Characteristics of patients with hypersensitivity reactions to chemotherapeutic and biological agents and desensitization behavior / Características de pacientes com reações de hipersensibilidade a agentes quimioterápicos e biológicos e comportamento de dessensibilização

Introduction: Hypersensitivity to chemotherapeutic and biological agents has increased in recent years due to their frequent use. Avoidance has been the first line of defense, leading to decreased treatment efficacy and increased adverse events. Objective: To characterize the sociodemographic and clinical aspects of patients with hypersensitivity reactions to chemotherapeutic agents who underwent desensitization and biological procedures in a Colombian city. Methods: This observational, descriptive, retrospective, multicenter study was conducted in patients with hypersensitivity reactions to chemotherapeutic and biological agents who underwent desensitization. Results: In the 14 included patients with a history of hypersensitivity reactions to chemotherapeutic and biological agents (57.1% women; median age 42.5 years), 45 desensitization procedures were performed. The most commonly prescribed drug was rituximab (57%). The skin was the most frequent reaction site (78.6%), and systemic corticosteroids were the most common treatment (78.6%). Breakthrough reactions occurred in 31.1% of the patients and only premedication with corticosteroids was associated with less severe reactions. All cases of desensitization were successful. Conclusions: Desensitization to chemotherapeutic and biological agents proved to be a useful and safe tool in a Colombian population.

Introdução: A hipersensibilidade aos agentes quimioterápicos e biológicos aumentou nos últimos anos devido ao seu uso frequente. Evitar tem sido a primeira linha de ação, levando à diminuição da eficácia do tratamento e ao aumento de eventos adversos. Objetivos: Caracterizar os aspectos sociodemográficos e clínicos de pacientes com reações de hipersensibilidade a agentes quimioterápicos submetidos a dessensibilização e procedimentos biológicos em uma cidade colombiana. Métodos: Foi realizado um estudo observacional, descritivo, retrospectivo e multicêntrico em pacientes com reações de hipersensibilidade a agentes quimioterápicos e biológicos submetidos à dessensibilização. Resultados: Foram incluídos 45 procedimentos de dessensibilização em 14 pacientes com histórico de reações de hipersensibilidade a agentes quimioterápicos e biológicos (57,1% mulheres, com mediana de idade de 42,5 anos). O medicamento mais relatado foi o rituximabe (57%). O envolvimento cutâneo foi o mais frequente (78,6%) e os corticosteroides sistêmicos foram o tratamento mais utilizado (78,6%). As reações ocorreram em 31,1% e apenas a pré-medicação com corticosteroides foi associada a uma menor gravidade destas. Todos os casos de dessensibilização foram bem-sucedidos. Conclusões: A dessensibilização a agentes quimioterápicos e biológicos provou ser uma ferramenta útil e segura em uma população colombiana.

Coexistência de doenças autoimunes: oportunidade para a associação de imunobiológicos? / Coexisting autoimmune diseases: an opportunity to associate immunobiologicals?

O tratamento das doenças autoimunes com imunobiológicos é uma opção segura na prática clínica. A simultaneidade na ocorrência de doenças imunomediadas em um mesmo indivíduo pode determinar a necessidade da associação dos imunobiológicos para controle dos sintomas e melhora da qualidade de vida dos doentes. Relatamos o caso de uma paciente com artrite reumatoide em uso de etanercepte, que necessitou da associação de omalizumabe para o tratamento de urticária crônica espontânea.

Autoimmune diseases can be safely treated in clinical practice with immunobiologicals. The simultaneous occurrence of multiple immune-mediated diseases in the same individual could require a combination of immunobiologicals to control symptoms and improve quality of life. We report the case of a patient with rheumatoid arthritis who was receiving etanercept and required additional omalizumab for chronic spontaneous urticaria.

Síndrome de Vogt-Koyanagi-Harada

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.

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.

