Fecal calprotectin and endoscopic scores: The cornerstones in clinical practice for evaluating mucosal healing in inflammatory bowel disease.

Managing inflammatory bowel disease (IBD) is becoming increasingly complex and personalized, considering the advent of new advanced therapies with distinct mechanisms of action. Achieving mucosal healing (MH) is a pivotal therapeutic goal in IBD management and can prevent IBD progression and reduce flares, hospitalization, surgery, intestinal damage, and colorectal cancer. Employing proactive disease and therapy assessment is essential to achieve better control of intestinal inflammation, even if subclinical, to alter the natural course of IBD. Periodic monitoring of fecal calprotectin (FC) levels and interval endoscopic evaluations are cornerstones for evaluating response/remission to advanced therapies targeting IBD, assessing MH, and detecting subclinical recurrence. Here, we comment on the article by Ishida et al Moreover, this editorial aimed to review the role of FC and endoscopic scores in predicting MH in patients with IBD. Furthermore, we intend to present some evidence on the role of these markers in future targets, such as histological and transmural healing. Additional prospective multicenter studies with a stricter MH criterion, standardized endoscopic and histopathological analyses, and virtual chromoscopy, potentially including artificial intelligence and other biomarkers, are desired.

ASSESSMENT OF QUALITY OF LIFE IN ELDERLY PATIENTS WITH INFLAMMATORY BOWEL DISEASE WITH MILD ACTIVITY AND IN CLINICAL REMISSION.

BACKGROUND: Inflammatory bowel disease (IBD), represented by Crohn's disease (CD) and ulcerative colitis (UC), is a chronic condition that affects all age groups, predominantly in young individuals. Currently, an increase in the prevalence of IBD has been documented, in parallel with the increase in the elderly population. The scarce number of studies that better characterize the impact of IBD on Quality of Life (QoL) in the elderly motivated the present study. OBJECTIVE: To evaluate the impact of IBD on the QoL of elderly people treated at a Tertiary IBD Center. METHODS: Prospective cross-sectional study that included elderly patients (age ≥60 years) with quiescent or mildly active IBD treated at the HU-UFJF IBD Center between March 2019 and December 2022. Elderly companions without severe comorbidities who attended the consultation with the patients were included as a control group. Sociodemographic and IBD-related characteristics were recorded. QoL was assessed using previously validated questionnaires (WHOQOL-BREF and IBDQ). Patients with IBD with moderate to severe activity, history of recent or imminent hospitalization, serious or opportunistic infections in the last 6 months, previous neoplasia, dementia, and difficulty understanding/fulfilling the questionnaires were excluded. RESULTS: A total of 123 patients were included (74 with IBD and 49 in the control group), with a mean age of 67±6.2 years, 52.7% with CD, and 47.3% with UC. Mild disease activity was observed in 31.1%. Both groups (IBD patients and control) were comparable based on age, sex, BMI, and the Charlson Comorbidity Index. Patients with IBD and controls had similar QoL scores in the different domains assessed by the WHOQOL-BREF. On the other hand, when evaluating the general facet of QoL, IBD patients had significantly lower scores in General QoL (3.71±0.87 versus 4.02±0.62, respectively; P=0.021) and General Health (3.32±1.05 versus 3.69±0.94, respectively; P=0.035). The presence of mildly active IBD negatively impacted the general health score (2.91±0.99 versus 3.47±1.04, respectively; P=0.035) and the physical domain of the WHOQOL-BREF (12.27±2.63 versus 13.86±2.61, respectively; P=0.019) when compared to patients in remission. Conversely, no impact on QoL was observed with the Application of the IBDQ questionnaire regarding the type of the disease (161±38.5 versus 163.1±42.6 for CD and UC, respectively; P=0.84) or the presence of activity (152.5±38.8 versus 166.4±40.5, respectively; P=0.17). CONCLUSION: No statistically significant differences were found between elderly patients with mildly active or quiescent IBD and elderly patients without IBD when observing global QoL scores. However, IBD negatively impacted the general facet of QoL, just as mild activity was associated with lower scores in general health and the physical domain assessed by the WHOQOL-BREF. Patients with IBD treated with biological therapy had better Qol than those on conventional therapy. Future studies are needed to choose the most appropriate tool for assessing QoL in this population.

Metabolic dysfunction-associated steatotic liver disease prevalence and risk factors in inflammatory bowel disease in tertiary center.

