Seguridad de las drogas biológicas y sintéticas dirigidas utilizadas en pacientes con enfermedades reumáticas inmunomediadas. Datos del registro BIOBADASAR 3.0 / Safety of biological and targeted synthetic drugs in patients with immune-mediated rheumatic diseases. Data from the BIOBADASAR 3.0 registry

Introducción: conocer la seguridad de las drogas actualmente disponibles para el tratamiento de las enfermedades reumáticas es muy importante al momento de tomar decisiones terapéuticas objetivas e individualizadas en la consulta médica diaria. Asimismo, datos de la vida real amplían el conocimiento revelado por los ensayos clínicos. Objetivos: describir los eventos adversos (EA) reportados, estimar su frecuencia e identificar los factores relacionados con su desarrollo. Materiales y métodos: se utilizaron datos BIOBADASAR, un registro voluntario y prospectivo de seguimiento de EA de tratamientos biológicos y sintéticos dirigidos en pacientes con enfermedades reumáticas inmunomediadas. Los pacientes son seguidos hasta la muerte, pérdida de seguimiento o retiro del consentimiento informado. Para este análisis se extrajeron datos recopilados hasta el 31 de enero de 2023. Resultados: se incluyó un total de 6253 pacientes, los cuales aportaron 9533 ciclos de tratamiento, incluyendo 3647 (38,3%) ciclos sin drogas modificadoras de la enfermedad biológicas y sintéticas dirigidas (DME-b/sd) y 5886 (61,7%) con DME-b/sd. Dentro de estos últimos, los más utilizados fueron los inhibidores de TNF y abatacept. Se reportaron 5890 EA en un total de 2701 tratamientos (844 y 1857 sin y con DME-b/sd, respectivamente), con una incidencia de 53,9 eventos cada 1000 pacientes/año (IC 95% 51,9-55,9). La misma fue mayor en los ciclos con DME-b/sd (71,1 eventos cada 1000 pacientes/año, IC 95% 70,7-77,5 versus 33,7, IC 95% 31,5-36,1; p<0,001). Las infecciones, particularmente las de la vía aérea superior, fueron los EA más frecuentes en ambos grupos. El 10,9% fue serio y el 1,1% provocó la muerte del paciente. El 18,7% de los ciclos con DME-b/sd fue discontinuado a causa de un EA significativamente mayor a lo reportado en el otro grupo (11,5%; p<0,001). En el análisis ajustado, las DME-b/sd se asociaron a mayor riesgo de presentar al menos un EA (HR 1,82, IC 95% 1,64-1,96). De igual manera, la mayor edad, el mayor tiempo de evolución, el antecedente de enfermedad pulmonar obstructiva crónica, el diagnóstico de lupus eritematoso sistémico y el uso de corticoides se asociaron a mayor riesgo de EA. Conclusiones: la incidencia de EA fue significativamente superior durante los ciclos de tratamientos que incluían DME-b/sd.

Introduction: knowing the efficacy and safety of the drugs currently available for the treatment of rheumatic diseases is very important when making objective and individualized therapeutic decisions in daily medical consultation. Likewise, real-life data extends the knowledge revealed by clinical trials. Objectives: to describe the reported adverse events (AEs), estimate their frequency and identify factors associated to them. Materials and methods: BIOBADASAR data were used, which is a voluntary, prospective follow-up registry of AEs of biological and synthetic treatments in patients with immune-mediated rheumatic diseases. Patients are followed until death, loss of followup, or withdrawal of informed consent. To carry out this analysis, the data collected up to January 31, 2023 was extracted. Results: a total of 6253 patients were included, who contributed with 9533 treatment periods, including 3647 (38.3%) periods without b/ts-DMARDs and 5886 (61.7%) with b/ts-DMARDs. Among the latter, the most used were TNF inhibitors and abatacept. A total of 5890 AEs were reported in a total of 2701 treatments (844 and 1857 without and with b/ts-DMARDs, respectively), with an incidence of 53.9 events per 1000 patients/ year (95% CI 51.9-55.9). It was higher during the periods with b/ts-DMARDs (71.1 events per 1000 patients/year, 95% CI 70.7-77.5 vs 33.7, 95% CI 31.5-36.1, p<0.001). Infections, particularly those of the upper respiratory tract, were the most frequent AEs in both groups. 10.9% were severe and 1.1% were associated with the death of the patient. 18.7% of the periods with b/ts-DMARDs were discontinued due to an AE, significantly higher than that reported in the other group (11.5%; p<0.001). In the adjusted analysis, b/ts-DMARDs were associated with a higher risk of presenting at least one AE (HR 1.82, 95% CI 1.64-1.96). Similarly, older age, longer evolution time, history of chronic obstructive pulmonary disease, diagnosis of systemic lupus erythematosus, and use of corticosteroids were associated with a higher risk of AE. Conclusions: the incidence of AEs was significantly higher during those treatment periods that included DME-b/sd.