A avaliação de níveis sérios de infliximabe favorece a manutenção do tratamento em pacientes com doença inflamatória intestinal / The evaluation of infliximab trough level favors maintenance therapy of patients with inflammatory bowel disease

ABSTRACT Background: Crohn's disease (CD) and ulcerative colitis (UC) are chronic diseases that result from the deregulation of the mucosal immune system of the gastrointestinal tract. The use of biological therapies, including infliximab (IFX), is one of the strategies to treat both CD and UC. The IFX treatment is monitored by complementary tests, namely: fecal calprotectin (FC); C-reactive protein (CRP); and endoscopic and cross-sectional imaging. Besides, serum IFX evaluation and antibody detection are also used. Objective: To evaluate trough levels (TL) and antibodies in a population with inflammatory bowel (IBD) disease undergoing treatment with IFX, and the factors that might impact the treatment effectiveness. Methods: Retrospective, cross-sectional study with patients with IBD that were assessed for TL and antibody (ATI) levels in a southern Brazilian hospital, from June 2014 to July 2016. Results: The study assessed 55 patients (52.7% female) submitted to serum IFX and antibody evaluations (95 blood samples, 55 first test; 30 second test, and 10 as third testing. Forty-five (47.3%) cases were diagnosed with CD (81.8%), and ten with UC (18.2%). Serum levels were adequate in 30 samples (31.57%), subtherapeutic in 41 (43.15%), and supratherapeutic in 24 (25.26%). IFX dosages were optimized for 40 patients (42.10%), maintained for 31 (32.63%), and discontinued for 7 (7.60%). The intervals between infusions were shortened in 17.85% of the cases. In 55 tests (55.79%), the therapeutic approach was exclusively defined according to IFX and/or serum antibody levels. The assessment of patients one year later indicated that: the approach was maintained with IFX for thirty-eight patients (69.09%); the class of biological agent was changed for eight (14.54%); changes using the same class of biological agent occurred for two patients (3.63%); the medication was discontinued and not replaced for three patients (5.45%), and four patients (7.27%) were lost to follow-up. Conclusion: There were no differences in TL between groups with or without immunosuppressants, serum albumin (ALB), erythrocyte sedimentation rate (ESR), FC, CRP, and endoscopic and imaging examinations. Current therapeutic approach could be maintained for almost 70% of patients. Thus, serum and antibody levels are a useful tool in the follow-up of patients undergoing maintenance therapy and after treatment induction in patients with inflammatory bowel disease.

RESUMO Contexto: A doença de Crohn e a colite ulcerativa são doenças crônicas nas quais existem desregulação do sistema imune da mucosa do trato gastrointestinal. Uma das terapias usadas no tratamento dessas doenças são as medicações biológicas, entre elas o Infliximabe. A monitorização do tratamento dos pacientes com Iinfliximabe é feita por exames complementares: calprotectina fecal, pesquisa de atividade inflamatória, exames endoscópicos e imagem. Utiliza-se, também a dosagem do nível sérico do Infliximabe e a pesquisa de anticorpos. Objetivo: Analisar uma população com doenças inflamatórias intestinais, em tratamento com Infliximabe, submetida a avaliação do nível sérico do Infliximabe e do anticorpo, além de possíveis fatores que possam alterar ou contribuir no tratamento. Métodos: Trata-se de estudo retrospectivo, transversal, realizado por meio da revisão dos prontuários dos pacientes com doença inflamatória intestinal, em um hospital sul-brasileiro, no período de junho de 2014 até julho de 2016, que foram submetidos a avaliação dos níveis séricos de Infliximabe e do anticorpo. Resultados: Foram incluídos 55 pacientes, submetidos a dosagem do Infliximabe e do anticorpo, totalizando 95 coletas sanguíneas. Destes, 55 realizaram uma primeira coleta, 30 tiveram uma segunda amostra coletada e 10 coletaram uma terceira vez. Vinte e nove pacientes eram do sexo feminino (52,7%) e vinte e seis do sexo masculino (43.2%). Quarenta e cinco (47,3%) casos tinham diagnóstico de doença de Crohn (81,8%) e 10 de colite ulcerativa (18,2%). Em relação ao nível sérico encontrou-se nível adequado em 30 coletas (31,57%), subterapêutico em 41 coletas (43,15%) e supraterapêutico em 24 coletas (25,26%). A prescrição foi otimizada em 40 (42,10%) casos, mantida em 31 (32,63%) pacientes, suspensa em 7 (7,60%) ou que o intervalo entre as infusões fosse aumentado (17,85%). Na análise geral, em 53 coletas (55,79%) a conduta foi definida em função exclusivamente da dosagem sérica do Infliximabe e/ou do anticorpo, já em relação, apenas a primeira coleta obteve-se 33 (60%) pacientes. Avaliando-se os pacientes um ano após, obteve-se: em 38 (69,09%) pacientes a conduta foi mantida com Infliximabe e, em 8 (14,54%) foi optado por troca de classe, em 2 (3,63%) foi optado por troca da medicação na mesma classe, em 3 (5,45%) pacientes a medicação foi suspensa e não foi substituída e, em 4 (7,27%), perdeu-se o seguimento. Conclusão: Não encontrou-se diferença entre os níveis de Infliximabe entre os grupos com ou sem imunossupressor, albumina sérica, velocidade de hemossedimentação, Calprotectina, Proteína C reativa, exames endoscópicos e exames de imagem. A conduta atual pode ser mantida em quase 70% dos pacientes. Concluindo, a dosagem do nível sérico e do anticorpo é ferramenta útil no acompanhamento dos pacientes em terapia de manutenção e após a indução de tratamento em pacientes com Doença Inflamatória Intestinal.