OBJECTIVE: The aim of this study was to evaluate the prevalence and risk factors related to metabolic dysfunction-associated steatotic liver disease in inflammatory bowel disease patients. METHODS: This is a cross-sectional study conducted on adults with inflammatory bowel disease from 2019 to 2021. Metabolic dysfunction-associated steatotic liver disease encompasses patients with steatosis and at least one cardiometabolic risk factor. Patients with alcohol consumption ≥20 g/day, chronic liver diseases, or methotrexate use were excluded. RESULTS: Almost 140 patients were included: 67.1% were female, with a mean age of 49.7±13.7 years, and 63.6% had Crohn's disease. The mean duration of inflammatory bowel disease was 9.7±7.9 years. Metabolic dysfunction-associated steatotic liver disease was observed in 44.3% and advanced liver fibrosis was excluded in 63.5% by Fibrosis-4. Patients with metabolic dysfunction-associated steatotic liver disease were older (p = 0.003) and had a higher number of metabolic syndrome components (2.9±1.1 versus 1.6±1.0; p<0.001), greater abdominal circumference (p<0.001), and body mass index (p<0.001). The only factor related to inflammatory bowel disease associated with metabolic dysfunction-associated steatotic liver disease was disease duration (11.6±9.5 versus 8.3±6.2; p = 0.017). A higher number of metabolic syndrome components and obesity increase by 2.2 times and an altered waist circumference by 2.6 times the occurrence of metabolic dysfunction-associated steatotic liver disease. CONCLUSION: A high prevalence of metabolic dysfunction-associated steatotic liver disease was observed in patients with inflammatory bowel disease, with the main risk factors being associated with metabolic syndrome predicting it, but not with inflammatory bowel disease features and/or its treatment.

Effectiveness and Safety of Ustekinumab for Ulcerative Colitis: A Brazilian Multicentric Observational Study.

Background: Real-world data on the effectiveness and safety of ustekinumab (UST) in ulcerative colitis (UC) are lacking in Latin America. In this study, we aimed to describe the effectiveness and safety of UST in a real-world multicenter cohort of Brazilian patients with UC. Methods: We conducted a multicenter retrospective observational cohort study, including patients with moderate-to-severe UC (total Mayo score 6-12, with an endoscopic subscore of 2 or 3) who received UST. The co-primary endpoints were clinical remission, defined as a total Mayo score ≤2 at 1 year, with a combined rectal bleeding and stool frequency subscore of ≤1, and endoscopic remission (endoscopic Mayo subscore of 0) within 1 year from baseline. Secondary endpoints included clinical response between weeks 12 and 16, endoscopic response within 1 year of starting UST, steroid-free clinical remission at week 52, and biochemical remission at week 52. We also evaluated UST treatment persistence and safety. Results: A total of 50 patients were included (female, n = 36, 72.0%), with a median disease duration of 9.2 years (1-27). Most patients had extensive colitis (n = 38, 76.0%), and 43 (86.0%) were steroid dependent at baseline. Forty patients (80.0%) were previously exposed to biologics (anti-TNF drugs, n = 31; vedolizumab [VDZ], n = 27). The co-primary endpoints of clinical remission at 1 year and endoscopic remission within 1 year were achieved by 50.0% and 36.0% of patients, respectively. Clinical response at weeks 12-16 was 56.0%, and endoscopic response, steroid-free clinical remission, and biochemical remission at week 52 were 68.0%, 46.5%, and 50.0%, respectively. The UST treatment persistence rate at 24 months was 73.7%. During the follow-up, 10 patients (20.0%) were hospitalized, mostly due to disease progression, and 3 patients required colectomy. Nine patients (18.0%) discontinued the drug mainly due to a lack of effectiveness. Twenty-seven adverse events (AEs) were reported, 16 of which were considered as serious AEs. Conclusions: In this real-world cohort of difficult-to-treat UC patients, UST was associated with improvements in clinical, biochemical, and endoscopic outcomes. The safety profile was favorable, consistent with the known profile of UST.

Interaction between diet and genetics in patients with inflammatory bowel disease.

