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.

Síndrome de Vogt-Koyanagi-Harada / Vogt-Koyanagi-Harada Syndrome

El síndrome de Vogt-Koyanagi-Harada es una enfermedad autoinmune multisistémica crónica, caracterizada por panuveítis difusa granulomatosa bilateral con desprendimiento exudativo de retina y papilitis. Compromete el sistema nervioso central (meninges, disacusia neurosensorial) así como piel y mucosas. A pesar de ser una enfermedad compleja y poco frecuente, se hace necesario comprender la importancia del diagnóstico rápido y el tratamiento oportuno con seguimiento especializado. Es por ello que se decidió realizar una revisión de la literatura con el objetivo de actualizar los conocimientos existentes sobre este tema. La búsqueda se realizó en diferentes publicaciones y textos básicos de la especialidad. Las fuentes consultadas fueron las bases de datos PubMed y Google Scholar. El diagnóstico de la enfermedad es esencialmente clínico y son los oftalmólogos quienes más lo sospechan por ser los síntomas oculares los más frecuentes y dramáticos. El pronóstico visual de los pacientes es generalmente bueno si el diagnóstico es precoz y se indica un tratamiento adecuado. Los corticosteroides sistémicos a altas dosis asociados a inmunosupresores y agentes biológicos tienen gran impacto en la evolución de la enfermedad, sobre todo estos últimos a nivel mundial, previniendo complicaciones y permitiendo resultados visuales satisfactorios para una mejor calidad de vida del paciente(AU)

Vogt-Koyanagi-Harada syndrome is a chronic multisystem autoimmune disease characterized by bilateral diffuse granulomatous panuveitis with exudative retinal detachment and papillitis. It involves the central nervous system (meninges, sensorineural dysacusis) as well as skin and mucous membranes. In spite of being a complex and infrequent disease, it is necessary to understand the importance of rapid diagnosis and timely treatment with specialized follow-up. For this reason, it was decided to carry out a review of the literature with the aim of updating the existing knowledge on this subject. The search was carried out in different publications and basic texts of the specialty. The sources consulted were the PubMed and Google Scholar databases. The diagnosis of the disease is essentially clinical and it is the ophthalmologists who suspect it the most because the ocular symptoms are the most frequent and dramatic. The visual prognosis of patients is generally good if the diagnosis is early and adequate treatment is indicated. Systemic corticosteroids at high doses associated with immunosuppressants and biological agents have a great impact on the evolution of the disease, especially the latter worldwide, preventing complications and allowing satisfactory visual results for a better quality of life of the patient(AU)

Efficacy and safety of ustekinumab in the treatment of moderate to severe plaque psoriasis in Singapore

INTRODUCTION@#Ustekinumab is a human monoclonal antibody that binds to the p40 subunit of both interleukin (IL)-12 and IL-23, and it is approved for the treatment of moderate to severe plaque psoriasis. In this study, we assessed the efficacy and safety of patients receiving ustekinumab for psoriasis.@*METHODS@#This retrospective study included all adults with chronic plaque psoriasis who were prescribed ustekinumab in a tertiary dermatologic centre between December 2009 and December 2015. Efficacy end points included a proportion of patients achieving at least 50% and 75% improvement from baseline psoriasis area and severity index (PASI) and body surface area (BSA) at Weeks 4 and 16.@*RESULTS@#A total of 99 patients were prescribed ustekinumab; 69% of these were Chinese, followed by 15% Indians and 9% Malays. 31 patients had documented PASI scores and 55 patients had documented BSA improvements. In patients with recorded PASI scores, 29 (93.5%) of 31 patients achieved PASI 50, and 21 (67.7%) of 31 achieved PASI 75 at week 16. In patients with recorded BSA, 43 (78.2%) of 55 had at least 50% BSA improvement, and 31 (56.4%) of 55 achieved 75% BSA improvement at 16 weeks. Regarding safety, no patient experienced tuberculosis reactivation. A total of 11 (11%) of 99 patients had latent tuberculosis infection and were treated with prophylactic isoniazid. No patient experienced serious adverse events. No cardiovascular events, cutaneous malignancies or deaths were reported over six years.@*CONCLUSION@#Ustekinumab is safe and efficacious in the treatment of patients with moderate to severe plaque psoriasis in a multiethnic Asian population.

