Clinical factors associated with severity in patients with inflammatory bowel disease in Brazil based on 2-year national registry data from GEDIIB.

The Brazilian Organization for Crohn's Disease and Colitis (GEDIIB) established a national registry of inflammatory bowel disease (IBD). The aim of the study was to identify clinical factors associated with disease severity in IBD patients in Brazil. A population-based risk model aimed at stratifying the severity of IBD based on previous hospitalization, use of biologics, and need for surgery for ulcerative colitis (UC) and Crohn's Disease (CD) and on previous complications for CD. A total of 1179 patients (34.4 ± 14.7y; females 59%) were included: 46.6% with UC, 44.2% with CD, and 0.9% with unclassified IBD (IBD-U). The time from the beginning of the symptoms to diagnosis was 3.85y. In CD, 41.2% of patients presented with ileocolic disease, 32% inflammatory behavior, and 15.5% perianal disease. In UC, 46.3% presented with extensive colitis. Regarding treatment, 68.1%, 67%, and 47.6% received biological therapy, salicylates and immunosuppressors, respectively. Severe disease was associated with the presence of extensive colitis, EIM, male, comorbidities, and familial history of colorectal cancer in patients with UC. The presence of Montreal B2 and B3 behaviors, colonic location, and EIM were associated with CD severity. In conclusion, disease severity was associated with younger age, greater disease extent, and the presence of rheumatic EIM.

A NORMOCALORIC, LOW-FIBER DIET FOR COLONOSCOPY PREPARATION IS MORE ACCEPTABLE AND NON-INFERIOR TO A LIQUID, LOW-CALORIE DIET: A RANDOMIZED CONTROLLED TRIAL.

•This is the first study in Brazil about diets to prepare for colonoscopy. •The normocaloric diet was not inferior to the liquid diet regarding the quality of the colonoscopy preparation. •Both diets were well tolerated, but the normocaloric diet was more accepted than the liquid diet. Background - Several publications have shown greater acceptance of less restrictive diets for colonoscopy preparation, without impairing the quality of the preparation, when compared to the clear liquid diet. Objective - To evaluate the quality, tolerance and preference regarding the colonoscopy preparation of a low-fiber, normocaloric diet compared with a hypocaloric liquid diet. Methods - This is a randomized, controlled, observer-blind study to compare two low-fiber colonoscopy preparation diets (hypocaloric liquid diet vs. normocaloric diet). The Boston Bowel Preparation Scale was used to evaluate the qua-lity of the preparations, being considered adequate BBPS ≥6 in the global assessment and ≥2 in each segment. The same laxative was used in both groups as well as the "split-dose" regimen. Results - A total of 136 individuals were enrolled in each group. Adequate preparation was achieved in 90.4% of the individuals allocated to the liquid diet group and 92.6% to the normocaloric group. There was no significant difference in the quality of preparation and tolerance between groups. A higher patient acceptance to repeat the procedure if necessary was observed in the normocaloric diet group compared with the liquid diet group (P=0.005). Conclusion - The normocaloric diet has shown to be not inferior to the liquid diet regarding the quality of the colonoscopy preparation. Patient tolerance rates were similar between both diets, but a higher accep-tance rate was observed with the normocaloric diet as compared with the liquid diet.

Dieta normocalórica e pobre em fibras, para preparo de colonoscopia, é melhor aceita e não inferior que uma dieta líquida hipocalórica: ensaio randomizado controlado / A normocaloric, low-fiber diet for colonoscopy preparation is more acceptable and non-inferior to a liquid, low-calorie diet: a randomized controlled trial

ABSTRACT Background: Several publications have shown greater acceptance of less restrictive diets for colonoscopy preparation, without impairing the quality of the preparation, when compared to the clear liquid diet. Objective: To evaluate the quality, tolerance and preference regarding the colonoscopy preparation of a low-fiber, normocaloric diet compared with a hypocaloric liquid diet. Methods: This is a randomized, controlled, observer-blind study to compare two low-fiber colonoscopy preparation diets (hypocaloric liquid diet vs. normocaloric diet). The Boston Bowel Preparation Scale was used to evaluate the qua­lity of the preparations, being considered adequate BBPS ≥6 in the global assessment and ≥2 in each segment. The same laxative was used in both groups as well as the "split-dose" regimen. Results: A total of 136 individuals were enrolled in each group. Adequate preparation was achieved in 90.4% of the individuals allocated to the liquid diet group and 92.6% to the normocaloric group. There was no significant difference in the quality of preparation and tolerance between groups. A higher patient acceptance to repeat the procedure if necessary was observed in the normocaloric diet group compared with the liquid diet group (P=0.005). Conclusion: The normocaloric diet has shown to be not inferior to the liquid diet regarding the quality of the colonoscopy preparation. Patient tolerance rates were similar between both diets, but a higher accep­tance rate was observed with the normocaloric diet as compared with the liquid diet.