In this editorial, we comment on the article by Marangoni et al, published in the recent issue of the World Journal of Gastroenterology 2023; 29: 5618-5629, about "Diet as an epigenetic factor in inflammatory bowel disease". The authors emphasized the role of diet, especially the interaction with genetics, in promoting the inflammatory process in inflammatory bowel disease (IBD) patients, focusing on DNA methylation, histone modifications, and the influence of microRNAs. In this editorial, we explore the interaction between genetics, gut microbiota, and diet, in an only way. Furthermore, we provided dietary recommendations for patients with IBD. The Western diet, characterized by a low fiber content and deficiency the micronutrients, impacts short-chain fatty acids production and may be related to the pathogenesis of IBD. On the other hand, the consumption of the Mediterranean diet and dietary fibers are associated with reduced risk of IBD flares, particularly in Crohn's disease (CD) patients. According to the dietary guidance from the International Organization for the Study of Inflammatory Bowel Diseases (IOIBD), the regular consumption of fruits and vegetables while reducing the consumption of saturated, trans, dairy fat, additives, processed foods rich in maltodextrins, and artificial sweeteners containing sucralose or saccharine is recommended to CD patients. For patients with ulcerative colitis, the IOIBD recommends the increased intake of natural sources of omega-3 fatty acids and follows the same restrictive recommendations aimed at CD patients, with the possible inclusion of red meats. In conclusion, IBD is a complex and heterogeneous disease, and future studies are needed to elucidate the influence of epigenetics on diet and microbiota in IBD patients.

Avaliação da qualidade de vida em pacientes idosos com doença inflamatória intestinal em atividade leve ou remissão / Assessment of quality of life in elderly patients with inflammatory bowel disease with mild activity and in clinical remission

ABSTRACT Background: Inflammatory bowel disease (IBD), represented by Crohn's disease (CD) and ulcerative colitis (UC), is a chronic condition that affects all age groups, predominantly in young individuals. Currently, an increase in the prevalence of IBD has been documented, in parallel with the increase in the elderly population. The scarce number of studies that better characterize the impact of IBD on Quality of Life (QoL) in the elderly motivated the present study. Objective: To evaluate the impact of IBD on the QoL of elderly people treated at a Tertiary IBD Center. Methods: Prospective cross-sectional study that included elderly patients (age ≥60 years) with quiescent or mildly active IBD treated at the HU-UFJF IBD Center between March 2019 and December 2022. Elderly companions without severe comorbidities who attended the consultation with the patients were included as a control group. Sociodemographic and IBD-related characteristics were recorded. QoL was assessed using previously validated questionnaires (WHOQOL-BREF and IBDQ). Patients with IBD with moderate to severe activity, history of recent or imminent hospitalization, serious or opportunistic infections in the last 6 months, previous neoplasia, dementia, and difficulty understanding/fulfilling the questionnaires were excluded. Results: A total of 123 patients were included (74 with IBD and 49 in the control group), with a mean age of 67±6.2 years, 52.7% with CD, and 47.3% with UC. Mild disease activity was observed in 31.1%. Both groups (IBD patients and control) were comparable based on age, sex, BMI, and the Charlson Comorbidity Index. Patients with IBD and controls had similar QoL scores in the different domains assessed by the WHOQOL-BREF. On the other hand, when evaluating the general facet of QoL, IBD patients had significantly lower scores in General QoL (3.71±0.87 versus 4.02±0.62, respectively; P=0.021) and General Health (3.32±1.05 versus 3.69±0.94, respectively; P=0.035). The presence of mildly active IBD negatively impacted the general health score (2.91±0.99 versus 3.47±1.04, respectively; P=0.035) and the physical domain of the WHOQOL-BREF (12.27±2.63 versus 13.86±2.61, respectively; P=0.019) when compared to patients in remission. Conversely, no impact on QoL was observed with the Application of the IBDQ questionnaire regarding the type of the disease (161±38.5 versus 163.1±42.6 for CD and UC, respectively; P=0.84) or the presence of activity (152.5±38.8 versus 166.4±40.5, respectively; P=0.17). Conclusion: No statistically significant differences were found between elderly patients with mildly active or quiescent IBD and elderly patients without IBD when observing global QoL scores. However, IBD negatively impacted the general facet of QoL, just as mild activity was associated with lower scores in general health and the physical domain assessed by the WHOQOL-BREF. Patients with IBD treated with biological therapy had better Qol than those on conventional therapy. Future studies are needed to choose the most appropriate tool for assessing QoL in this population.