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.

Belimumabe comparado à terapia padrão do Sistema Único de Saúde no tratamento da nefrite lúpica nos estágios III, IV e V: revisão rápida / Belimumab compared to standard therapy of the Brazilian Public Health System in the treatment of lupus nephritis in stage III, IV, and V: rapid review

Belimumabe, rituximabe, terapia imunossupressora. Indicação: Nefrite lúpica nos estágios III, IV, V, refratária à terapia imunossupressora. Pergunta: Belimumabe é eficaz (remissão da nefrite, normalização da perda da função renal, qualidade de vida) e seguro (descontinuação devido a eventos adversos totais e eventos adversos graves) para o tratamento de pacientes com nefrite lúpica refratária nos estágios III, IV, V em comparação aos medicamentos disponíveis no Sistema Único de Saúde? Objetivo: Avaliar a segurança e eficácia do belimumabe em comparação com os medicamentos disponíveis no Sistema Único de Saúde em pacientes adultos com nefrite lúpica. Métodos: Revisão rápida de revisões sistemáticas. Levantamento bibliográfico foi realizado nas bases de dados PUBMED, EMBASE, SCOPUS, BVS, EPISTEMONIKOS, Cochrane Library e em registros de revisões sistemáticas e ensaios clínicos. Seguiu estratégias de buscas predefinidas. Foi feita avaliação da qualidade metodológica dos estudos incluídos através da ferramenta AMSTAR-2 (Assessing the Methodological Quality of Systematic Reviews Version 2). Resultados: Foram selecionadas duas revisões sistemáticas que atendiam aos critérios de elegibilidade, mas nenhum ensaio clínico foi escolhido, pois não atendiam aos critérios de inclusão. Conclusão: a terapia combinada de belimumabe, ou de rituximabe, com tratamento imunossupressor padrão é mais eficaz que o tratamento padrão para alcançar remissão clínica da nefrite lúpica. A terapia combinada é tão segura quanto o tratamento padrão. Belimumabe e rituximabe tem eficácia similar entre si

Belimumab, rituximab, and immunosuppressive therapy. Indication: Refractory lupus nephritis to immunosuppressive therapy in stages III, IV, V. Question: Is belimumab effective (for remission of nephritis, normalization of loss of renal function, quality of life) and safe (for discontinuation due to total adverse events and serious adverse events) in the treatment of patients with refractory lupus nephritis in stages III, IV, V compared to the drugs available in the Brazilian Public Health System? Objective: To evaluate the safety and efficacy of belimumab compared to drugs available in the Brazilian Public Health System in adult patients with lupus nephritis. Methods: Rapid review of systematic reviews. A bibliographic search was done in the PUBMED, EMBASE, SCOPUS, BVS, EPISTEMONIKOS, Cochrane Library databases and in records of systematic reviews and clinical trials. It has followed predefined search strategies. The methodological quality of the included studies was evaluated using the AMSTAR-2 tool (Assessing the Methodological Quality of Systematic Reviews Version 2). Results: Two systematic reviews were selected, which met the eligibility criteria, but no clinical trials were chosen, as they did not meet the inclusion criteria. Conclusion: Combination therapy of belimumab or rituximab with standard immunosuppressive treatment is more effective than standard treatment in achieving clinical remission of lupus nephritis. Combination therapy is as safe as standard treatment. Belimumab and rituximab have similar efficacy to each other