New progress on the use of Dual Biologic Therapy for patients with Inflammatory Bowel Disease / 中国综合临床

At present, the incidence of inflammatory bowel disease in China is increasing. Although new biological agents continue to emerge, which induce a higher clinical remission rate in moderate and severe patients than traditional drugs and have much advantages in reducing the risk of surgery and changing the natural history, the remission rate of biological agents monotherapy is still not enough. In this context, dual biologic therapy is a viable strategy. Dual biologic therapy is mainly indicated for patients with inflammatory bowel disease that is refractory or complicated with extraintestinal manifestations.It is often used in combination with clinical practice according to the characteristics of drugs, showing relatively great efficacy and safety, but a series of key questions still need a high level of research evidence to explore.

Application of biologic agents in the treatment of bullous pemphigoid / 中华皮肤科杂志

In recent years, new therapeutic targets for bullous pemphigoid (BP) have continued to emerge, and new biologic agents targeting pathogenic antibodies, complements, T helper type 2 (Th2) and Th17 cytokines in BP have also successively entered clinical trials, e.g., the CD20-targeting antibody rituximab and the IgE-targeting antibody omalizumab have been applied in clinical practice and have benefited some patients with refractory BP. This review summarizes the literature and clinical trials related to biologic agents as the treatment strategy for BP, analyzes and discusses clinical application of new biological agents in BP, in order to provide new ideas for the treatment of refractory BP.

The value of drug concentration and anti-drug antibody monitoring in biologic therapy for inflammatory bowel disease / 中华检验医学杂志

Inflammatory bowel disease (IBD) is a chronic relapsing autoimmune disorder of the gastrointestinal tract. In recent years, biologic agents have been widely used in the treatment of IBD, significantly ameliorating symptoms in affected individuals. However, immunogenicity of these medications remains a limiting factor in IBD biologic therapy. The appropriate drug concentration is of great significance in improving the efficacy of biological agents, reducing the production of anti-drug antibodies, and reducing adverse reactions. Therefore, monitoring drug trough concentrations and anti-drug antibody levels during treatment can optimize medication usage and facilitate more informed adjustments to treatment strategies. This article elaborates on the mechanism and reasons for the generation of anti-drug antibodies, as well as the significance, timing, effectiveness, and detection methods of drug concentration and anti-drug antibody monitoring. Thus, it underscores the value of drug concentration and anti-drug antibody monitoring in the context of biologic therapy for IBD.

Potential biological factors affecting the efficacy of immunotherapy for triple-negative breast cancer / 肿瘤

Triple-negative breast cancer(TNBC)is characterized by strong aggressiveness,high metastatic potential,easy recurrence and poor prognosis.Due to lack of expression for estrogen receptor(ER),progesterone receptor(PR)and human epidermal growth factor(HER2)in TNBC patients,there is a lack of specific therapeutic targets and effective treatment plans for TNBC.At present,immunotherapy has been widely used in solid tumors.Immune checkpoint inhibitors(ICIs)have shown some preliminary clinical effects in the treatment of TNBC,but there were still some patients who do not respond to ICIs therapy or develop resistance,and multiple clinical studies cannot obtain consistent results on the efficacy of ICIs.Therefore,,we reviewed the potential biological factors that influence the efficacy of ICIs in TNBC,aiming to explore the mechanisms affecting the efficacy of ICIs and analyze its potential clinical value.

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.

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.

Application progress of mesh in the environment of potential contaminated and contaminated abdominal hernia repair / 国际外科学杂志

Abdominal hernia repair is a challenging surgery with high complication rate and recurrence rate, especially in potentially contaminated or contaminated abdominal wall hernias. The application of hernia mesh has significantly reduced the recurrence rate. However, different types of meshes have their own advantages and disadvantages. There are still controversies regarding the selection of mesh in the environment of potential contaminated and contaminated abdominal hernia repair. The biological mesh, which was once considered that have anti-infection advantages and was widely used, has not been found to reduce the infection rate in recent studies, but instead leads to a higher recurrence rate and expensive medical costs. On the contrary, synthetic mesh represented by monofilament and large mesh polypropylene mesh have achieved good results in potentially contaminated or contaminated hernia repairs recently. The emergence of new types of meshes such as absorbable synthetic mesh may be a better choice for potentially contaminated or contaminated abdominal hernia repair. This article reviews the application progress of mesh in the environment of potential contaminated and contaminated abdominal hernia repair, aiming to provide reliable evidence for the selection of mesh for these patients.