RESUMO Contexto: Diversas publicações têm evidenciado uma maior aceitação de dietas menos restritivas para preparo de colonoscopia, sem prejuízo na sua qualidade, quando comparadas com a dieta de líquidos claros. Objetivo: Avaliar a qualidade, tolerância e preferência do preparo para colonoscopia de uma dieta líquida hipocalórica, quando comparada com uma dieta normocalórica, ambas pobres em fibras. Métodos: Trata-se de um estudo randomizado, controlado, observador "cego", para comparar duas dietas de preparo para colonoscopia (dieta líquida hipocalórica e dieta normocalórica, ambas pobres em fibras). Foi utilizada a escala de Boston para avaliar a qualidade do preparo, sendo considerado adequado BBPS ≥6 na avaliação global e ≥2 em cada segmento. Foram prescritos o mesmo laxativo e o regime "dose fracionada" para ambos os grupos. Resultados: Foram incluídos 136 indivíduos em cada grupo. O preparo adequado foi alcançado em 90,4% dos indivíduos alocados no grupo da dieta líquida e 92,6% da normocalorica. Não houve diferença significativa na qualidade do preparo e na tolerância entre ambas as dietas. Observou-se maior aceitação de repetir o procedimento se necessário, no grupo da dieta normocalórica quando comparado ao da dieta líquida (P=0,005). Conclusão: A dieta normocalórica não é inferior que à líquida na qualidade do preparo para colonoscopia, ambas apresentam tolerância similar, porém com maior aceitação da dieta normocalórica quando comparada à líquida.

SECOND BRAZILIAN CONSENSUS ON THE MANAGEMENT OF ULCERATIVE COLITIS IN ADULTS: A CONSENSUS OF THE BRAZILIAN ORGANIZATION FOR CROHN'S DISEASE AND COLITIS (GEDIIB).

BACKGROUND: Inflammatory bowel diseases are immune-mediated disorders that include Crohn's disease (CD) and ulcerative colitis (UC). UC is a progressive disease that affects the colorectal mucosa causing debilitating symptoms leading to high morbidity and work disability. As a consequence of chronic colonic inflammation, UC is also associated with an increased risk of colorectal cancer. OBJECTIVE: This consensus aims to provide guidance on the most effective medical management of adult patients with UC. METHODS: A consensus statement was developed by stakeholders representing Brazilian gastroenterologists and colorectal surgeons (Brazilian Organization for Crohn's Disease and Colitis [GEDIIB]). A systematic review including the most recent evidence was conducted to support the recommendations and statements. All recommendations/statements were endorsed using a modified Delphi Panel by the stakeholders/experts in inflammatory bowel disease with at least 80% or greater consensus. RESULTS AND CONCLUSION: The medical recommendations (pharmacological and non-pharmacological) were mapped according to the stage of treatment and severity of the disease onto three domains: management and treatment (drug and surgical interventions), criteria for evaluating the effectiveness of medical treatment, and follow-up/patient monitoring after initial treatment. The consensus targeted general practitioners, gastroenterologists and surgeons who manage patients with UC, and supports decision-making processes by health insurance companies, regulatory agencies, health institutional leaders, and administrators.

SECOND BRAZILIAN CONSENSUS ON THE MANAGEMENT OF CROHN'S DISEASE IN ADULTS: A CONSENSUS OF THE BRAZILIAN ORGANIZATION FOR CROHN'S DISEASE AND COLITIS (GEDIIB).

BACKGROUND: Inflammatory bowel disease (IBD) is an immune-mediated disorder that includes Crohn's disease (CD) and ulcerative colitis. CD is characterized by a transmural intestinal involvement from the mouth to the anus with recurrent and remitting symptoms that can lead to progressive bowel damage and disability over time. OBJECTIVE: To guide the safest and effective medical treatments of adults with CD. METHODS: This consensus was developed by stakeholders representing Brazilian gastroenterologists and colorectal surgeons (Brazilian Organization for Crohn's disease and Colitis (GEDIIB)). A systematic review of the most recent evidence was conducted to support the recommendations/statements. All included recommendations and statements were endorsed in a modified Delphi panel by the stakeholders and experts in IBD with an agreement of at least 80% or greater consensus rate. RESULTS AND CONCLUSION: The medical recommendations (pharmacological and non-pharmacological interventions) were mapped according to the stage of treatment and severity of the disease in three domains: management and treatment (drug and surgical interventions), criteria for evaluating the effectiveness of medical treatment, and follow-up/patient monitoring after initial treatment. The consensus is targeted towards general practitioners, gastroenterologists, and surgeons interested in treating and managing adults with CD and supports the decision-making of health insurance companies, regulatory agencies, and health institutional leaders or administrators.

Segundo Consenso Brasileiro de Manejo da Doença de Crohn em adultos: um consenso da Organização Brasileira de Doença de Crohn e Colite (GEDIIB) / Second brazilian consensus on the management of crohn's disease in adults: a consensus of the brazilian organization for crohn's disease and colitis (gediib)

ABSTRACT Background: Inflammatory bowel disease (IBD) is an immune-mediated disorder that includes Crohn's disease (CD) and ulcerative colitis. CD is characterized by a transmural intestinal involvement from the mouth to the anus with recurrent and remitting symptoms that can lead to progressive bowel damage and disability over time. Objective: To guide the safest and effective medical treatments of adults with CD. Methods: This consensus was developed by stakeholders representing Brazilian gastroenterologists and colorectal surgeons (Brazilian Organization for Crohn's disease and Colitis (GEDIIB)). A systematic review of the most recent evidence was conducted to support the recommendations/statements. All included recommendations and statements were endorsed in a modified Delphi panel by the stakeholders and experts in IBD with an agreement of at least 80% or greater consensus rate. Results and conclusion: The medical recommendations (pharmacological and non-pharmacological interventions) were mapped according to the stage of treatment and severity of the disease in three domains: management and treatment (drug and surgical interventions), criteria for evaluating the effectiveness of medical treatment, and follow-up/patient monitoring after initial treatment. The consensus is targeted towards general practitioners, gastroenterologists, and surgeons interested in treating and managing adults with CD and supports the decision-making of health insurance companies, regulatory agencies, and health institutional leaders or administrators.