Approaches in the treatment of perianal fistula in Crohn disease

Perianal fistula is a common complication of Crohn disease, and it is a great burden on the life and psychology of patients, but its treatment is still a difficult problem to face. In recent years, progress in the treatment of Crohn disease has progressed rapidly due to the advent of biological agents, but there has been a lack of research on perianal fistula in Crohn disease, and the direction of research has been scattered; therefore, the author reviews the traditional treatment of perianal fistula in Crohn disease in the context of the available literature and discusses emerging and potential therapeutic approaches. (AU)

Tratamientos y bioterapias para COVID-19 / Therapeutics and biotherapies for covid-19

INTRODUCCIÓN: Un nuevo brote de coronavirus surgió en 2019 en Wuhan, China, causando conmoción en el sistema sanitario de todo el mundo; el Comité Internacional de Taxonomía de Virus lo denominó SARS-CoV-2, agente causante de la enfermedad COVID-19.El espectro de gravedad de la enfermedad es muy amplio: la mayoría de los pacientes no presentan gravedad, pero otros pueden desarrollar neumonías, y la insuficiencia respiratoria aguda es la causa más frecuente de mortalidad. Objetivo: analizar y desarrollar las distintas alternativas terapéuticas aportadas por la Biotecnología para tratar los síntomas de aquellos pacientes con COVID-19. Metodología: se realizó una revisión de la bibliografía disponible, a partir de enero de 2020 en PubMed, acerca de los tratamientos que se encuentran aún en ensayos clínicos y aquellos que cuentan con aprobación bajo uso de emergencia para la enfermedad COVID-19. También se realizaron búsquedas a través de Google y Google Académico para publicaciones de organismos de Salud en referencia a políticas de salud establecidas para la terapéutica durante dicha pandemia. Resultados: este trabajo aborda las nuevas alternativas terapéuticas para COVID-19 derivadas de la Biotecnología, que se encuentran tanto en uso como en etapas de ensayos clínicos comprendidos dentro del segmento de los biofármacos y las bioterapias. Se incluye un breve resumen del estatus regulatorio de entidades de salud, el mecanismo de acción de dichas terapias y características generales de cada uno. Se incluyen novedosas bioterapias que se empezaron a implementar para afrontar la pandemia. Conclusiones: la pandemia de coronavirus está poniendo a prueba el sistema sanitario internacional, para brindar soluciones tanto desde el diagnóstico y prevención como para el tratamiento de la población a fin de disminuir la mortalidad. Esto incluyó, obviamente también, al área de la Biotecnología aplicada a la salud, que ha aportado en los tres aspectos mencionados; el presente trabajo se centra en las respuestas de tipo terapéutico que ha brindado y que están comercializadas o en fases clínicas. (AU)

INTRODUCTION: A new coronavirus outbreak emerged in 2019 in Wuhan, China, causing a shock to the healthcare system around the world; the International Committee on Taxonomy of Viruses named it SARS-CoV- 2, the infectious agent of the COVID-19 disease. The spectrum of severity of the disease is very wide, most patients are not serious, but others can develop pneumonia, with acute respiratory failure being the most frequent cause of mortality. Objective: to analyze and develop the different therapeutic alternatives provided by Biotechnology dedicated to Health, to treat the symptoms of those COVID-19 patients who require it, and thus reduce mortality.Methodology: a review of the available literature from January 2020 in PubMed of the treatments that are still in clinical trials and those that have been approved under emergency use for the disease COVID-19 was performed. Searches were also carried out through Google and Google Scholar for publications of Health organizations in reference to health policies established for therapeutics during the mentioned pandemic. Results: this work addresses the new therapeutic alternatives derived from Biotechnology, which are both in use and in stages of clinical trials, to treat patients who developed COVID-19 included within the segment of biopharmaceuticals and biotherapies. A brief summary of the regulatory status of health entities, the mechanism of action of said therapies and general characteristics of each one is included. Innovative biotherapies that began to be implemented to face the pandemic are included. Conclusions: The coronavirus pandemic has driven the international health system to the test, to provide solutions both from the diagnosis, prevention and treatment of the population to reduce the mortality of patients. This obviously also included the area of Biotechnology applied to health, which has contributed in the three aspects mentioned. The present work focuses on the therapeutic responses that it has provided and that are commercialized or in clinical phases. (AU)

Criptococosis diseminada por terapia biológica, se debe gestionar el riesgo / Disseminated cryptococcosis by biological therapy: We must manage the risk

Introducción. Se han descrito múltiples efectos adversos con el uso de la terapia biológica para enfermedades autoinmunitarias, muchos de ellos secundarios al estado de inmunosupresión, como las infecciones bacterianas, fúngicas o virales. Caso clínico. Se presenta el caso de una mujer de 64 años con diagnóstico comprobado de criptococosis diseminada secundaria al uso de tofacitinib. Se descartaron otras causas de inmunosupresión, como infección por el virus de la inmunodeficiencia humana (HIV). Tres años antes se le había diagnosticado artritis reumatoide y se encontraba en tratamiento farmacológico con un agente biológico que inhibe las enzimas JAK. Se han descrito muy pocos casos de criptococosis pulmonar y meníngea en este tipo de pacientes. Conclusión. Este reporte de caso es útil para que otros médicos tratantes tengan presente la posibilidad de este tipo de infección fúngica invasora asociada con la terapia biológica y el enfoque de gestión de riesgo.

Introduction: Multiple adverse effects have been described for the biological therapy in autoimmune diseases including many secondary to immunosuppression producing bacterial, fungal, or viral infections. Clinical case: We present the case of a 64-year-old female patient with proven disseminated cryptococcosis secondary to the use of tofacitinib. Other possible causes of immunosuppression such as the human immunodeficiency virus (HIV) were ruled out. The patient had been in treatment for rheumatoid arthritis diagnosed three years before. This drug is a biological agent that inhibits JAK enzymes. Very few cases of pulmonary and meningeal cryptococcosis in this type of patient have been described in the literature. Conclusion: This case report should be useful for other clinicians to bear in mind the possibility of this type of invasive fungal infection associated with biological therapy and to take a risk-management approach.