Clinical value of peripheral blood circulating tumor cells in the diagnosis and treatment of prostate cancer / 中国基层医药

Objective:To investigate the clinical value of peripheral blood circulating tumor cells (CTC) in the diagnosis and treatment of prostate cancer.Methods:Sixty-four patients with prostate cancer who received treatment in Xinjiang Production and Construction Corps Hospital, China between June 2018 and May 2020 were included in the cancer group. An additional 35 patients with benign prostatic lesions who concurrently received treatment in the same hospital were included in the benign disease group. Twenty male patients with non-prostate disease were included in the control group. Cell enrichment, separation, staining and identification together with Gleason score and pathological stage were subjected to one-way analysis of variance.Results:The percentage of patients with CTC count ≥ 3 in the cancer, benign disease and control groups was 73.43% (47/64), 17.14% (6/35) and 10.00% (2/20), respectively. The level of prostate-specific antigen in patients with CTC was significantly higher than that in patients without CTC ( t = 2.89, P < 0.05). There was significant difference in CTC count between different Gleason score groups ( F = 3.25, P < 0.05) and between different pathological stage groups ( F = 3.42, P < 0.05). Conclusion:Peripheral blood CTC measurement can be used as an auxiliary method for the differentiation of benign and malignant prostate diseases. CTC count in patients with prostate cancer is correlated with prostate-specific antigen level, Gleason score, and pathological stage. Therefore, peripheral blood CTC measurement plays an auxiliary role in predicting prognosis in patients with CTC. This study is innovative and scientific.

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.

A framework for advanced technology medicines from the perspective of community pharmacists; with or without technology

Abstract Nowadays, the number of medicines manufactured using advanced technologies such as biotechnology, nanotechnology, and 3D printing is increasing along with the accelerated pace of technological change. Evaluating high technology medicines from the perspective of community pharmacists is important for the quality of the pharmacy practice. The aim is to analyze the knowledge, attitude, and behavior of community pharmacists regarding advanced technology medicines and to examine the social and ethical aspects from the pharmacist's perspective. A face-to-face cross-sectional survey was conducted with each of the 879 community pharmacists in Istanbul using a stratified sampling method. In this context, the gaps in pharmacists' knowledge of high technology medicines were determined. It has been found that the pharmacists' level of knowledge and willingness to learn new technologies differs according to the current education levels of the pharmacists and diversity in patient profiles. The pharmacists should close the knowledge gaps and update their information about medicines that are manufactured via the implementation of advanced technologies. The more pharmacists adapt to technology, the better guidance they can offer to society. This will also ensure that communication between the pharmacist and the patient to be built on trust, and significantly improve pharmacy practice.

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.

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.

Presente y futuro del tratamiento biológico y moléculas pequeñas en la dermatitis atópica / Present and future of biological treatment and small molecules in atopic dermatitis

La dermatitis atópica (DA) es una condición inflamatoria crónica de la piel de etiología multifactorial. Buscando mejorar la respuesta clínica minimizando los efectos adversos y ampliar el arsenal terapéutico disponible, se ha dado pie al desarrollo de nuevos fármacos con resultados prometedores en la calidad de vida. Los inmunomoduladores sistémicos clásicos son considerados el tratamiento estándar en los casos de DA moderada a severa refractaria al tratamiento con corticoides tópicos. Estos se encasillan dentro de las denominadas moléculas pequeñas, junto con los inhibidores de Janus- en un efecto pleiotrópico en las citoquinas y por ende, no selectivo. Los medicamentos biológicos poseen ventajas frente a los inmunomoduladores clásicos, principalmente su mayor especificidad gracias a la similitud con las moléculas endógenas. Dupilumab se mantiene siendo el único fármaco biológico aprobado por la FDA para el tratamiento de la DA, con una seguridad a corto plazo demostrada. Algunas moléculas nuevas, como el tralokinumab y los inhibidores JAK, presentan resultados prometedores. De este grupo, abrocitinib pareciera posicionarse como una alternativa al menos similar que dupilumab. La creciente investigación de nuevas alternativas ha creado una revolución terapéutica para que nuestros pacientes puedan acceder a una mejor calidad de vida. No obstante, es difícil lograr comprender la efectividad y seguridad de cada uno de los tratamientos disponibles, por la falta de estudios comparativos. La siguiente revisión muestra las nuevas terapias biológicas y algunas moléculas pequeñas con evidencia para su uso en DA

Atopic dermatitis (AD) is a chronic inflammatory condition of the skin with a multifactorial etiology. Seeking to improve the clinical response by minimizing adverse effects and expanding the available therapeutic arsenal, the development of new drugs has led to promising results on quality of life. Classic systemic immunomodulators are considered the standard treatment in cases of moderate to severe AD refractory to treatment with topical corticosteroids. These are classified into molecules, along with Janus kinase inhibitors (JAKs). Small molecules act on intracellular targets, with the inconveniency of producing a pleiotropic effect on cytokines and, therefore, non-selective actions. Biologics have advantages over classical immunomodulators, mainly their greater specificity thanks to the similarity between endogenous molecules. Dupilumab remains the only biologic drug approved by the FDA for the treatment of AD, with demonstrated short-term safety. Some new molecules, such as tralokinumab and JAK inhibitors, have shown promising results. Of this group, abrocitinib seems to be positioned as an alternative at least similar to dupilumab. The current investigation of new alternatives has created a therapeutic revolution so that we can offer our patients a better quality of life. However, it is difficult to understand the efficacy and safety of each of the available treatments due to the lack of comparative studies. The following review shows the new biological therapies and small molecules with evidence for their use in DA.