RESUMO Contexto: A doença inflamatória intestinal (DII) é uma doença imunomediada que inclui a doença de Crohn (DC) e a retocolite ulcerativa. A DC é caracterizada por um envolvimento intestinal transmural da boca ao ânus com sintomas recorrentes e remitentes que podem levar a danos intestinais progressivos e incapacidade ao longo do tempo. Objetivo: Orientar os tratamentos médicos mais seguros e eficazes de adultos com DC. Métodos: Este consenso foi desenvolvido por autores que representam gastroenterologistas e cirurgiões brasileiros especialistas em doenças colorretais (GEDIIB, Organização Brasileira de Doença de Crohn e Colite). Uma revisão sistemática das evidências mais recentes foi realizada para apoiar as recomendações/declarações. Todas as recomendações e declarações incluídas foram endossadas em um painel Delphi modificado pelas partes interessadas e especialistas em DII com uma concordância de pelo menos 80% ou mais. Resultados e conclusão: As recomendações médicas (intervenções farmacológicas e não farmacológicas) foram mapeadas de acordo com o estágio de tratamento e gravidade da doença em três domínios: manejo e tratamento (intervenções medicamentosas e cirúrgicas), critérios para avaliar a eficácia do tratamento médico, e acompanhamento/monitoramento do paciente após o tratamento inicial. O consenso é direcionado a clínicos gerais, gastroenterologistas e cirurgiões interessados em tratar e gerenciar adultos com DC e apoia a tomada de decisões de companhias de seguro de saúde, agências reguladoras e líderes ou administradores de instituições de saúde.

Segundo Consenso Brasileiro no manejo da retocolite ulcerativa em adultos: um consenso da Organização Brasileira para Doença de Crohn e Colite (GEDIIB) / Second brazilian consensus on the management of ulcerative colitis in adults: a consensus of the brazilian organization for crohn's disease and colitis (gediib)

ABSTRACT Background: Inflammatory bowel diseases are immune-mediated disorders that include Crohn's disease (CD) and ulcerative colitis (UC). UC is a progressive disease that affects the colorectal mucosa causing debilitating symptoms leading to high morbidity and work disability. As a consequence of chronic colonic inflammation, UC is also associated with an increased risk of colorectal cancer. Objective: This consensus aims to provide guidance on the most effective medical management of adult patients with UC. Methods: A consensus statement was developed by stakeholders representing Brazilian gastroenterologists and colorectal surgeons (Brazilian Organization for Crohn's Disease and Colitis [GEDIIB]). A systematic review including the most recent evidence was conducted to support the recommendations and statements. All recommendations/statements were endorsed using a modified Delphi Panel by the stakeholders/experts in inflammatory bowel disease with at least 80% or greater consensus. Results and conclusion: The medical recommendations (pharmacological and non-pharmacological) were mapped according to the stage of treatment and severity of the disease onto three domains: management and treatment (drug and surgical interventions), criteria for evaluating the effectiveness of medical treatment, and follow-up/patient monitoring after initial treatment. The consensus targeted general practitioners, gastroenterologists and surgeons who manage patients with UC, and supports decision-making processes by health insurance companies, regulatory agencies, health institutional leaders, and administrators.

RESUMO Contexto: As doenças inflamatórias intestinais são doenças imunomediadas que incluem a doença de Crohn (DC) e a retocolite ulcerativa (RCU). A RCU é uma doença progressiva que acomete a mucosa colorretal causando sintomas debilitantes levando a alta morbidade e incapacidade laboral. Como consequência da inflamação crônica do cólon, a RCU também está associada a um risco aumentado de câncer colorretal. Objetivo: Este consenso visa fornecer orientações sobre o manejo médico mais eficaz de pacientes adultos com RCU. Métodos: As recomendações do consenso foram desenvolvidas por gastroenterologistas e cirurgiões colorretais referências no Brasil (membros da Organização Brasileira para Doença de Crohn e Colite [GEDIIB]). Uma revisão sistemática, incluindo as evidências mais recentes, foi conduzida para apoiar as recomendações. Todas as recomendações foram endossadas pelas partes interessadas/especialistas em doença inflamatória intestinal usando um Painel Delphi modificado. O nível de concordância para alcançar consenso foi de 80% ou mais. Resultados e conclus ão: As recomendações médicas (farmacológicas e não farmacológicas) foram mapeadas de acordo com o estágio de tratamento e gravidade da doença em três domínios: manejo e tratamento (intervenções medicamentosas e cirúrgicas), critérios para avaliar a eficácia do tratamento médico, e acompanhamento/monitoramento do paciente após o tratamento inicial. O consenso foi direcionado a clínicos gerais, gastroenterologistas e cirurgiões que tratam pacientes com RCU e apoia os processos de tomada de decisão por companhias de seguro de saúde, agências reguladoras, líderes institucionais de saúde e administradores.

Clinical and Demographic Profile of Inflammatory Bowel Disease Patients in a Reference Center of São Paulo, Brazil.