RESUMO Contexto: Doença inflamatória intestinal (DII), representada pela doença de Crohn (DC) e retocolite ulcerativa (RCU), é uma condição crônica e progressiva que afeta todas as faixas etárias, embora predomine em indivíduos jovens. Atualmente, tem sido documentado um aumento na prevalência de DII, de forma paralela ao aumento da população idosa. O escasso número de estudos que melhor caracterizem o impacto da DII na qualidade de vida (QV) em idosos motivou o presente estudo. Objetivo: Avaliar o impacto da DII na QV de idosos atendidos em um centro terciário de DII. Métodos: Estudo prospectivo transversal que incluiu pacientes idosos (idade ≥60 anos) com DII, atendidos pelo Centro de DII do HU-UFJF, entre março de 2019 a dezembro de 2022, e que apresentavam remissão clínica ou atividade leve de doença. Acompanhantes idosos sem comorbidades graves que compareceram à consulta com os pacientes foram incluídos como grupo controle. Foram registradas características sociodemográficas e relativas a DII. A QV foi avaliada por meio de questionários previamente validados (WHOQOL-BREF e IBDQ). Pacientes com DII com atividade moderada a grave, história de hospitalização recente ou iminente, infecções graves ou oportunistas nos últimos 6 meses, neoplasia prévia, demência, dificuldade de compreensão/ preenchimento dos questionários foram excluídos. Resultados: Foram incluídos 123 pacientes (74 com DII e 49 no grupo controle), com idade média de 67±6,2 anos, sendo 52,7% com DC e 47,3% com RCU. Atividade leve da doença foi observada em 31,1%. Ambos os grupos (pacientes com DII e controle) foram comparáveis com base na idade, sexo, IMC e Índice de Comorbidade de Charlson. Pacientes com DII e controle apresentaram escores de QV similares nos diferentes domínios avaliados pelo WHOQOL-BREF. Por outro lado, quando avaliada a faceta geral de QV, pacientes com DII apresentaram escores significativamente menores na QV geral (3,71±0,87 versus 4,02±0,62, respectivamente; P=0,021) e na saúde geral (3,32±1,05 versus 3,69±0,94, respectivamente; P=0,035). A presença de atividade leve impactou negativamente nos escores de saúde geral e de domínio físico do WHOQOL-BREF quando comparados com pacientes em remissão (2,91±0,99 versus 3.47±1,04, respectivamente; P=0,035 e 12,27±2.63 versus 13,86±2,61, respectivamente; P=0,019). Não foi observado impacto na QV com a aplicação do questionário IBDQ no que se refere ao tipo de DII (161±38.5 versus 163.1±42,6 para DC e RCU, respectivamente; P=0.84) ou a presença de atividade (152.5±38.8 versus 166.4±40.5, respectivamente; P=0.17). Conclusão: Não foram encontradas diferenças estatisticamente significativas entre pacientes idosos com DII em atividade leve ou quiescente e pacientes idosos sem DII quando observados os escores globais de QV. Porém, a DII impactou negativamente a faceta geral de QV, assim como a presença de atividade leve esteve associada a menores escores na saúde geral e no domínio físico avaliado pelo WHOQOL-BREF. Pacientes com DII tratados com terapia biológica apresentaram melhor QV do que aqueles em terapia convencional. Estudos futuros são necessários para escolha de ferramenta mais adequada para avaliação de QV nessa população.

Metabolic dysfunction-associated steatotic liver disease prevalence and risk factors in inflammatory bowel disease in tertiary center

SUMMARY OBJECTIVE: The aim of this study was to evaluate the prevalence and risk factors related to metabolic dysfunction-associated steatotic liver disease in inflammatory bowel disease patients. METHODS: This is a cross-sectional study conducted on adults with inflammatory bowel disease from 2019 to 2021. Metabolic dysfunction-associated steatotic liver disease encompasses patients with steatosis and at least one cardiometabolic risk factor. Patients with alcohol consumption ≥20 g/day, chronic liver diseases, or methotrexate use were excluded. RESULTS: Almost 140 patients were included: 67.1% were female, with a mean age of 49.7±13.7 years, and 63.6% had Crohn's disease. The mean duration of inflammatory bowel disease was 9.7±7.9 years. Metabolic dysfunction-associated steatotic liver disease was observed in 44.3% and advanced liver fibrosis was excluded in 63.5% by Fibrosis-4. Patients with metabolic dysfunction-associated steatotic liver disease were older (p = 0.003) and had a higher number of metabolic syndrome components (2.9±1.1 versus 1.6±1.0; p<0.001), greater abdominal circumference (p<0.001), and body mass index (p<0.001). The only factor related to inflammatory bowel disease associated with metabolic dysfunction-associated steatotic liver disease was disease duration (11.6±9.5 versus 8.3±6.2; p = 0.017). A higher number of metabolic syndrome components and obesity increase by 2.2 times and an altered waist circumference by 2.6 times the occurrence of metabolic dysfunction-associated steatotic liver disease. CONCLUSION: A high prevalence of metabolic dysfunction-associated steatotic liver disease was observed in patients with inflammatory bowel disease, with the main risk factors being associated with metabolic syndrome predicting it, but not with inflammatory bowel disease features and/or its treatment.