Dupilumabe e upadacitinibe comparados a medicamentos imunossupressores para o tratamento de dermatite atópica moderada a grave refratária a terapia tópica: revisão rápida de evidências / Dupilumab and upadacitinib compared to immunosuppressive drugs for the treatment of moderate to severe atopic dermatitis refractory to topical therapy: rapid review of evidence

Tecnologia: Dupilumabe e upadacitinibe. Comparadores: Azatioprina, metotrexato, ciclosporina, micofenolato de mofetila. Indicação: Tratamento de dermatite atópica severa em pacientes adultos. Pergunta: Dupilumabe e upadacitinibe são mais eficazes e tão seguros quanto ciclosporina ou outros agentes imunossupressores para obter os desfechos de saúde no tratamento sistêmico de dermatite atópica moderada a grave refratária à terapia atópica? Métodos: Levantamento bibliográfico foi realizado na base de dados PUBMED e Cochrane Library, seguindo estratégias de buscas predefinidas. Foi feita avaliação da qualidade metodológica das revisões sistemáticas com a ferramenta AMSTAR2 (Assessing the Methodological Quality of Systematic Reviews Version 2). Resultados: Foram selecionados três estudos que atenderam aos critérios de inclusão. Conclusão: Dupilumabe, upadacitinibe, ciclosporina e azatioprina são mais eficazes que placebo nos desfechos de eficácia (reduzir sinais clínicos em escalas, reduzir sintomas em escalas) para tratamento da dermatite atópica moderada a grave refratária à terapia tópica, mas esses medicamentos não diferem entre si. Dupilumabe, upadacitinibe, ciclosporina e azatioprina são bem tolerados e seguros

Technology: Dupilumab, upadacitinibe. Comparators: Azathioprine, methotrexate, cyclosporine, mycophenolate mofetil. Indication: Treatment of severe atopic dermatitis in adult patients. Question: Are dupilumab and upadacitinib more effective and as safe as cyclosporine or other immunosuppressive agents for achieving health outcomes in the systemic treatment of moderate to severe atopic dermatitis refractory to atopic therapy? Methods: A bibliographic survey was done in the PUBMED e Cochrane Library databases, following predefined search strategies. The methodological quality of systematic reviews was evaluated using the AMSTAR-2 tool (Assessing the Methodological Quality of Systematic Reviews Version 2). Results: Three studies that met the inclusion criteria were selected. Conclusion: Dupilumab, upadacitinib, cyclosporine, and azathioprine are more effective than placebo on efficacy endpoints (reduce clinical signs on scales, reduce symptoms on scales) for treating moderate to severe atopic dermatitis refractory to topical therapy, but these drugs do not differ from each other. Dupilumab, upadacitinib, cyclosporine, and azathioprine are well tolerated and safe

Risk factors for early postoperative complications in acute colitis in the era of biologic therapy / Fatores de risco para complicações pós-operatórias precoces em colite aguda na era da terapia biológica