BACKGROUND: Crohn's disease (CD) and ulcerative colitis (UC) are chronic inflammatory diseases of the gastrointestinal tract with an increasing incidence in developing countries. PURPOSE: To report clinical and demographic data of CD and UC at a referral center for inflammatory bowel disease (IBD) in São Paulo. PATIENTS AND METHODS: We conducted a retrospective cross-sectional study on adult patients with established IBD. Demographic and clinical data were obtained by medical records analysis from the IBD Outpatient Clinic of EPM-UNIFESP, from October 1997 to October 2017. RESULTS: Of 658 patients included, 355 had UC (54%) and 303 had CD (46%). UC was more prevalent in women than CD (219 [61.7%] vs 152 [50.2%], p=0.003). The median time between the onset of symptoms and diagnosis was 13 (5-38) months, with a longer duration for CD patients. CD mostly affected the ileocolonic location (47.9%). CD patients with stricture, fistula and/or perianal disease (213/303, 70.3%) were younger at diagnosis, had a longer disease duration, higher rates of corticosteroid, immunomodulatory, and biological therapy, hospitalization, and referral to surgery, compared to patients without complication. Extensive colitis was the most common extension of UC (50.6%), which was more frequently associated with younger age at diagnosis, hepatobiliary disease, increased need for hospitalization, higher use of immunomodulatory, and biologic therapy, compared to patients with less extensive disease. In the last 5 years, CD patients were more frequently on biologic and/or immunomodulatory (70.9%) therapy, and UC patients often received salicylates (78.1%) and immunomodulatory (28.1%) treatments. There was a consistent reduction in salicylate usage for CD in the last 5 years compared to the total period of follow-up. CONCLUSION: Despite the increasing incidence, we highlight the diagnostic delay and a more complicated CD and extensive UC in this cohort, reflecting a high need for immunomodulatory and biological treatment, hospitalization, and surgery.

Ulcerative colitis - treatment with biologicals

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

Avaliação do consumo alimentar de pacientes com síndrome do intestino irritável em acompanhamento ambulatorial / Evaluation of carbohydrate and fiber consumption in patients with irritable bowel syndrome in outpatient treatment

ABSTRACT BACKGROUND: Irritable bowel syndrome (IBS) is a chronic functional condition, which main symptoms of pain, discomfort and abdominal distension, constipation, diarrhea, altered fecal consistency and sensation of incomplete evacuation can be influenced by the presence of dietary fiber and fermentable carbohydrates (FODMAPs). This study aimed to assess the relationship between the quantity of fermentable carbohydrates (FODMAP) and fiber consumed by individuals diagnosed with IBS, and their classification according to the Rome III criteria. METHODS: A transversal study was carried out in the Intestinal Outpatient Clinic of the Gastroenterology Discipline of UNIFESP. The nutrients of interest for the study were: fiber, general carbohydrates and FODMAPs, with intake quantity measured in grams, analyzed through portions consumed. A nutrition log was used, along with a semi-quantitative questionnaire of consumption frequency. RESULTS: The sample included 63 adult patients; 21 with constipated IBS, 21 with diarrhea IBS, and 21 with mixed IBS. Carbohydrate intake was suboptimal in 55.6% of patients in all groups; excessive consumption was identified in 38.1% of the diarrhea group, 14.3% of the mixed group and 38.1% of the constipated group. Low consumption of carbohydrates was found in 28.6% of diarrhea patients and 47.6% of the mixed group. A mean intake of 23 g of fiber per day was identified, lower than recommended. CONCLUSION: The study identified a number of inadequacies in the consumption of different nutrients, excessive carbohydrate intake, especially FODMAPs, identified by the respondents as responsible for a worsening of their conditions. By contrast, other food groups such as meat, eggs and dairy were consumed by the sample population in insufficient quantities.

RESUMO CONTEXTO: A síndrome do intestino irritável é um distúrbio funcional crônico, no qual a dieta, principalmente o teor de fibra dietética e presença de carboidratos fermentativos (FODMAPs) podem influenciar nos principais sintomas: dores, desconforto e/ou distensão abdominal, constipação, diarreia, alteração na consistência das fezes, sensação de evacuação incompleta. OBJETIVO: Este estudo teve como objetivo avaliar as quantidades de carboidratos fermentativos (FODMAP) e fibras consumidas por indivíduos com o diagnóstico de síndrome do intestino irritável e relacionar com seu modelo da classificação, segundo os critérios Roma III. MÉTODOS: Estudo transversal, realizado no Ambulatório de Doenças Intestinais da Disciplina de Gastroenterologia/UNIFESP. Os nutrientes de interesse para o estudo foram: fibras, carboidratos em geral e FODMAPs, calculando-se suas quantidades em gramas, analisadas através das porções consumidas. Os instrumentos de pesquisa utilizados: ficha de acompanhamento nutricional e questionário de frequência alimentar semi-quantitativo. RESULTADOS: A amostra incluiu 63 pacientes adultos, com síndrome do intestino irritável constipado (21), diarreico (21) e misto (21). O consumo de carboidratos mostrou-se inadequado em 55,6% dos indivíduos em todos os grupos; os que tinham alto consumo (38,1%) pertenciam ao grupo diarreia, 14,3% ao misto e 38,1 % ao constipado. Baixo consumo deste nutriente foi 28,6% nos casos de diarreia e 47,6% do misto. Observamos uma ingestão média de fibras equivalente à 23 g/dia, nos três grupos, inferior ao recomendado. CONCLUSÃO: O estudo permitiu reconhecer várias inadequações no consumo dos diferentes grupos de alimentos, particularmente excesso de carboidratos, incluindo os classificados como FODMAPs, identificados pelos doentes como responsáveis pela piora das suas queixas. Em contrapartida, nutrientes fundamentais, como carnes, ovos, leite e derivados estiveram referidos em níveis abaixo do recomendado.