The Role of Pharmacogenetics in the Therapeutic Response to Thiopurines in the Treatment of Inflammatory Bowel Disease: A Systematic Review.

This study focuses on the use of thiopurines for treating inflammatory bowel diseases (IBD). These drugs undergo enzymatic changes within the body, resulting in active and inactive metabolites that influence their therapeutic effects. The research examines the role of genetic polymorphisms in the enzyme thiopurine S-methyltransferase (TPMT) in predicting the therapeutic response and adverse effects of thiopurine treatment. The TPMT genotype variations impact the individual responses to thiopurines. Patients with reduced TPMT activity are more susceptible to adverse reactions (AEs), such leukopenia, hepatotoxicity, pancreatitis, and nausea, which are common adverse effects of thiopurine therapy. The therapeutic monitoring of the metabolites 6-thioguanine nucleotides (6-TGN) and 6-methyl mercaptopurine (6-MMP) is proposed to optimize treatment and minimize AEs. Patients with higher 6-TGN levels tend to have better clinical responses, while elevated 6-MMP levels are linked to hepatotoxicity. Genotyping for TPMT before or during treatment initiation is suggested to tailor dosing strategies and enhance treatment efficacy while reducing the risk of myelosuppression. In conclusion, this study highlights the importance of considering genetic variations and metabolite levels in optimizing thiopurine therapy for IBD patients, focusing on balance therapeutic efficacy with the prevention of adverse effects and contributing to personalized treatment and better patient outcomes.

Vedolizumab in Mild-to-Moderate Crohn's Disease Patients Naïve to Biological Therapy: A Multicentric Observational Study.

Background: In real-world experience, the number of patients using vedolizumab as first-line biological therapy was low. We aimed to evaluate the effectiveness and safety of vedolizumab in mild-to-moderate Crohn's disease (CD) biologic-naïve patients. Methods: We performed a retrospective multicentric cohort study with patients who had clinical activity scores (Harvey-Bradshaw Index [HBI]) measured at baseline and weeks 12, 26, 52, as well as at the last follow-up. Clinical response was defined as a reduction ≥3 in HBI, whereas clinical remission as HBI ≤4. Mucosal healing was defined as the complete absence of ulcers in control colonoscopies. Kaplan-Meier survival analysis was used to assess the persistence with vedolizumab. Results: From a total of 66 patients, 53% (35/66) reached clinical remission at week 12. This percentage increased to 69.7% (46/66) at week 26, and 78.8% (52/66) at week 52. Mucosal healing was achieved in 62.3% (33/53) of patients. Vedolizumab was well tolerated, and most adverse events were minor. During vedolizumab treatment, 3/66 patients underwent surgery. Conclusions: This study demonstrates the effectiveness and safety of vedolizumab as a first-line biological agent in patients with mild-to-moderate CD.

Efficacy of Early Optimization of Infliximab Guided by Therapeutic Drug Monitoring during Induction-A Prospective Trial.

Therapeutic drug monitoring (TDM) during induction therapy with anti-tumor necrosis factor drugs has emerged as a strategy to optimize response to these biologics and avoid undesired outcomes related to inadequate drug exposure. This study aimed to describe clinical, biological, and endoscopic remission rates at six months in Brazilian inflammatory bowel disease (IBD) patients following a proactive TDM algorithm guided by IFX trough levels (ITL) and antibodies to IFX (ATI) levels during induction, at week six. A total of 111 IBD patients were prospectively enrolled, excluding those previously exposed to the drug. ITL ≥ 10 µg/mL was considered optimal. Patients with suboptimal ITL (<10 µg/mL) were guided according to ATI levels. Those who presented ATI ≤ 200 ng/mL underwent dose intensification in the maintenance phase, and patients with ATI > 200 ng/mL discontinued IFX. In our study, proactive TDM was associated with persistence in the IFX rate at six months of 82.9%. At that time, rates of clinical, biological, and endoscopic remission in patients under IFX treatment were 80.2%, 73.9%, and 48.1%, respectively. Applying a simplified TDM-guided algorithm during induction seems feasible and can help improve patients' outcomes in clinical practice.