ABSTRACT BACKGROUND: Despite major advances in the clinical treatment of inflammatory bowel disease, some patients still present with acute colitis and require emergency surgery. AIMS: To evaluate the risk factors for early postoperative complications in patients undergoing surgery for acute colitis in the era of biologic therapy. METHODS: Patients with inflammatory bowel disease admitted for acute colitis who underwent total colectomy at a single tertiary hospital from 2012 to 2022 were evaluated. Postoperative complications were graded according to Clavien-Dindo classification (CDC). Patients with more severe complications (CDC≥2) were compared with those with less severe complications (CDC<2). RESULTS: A total of 46 patients underwent surgery. The indications were: failure of clinical treatment (n=34), patients' or surgeon's preference (n=5), hemorrhage (n=3), toxic megacolon (n=2), and bowel perforation (n=2). There were eight reoperations, 60.9% of postoperative complications classified as CDC≥2, and three deaths. In univariate analyses, preoperative antibiotics use, ulcerative colitis diagnosis, lower albumin levels at admission, and preoperative hospital stay longer than seven days were associated with more severe postoperative complications. CONCLUSIONS: Emergency surgery for acute colitis was associated with a high incidence of postoperative complications. Preoperative use of antibiotics, ulcerative colitis, lower albumin levels at admission, and delaying surgery for more than seven days were associated with more severe early postoperative complications. The use of biologics was not associated with worse outcomes.

RESUMO RACIONAL: Apesar dos enormes avanços no tratamento das doenças inflamatórias intestinais (DII), alguns pacientes apresentam quadros de colite aguda refratária ao tratamento clínico, e necessitam de cirurgia de urgência. OBJETIVOS: Avaliar os fatores de risco associados com complicações pós-operatórias precoces nos pacientes com colite aguda submetidos a colectomia na era das terapias biológicas. MÉTODOS: Pacientes com DII admitidos com colite aguda grave submetidos a colectomia total em hospital terciário no período de 2012 a 2022 foram analisados. As complicações pós-operatórias foram graduadas de acordo com a classificação Clavien-Dindo (CCD). Pacientes com complicações mais graves (CCD≥2) foram comparados com os menos graves (CCD<2). RESULTADOS: Foram submetidos a cirurgia 46 pacientes. As indicações foram: falha do tratamento conservador (n=34), preferência do paciente ou do cirurgião (n=5), hemorragia (n=3), megacólon tóxico (n=2) e perfuração intestinal (n=2). Reoperação foi necessária em oito pacientes, 60,9% tiveram complicações classificadas como CCD≥2, e três pacientes foram a óbito. Análise univariada identificou que uso de antibióticos no pré-operatório, diagnóstico de colite ulcerativa, hipoalbuminemia na admissão e período de internação maior que sete dias foi associada à complicações pós-operatória mais graves. CONCLUSÕES: Pacientes com colite aguda submetidos a cirurgia de urgência apresentaram alta taxa de complicações pós-operatórias. Uso pré-operatório de antibióticos, diagnóstico de retocolite ulcerativa, hipoalbuminemia na admissão e retardo na operação por mais que sete dias, esteve associado a complicações pós-operatórias mais graves. Uso de biológicos não se associou a piores desfechos.

Terapia biológica en artritis reumatoidea: una revisión de reacciones adversas / Biological therapy in rheumatoid arthritis: A review of adverse reactions

RESUMEN Introducción: La relación entre eventos adversos y aplicación de medicamentos biológicos en pacientes con diagnóstico de artritis reumatoide ha sido documentada a escala mundial, pero con escasa evidencia en Colombia. Si se asume que los eventos adversos o reacciones medicamentosas con hallazgos clínicos relevantes en la salud, como consecuencia de este tratamiento terapéutico, recaen sobre la calidad de vida del paciente e influyen en los indicadores de salud a escala nacional y en los recursos del sistema, se hace importante evaluar su impacto. Objetivos: Determinar la frecuencia de eventos adversos o reacciones adversas relacionados con el uso de medicamentos biológicos en una cohorte de pacientes con diagnóstico de artritis reumatoide de una aseguradora nacional, en el periodo comprendido entre los arios 2000 y 2019. Metodología: Se realizó un estudio descriptivo, transversal y retrospectivo, con alcance analítico, en pacientes diagnosticados de artritis reumatoide, con terapia biológica, en una aseguradora a escala nacional, con registros en historias clínicas del año 2000 al 2019. Resultados: Se analizaron 252 registros clínicos de usuarios con diagnóstico de artritis reumatoide y terapia biológica. El 62,7% presentó al menos una reacción adversa y se evaluaron 9 fármacos: tocilizumab, etanercept, adalimumab, abatacept, certolizumab, golimumab, infliximab, rituximab y tofacitinib. Este último es un fármaco incluido en este estudio por solicitud de la aseguradora fuente de la información. Conclusiones: En la terapia biológica de pacientes con artritis reumatoide las reacciones adversas son frecuentes, y en un 27,3% resultan severas, lo cual describe una situación previamente desconocida en Colombia.