Oral administration of exogenous lactase in tablets for patients diagnosed with lactose intolerance due to primary hypolactasia / Administração oral de lactase exógena em comprimidos em pacientes portadores de intolerância à lactose devido à hipolactasia primária

ABSTRACT Background Primary hypolactasia is a common condition where a reduced lactase activity in the intestinal mucosa is present. The presence of abdominal symptoms due to poor absorption of lactose, which are present in some cases, is a characteristic of lactose intolerance. , Objective Evaluate the efficacy of a product containing exogenous lactase in tablet form compared to a reference product with proven effectiveness in patients with lactose intolerance. Methods Multicentre, randomized, parallel group, single-blind, comparative non-inferiority study. One hundred twenty-nine (129) adult lactose intolerance patients with hydrogen breath test results consistent with a diagnosis of hypolactasia were randomly assigned to receive the experimental product (Perlatte(r) - Eurofarma Laboratórios S.A.) or the reference product (Lactaid(r) - McNeilNutritionals, USA) orally (one tablet, three times per day) for 42 consecutive days. Results Data from 128 patients who actually received the studied treatments were analysed (66 were treated with the experimental product and 62 with the reference product). The two groups presented with similar baseline clinical and demographic data. Mean exhaled hydrogen concentration tested at 90 minutes after the last treatment (Day 42) was significantly lower in the experimental product treated group (17±18 ppm versus 34±47 ppm) in the per protocol population. The difference between the means of the two groups was -17 ppm (95% confidence interval [95% CI]: -31.03; -3.17). The upper limit of the 95% CI did not exceed the a priori non-inferiority limit (7.5 ppm). Secondary efficacy analyses confirmed that the treatments were similar (per protocol and intention to treat population). The tolerability was excellent in both groups, and there were no reports of serious adverse events related to the study treatment. Conclusion The experimental product was non-inferior to the reference product, indicating that it was an effective replacement therapy for endogenous lactase in lactose intolerance patients.

RESUMO Contexto A hipolactasia primária é uma condição muito frequente na qual há redução da atividade da lactase na mucosa intestinal.A presença de sintomas abdominais devidos à má absorção da lactose presente em alguns casos caracteriza a intolerância à lactose. Objetivo Avaliar a eficácia de um produto contendo lactase exógena em comprimidos comparativamente a de um produto comparador com eficácia comprovada em pacientes portadores de intolerância à lactose. Métodos Estudo multicêntrico, randomizado, de grupos paralelos, com investigador cego, comparativo de não-inferioridade. Cento e vinte e nove (129) pacientes adultos portadores de intolerância à lactose e teste do hidrogênio no ar expirado compatível com o diagnóstico de hipolactasia foram randomizados para receber o produto experimental (Perlatte(r) - Eurofarma Laboratórios S.A.) ou o produto comparador (Lactaid(r) - McNeil Nutritionals, EUA), por via oral (um comprimido, três vezes ao dia), durante 42 dias consecutivos. Resultados Os dados dos 128 pacientes que efetivamente receberam o tratamento do estudo foram avaliados (66 tratados com o produto experimental e 62 com o produto comparador). Os dois grupos se mostraram homogêneos quanto aos dados demográficos e clínicos basais. A média da concentração do hidrogênio expirado aos 90 minutos no teste realizado ao final do tratamento (Dia 42) foi significativamente menor no grupo tratado com o produto experimental (17±18 ppm versus 34±47 ppm na população por protocolo). A diferença entre as médias dos dois grupos foi de -17 ppm (intervalo de confiança de 95% [IC95%]: -31,03; -3,17). O limite superior do IC95% não ultrapassou a margem de não-inferioridade estipulada a priori (7,5 ppm). As análises secundárias de eficácia confirmaram a semelhança entre os tratamentos (populações por protocolo e com intenção de tratamento). A tolerabilidade foi excelente em ambos os grupos e não houve relato de eventos adversos graves relacionados ao produto. Conclusão O produto experimental se mostrou não-inferior ao produto comparador, indicando sua eficácia no tratamento substitutivo da lactase endógena em pacientes portadores de intolerância à lactose.

Biosimilars in inflammatory bowel diseases: an important moment for Brazilian gastroenterologists.

Biosimilars are not generic drugs. These are more complex medications than small molecules, with identical chemical structures of monoclonal antibodies that lost their patency over time. Besides identical to the original product at the end, the process of achieving its final forms differs from the one used in the reference products. These differences in the formulation process can alter final outcomes such as safety and efficacy of the drugs. Recently, a biosimilar of Infliximab was approved in some countries, even to the management of inflammatory bowel diseases. However, this decision was based on studies performed in rheumatologic conditions such as rheumatoid arthritis and ankylosing spondylitis. Extrapolation of the indications from rheumatologic conditions was done for Crohn's disease and ulcerative colitis based on these studies. In this article, the authors explain possible different mechanisms in the pathogenesis between rheumatologic conditions and inflammatory bowel diseases, that can lead to different actions of the medications in different diseases. The authors also alert the gastroenterological community for the problem of extrapolation of indications, and explain in full details the reasons for being care with the use of biosimilars in inflammatory bowel diseases without specific data from trials performed in this scenario.

