Diabetes in Rheumatoid Arthritis Patients: A Propensity Score Analysis

BACKGROUND: Rheumatoid arthritis (RA) is a systemic inflammatory disease that manifests as joint damage or athletic disability via sustained inflammation of the synovial membrane. The risk of cardiovascular disease (CVD) is higher in RA patients. This study aimed at evaluating the association between CVD comorbidities and RA by comparing a pharmacotherapy group with a non-pharmacotherapy group. METHODS: Patient sample data from the Health Insurance Review and Assessment Service (HIRA-NPS-2016) were used. Inverse probability of treatment weighting (IPTW) using the propensity score was used to minimize the differences in patient characteristics. Logistic regression analysis was used to evaluate the risk of CVD comorbidities. RESULTS: The analyses included 1,207,213 patients, of which 33,122 (2.8%) had RA. The odds ratios (OR) of CVD comorbidities were increased in RA patients; ischemic heart disease (IHD: OR 1.75; 95% CI 1.73, 1.77), cerebral infarction (CERI: OR 1.28; 95% CI 1.26, 1.30), hypertension (HTN: OR 1.44; 95% CI 1.43, 1.45), diabetes mellitus (DM: OR 2.04; 95% CI 2.03, 2.06), and dyslipidemia (DL: OR 3.49; 95% CI 3.47, 3.51). The ORs of IHD, CERI, HTN, and DM in the traditional DMARD and biologic treatment groups were decreased, compared with those in the non-pharmacotherapy group. CONCLUSIONS: Thus, CVD risk was higher in RA patients, considering age, sex, and socioeconomic status. Appropriate pharmacotherapy could decrease the risk of CVD comorbidities in RA patients.

Vaccination for Patients with Rheumatic Diseases in the Era of Biologics

A large proportion of patients with rheumatic disease have an immunocompromised status resulting from disease pathogenesis itself and/or several immunosuppressive drugs including biologics. These conditions are closely related to a higher risk of a variety of infectious diseases. Therefore, a few vaccinations for vaccine‐preventable pathogens should be considered in patients with rheumatic disease at the appropriate time. The quadrivalent inactivated influenza and pneumococcal vaccinations, including both 13‐valent conjugate and 23‐valent polysaccharide vaccines, are strongly recommended in all patients with rheumatic disease. The immunogenicity of influenza and pneumococcal vaccination have generally been demonstrated in patients with rheumatic disease on biologics except for rituximab and abatacept. Vaccines can be administered during therapy with tumor necrosis factor-α antagonists but may be more ideal during a stable or remission status without immunosuppressive therapy. In particular, vaccination should be done at least 6 months after an injection of rituximab as a B‐lymphocyte‐depleting biologic. Basically, all live-attenuated vaccines should be avoided in highly immunocompromised rheumatic disease patients. The vaccination for herpes zoster (HZ) can be taken carefully according to degree of immunosuppression because the currently available vaccine is only live‐attenuated. The newly developed subunit HZ vaccine is promising in immunocompromised patients with rheumatic disease.

Ustekinumab treats psoriasis by suppressing RORC and T-box but its suppression of GATA restrains its efficacy

Psoriasis is a T-cell mediated disease that involves IL-23/Th17 and IL-12/Th1 axes. Ustekinumab, a fully human monoclonal antibody targeting the p40 subunit of both IL-12 and IL-23, has proven to be efficient and safe for treating patients with psoriasis. Yet, there have been no reports with human skin/blood samples that would elucidate the molecular mechanisms by which ustekinumab calms psoriasis skin lesions. To investigate the efficacy and molecular pathway (RORC, t-BOX and GATA) of ustekinumab in treating patients with psoriasis skin lesions. A total of 30 patients with psoriasis were randomized into placebo group and treatment group. PASI of each patient was calculated at 0, 12 and 24 weeks post-treatment. The mRNA levels of RORC, t-BOX and GATA in peripheral blood mononuclear cells separated from patients' whole blood were analyzed using qPCR. Decreased mRNA of RORC, t-BOX and GATA were observed after continuous injections, indicating that ustekinumab exerts its effect by interacting with these molecules; while no significant difference in foxp3 mRNA levels were found between placebo group and treatment group.