Hyperadrenocorticism treatment of a dog with high dilution: case report

Hyperadrenocorticism is a common endocrinopathy in dogs, associated to an excessive production or administration of cortisol.Aims:Report the evolution of homeopathic treatment in spontaneous hyperadrenocorticism analyzing with basal and post-acth stimulation cortisol values of a yorkshire male dog with 10 years old, diagnosed from the suppression test with low dose of dexamethasone and stimulation with ACTH, as well as complementary tests.Methodology: Homeopathic treatment was chosen, based on the principle of similitude usingIgnatia amarabecause the patient presents repertorized mental symptoms such as separation anxiety syndrome, docility, annoyances and jealousy and also because it is efficient and less harmful. It was associated to cortisol biotherapy to inhibit cortisol production and adrenal biotherapy to control the response of excess of the cortisol producted by the gland. The exposed information is consented by the tutor.Results:The dog was in convencional treatment with trilostane but didn't response to the therapy, showing 5,41 µg/dL of basal result and 11,8 µg/dL of post-acth result and the symptoms were worst on 12/12/2021, presenting lethargic, panting, more evident alopecia and severe muscle weakness which the patient unable to stand. Therefore, the protocol was recommended for 3 months, included 3 globules ofIgnatia amara30cH orally, every 12 hours, 3 globules of cortisol biotherapy 30 cH and also of adrenal biotherapy 6 cH every 24 hours. On 03/28/2022 the basal and post-acth stimulation results was 3,71 µg/dL e 5,79 µg/dL respectively and the patient was more active, the skin was better and even with difficulty it was movingand having more independence.Conclusion: Homeopathic treatment with high dilution was effective, keeping the indices with the recommended range of post acth between 2.0 and 5.0, confirming an adequate therapeutic monitoring and symptomatic improvement.

Biological therapy in psoriatic arthritis patients with and without previous biologic experience / Terapia biológica em pacientes com artrite psoriásica com e sem experiência prévia no uso de medicamentos biológicos

Objective: this study evaluated the biological therapy effects on disease activity, functionality, quality of life, drug survival, and safety of patients with psoriatic arthritis naïve and experienced in biological therapy. Methods: a one-year prospective observational study was performed. The outcomes assessed were drug survival, disease activity, functionality, quality of life, and safety. Multiple linear regression was used to assess predictive factors for clinical re-sponse. Results: a total of 205 patients were included, 155 of whom were biologic naïve and 50 biologic experienced. Drug survival rate was greater for naïve patients than experienced patients at 6 months, but not at 12 months. Drug survival rates were 71.5% for naïve patients and 70.0% for experienced patients at 12 months. All clinical parameters improved for both biologic naïve and experienced patients. At 12 months, 63% of naïve patients and 52% of expe-rienced patients had an improvement in their quality of life. Besides, 48% of naïve patients and 42% of experienced patients had an improvement in functionality. The axial disease improved in 67% of naïve individuals and 56% of experienced patients. Good control of peripheral disease was achieved by 49% of naïve patients and 44% of experi-enced patients. Female sex, use of etanercept or infliximab, and lower functionality or quality of life at baseline were the main predictors of poor clinical response. Conclusion: Patients' health improved after starting biological therapy. In general, biologic experienced patients had more adverse reactions and lesser effectiveness (AU)

Objetivo: avaliar os efeitos da terapia biológica sobre a atividade da doença, funcionalidade, qualidade de vida, per-sistência no tratamento e segurança em pacientes com artrite psoriásica sem experiência e com experiência prévia em terapia biológica. Métodos: um estudo observacional prospectivo de um ano foi realizado. Os desfechos avaliados foram a persistência no tratamento, atividade da doença, funcionalidade, qualidade de vida e segurança. Um modelo de regressão linear múltipla foi utilizado para avaliar os fatores preditores de resposta clínica. Resultados: foram incluídos 205 pacientes, dos quais 155 não tinham e 50 tinham experiência prévia com medicamentos biológicos. As taxas de persistência no tratamento foram maiores para pacientes sem experiência prévia em comparação aos experientes em seis meses de acompanhamento, mas não em 12 meses. As taxas de persistência no tratamento foram 71,5% em pa-cientes sem experiência prévia e 70% em pacientes com experiência prévia em 12 meses. Todos os desfechos clínicos avaliados melhoraram em ambos os grupos de pacientes. Aos 12 meses, 63% dos pacientes sem experiência prévia e 52% dos pacientes com experiência prévia apresentaram melhora na qualidade de vida. Além disso, 48% dos pacientes sem experiência prévia e 42% dos pacientes com experiência prévia apresentaram melhora na funcionalidade. A do-ença axial melhorou em 67% dos pacientes sem experiência prévia e em 56% dos pacientes com experiência prévia. Um bom controle da doença articular periférica foi observado em 49% dos pacientes sem experiência prévia e em 44% dos pacientes com experiência prévia. Os principais fatores preditores de pior resposta clínica foram sexo feminino, uso de etanercepte ou infliximabe, bem como pior funcionalidade e qualidade de vida no início do estudo. Conclusão:a saúde dos pacientes melhorou após o início do tratamento com os medicamentos biológicos. Em geral, pacientes com experiência prévia com medicamentos biológicos apresentaram mais reações adversas e menor efetividade (AU)

Guía práctica de seguimiento y manejo del paciente con asma grave tratado con biológicos / Practical guide for the follow-up and management of patients with severe asthma treated with biologics

El manejo del asma grave descontrolada con biológicos es un área de extrema dificultad, dada la escasez de información respecto a los criterios de inicio de los mismos, las variables a evaluar para determinar la eficacia y seguridad de su manejo, los puntos de corte para determinar el momento oportuno para cambiar o agregar otro biológico y el proceso para disminuir o retirar los esteroides. Esta revisión incorpora la información más reciente y realiza una propuesta con base en ella.