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.

Análise crítica do uso dos anti-TNF na era dos novos agentes biológicos na doença inflamatória intestinal / Critical analysis of anti-tnf use in the era of new biological agents in inflammatory bowel disease

ABSTRACT BACKGROUND: Inflammatory bowel diseases (IBD), both Crohn's disease and ulcerative colitis, are chronic immune-mediated diseases that present a relapsing and remitting course and requires long-term treatment. Anti-tumor necrosis factor (anti-TNF) therapy has changed the management of the disease by reducing the need for hospitalizations, surgeries and improving patient´s quality of life. OBJECTIVE: The aim of this review is to discuss the role of anti-TNF agents in IBD, highlighting the situations where its use as first-line therapy would be appropriate. METHODS: Narrative review summarizing the best available evidence on the topic based on searches in databases such as MedLine and PubMed up to April 2020 using the following keywords: "inflammatory bowel disease'', "anti-TNF agents" and ''biologic therapy''. CONCLUSION: Biological therapy remains the cornerstone in the treatment of IBD. In the absence of head-to-head comparisons, the choice of the biological agent may be challenging and should take into account several variables. Anti-TNF agents should be considered as first line therapy in specific scenarios such as acute severe ulcerative colitis, fistulizing Crohn's disease and extra-intestinal manifestations of IBD, given the strong body of evidence supporting its efficacy and safety in these situations.

RESUMO CONTEXTO: As doenças inflamatórias intestinais (DII), tanto a doença de Crohn (DC) como a retocolite ulcerativa (RCU), são doenças crônicas imunomediadas que se apresentam com períodos de surto e remissão e requerem terapia a longo prazo. A terapia com anti-fator de necrose tumoral (anti-TNF) tem mudado o manejo da doença reduzindo a necessidade de hospitalizações, cirurgias e melhorando a qualidade de vida dos pacientes. OBJETIVO: O objetivo do presente trabalho é apresentar uma revisão sobre a importância dos agentes anti-TNF no contexto da DII, levando em consideração situações em que essas drogas são usadas como terapia de primeira linha. MÉTODOS: Revisão narrativa baseada nas melhores evidências disponíveis na literatura através de buscas feitas nas bases de dados MedLine e PubMed até abril de 2020, utilizando as seguintes palavras chaves: "doença inflamatória intestinal'', "agentes anti-TNF" e "terapia biológica". CONCLUSÃO: A terapia biológica permanece sendo fundamental no tratamento da DII. Na ausência de estudos "head-to-head'' comparando os biológicos entre si, a escolha do agente biológico pode ser um desafio na prática clínica e múltiplas variáveis devem ser levadas em consideração. Os agentes anti-TNF devem ser considerados terapia de primeira linha em situações específicas como na colite ulcerativa aguda grave, na doença de Crohn fistulizante e nas manifestações extra-intestinais da doença inflamatória intestinal, uma vez que há evidências científicas robustas que sustentam a sua eficácia e segurança nessas situações.

Vacunas en salud laboral: una oportunidad para prevenir e invertir en salud / Vaccines in occupational medicine: an opportunity to prevent and invest in health

La vacunación es la medida preventiva más costo-efectiva para evitar las enfermedades infecciosas inmunoprevenibles, a nivel individual y comunitario. Los riesgos biológicos laborales, deben ser manejados en un sistema de gestión del riesgo, donde la vacuna es el elemento clave de protección personal (EPP) específico cuya provisión y uso obligatorio tiene normas legislativas referidas a la entrega por el empleador, la capacitación en la prevención y el uso por el trabajador. En Chile, hay 8.364.282 trabajadores según datos de Superintendencia de Seguridad Social (SUSESO). La Ley 16.744 y sus Decretos Supremos (DS) indican las condiciones que se deben mantener en los lugares de trabajo y el derecho a saber por parte del trabajador; también existen circulares del Ministerio de Salud que incluyen situaciones y grupos especiales laborales a vacunar, pero es necesaria una normativa que oriente a trabajadores dependientes e independientes y a empleadores sobre qué vacunas colocar, en qué situaciones y a quiénes dependiendo de la actividad laboral. En este artículo, hacemos una reseña de la situación legal, de recomendaciones en otros países y enumeramos algunas vacunas que podrían implementarse en la población expuesta a riesgo.