ABSTRACT Introduction: The relationship between adverse events and the application of biological drugs in patients with a diagnosis of rheumatoid arthritis has been documented worldwide, but with little evidence of the situation in Colombia. If adverse events and / or drug reactions with relevant clinical findings in health because of this therapeutic treatment affect the patient's quality of life and influence health indicators at the national level and system resources, it is important to assess their impact. Objectives: To determine the frequency of adverse events and / or adverse reactions related to the use of biological drugs in a cohort of patients diagnosed with rheumatoid arthritis from a national insurer, in the period from 2000 to 2019. Methodology: A descriptive, cross-sectional, and retrospective study with analytical scope was carried out in patients diagnosed with rheumatoid arthritis, on biological therapy, under a nationwide insurer, with records in their medical records from 2000 to 2019. Results: 252 clinical records of users with a rheumatoid arthritis diagnosis and biological therapy were analysed; 62.7% had at least one adverse reaction; nine drugs were evaluated in this study: Tocilizumab, Etanercept, Adalimumab, Abatacept, Certolizumab, Golimumab, Infliximab, Rituximab, and Tofacitinib. Tofacitinib was included in this study at the request of the insurer providing the information. Conclusions: Adverse reactions with biological therapy in patients with rheumatoid arthritis are frequent and were severe in 27.3%. This is a situation previously unknown in Colombia.

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.

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

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)

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.

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.

Utilização da monitorização terapêutica com níveis séricos de infliximabe nas doenças inflamatórias intestinais: um algoritmo simplificado baseado em evidências / Induction therapeutic drug monitoring regimen with infliximab: a simplified evidence-based algorithm for inflammatory bowel disease

ABSTRACT Therapeutic drug monitoring (TDM) of infliximab (IFX) has been recognized as an important strategy in the management of secondary loss of response to this agent, guiding clinical decision-making in the management of inflammatory bowel diseases (IBD). Although most of the data on the application of TDM for IFX refer to the maintenance phase of treatment, many studies have associated higher drug concentrations, specially in the induction phase, with achievement of important treatment targets, such as clinical remission and mucosal healing. This brief communication aims to summarize the literature on the use of TDM during induction phase of IFX and propose application of a simplified approach which can be useful into clinical practice, aiming better outcomes to IBD patients.

RESUMO A monitorização terapêutica dos níveis séricos (Therapeutic drug monitoring - TDM) de infliximabe (IFX) é uma estratégia reconhecida na tomada de decisão clínica frente a perda de resposta secundária a esta droga no manejo das doenças inflamatórias intestinais (DII). Embora a maioria dos dados sobre a aplicação dessa estratégia para IFX se refira à fase de manutenção do tratamento, muitos estudos associaram concentrações mais altas de IFX, especialmente na fase de indução, com o alcance de importantes alvos de tratamento, como remissão clínica e cicatrização da mucosa. Este artigo visa resumir as evidências da literatura sobre o uso de níveis séricos durante a fase de indução do IFX e propor a aplicação de uma abordagem simplificada que pode ser extremamente útil na prática clínica, visando melhores resultados para os pacientes.

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.

Guía para el manejo de colitis ulcerativa en población adulta (actualización) / Guidelines for the management of ulcerative colitis in the adult population (update)