Changes in serum levels of antinuclear antibody, anti-double-stranded DNA antibody and anti-extractable nuclear antigens antibody before and after anti-tumor necrosis factor-α therapy in psoriatic patients / 中华皮肤科杂志

Objective To investigate changes in serum levels of antinuclear antibody(ANA), anti?double?stranded DNA(dsDNA)antibody and anti?extractable nuclear antigen(ENA)antibody before and after anti?tumor necrosis factor?α(TNF?α)therapy in psoriatic patients. Methods Clinical data obtained from 32 patients with psoriasis were analyzed retrospectively. Of the 32 patients, 13 received intravenous injection of 5 mg/Kg infliximab at week 0, 2, 6 for 3 sessions, then once every 8 weeks(infliximab group), while other 19 received subcutaneous injection of 25 mg etanercept twice every week(etanercept group). The treatments in the 2 groups both lasted more than 3 months. Serum levels of ANA, anti?dsDNA antibody and anti?ENA antibody and changes of clinical symptoms were detected and observed respectively before each treatment in the infliximab group, as well as every 3- 6 months in the etanercept group. The 75%reduction in psoriasis area and severity index(PASI75)and disease activity score of 28 joints(DAS28) were used to evaluate clinical efficacy. Serum levels of ANA, anti?dsDNA antibody and anti?ENA antibody were measured by indirect immunofluorescence(IIF)assay, Western blot analysis combined with enzyme?linked immunosorbent assay(ELISA), and Western blot analysis, respectively. Results After 3?month treatment, the 32 patients achieved clinical remission to different extents. Of 32 patients receiving anti?TNF?αtherapy, 7(21.9%)developed new autoantibodies. Concretely speaking, 4 patients in the infliximab group developed autoantibodies in 8.3 ± 5.1 months, including 3 cases positive for ANA and 3 for anti?ENA antibody. Three patients in the etanercept group developed autoantibodies in 9.0 ± 3.0 months, including 3 cases positive for ANA and 1 for anti?ENA antibody. Conclusion Partial patients with psoriasis may develop autoantibodies after anti?TNF?αtherapy.

Biologic and small molecular agents for simultaneous treatment of psoriasis and psoriatic arthritis: Research progress / 第二军医大学学报

A quarter of the psoriasis patients develop psoriatic arthritis, and it would be beneficial if a preparation which can be used to treat the skin and joint symptoms at the same time. Currently these biologic agents could serve both include tumor necrosis factor inhibitors such as adalimumab, etanercept, infliximab, golimumab and certolizumab; anti-IL-12/IL-23 p40 antibodies such as ustekinumab; and anti-IL-17 agents such as secukinumab, brodalumab. Recently another group of small molecule agents has been found for the purpose: phosphodiesterase-4 inhibitor, apremilast, JAK inhibitor, tofacitinib and INCBO18424. This review provides an overview on the agents that can be used for the concurrent treatment of skin and joint psoriasis.

Listeria Meningitis After Infliximab in Ulcerative Colitis: Does the Risk of Treatment Outweigh the Benefit.

Biologic agents have become important treatment options for the management of inflammatory bowel disease (IBD). With more than 10 years of experience behind us these agents have changed the natural history of the disease and have established themselves as a valid choice in the repertoire used in treating not only advanced patients but also newly diagnosed ones. We report two cases of ulcerative colitis who developed listeria meningitis after a single dose of infliximab therapy. We also examined the significance of the infection and the known details and morbidity about it. We assessed the close link between the use of biologics and the risk of serious infections in patients with IBD, as well as the published cases in the literature so far. Therefore, despite the excitement and hype surrounding their use we should not forget that these are agents that carry a substantial toll of side effects and this should be kept in mind when the choice of therapy is made.