The management of severe uncontrolled asthma with biologics is an area of extreme difficulty given the scarcity of information regarding their starting criteria, the variables to be evaluated to determine the efficacy and safety of their management, the cut-off points to determine the timing to change or add another biological and the process to decrease or withdraw steroids. This review incorporates the latest information and makes a proposal based on it

Terapias biológicas y tuberculosis en pediatría / Biological therapies and tuberculosis in pediatrics

En los últimos años, ha habido un aumento sostenido del uso de terapias inmunomoduladoras como las terapias biológicas y en un período más reciente, de las terapias con moléculas pequeñas. Estos tratamientos constituyen un factor de riesgo más para enfermar de tuberculosis en adultos y aunque en menor grado, también en niños, especialmente con el uso de anti TNF-α, por lo que antes de iniciar una terapia biológica, hay que descartar la tuberculosis activa y la latente. En el tratamiento de una tuberculosis activa producida por un biológico se debe prolongar la etapa de continuación a 9 meses. Es importante el seguimiento clínico prolongado en años de quienes usan o han completado el uso de estas terapias. Hay que posponer la vacunación BCG en los hijos de madres que usaron terapias biológicas durante la gestación hasta la edad 6 a 12 meses de los niños. El foco de esta revisión está centrado en la tuberculosis por progresión de una forma latente a una activa o por un contacto estrecho con una persona con tuberculosis pulmonar en pacientes que reciben terapias biológicas anti TNF alfa de uso inmunoreumatológico.

In recent years, there has been a sustained increase in the use of immunomodulatory therapies such as biologic therapies and, more recently, small molecule therapies. Those therapies have become another risk factor for tuberculosis in adults and, although to lesser degree, also in children, especially some of them, such as anti-TNF α. Before starting biological therapy, active tuberculosis and latent tuberculosis must be ruled out. In the treatment of active tuberculosis caused by a biologic, the continuation stage should be extended to 9 months. Long-term clinical follow-up in years of those who use them or have completed their use, is important. BCG vaccine should be postponed in children of mother who used biologic therapies during pregnancy until the children ́s age 6 to 12 months. The focus of this review is centered on tuberculosis due to progression from a latent to an active form or due to close contact with a person with pulmonary tuberculosis in patients receiving anti-TNF alpha biological therapies for immunorheumatology use.

Reacciones de hipersensibilidad a quimioterapéuticos y biológicos / Hypersensitivity reactions to chemotherapeutics and biologics

Las reacciones a medicamentos han aumentado con el tiempo, estas implican ahora una carga importante de enfermedad, principalmente en los servicios de hospitalización. Los agentes quimioterapéuticos y biológicos son fármacos utilizados con frecuencia en enfermedades reumatológicas y neoplasias de diferente orden. Las reacciones de hipersensibilidad a quimioterapéuticos y monoclonales impactan en la calidad de vida, el pronóstico y la mortalidad de los pacientes con enfermedades autoinmunes y cáncer, es por eso que deben ser reconocidas y manejadas por un equipo de trabajo multidisciplinar. La desensibilización es una herramienta terapéutica que ofrece grandes beneficios a los pacientes con reacciones de hipersensibilidad, permitiéndoles la utilización de medicamentos de primera línea de manera segura y costoefectiva, con un impacto importante en la morbilidad y mortalidad de estos pacientes. El objetivo de este artículo fue revisar la información y evidencia más reciente sobre las reacciones de hipersensibilidad a quimioterapéuticos y biológicos, y los datos sobre las opciones de desensibilización con estos medicamentos y su desenlace

Drug reactions have increased over time, they now imply a significant burden of disease mainly in hospital services. Chemotherapeutic and biological agents are drugs frequently used in different rheumatological diseases and neoplasms. Hypersensitivity reactions to chemotherapeutic and monoclonal drugs impact the quality of life, prognosis and mortality of patients with autoimmune diseases and cancer, that is why they must be recognized and managed by a multidisciplinary team. Desensitization is a therapeutic tool that offers great benefits to patients with hypersensitivity reactions, allowing them to use first-line drugs in a safe and cost-effective manner, with a significant impact on patient morbidity and mortality. The objective of this article was to review the most recent information and evidence on hypersensitivity reactions to chemotherapeutics and biologics, and data on desensitization options with these drugs and their outcome

Inmunohistoquímica con anticuerpos monoclonales en mujeres indígenas peruanas con cáncer de mama, para pronosticar sobrevida global / Immunohistochemistry with monoclonal antibodies in peruvian indigenous with breast cancer, to forecast Global Survival

Resumen Objetivo: Aplicar la técnica de anticuerpos monoclonales para HER2/neu (human epidermal growth 2/neuro glioblastoma), en tumores de indígenas nativos de Perú con diagnóstico de cáncer de mama, así como correlacionar la sobreexpresión molecular con la sobrevida global. Pacientes y Métodos: Estudio experimental, prospectivo y analítico. Se evaluaron 23 muestras biológicas de tumores de pacientes indígenas andinos de Arequipa, con diagnóstico definitivo de adenocarcinoma de mama. La expresión del receptor HER2/neu se determinó mediante inmunohistoquímica con anticuerpos monoclonales. Resultados: El 43,4% (10 casos) fueron positivos para sobreexpresión del receptor. Los casos negativos fueron 56,6%. La supervivencia global de las pacientes a los 3 años fue 69,9% cuando los tumores tenían HER2/neu sobreexpresados y 84,6% para los negativos, mostrando diferencia estadísticamente significativa (p=0,017). Conclusiones: La técnica de inmunohistoquímica en tumores mamarios de indígenas andinos puede aplicarse siguiendo los protocolos mundiales. Así mismo, hubo correlación entre la sobreexpresión del receptor HER2/neu con menor sobrevida global. El principal beneficio de esta técnica es justificar el uso de terapia biológica con anticuerpos monoclonales, según el perfil molecular, en población nativa de Arequipa, en un hospital cercano a su residencia.