Vaccination is the most cost-effective measure for immune-preventable infectious diseases, at individual and community level. Biological occupational hazards must be faced in a risk management system, where the vaccine is a specific key as an element of personal protection, whose provision and obligatory use has legislative norms related to the delivery by the employer, the training in the prevention and the use by the worker. Several countries count with technical guides for vaccination in the working population. In Chile in 2018, there were 8.364.282 workers according with Superintendence of Social Security. Law 16.744 and Supreme Decrees indicate the environmental conditions for workers and the right to know the risks; also, Ministry of Health has issued circulars where some working conditions need specific vaccination. Is for that reason that is necessary a regulation that guides dependent and independent workers and employers on when and which vaccines must be used depending on the labor activity. In this article, we review the legal situation, other guides in different countries and list some vaccines that could be implemented in the population at specifical risks.

Guselkumab in moderate-to-severe plaque psoriasis: effectiveness in real clinical practice / Guselkumab en placa de moderada a grave psoriasis: eficacia en la práctica clínica real

Introducción: La psoriasis es una enfermedad cutánea inflamatoria crónica inmunomediada que afecta a casi el 1-2% de la población mundial. El tratamiento biológico de la psoriasis moderada a grave ha cambiado el paradigma de manejo de la enfermedad, permitiendo un mejor control de la misma. Métodos: Se llevo a cabo un estudio observacional retrospectivo que incluyó a pacientes con psoriasis moderada a grave que fueron tratados durante al menos 36 semanas con guselkumab. La eficacia se evaluó mediante la estimación de pacientes que alcanzaron las respuestas PASI 75, PASI 90 y PASI 100 en las semanas 16, 24 y 36. Se utilizó la prueba T de Student para muestras pareadas para determinar la significación estadística entre PASI al inicio y respuesta PASI en las semanas 16, 24 y 36. Resultados: Se incluyeron 22 pacientes, 14 mujeres (63, 6%), con una edad media de 48, 7 ± 15, 5 años. El tratamiento con guselkumab redujo el PASI medio de 10, 3 ± 6 al inicio del estudio a 2, 4 ± 2 (p = 0,003), 1, 3 ± 1, 8 (p = 0,001) y 0, 3 ± 0, 6 (p = 0,001) a las 16, 24 y 36 semanas, respectivamente. Discusión: El primer fármaco en unirse al arsenal terapéutico anti-IL23 fue guselkumab. La eficacia obtenida fue superior a la observada en estudios fase III para PASI 90 y 100 a la semana 36. Existen algunos estudios que han evaluado la eficacia a corto plazo de guselkumab en la práctica clínica real; sin embargo, este fármaco se ha comercializado recientemente, limitando la posibilidad de evaluación durante períodos de tiempo más prolongados. Conclusión: Guselkumab presenta buenos resultados en el manejo de la psoriasis en adultos. La práctica clínica real a medio y largo plazo será fundamental, con un mayor tamaño muestral y período de seguimiento.

Introduction: Psoriasis is a chronic immune­ mediated inflammatory skin disease that affects nearly 1­2% of the population worldwide. Biologic treatment of moderate-to-severe psoriasis has changed the disease management paradigm, allowing for better disease control. Methods: A retrospective observational study including patients with moderate-to-severe psoriasis who were treated for at least 36 weeks with guselkumab. Efficacy was evaluated by estimating the proportion of patients achieving PASI 75, PASI 90 and PASI 100 responses at weeks 16, 24 and 36. The Student t-test for paired samples was used to determine the significant difference in outcome of patients between PASI at baseline and PASI response at weeks 16, 24 and 36. Reslts: 22 patients were included, 14 women (63.6%), with mean age of 48.7±15.5. Guselkumab treatment decreased mean PASI from 10.3±6 at baseline to 2.4±2 (p=0.003), 1.3±1.8 (p=0.001) and 0.3±0.6 (p=0.001) at 16, 24 and 36 weeks, respectively. Discussion: The first anti-IL23 drug family to join the therapeutic arsenal is guselkumab. The efficacy obtained is higher than that observed in phase III studies for PASI 90 and 100 at week 36. There are some studies that have evaluated the short-term effectiveness of guselkumab in real clinical practice; however, this drug has only recently been marketed, limiting the possibility of as yet longer treatment periods. Conclusion: Guselkumab shows great results in the management of psoriasis in adults. Medium- and long-term real clinical practice will be essential, with a larger sample size and longer follow-up period.