Especies vegetaees investigadas por sus propieddes antimicrobianas, inmunomoduuladoras e hipoglicemiantes en el departamento de caldas (Colombia, sudamérica) / Veetal species sstudied by their antimicrobial, immunomodulatory and hypoglicemic properties in caldas-Colombia, south mmerica

El uso de plantas con fines terapéuticos en la atención primaria en salud, es una práctica común en la zona del Eje Cafetero colombiano. Nuestra Línea de Investigación ha realizado varios estudios etnofarmacológicos en esta zona, seleccionando algunas especies vegetales para evaluar la posible actividad antibacteriana, hipoglicemiante e inmunomoduladora. El presente trabajo describe las nueve especies estudiadas, con una breve descripción botánica, nombres comunes, usos empíricos tradicionales, fitoquímica y enfatizando en la actividad biológica hallada en la literatura o encontrada por nosotros. Los hallazgos de esta revisión muestran que -en nuestro medio- el uso medicinal de plantas es una práctica habitual, con varias indicaciones para una misma especie vegetal (muchas de ellas no validadas científicamente), no siempre coinciden los usos en diferentes regiones de ancestro étnico o cultural común y menos aún en las más dispersas; a veces el resultado experimental no valida la indicación terapéutica tradicional y empírica, pero antes de declarar dicha indicación como inválida, deben hacerse varios ensayos preclínicos y clínicos indagando eficacia y seguridad. Debido a la enorme biodiversidad de la flora colombiana se pensaría que existe una amplia investigación en su farmacología y fitoquímica, pero la realidad es que existen pocas especies que se hayan validado mediante estudios químicos y biológicos; por ello, son muy bajos el aprovechamiento medicinal más generalizado y la explotación económica de dicha flora. En nuestro país solo unas pocas universidades estimulan las investigaciones en este campo y no se observa apoyo de la industria farmacéutica o de otras entidades gubernamentales o privadas. Por razones políticas y culturales, las comunidades indígenas se muestran renuentes a compartir sus conocimientos ancestrales etnofarmacológicos empíricos con otros grupos sociales. Cinco especies mostraron una promisoria actividad inmunoestimulante, aumentando el recuento leucocitario: Alternanthera williamsii (Standley) Standley var. purpurea, familia Amaranthaceae, Ludwigia polygonoides H.B.K., familia Onagraceae, Phenax rugosus (Poir.) Wedd, familia Urticaceae, Solanum dolichosepalum Bitter, familia Solanaceae y Tabebuia chrysantha (Jacq) Nichols, familia Bignoniaceae; cinco plantas: Alternanthera williamsii (Standley) Standley var. purpurea, Ludwigia polygonoides H.B.K., Austroeupatorium inulaefolium (H.B.K.) R. M. King & H. Rob., Senna reticulata (Willd) H. Irwin y Solanum dolichosepalum Bitter, tienen algún efecto antibacteriano importante particularmente sobre Staphylococcus aureus, Escherichia coli y Pseudomona aeruginosa.

The use of medicinal herbage plants with therapeutic purposes in the primary health careattention of the health, is a frequent practice in the Colombian coffee zonetriangle. Our research line group has done carried out some ethnopharmacologic studies in this zone, selecting some vegetal species to evaluate the possible antimicrobial, immunomodulating and hypoglycemic activity. The present review describes the nine species studied, with a short brief botanic description, common names, traditional empiric uses, phytochemistry, and emphasizing in on the biological activity found in the literature or in our assaysresearch. The findings of this review establish that, in this region environment, the medical use of plants is a habitual usual practice, with different indications for a the same vegetal species (a lot of them do notnot even validated scientifically), not always match the uses in different regions of common ethnic or culture cultural common ancestry not always match and even less in dispersewhen there are different ancestry regions; sometimes the experimental result does not validate the tradicional and empiric therapeutic indication but before to stablishestablishing such this indication as invalid, several pre-clinic and clinic trials must be carried out in order toshould be done some preclinical and clinical assays to search for the efficacy and safety. Due to the enormous biodiversity of Colombian flora it would be thought that there is have an extensive research about their its pharmacology and phytochemistry, but really there are a very few species validated by chemical and biological studies.; forFor this reason, there are very low medical and economic exploitation of this flora. In our country only a few Universities promote the research in this field and have not support of the pharmaceutical industry or of the government or private agencies is not observed. By Because of political and cultural reasons, the Indian indigenous communities are reluctant to share his their ancestral empiric ethnopharmacologic knowledgment knowledge with other social groups. Five species shown showed promissory immunostimulant activity by increasing leukocyte counts:. Alternanthera williamsii (Standley) Standley var. purpurea, Amaranthaceae family, Ludwigia polygonoides H.B.K., Onagraceae family, Phenax rugosus (Poir.) Wedd, Urticaceae family, Solanum dolichosepalum Bitter, Solanaceae family and Tabebuia chrysantha (Jacq) Nichols, Bignoniaceae family; five species: Alternanthera williamsii (Standley) Standley var. purpurea, Ludwigia polygonoides H.B.K., Austroeupatorium inulaefolium (H.B.K.) R. M. King & H. Rob., Senna reticulata (Willd) H. Irwin and Solanum dolichosepalum Bitter, have some important antibacterial effect on Staphylococcus aureus, Escherichia coli y Pseudomona aeruginosa.