Abstract Objective: To apply the monoclonal antibody technique for HER2/neu, in tumors of indigenous natives of Peru with breast cancer, as well as to correlate molecular overexpression with global survival. Patients and methods: Experimental, prospective and analytical study. 23 biological samples of tumors from indigenous Andean patients from Arequipa, with a definitive diagnosis of breast adenocarcinoma, were evaluated. HER2/neu expression was determined by immunohistochemistry with monoclonal antibodies. Results: 43.4% (10 cases) were positive for receptor overexpression. The negative cases were 56.6%. The overall survival of the patients at 3 years was 69.9% when the tumors had overexpressed HER2/neu and 84.6% for the negative ones, showing a statistically significant difference (p = 0.017) Conclusions: The immunohistochemical technique in Andean indigenous mammary tumors can be applied following world protocols. Likewise, there was a correlation between the overexpression of the HER2 / neu receptor with lower overall survival. The main benefit of this technique is to justify the use of biological therapy with monoclonal antibodies, according to the molecular profile, in the native population of Arequipa, in a hospital near their residence.

Primer consenso cubano sobre el uso de terapia convencional y biológica en pacientes con artritis reumatoide / First Cuban consensus on the use of conventional and biological therapy in patients with rheumatoid arthritis

resumen está disponible en el texto completo

Introduction: The development of recommendations for the treatment of rheumatoid arthritis (RA) in the Cuban context may be one of the ways to achieve better control of this disease. Objective: To reach a consensus and update relevant aspects of conventional and biological RA modifier therapy in Cuba. Methods: 18 specialists from 8 Cuban provinces, experts in RA care, were summoned, according to the years of dedication to the specialty, the conferences on this topic and their publications. The first meeting took place in March 2016 in the provincial hospital of Villa Clara, Cuba, with the participation of all the experts. A review of the literature on conventional and biological therapy previously collected by the participants was developed, and two teams were formed: the first would address everything related to conventional therapy in RA (HRCT) and the other, biological therapy in RA (TBAR). Three questionnaires related to the use of corticosteroids, HRCT and TBAR, were prepared, answered by the participants via email. In a second meeting, held in October 2016 in Havana, the analysis of all the responses provided was carried out. Questions with a response of 90% or more votes were considered as recommendations. Results: The questionnaires were answered by 95% of the participants. 9 recommendations and 1 algorithm were established. The recommendations are as follows: methotrexate is the drug of choice in the treatment of RA after diagnosis; The administration of another conventional drug (DMARDc) (azathioprine, salazosulfapyridine, antimalarials and leflunomide) is recommended in patients with a diagnosis of active RA in whom methotrexate is contraindicated or there is a failure in response - consider the administration of low doses of prednisone or equivalent (<7.5 mg/d) associated with DMARDc in patients with active moderate to severe RA, for the shortest possible time; perform serological control including tests for hepatitis B and C viruses and screening for HIV in all patients diagnosed with RA before starting treatment with DMARDc and biologics; in patients in remission or, at least, with a DAS-28 below 3.2, consideration should be given to withdrawing one of the DMARDs or reducing, to the minimum possible expression, the dose of both disease modifiers; if methotrexate fails, tocilizumab in combination with methotrexate or as monotherapy will be indicated. Conclusions: Aspects related to conventional therapy with methotrexate, azathioprine, salazosulfapyridine, antimalarials and leflunomide were agreed. The value of early diagnosis and immediate initiation of DMARDc therapy and the use of glucocorticoids was analyzed. Treatment with tocilizumab, the only biological available in Cuba against RA, will be administered when there is a failure in the response to conventional therapy and combinations between these drugs. It is recommended to hold educational conferences through the mass media aimed at patientshttp(AU)

Microbiota intestinal y los primeros 1000 días de vida / Gut microbiota and the first 1000 days of life

Introducción: El proceso de colonización del microbioma intestinal en los primeros 1000 días de vida tiene repercusión en la salud y enfermedades del niño dependientes de factores de riesgo. Objetivos: Revisar evidencias importantes sobre el significado de la relación entre la microbiota Intestinal y los primeros 1000 días de vida, y repercusión de los principales factores de riesgo. Métodos: Se revisaron publicaciones en idiomas español e inglés en PubMed, Google Scholar y SciELO: enero 2005-febrero 2020 usando los términos microbiota intestinal, microbiomas, primeros 1000 días de vida, factores de riesgo, enterocolitis necrosante, probióticos y prebióticos. Análisis e integración de la información: Hay demostrados argumentos que vinculan la microbiota intestinal y primeros 1000 días de vida del niño, según modo de parto, tiempo de gestación y lactancia. Se examina los beneficios del parto vaginal, lactancia materna y la aparición de enfermedades a mediano y largo plazo, relacionadas con factores de riesgo, como cesárea, prematuridad, lactancia artificial y exposición antibiótica prenatal y posnatal. Se describe resultados favorables con el uso de bioterapia con probióticos y prebióticos en la enterocolitis necrosante. Conclusiones: Se expone el valor de la microbiota intestinal en los primeros 1000 días de vida para la salud del niño, influenciada por condiciones de normalidad como el parto vaginal y la lactancia materna e implicaciones clínicas relacionadas con factores de riesgo mencionado. Es importante el tratamiento con probióticos multicepas y prebióticos para la recuperación de la microbiota en el niño en enfermedades como la enterocolitis necrosante y estados de sepsis grave(AU)