Hepatotoxicidade induzida por Hypericum perforatum com possível associação a copaíba (Copaifera langsdorffii Desf): relato de caso / Hypericum perforatum-induced hepatotoxicity with possible association with copaiba (Copaifera langsdorffii Desf):case report

Relatamos um caso de dano hepático em paciente idosa após uso de produtos naturais à base de Hypericum perforatum e copaíba (Copaifera langsdorffii Desf). A hepatotoxicidade do Hypericum perforatum é conhecida por relatos, mas a respeito da copaíba, largamente usada como anti-inflamatório, há apenas dados experimentais na literatura nacional. Essa apresentação visou chamar a atenção para possível efeito tóxico dessa associação, bem como para a recuperação clínica da paciente após interrupção de seu uso. Há uma tendência de suspeitar sobre a ação de medicamentos para justificar a lesão hepática aguda não viral, em razão do grande número de fármacos responsáveis por hepatotoxicidade. A literatura tem publicado experimentos e relatos clínicos em que produtos fitoterápicos, inclusive Hypericum perforatum, são o agente causador dessa agressão, considerados inócuos e utilizados livremente. É preciso lembrar que reações adversas ocorrem também com essas substâncias, merecendo sua investigação na obtenção da anamnese, pela possibilidade de promoverem quadros graves de falência hepática.

We report a case of liver damage in an elderly patient after the use of herbal products of Hypericum perforatum and copaiba (Copaifera langsdorffii Desf). Hepatotoxicity related to Hypericum perforatum is anecdotally known, but for copaiba, widely used as anti-inflammatory, there is just experimental data in the national literature. This report aimed to draw attention to the possible toxic effects of this association as well as to the clinical recovery of the patient after discontinuing their use. There is a tendency to suspect of the action of drugs to justify a non-viral acute liver injury, because of the large number of drugs responsible for hepatotoxicity. There are experiments and clinical reports in the literature describing some herbal products, including Hypericum perforatum, as the causative agents of this aggression, and are considered innocuous and used with no restrictions. We must remember that adverse reactions also occur with these substances; hence, they should be investigated when collecting the patient´s history, for leading to severe liver failure.

Anemia in inflammatory bowel disease: prevalence, differential diagnosis and association with clinical and laboratory variables.

CONTEXT AND OBJECTIVES: Anemia is the most frequent extraintestinal complication of inflammatory bowel disease. This study aimed to: 1) determine the prevalence of anemia among patients with inflammatory bowel disease; 2) investigate whether routine laboratory markers are useful for diagnosing anemia; and 3) evaluate whether any association exists between anemia and clinical/laboratory variables. DESIGN AND SETTING: Cross-sectional at a federal university. METHODS: 44 outpatients with Crohn's disease and 55 with ulcerative colitis were evaluated. Clinical variables (disease activity index, location of disease and pharmacological treatment) and laboratory variables (blood count, iron laboratory, vitamin B12 and folic acid) were investigated. RESULTS: Anemia and/or iron laboratory disorders were present in 75% of the patients with Crohn's disease and in 78.2% with ulcerative colitis. Anemia was observed in 20.5% of the patients with Crohn's disease and in 23.6% with ulcerative colitis. Iron-deficiency anemia was highly prevalent in patients with Crohn's disease (69.6%) and ulcerative colitis (76.7%). Anemia of chronic disease in combination with iron deficiency anemia was present in 3% of the patients with Crohn's disease and in 7% of the patients with ulcerative colitis. There was no association between anemia and disease location. In ulcerative colitis, anemia was associated with the disease activity index. CONCLUSIONS: Most patients present iron laboratory disorders, with or without anemia, mainly due to iron deficiency. The differential diagnosis between the two most prevalent types of anemia was made based on clinical data and routine laboratory tests. In ulcerative colitis, anemia was associated with the disease activity index.

Anemia in inflammatory bowel disease: prevalence, differential diagnosis and association with clinical and laboratory variables / Anemia na doença inflamatória intestinal: prevalência, diagnóstico diferencial e associação com variáveis clínicas e laboratoriais

CONTEXT AND OBJECTIVES: Anemia is the most frequent extraintestinal complication of inflammatory bowel disease. This study aimed to: 1) determine the prevalence of anemia among patients with inflammatory bowel disease; 2) investigate whether routine laboratory markers are useful for diagnosing anemia; and 3) evaluate whether any association exists between anemia and clinical/laboratory variables. DESIGN AND SETTING: Cross-sectional at a federal university. METHODS: 44 outpatients with Crohn's disease and 55 with ulcerative colitis were evaluated. Clinical variables (disease activity index, location of disease and pharmacological treatment) and laboratory variables (blood count, iron laboratory, vitamin B12 and folic acid) were investigated. RESULTS: Anemia and/or iron laboratory disorders were present in 75% of the patients with Crohn's disease and in 78.2% with ulcerative colitis. Anemia was observed in 20.5% of the patients with Crohn's disease and in 23.6% with ulcerative colitis. Iron-deficiency anemia was highly prevalent in patients with Crohn's disease (69.6%) and ulcerative colitis (76.7%). Anemia of chronic disease in combination with iron deficiency anemia was present in 3% of the patients with Crohn's disease and in 7% of the patients with ulcerative colitis. There was no association between anemia and disease location. In ulcerative colitis, anemia was associated with the disease activity index. CONCLUSIONS: Most patients present iron laboratory disorders, with or without anemia, mainly due to iron deficiency. The differential diagnosis between the two most prevalent types of anemia was made based on clinical data and routine laboratory tests. In ulcerative colitis, anemia was associated with the disease activity index. .