The Present State and Future Direction of Rehabilitation Medicine in the Treatment of Rheumatoid Arthritis / The Japanese Journal of Rehabilitation Medicine

Protraction of RA induces joint function disorders resulting in a deterioration in the activities of daily living (ADL), which can cause a change in the patient's household role and limit their social participation. As there is not at present a curative treatment for RA, once functional disorders develop, they cannot be recovered easily or completely. However, it was recently reported that disorders progress rapidly within a few years from RA disease onset in terms of the changes wrought by joint damage and the resulting functional disorder inflicted on the patient. Therefore, it is proposed that adequate administration of methotrexate should be started initially and that RA treatment should be based on the recommendations under the regime of Treat to Target (T2T). Rehabilitation for RA patients includes various kinds of exercises and approaches such as physical therapy in the early stage and nursing home service with caregiver insurance in the terminal RA phase. In terms of the principles of T 2 T, the aim of the RA treatment is to improve the patients' long-term QOL as much as possible during their lifetime through the restoration of body functions and their participation in social activities. The ultimate aim of rehabilitation is the same as that of T 2 T because it is to let people with disabilities live normal lives by diminishing the difficulties RA patients face in daily life and improving their QOL. It is therefore very important to keep in mind that RA is a complex condition that includes people with various afflictions and difficulties in meeting their daily living tasks and not just one disease.

Biologic Agent for Rheumatoid Arthritis / 한양의대학술지

Decades of accumulated knowledge and improved comprehension of various perspectives on rheumatoid arthritis (RA) pathophysiology has led to the development of new biologic agents that inhibit a specific component of the RA inflammatory process. Especially during the last two decades, several epochal agents which target tumor necrosis factor-alpha, interleukin-1, interleukin-6, CD20-expressing B cell, and cytotoxic T lymphocyte antigen-4 were used in the management of RA and other autoimmune diseases with highly comparable efficacy and safety. Moreover, dozens of innovative agents queue up for clinical trials day by day. Herein, we review the current scenario of RA management in terms of pathogenesis and targeted molecular pathways, and some important controversies in this field as well. Based on the complications that these kinds of diseases pose, it is highly reasonable to hope that further improved therapies and more tailored drugs for RA will be introduced in the near future.

Curso de reumatologia: aula 10: tratamento atual da artrite reumatoide / Course of rheumatology: class 10: current treatment of rheumatoid arthritis

Os autores discutem a terapêutica para a artrite reumatoide (AR), com foco no tratamento biológico. Novos conhecimentos dos mecanismos patogênicos da AR mais a aplicação de biotecnologia propiciaram o desenvolvimento de tratamentos específicos contra moléculas envolvidas na inflamação da doença, os chamados tratamentos biológicos. Estes fármacos representam o maior avanço no controle da AR nesta última década. 0s agentes biológicos habitualmente aprovados para uso na AR são: etanercepte, receptor solúvel do TNE infliximabe e adalimumabe, ambos anticorpos monoclonais contra TNF. Todos estão disponíveis para uso pela secretaria de saúde. Outros aprovados para uso e não disponibilizados pela secretaria são o rituximabe e o abatacepte. Neste artigo discutimos cada um destes biológicos.

Authors discuss the therapies for rheumatoid arthritis focused on biological therapies. Biological therapies are the result of new insights into the pathogenic mechanisms of RA and the application of biotechnology on the development of therapies directed specifically against molecules involved with the inflammatory process of the disease. These agents represent the greatest advance in the control of RA during the last decade. Biological agents currently approved and accessible by government for the treatment of RA include: etanercept, a soluble recombinant anti-TNF receptor construct, in fliximab and adalimumab, both monoclonal antibodies against TNF. The others biologic, rituximab and abatacept, are also approved for treatment of RA but not available by government. In this essay authors study each one of these biologics agents.