Introduction: The process of colonizing the gut microbiome in the first 1000 days of life has an impact on the health and diseases dependent on risk factors of the child. Objectives: Review important evidence on the meaning of the relation between the gut microbiota and the first 1000 days of life and the impact of the main risk factors. Methods: Spanish and English language publications were reviewed on PubMed, Google Scholar and SciELO, from January 2005 to February 2020 using the terms: gut microbiota, microbiomes, first 1000 days of life, risk factors, necrotizing enterocolitis, probiotics and prebiotics. Analysis and information integration: Arguments linking the gut microbiota and the child's first 1000 days of life are demonstrated, depending on the child's mode of delivery, gestation time and lactation. It is conducted an assessment of benefits of vaginal delivery, breastfeeding and the onset of medium- and long-term diseases related to risk factors, such as C-section, prematurity, artificial lactation, and prenatal and postnatal antibiotic exposure. Favorable results with the use of biotherapy with probiotics and prebiotics in necrotizing enterocolitis are described. Conclusions: It is presented the value of the gut microbiota in the first 1000 days of life for the health of the child, influenced by normal conditions such as vaginal delivery and breastfeeding, and clinical implications related to the mentioned risk factors. Treatment with multi-strain probiotics and prebiotics for microbiota recovery in the child is important in diseases such as necrotizing enterocolitis and states of severe sepsis(AU)

Frecuencia de positividad de la prueba de intradermorreacción a tuberculina en una cohorte de pacientes con artritis reumatoide / Frequency of positivity of the tuberculin intradermorreaction test in a cohort of patients with rheumatoid arthritis

Resumen Introducción. La artritis reumatoide es una enfermedad autoinmunitaria, crónica y deformante asociada con discapacidad. Quienes la padecen reciben inmunosupresores y tienen un gran riesgo de desarrollar tuberculosis. La prueba de intradermorreacción a la tuberculina se utiliza como tamización en quienes van a recibir terapia biológica. Objetivo. Evaluar la frecuencia de positividad en la prueba de intradermorreacción a la tuberculina en una cohorte de pacientes con artritis reumatoide. Materiales y métodos. Se hizo un estudio descriptivo de corte transversal de una cohorte de pacientes con artritis reumatoide a quienes se les practicó la prueba de tuberculina antes de iniciar la terapia biológica o en el momento del cambio de tratamiento. Los pacientes presentaban enfermedad moderada o grave y eran candidatos para iniciar o cambiar de terapia biológica. Se definió el valor de ≥6 mm como punto de corte para la positividad de la prueba y se hizo un análisis descriptivo de cada una de las variables. Resultados. Se incluyeron 261 pacientes con artritis reumatoide, 92 % de ellos eran mujeres, la edad promedio fue de 55 años (desviación estándar, DE=13,92) y el tiempo desde el diagnóstico era de 12,3 años (DE=8,54). La frecuencia de positividad de la prueba fue de 15,71 % (n=41). Nueve de los 41 pacientes positivos habían recibido la prueba previamente (entre 1 y 6 años antes), todos con resultado negativo; 18 (43,9 %) de ellos venían recibiendo tratamiento con glucocorticoides y todos los 41 (100 %) recibían metotrexate. Conclusiones. La frecuencia de positividad de la prueba de tuberculina en pacientes colombianos con artritis reumatoide fue de aproximadamente 16 %. Se recomienda optimizar las estrategias para detectar esta condición y darle un tratamiento oportuno y, así, disminuir el riesgo de reactivación de la tuberculosis.

Abstract Introduction: Rheumatoid arthritis is an autoimmune, chronic, and deforming condition associated with disability. Patients are immunosuppressed and at high risk of developing tuberculosis. The tuberculin skin test is used to screen candidates for biological therapy. Objective: To evaluate the frequency of positivity of the tuberculin skin test in a cohort of Colombian patients with rheumatoid arthritis. Materials and methods: We conducted a descriptive cross-sectional study including patients with rheumatoid arthritis receiving the tuberculin skin test prior to the start or at the time of the change of biological therapy. The patients' condition was moderate or severe and they were candidates for initiation or change of biological therapy. We defined the value of ≥6 mm as the cut-off point for a positive tuberculin skin test and performed a descriptive analysis for each of the variables considered. Results: In total, 261 patients with rheumatoid arthritis were included, 92 % of whom were women; the average age was 55 years (SD=13.92) and the time from diagnosis, 12.3 years (SD=8.54). The frequency of positive tuberculin skin tests was 15.71% (n=41). Of the 41 positive patients, nine had previously had the test (1 to 6 years before), all of them with negative results; 18 of these were receiving glucocorticoids (43.9%) and all of them (100%) were being treated with methotrexate. Conclusions: The frequency of positivity of the tuberculin skin test in these Colombian patients diagnosed with rheumatoid arthritis was around 16%. We recommend optimizing strategies aimed at an optimal detection of this condition and the timely initiation of treatment to reduce the risk of tuberculosis reactivation.