CONTEXTO E OBJETIVOS: Anemia é a mais frequente complicação extraintestinal na doença inflamatória intestinal. Este estudo objetivou: 1) determinar a prevalência de anemia em portadores de doença inflamatória intestinal; 2) investigar se os marcadores laboratoriais de uso rotineiro são úteis para o diagnóstico da anemia; 3) avaliar se existe associação entre anemia e variáveis clínico-laboratoriais. TIPO DE ESTUDO E LOCAL: Estudo transversal em uma universidade federal. MÉTODOS: Foram avaliados 44 pacientes ambulatoriais com doença de Crohn e 55 com retocolite ulcerativa. Foram investigados aspectos clínicos (índice de atividade da doença, localização da doença e tratamento farmacológico) e laboratoriais (hemograma, ferrocinética, vitamina B12 e ácido fólico). RESULTADOS: Anemia e/ou anormalidades na ferrocinética estavam presentes em 75% dos pacientes com doença de Crohn e em 78,2% dos pacientes com retocolite. Anemia foi observada em 20,5% do grupo com doença de Crohn e em 23,6% do grupo com retocolite. Anemia por deficiência de ferro predominou entre os pacientes com doença de Crohn (69,6%) e com retocolite (76,7%). Anemia de doença crônica associada à anemia ferropriva estava presente em 3% dos pacientes com doença de Crohn e em 7% daqueles com retocolite. Na retocolite, a anemia estava associada com o índice de atividade da doença. CONCLUSÕES: A maioria dos pacientes apresentava alterações na ferrocinética com ou sem anemia, principalmente decorrente da ferropenia. O diagnóstico diferencial entre os dois tipos mais prevalentes de anemia foi baseado nos dados clínicos e nos testes laboratoriais de rotina. Anemia estava associada com o índice de atividade na retocolite. .

Assessment of the response of patients with Crohn's disease to biological therapy using new non-invasive markers: lactoferrin and calprotectin.

CONTEXT: The use of fecal markers to monitor Crohn's disease is crucial for assessing the response to treatment. OBJECTIVE: To assess the inflammatory activity of Crohn's disease by comparing fecal markers (calprotectin and lactoferrin), colonoscopy combined with biopsy, and the Crohn's disease activity index (CDAI), as well as serum markers, before treatment with infliximab, after the end of induction, and after the end of maintenance. METHODS: Seventeen patients were included who had been previously diagnosed with Crohn's disease and were using conventional treatment but required the introduction of biological therapy with infliximab. Each patient underwent a colonoscopy with biopsy, serum, and fecal (calprotectin and lactoferrin) tests to assess inflammatory activity, and CDAI assessments before treatment with infliximab, after induction (week 8), and after maintenance (week 32). RESULTS: The calprotectin levels exhibited significant reductions (P=0.04) between the assessment before treatment with infliximab and the end of induction, which did not occur after the end of the maintenance phase. Lactoferrin remained positive throughout the three phases of the study. Regarding the histological assessment, a significant difference was found only between the assessment before treatment and after the end of maintenance (P=0.036), and 60% of the patients exhibited histological improvements after the completion of the follow-up period. The CDAI exhibited a significant difference between the assessment before treatment with infliximab and after induction, as well as before treatment and after maintenance (P<0.01). CONCLUSION: Calprotectin and lactoferrin are not useful for monitoring inflammatory activity in Crohn's disease patients who are subjected to biological therapy.

ASSESSMENT OF THE RESPONSE OF PATIENTS WITH CROHN'S DISEASE TO BIOLOGICAL THERAPY USING NEW NON-INVASIVE MARKERS: lactoferrin and calprotectin

Context The use of fecal markers to monitor Crohn's disease is crucial for assessing the response to treatment. Objective To assess the inflammatory activity of Crohn's disease by comparing fecal markers (calprotectin and lactoferrin), colonoscopy combined with biopsy, and the Crohn's disease activity index (CDAI), as well as serum markers, before treatment with infliximab, after the end of induction, and after the end of maintenance. Methods Seventeen patients were included who had been previously diagnosed with Crohn's disease and were using conventional treatment but required the introduction of biological therapy with infliximab. Each patient underwent a colonoscopy with biopsy, serum, and fecal (calprotectin and lactoferrin) tests to assess inflammatory activity, and CDAI assessments before treatment with infliximab, after induction (week 8), and after maintenance (week 32). Results The calprotectin levels exhibited significant reductions (P = 0.04) between the assessment before treatment with infliximab and the end of induction, which did not occur after the end of the maintenance phase. Lactoferrin remained positive throughout the three phases of the study. Regarding the histological assessment, a significant difference was found only between the assessment before treatment and after the end of maintenance (P = 0.036), and 60% of the patients exhibited histological improvements after the completion of the follow-up period. The CDAI exhibited a significant difference between the assessment before treatment with infliximab and after induction, as well as before treatment and after maintenance (P<0.01). Conclusion Calprotectin and lactoferrin are not useful for monitoring inflammatory activity in Crohn's disease patients who are subjected to biological therapy. .