Artrite reumatóide / Rheumatoid arthritis

A artrite reumatóide (AR) é uma doença crônica, sistêmica, auto-imune, de etiologia desconhecida, que envolve, predominantemente, as pequenas articulações das mãos e dos pés. Punhos, articulações metacarpofalangeanas, interfalangeanas proximais e metatarsofalangeanas são as articulações mais envolvidas. A patogênese é complexa e multifatorial, com participação de fatores genéticos, ambientais e hormonais. A realização do diagnóstico o mais rápido possível e o estabelecimento imediato de terapia adequada nas fases mais iniciais da doença são de fundamental importância para o prognóstico do paciente. O diagnóstico da AR é realizado através da avaliação das manifestações clínicas, achados laboratoriais e de imagem. O paciente apresenta, na maioria das vezes, um quadro de poliartrite tendendo a evoluir para deformidades articulares, com importante perda funcional devido à característica crônica e progressiva da doença. O fator reumatóide (FR) se encontra positivo em 70% a 80% dos pacientes com AR. Corresponde a um auto-anticorpo, geralmente classe IgM, dirigido contra a porção Fc da imunoglobulina IgG. Quando presente em títulos elevados, a doença é, geralmente, mais agressiva e tem maiores chances de apresentar manifestações extra-articulares. O início da terapêutica o mais rápido possível é baseado em dados de estudos clínicos, que demonstraram o benefício no curso evolutivo, prevenindo o dano articular, a perda da função e a redução da dor. O principal objetivo do tratamento é o de atingir a remissão. A base do tratamento da AR é a utilização das drogas modificadoras do curso da doença (DMCD), associadas a antiinflamatórios não hormonais (AINH) e antiinflamatórios hormonais (AIH). Os agentes biológicos são novas drogas que têm indicação nos pacientes que não responderam adequadamente ao uso dos DMCD.

Review of Tumor Necrosis Factor Inhibitors on Rheumatoid Arthritis / 대한류마티스학회지

Advanced knowledges of cellular and molecular biology led to the development of therapies of rheumatoid arthritis (RA). The introduction of biologic agents into clinical practice has had a profound effect on the current management of RA. These agents can rapidly enhance functional status and inhibit the progression of joint damage from the disease. Tumor necrosis factor (TNF) inhibitors are the representative biologic agents for the treatment of RA. Their clinical efficacy and safety were revealed through many clinical trails. Novel TNF inhibitors and other biologic agents for the treatment of RA are developing continuously. Promising biologic agents such as TNF inhibitors have become an important part of treatment armamentarium for RA, although they have some side effects and problems to be solved. These agents may contribute to achieve the sustained remission and eventually cure of RA. Currently available TNF inhibitors in Korea include etanercept, infliximab and adalimumab. This review article introduces past, present, and future of the TNF inhibitors and suggests guidelines for the proper use of them on RA.

Biologic Therapy in Rheumatoid Arthritis / 한양의대학술지

Rheumatoid arthritis (RA) is a common autoimmune disease of unknown etiology characterized by symmetric and erosive synovitis. The course of RA is usually chronic and progressive, so it can result destructive joint damages. Nonsteroidal anti-inflammatory drugs, disease modifying anti-rheumatic drugs (DM ARDs) and low-dose corticosteroid have been used for the treatments of RA. The importance of early usage of DMARDs are stressed recently, however, the effects of DMARDs on long-term prognosis is not convincing. Since 1998, several biologic agents were developed for RA and showed promising results. These agents include TNF-alpha blockers such as etanercept, infliximab, adalimumab, and IL-1 receptor antagonist such as anakinra. Clinical studies for rituximab, anti-IL-6 receptor monoclonal antibody, and CTLA4-Ig are underway. The biologic agents show rapid improvement in clinical and laboratory parameters and may prevent the erosions on Xray, but because of costs and unknown long-term side effects, we should be more careful for using these drugs.

Toward the cure of rheumatoid arthritis / 대한내과학회지

No abstract available.