Resumen Objetivo: desde 2015, la Asociación Colombiana de Gastroenterología, con el apoyo del Instituto de Investigaciones Clínicas de la Universidad Nacional de Colombia, realizó la guía de práctica clínica para el diagnóstico y tratamiento de colitis ulcerativa. Desde la publicación de esta guía, han aparecido nuevas alternativas terapéuticas y nuevos conceptos sobre los objetivos del tratamiento, por lo cual se consideró necesaria su actualización. Materiales y métodos: esta actualización fue realizada por un equipo multi-disciplinario con apoyo de la Asociación Colombiana de Gastroenterología y el Instituto de Investigaciones Clínicas de la Universidad Nacional de Colombia. Se desarrollaron preguntas relevantes a nuevos tratamientos y vigilancia endoscópica de los pacientes adultos con colitis ulcerativa y se realizó la búsqueda de guías nacionales e internacionales en bases de datos especializadas. Las guías fueron evaluadas en términos de calidad y aplicabilidad. El Grupo Cochrane llevó a cabo la búsqueda sistemática de la literatura. Las tablas de evidencia y recomendaciones fueron realizadas usando la metodología GRADE. Resultados: se realizó una actualización de la guía para el tratamiento de la colitis ulcerativa en adultos en Colombia y se diseñaron nuevos algoritmos de tratamiento, teniendo en cuenta la extensión y la actividad de la enfermedad y los diferentes niveles de atención. Conclusiones: se estableció la importancia para el tratamiento de la evaluación clínica y endoscópica y se especificaron las indicaciones para el adecuado tratamiento de los pacientes con colitis ulcerativa. Adicionalmente, se dieron recomendaciones de vigilancia endoscópica de cáncer colorrectal y la importancia de la cromoendoscopia.

Abstract Objective: In 2015, the Asociación Colombiana de Gastroenterología (Colombian Association of Gastroenterology), with the support of the Institute of Clinical Research of the Universidad Nacional de Colombia, created the Clinical Practice Guideline for the diagnosis and treatment of ulcerative colitis. Since then, new therapeutic alternatives and concepts about treatment goals have emerged, making it necessary to update its contents. Materials and methods: The present update was carried out by a multidisciplinary team with support from the Asociación Colombiana de Gastroenterología and the Clinical Research Institute of the Universidad Nacional de Colombia. Questions regarding new treatments and endoscopic surveillance of adult patients with ulcerative colitis were developed, and national and international guidelines were searched in specialized databases. The guidelines were evaluated in terms of quality and applicability. The Cochrane Group conducted a systematic search of the existing literature, and evidence tables and recommendations were made using the GRADE methodology. Results: The guideline for the treatment of ulcerative colitis in adults in Colombia was updated, and new treatment algorithms were designed, taking into account the extent and activity of the disease and the different levels of care. Conclusions: The relevance of clinical and endoscopic assessment for treatment was established, and the indications for the proper management of patients with ulcerative colitis were specified. Furthermore, recommendations were made for endoscopic surveillance of colorectal cancer, and the importance of chromoendoscopy was established.

Guía de práctica clínica para el tratamiento de la enfermedad de Crohn en población adulta / Clinical practice guidelines for the treatment of Crohn's disease in the adult population

Resumen Objetivo: La enfermedad de Crohn es un trastorno inflamatorio idiopático de etiología desconocida con características genéticas, inmunológicas e influencias del medio ambiente. La incidencia y la prevalencia de la enfermedad de Crohn han aumentado en Colombia. El tratamiento de estos pacientes no es fácil y ha evolucionado en los últimos años; por lo tanto, es necesario desarrollar una guía de práctica clínica en Colombia, orientada al tratamiento de esta compleja enfermedad, para unificar criterios. Materiales y métodos: Esta guía fue desarrollada por un equipo multidisciplinario con apoyo de la Asociación Colombiana de Gastroenterología, el Grupo Cochrane ITS y el Instituto de Investigaciones Clínicas de la Universidad Nacional de Colombia. Se desarrollaron preguntas clínicas relevantes a la entidad y se realizó la búsqueda de guías nacionales e internacionales en bases de datos especializadas. Las guías existentes fueron evaluadas en términos de calidad y aplicabilidad. El Grupo Cochrane realizó la búsqueda sistemática de la literatura. Las tablas de evidencia y recomendaciones fueron realizadas usando la metodología GRADE. Resultados: Se realizó una guía de práctica clínica basada en la evidencia, para el tratamiento tanto médico como quirúrgico de la enfermedad de Crohn en población adulta en Colombia. Se diseñaron algoritmos de manejo teniendo en cuenta la actividad, el comportamiento y la localización de la enfermedad. Conclusiones: Se estableció que una adecuada evaluación clínica, endoscópica e imagenológica, así como una estratificación de riesgo individual son importantes para el manejo, y se especificaron las indicaciones para el adecuado tratamiento tanto médico como quirúrgico de estos pacientes.