Fatores associados com a escolha da terapia nos pacientes com doença inflamatória intestinal no Brasil / Factors associated with patient´s preference in choosing their therapy for inflammatory bowel disease in brazil

BACKGROUND: Biological therapy and new drugs have revolutionized the treatment of inflammatory bowel disease. Ideally, the choice of medication should be a shared decision with the patient, aiming at greater satisfaction, compliance, and consequently, favorable clinical outcome. OBJECTIVE: This study aims to evaluate patient's preferences in the choice of their therapy and the factors that influence this choice. METHODS: This cross-sectional study enrolled 101 outpatients with Crohn's disease or ulcerative colitis. The inclusion criteria were age ≥18 years and no previous exposure to biological therapy. Patients' preferences were assessed through questions that addressed the preferred mode of administration (oral, subcutaneous, or intravenous) and the factors that determined the choice of medication (efficacy, medical indication, fear of medication, convenience, mode of application, and personal doctors' indication). RESULTS: The mean age was 43.6±13.5 years, 75.3% were female, and 81.2% were cases of ulcerative colitis. Regarding the mode of administration, the majority of patients preferred oral (87.1%), followed by intravenous (6.93%) and subcutaneous (5.94%) medications. The reasons were "I prefer to take it at home" (42.57%), "I have more freedom" (36.63%), "I don't like self-application" (29.70%), and "I believe it works better" (19.80%). Younger patients and patients in clinical disease activity preferred intravenous mode compared to the oral route (P<0.05). Doctor's opinion (98%) was an important factor associated with the medication choice. CONCLUSION: Oral route was the preferred mode of administration and most patients took their physician's opinion into account in their choice of medication.

RESUMO CONTEXTO: A terapia biológica e os novos medicamentos revolucionaram o tratamento da doença inflamatória intestinal. A escolha do medicamento deve ser compartilhada com o paciente, visando maior satisfação, adesão e, consequentemente, desfecho clínico favorável. OBJETIVO: Este estudo teve como objetivo avaliar as preferências do paciente na escolha de sua terapia e os fatores que influenciaram essa escolha. MÉTODOS: Este estudo transversal incluiu 101 pacientes ambulatoriais com doença de Crohn ou retocolite ulcerativa. Os critérios de inclusão foram idade ≥18 anos e nenhuma exposição prévia à terapia biológica. A preferência dos pacientes foi avaliada por meio de perguntas que abordaram o modo de administração preferido (oral, subcutâneo ou intravenoso) e os fatores que determinaram a escolha do medicamento (eficácia, indicação médica, medo da injeção, conveniência, modo de aplicação e opinião pessoal do médico). RESULTADOS: A idade média foi de 43,6±13,5 anos, 75,3% eram mulheres e 81,2% eram portadores de retocolite ulcerativa. Em relação ao modo de administração, a maioria dos pacientes preferiu os medicamentos orais (87,1%), seguidos dos endovenosos (6,93%) e subcutâneos (5,94%). Os motivos foram "prefiro aplicar em casa" (42,57%), "tenho mais liberdade com essa medicação" (36,63%), "não gosto de autoaplicação" (29,70%) e "acredito que funcione melhor" (19,80%). Pacientes jovens e pacientes em atividade clínica preferiram a via intravenosa em comparação com a via oral (P<0,05). A opinião do médico (98%) foi um fator importante associado à escolha do medicamento. CONCLUSÃO: A via oral foi preferida e a maioria dos pacientes levou em consideração a opinião do seu médico na escolha do medicamento.

Caracterización clínica y epidemiológica de pacientes con psoriasis y prescripción de terapia biológica en Venezuela: estudio transversal / Clinical and epidemiological characterization of patients with psoriasis and the prescription of biological therapy in Venezuela: a cross-sectional study

Introducción La psoriasis es una enfermedad crónica que compromete la piel, padecida por cerca de 125 millones de personas en todo el mundo. En un grupo determinado de pacientes, también puede afectar el sistema articular. Para el control y seguimiento de los pacientes con psoriasis se estableció la aplicación de los índices de severidad del área de psoriasis y de calidad de vida dermatológica. Ambos parámetros son necesarios para el inicio de terapia biológica, según lo establecido en la guía de manejo de psoriasis (2015) del comité nacional de enfermedades reumatológicas, inmunológicas y de metabolismo óseo del Instituto Venezolano de los Seguros Sociales. Objetivo Caracterizar las variables clínicas, epidemiológicas y la prescripción de terapia biológica en los pacientes con psoriasis que acceden al programa de dispensación de alto costo de la farmacia del Instituto Venezolano de los Seguros Sociales. Método Es un estudio descriptivo, transversal. Resultados Se evaluaron 374 expedientes, donde el sexo masculino fue más frecuente con 56,1% (p < 0,001), provenientes en su mayoría de la ciudad de Caracas, en la comparación de los grupos de edad con el sexo, se observó que existía una diferencia entre estos (p < 0,05). El 57,5% usó previamente metotrexato; 6,68% biológicos; 3,2% esteroides tópicos y 31% no reportó qué tipo de terapia previa recibía. Dentro de las presentaciones clínicas, 70% correspondió a la psoriasis en placa. El 79% de los pacientes presentaba actividad moderada según el índice de la severidad del área de psoriasis, y al 11% se les realizó el índice de calidad de vida dermatológica, de los cuales 39% presentaban un efecto extremadamente importante. El rango anérgico de la prueba de Mantoux representó 70,9% de los casos, donde al 0,3% le fue realizado la prueba de Booster, y la radiografía de tórax se reportó normal en 95%. El medicamento biológico más demandado fue el etanercept con 52% de los casos. Conclusiones El sexo masculino y su relación con la psoriasis fue un hallazgo de importancia, como también se evidenció la necesidad de mejorar los componentes administrativos en la gestión de los formatos de solicitud de medicamentos y fortalecer la aplicación de la clinimetría con elemento de buena práctica médica.