Contexto O uso de marcadores fecais para a monitorização da doença de Crohn é muito importante para a avaliação da resposta ao tratamento instituído. Objetivo Avaliar a atividade inflamatória da doença de Crohn comparando os marcadores fecais (calprotectina e lactoferrina), colonoscopia com biópsias, Crohn's Disease Activity Index (CDAI) e marcadores séricos antes do uso do Infliximabe, após a fase de indução e após a fase de manutenção. Método Foram incluídos 17 pacientes com diagnóstico prévio de doença de Crohn, que faziam uso da terapia convencional, mas que necessitaram da introdução da terapia biológica: Infliximabe. Esses pacientes realizaram colonoscopias com biópsias, exames de atividade inflamatória sérica, fecal (calprotectina e lactoferrina) e análise do CDAI nas fases pré Infliximabe, pós indução (semana 8) e pós manutenção (semana 32). Resultados Houve queda significativa (P = 0,04) da calprotectina entre as fases pré Infliximabe e pós indução, o mesmo não ocorrendo após a fase de manutenção. A lactoferrina manteve-se positiva nas três fases do estudo. Na análise histológica, houve diferença significativa apenas entre as fases pré Infliximabe e pós manutenção (P = 0,036), com 60% dos pacientes apresentando melhora histológica após o período de acompanhamento. O CDAI apresentou diferença significativa entre as fases pré Infliximabe e pós indução e entre as fases pré Infliximabe e pós manutenção (P<0,01). Conclusão A calprotectina e a lactoferrina não foram capazes de monitorizar a atividade inflamatória ...

Effect of COX-2 inhibitor lumiracoxib and the TNF-α antagonist etanercept on TNBS-induced colitis in Wistar rats.

Crohn's disease (CD) is associated with gut barrier dysfunction. Besides the baseline barrier defect, a subgroup of patients also expresses an intestinal barrier hyperresponsiveness to nonsteroidal anti-inflammatory drugs. On the other hand, the anti-tumour necrosis factor alpha (TNF-α) treatment has brought benefits to these patients. Thus, this study aimed to evaluate the effect of lumiracoxib, a selective-cyclooxygenase-2 (COX-2) inhibitor, and Etanercept (ETC), a TNF-α antagonist on the 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced experimental colitis. A total of 47 Wistar rats were randomized into seven groups, as follows: (1) Sham: sham induced-colitis; (2) TNBS: nontreated induced-colitis; (3) Lumiracoxib control; (4) Lumiracoxib-treated induced-colitis; (5) ETC control; (6) ETC-treated induced-colitis; (7) Lumiracoxib-ETC-treated induced-colitis. Rats from groups 6 and 7 presented significant improvement of macroscopic and histopathological damages in the distal colon. The gene expression of COX-2 mRNA, as well of TNF-α mRNA, decreased significantly in groups 6 and 7 compared to the TNBS nontreated and lumiracoxib-treated groups. The treatment only with lumiracoxib did not reduce the inflammation on TNBS-induced experimental colitis. ETC attenuated the damage seen in the colon and reduced the inflammation caused by TNBS. Our results suggest that down-regulation of TNF-α and COX-2 resulted in a decrease in inflammation caused by TNBS and thus provided some protection from the colonic damage caused by TNBS.

Biological therapy in the treatment of moderate-to-severe ulcerative colitis patients: can colectomy be prevented?

Ulcerative colitis treatment intends to induce remission, and its maintenance. Biological drugs, such as infliximab, have been indicated in moderate and severe cases of the disease, which are unresponsive to conventional medication. Randomized controlled trials proved the efficacy of biological treatment with high rates of sustained disease remission and mucosal healing. Recently, the concept of mucosal healing has been inversely associated with surgical treatment. Patients treated with infliximab have lower colectomy rates than those receiving conventional therapies. We suppose that earlier use of biological drugs in disease's course would lead to better clinical control and mucosal healing, with a consequent reduction in colectomy rates. To support this hypothesis, a literature review from January, 1996 to April, 2011 was performed. (AU)

O tratamento da colite ulcerativa tem como objetivo induzir a remissão, além da manutenção da remissão da doença. Agentes biológicos como o infliximabe têm sido indicados em casos moderados e graves da doença, os quais não respondem à medicação convencional. Ensaios clínicos randomizados comprovaram a eficácia do tratamento biológico com altas taxas de remissão da doença e cicatrização sustentada da mucosa. Recentemente, o conceito de cicatrização da mucosa tem sido inversamente associado com o tratamento cirúrgico. Pacientes tratados com infliximabe têm taxas mais baixas de colectomia se comparados com aqueles que receberam terapias convencionais. Supõe-se que quanto mais cedo for introduzida a terapia biológica no curso da doença, melhor seriam o controle clínico e a cicatrização da mucosa, com consequente redução nas taxas de colectomia. Para apoiar esta hipótese, foi realizada uma revisão da literatura entre janeiro de 1996 e abril de 2011. (AU)

Etanercept attenuates TNBS-induced experimental colitis: role of TNF-α expression.

Crohn's disease (CD) is associated with gut barrier dysfunction. Tumour necrosis factor-α (TNF-α) plays an important role into the pathogenesis of several inflammatory diseases because its expression is increased in inflamed mucosa of CD patients. Anti-TNF therapy improves significantly mucosal inflammation. Thus, this study aimed to evaluate the effect of Etanercept (ETC), a tumour necrosis factor alpha (TNF-α) antagonist on the 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced experimental colitis. A total of 18 Wistar rats were randomized into four groups, as follows: (1) Sham: sham induced-colitis; (2) TNBS: non-treated induced-colitis; (3) ETC control; (4) ETC-treated induced-colitis. Rats from group 4 presented significant improvement either of macroscopic or of histopathological damage in the distal colon. The gene expression of TNF-α mRNA, decreased significantly in this group compared to the TNBS non-treated group. The treatment with etanercept attenuated the colonic damages and reduced the inflammation caused by TNBS. Taken together, our results suggest that ETC attenuates intestinal colitis induced by TNBS in Wistar rats by TNF-α downregulation.