Abstract Objective: Crohn's disease is an idiopathic inflammatory disorder of unknown origin, influenced by genetic, immunological, and environmental factors. The incidence and prevalence of Crohn's disease have increased in Colombia. The treatment of these patients is not easy and has improved in recent years. Therefore, it is necessary to develop the Colombian Clinical Practice Guideline to guide the treatment of this complex disease and unify criteria. Materials and methods: The present guideline was carried out by a multidisciplinary team with support from the Asociación Colombiana de Gastroenterología, the Cochrane ITS Team, and the Clinical Research Institute of the Universidad Nacional de Colombia. Clinical questions regarding this disease were developed, and national and international guidelines were searched in specialized databases. The existing guidelines were evaluated in terms of quality and applicability. The Cochrane Group conducted a systematic search of the existing literature. Evidence tables were elaborated, and recommendations were made using the GRADE methodology. Results: An evidence-based clinical practice guideline was developed for the medical and surgical treatment of Crohn's disease in the adult population in Colombia. Treatment algorithms were designed, taking into account the activity, behavior, and location of the disease. Conclusions: It was established that proper clinical, endoscopic, and imaging assessment, as well as individual risk stratification, are important for treatment. Also, the indications for adequate medical and surgical treatment of these patients were specified.

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.

Opciones terapéuticas al síndrome de liberación de citocinas en pacientes con la COVID-19 / Therapeutic options to cytokine release syndrome in patients with COVID-19

Sin duda alguna la COVID-19 ha suscitado la atención de la población mundial durante el año 2020. La rápida propagación de la enfermedad, así como el número de contagios, complicaciones y muertes, constituyen los principales elementos distintivos de la enfermedad. El proceso inflamatorio, dado por una elevada producción de citocinas proinflamatorias constituye la base de las complicaciones respiratorias. El objetivo de este trabajo es dar a conocer las opciones terapéuticas disponibles para tratar el síndrome de liberación de citoquinas. En este sentido, es importante destacar que fármacos biológicos como el tocilizumab, anakinra y el roxulitinib, así como los glucocorticoides, inmunoglobulinas intravenosas y algunos inmunosupresores como la ciclosporina A, constituyen opciones terapéuticas, con opciones teóricas para combatir el proceso inflamatorio en pacientes graves y que han mostrado resultados alentadores en el transcurso de la crisis sanitaria mundial por la COVID-19.Se concluye que existen opciones terapéuticas para enfrentar la tormenta de citocinas proinflamatorias que caracterizan este síndrome, observado en pacientes graves y críticos con esta enfermedad. Constituye ahora el reto para los científicos y profesionales de la salud, identificar el momento oportuno para las indicaciones terapéuticas y el algoritmo de utilización, en dependencia de las características del cuadro clínico y las condiciones de salud del paciente(AU)

Without doubt, COVID-19 has attracted the attention of the world population during the year 2020. The rapid spread of the disease, as well as the number of infections, complications and deaths, constitute the main distinctive elements of the disease. The inflammatory process, given by a high production of proinflammatory cytokines, forms the basis of respiratory complications. The objective of this work is to publicize the therapeutic options available to treat cytokine release syndrome. In this sense, it is important to highlight that biological drugs such as tocilizumab, anakinra and roxulitinib, as well as glucocorticoids, intravenous immunoglobulins and some immunosuppressants such as cyclosporin A, are therapeutic options, with theoretical options to combat the inflammatory process in seriously ill patients and which have shown encouraging results in the course of the global health crisis caused by COVID-19. It is concluded that there are therapeutic options to face the storm of proinflammatory cytokines that characterize this syndrome, observed in critically ill patients with this disease. It is now a challenge for scientists and health professionals to identify the right time for therapeutic indications and the algorithm of use, depending on the characteristics of the clinical picture and the patient's health conditions(AU)