Introduction Psoriasis is a chronic disease that affects the skin. One hundred twenty-five million people around the world suffer from this condition. In specific groups of patients, the joints may also be involved. To control and follow-up patients with psoriasis, psoriasis area severity and dermatological quality of life measurements were established. Both parameters are necessary for the initiation of biological therapy, as specified in the psoriasis management guide (2015) of the national committee of rheumatological, immunological, and bone metabolism diseases of the Venezuelan Institute of Social Security. Objective To characterize the clinical and epidemiological variables and the prescription of biological therapy in patients with psoriasis who access the high-cost dispensing program of the Venezuelan Institute Social Security (IVSS) pharmacy. Methods This is a descriptive, cross-sectional study. Results A total of 374 patient records were assessed. The male gender was more frequent, with 56.1% (p <0.001), mostly from Caracas city. In comparing age groups with sex, a difference among these was observed (p <0.05). 57.5% previously used methotrexate, 6.68% biological, 3.2% topical steroids, and 31% did not report which type of previous therapy they had received. Amongst the clinical presentations, 70% corresponded to plaque psoriasis. 79% of the patients presented moderate activity according to the Psoriasis Area and Severity Index (PASI): Eleven percent were assessed with the Dermatology Life Quality Index (DLQI); 39% of them reported an extremely important effect. The anergic range of the Mantoux test represented 70.9% of the cases, and 0.3% took the booster evaluation. Chest X-ray was reported normal in 95% of the cases. The most demanded biological medicine was etanercept, in 52% of the cases. Conclusions Male gender and its association with psoriasis was an important finding. The need to improve the administrative components in completing the medication request formats and strengthen clinical measurements and good medical practice was also found.

Aportes de la biotecnología al diagnóstico y tratamiento de la enfermedad renal crónica y comorbilidades frecuentes / Biotechnology contribution to the diagnosis and treatment of chronic kidney disease and frequent comorbidities

Este trabajo tiene como objetivo revisar las contribuciones de la biotecnología, en relación con el tratamiento, diagnóstico y la monitorización de la enfermedad renal crónica (ERC) y sus comorbilidades más frecuentes, especialmente la anemia. En relación con los tratamientos, enfocamos el desarrollo de productos biofarmacéuticos como los agentes estimulantes de la eritropoyesis (ESA), que fueron los primeros biofármacos utilizados para el tratamiento de la anemia asociada a la ERC; analizamos sus características y utilización actual después de varios años de experiencia clínica, así como también otras alternativas en desarrollo. Revisamos distintos tipos de bioterapias, la utilización de las células estromales mesenquimales de médula ósea (MSC) y tratamientos alternativos con modificaciones dietarias, que se basan en la asociación entre la microbiota intestinal de los pacientes renales crónicos y sus condiciones fisiopatológicas. Finalmente, en relación con el diagnóstico y monitorización, nos referimos al estudio y validación de biomarcadores diagnósticos, predictivos y terapéuticos que han permitido optimizar los resultados clínicos en este tipo de pacientes. (AU)

The aim of this work is to review the contributions of biotechnology, in relation to the treatment, diagnosis and monitoring of chronic kidney disease (CKD) and its most frequent comorbidities, especially anemia. Regarding the treatment, we focus on the development of biopharmaceutical products such as erythropoiesis stimulating agents (ESA), which were the first biopharmaceuticals used to treat anemia associated with chronic kidney disease (CKD). We analyzed their characteristics and their current use after several years of clinical experience, as well as other alternatives in development. We also review different types of biotherapies, the use of bone marrow mesenchymal stromal cells (MSC) and alternative treatments with dietary modifications, which are based on the association between the intestinal microbiota of chronic kidney patients and their pathophysiological conditions. Finally, in relation to diagnosis and monitoring, we refer to the study and validation of diagnostic, predictive and therapeutic biomarkers that have made clinical results possible to be optimized in this type of patient. (AU)

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.

Riesgo de infección en pacientes con enfermedades inmunológicas y oncológicas tratados con biológicos: revisión panorámica

Biological medications are effective for the treatment of cancer and inflammatory diseases. The aim of this review is to summarize the available evidence in systematic reviews or meta-analyses about the risk of infection in patients with cancer, arthritis, psoriasis and inflammatory bowel disease who use biological medications. We included systematic reviews or meta-analyses of controlled clinical trials and case/control studies that analyze infections during and after treatment with FDA-approved biological medications for the treatment of cancer, arthritis, inflammatory bowel disease and psoriasis, both in adults and children. The following databases were consulted: PubMed, Epistemonikos, Crochrane reviews, JIB, and Prospero. A quality guideline (AMSTAR) was applied to the selected studies. We included 26 studies. The risk of infections in patients with solid organ cancer is consistent in the literature. In psoriasis there is a risk of non-serious infections. In arthritis and other inflammatory diseases there is a risk of serious infections. In inflammatory bowel disease there is a risk for opportunistic infections. In conclusion, in patients with cancer and inflammatory diseases use biological medications entails a risk of infection. The evidence is different depending on the underlying disease of each patient.