Leukocytoclastic Vasculitis Secondary to Anti-Tumor Necrosis Factor Therapy in Inflammatory Bowel Diseases: A Multicenter Retrospective Cohort Study.

BACKGROUND: Vasculitis is an uncommon complication of biologics used to treat inflammatory bowel disease (IBD). This study describes a case series of vasculitis induced by anti-tumor necrosis factor (TNF) therapy in IBD patients. METHODS: Retrospective assessments were performed using the medical records of adult IBD patients who underwent outpatient clinical follow-ups between January 2010 and December 2019 in order to identify patients with vasculitis caused by anti-TNF therapy. RESULTS: There were 2442 patients altogether. Of these, 862 (35%) took anti-TNF medication. Five patients (0.6% of the overall patients; n = 3 (60%) Crohn's disease; n = 2 (40%), ulcerative colitis) were identified as having leukocytoclastic vasculitis (LCV) due to anti-TNF therapy; these patients were white, female, and non-smokers. The mean age of LCV diagnosis was 32.2 years, and the mean IBD duration was 7.2 years. The mean time between the start of biologic therapy and LCV onset was 30.8 months. Most of the patients were using adalimumab (80%; n = 4). All the patients were in remission at the time of the LCV diagnosis, and the vasculitis affected the skin in all cases. Anti-TNF therapy was discontinued in the five abovementioned patients, and the response of LCV to the oral steroids was significantly positive. Remarkably, all five patients experienced complete remission from LCV within 4-12 weeks after starting prednisone therapy, and none of them had LCV recurrence in the follow-up period (a mean duration of 28 months). CONCLUSIONS: LCV is an unusual complication of anti-TNF therapy in the IBD setting. In this context, clinicians should have a high degree of suspicion of LCV in patients who develop an unexplained cutaneous rash.

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.

Effectiveness and Safety of Ustekinumab for Moderate to Severely Active Crohn's Disease: Results from an Early Access Program in Brazil.

This prospective, observational, open-label study aimed to provide access to ustekinumab prior to market authorization and assess its safety and effectiveness in patients with Crohn's disease (CD) refractory to anti-tumor necrosis factor-α and conventional drugs in Brazil. Patients with a diagnosis of moderate-to-severe active CD for ≥3 months before screening received ustekinumab in a single intravenous induction dose (~6 mg/kg) at week 0, and a 90 mg maintenance dose, subcutaneously, every 8 or 12 weeks, from week 8 through to 80. Serious adverse events (SAE), adverse drug reactions (ADR), clinical response (per CD Activity Index and Harvey Bradshaw Index (HBI) scores), remission (per HBI scores), biomarkers (C-reactive protein (CRP) and fecal calprotectin (FC)) and endoscopic improvement rate over 80 weeks were assessed. Patients with a mean age of 39.9 years were assessed. Discontinuation rate was low (23%) and most adverse events were mild (68.7%). The SAE rate was 21% (mostly infections/infestations or gastrointestinal disorder), and ADR rate was 44%. The CD Activity Index and HBI scores decreased (by 74% and 81%, respectively) with 50% of patients showing normalized CRP and FC, and 63% achieved endoscopic improvement. Ustekinumab was fairly safe, well tolerated and effective in a Brazilian cohort of CD patients.

A Rare Presentation of a Solid Pseudopapillary Neoplasm of the Pancreas.

Solid pseudopapillary neoplasms (SPN) are rare and represent a minority of all pancreatic cystic tumors. Symptoms, if present, are generally nonspecific and upper gastrointestinal bleeding is extremely uncommon as an initial presentation. A 31-year-old woman with no prior medical history presented with a 3-week period of epigastric pain, which she reported as persistent, exacerbated by eating, and associated with progressive asthenia, fatigue, and exertional dyspnea. One month prior, she had had experienced 2 episodes of melena. Upon physical examination her skin was pale, with no other changes. Through diagnostic investigation, an esophagogastroduodenoscopy showed a giant ulcer in the duodenal bulb and a suspect fistulous orifice localized on the posterior wall of the duodenal bulb. In addition, a bulge on the duodenal bulb, suggestive of an extrinsic compression, was noticed. An abdominal computed tomography scan and magnetic resonance imaging showed a mixed solid and cystic lesion in the head of the pancreas in direct proximity to the duodenum, which contained an image compatible with a fistula. The patient successfully underwent pancreaticoduodenectomy. The histopathology, including microscopic analysis and immunohistochemistry, was consistent with an SPN of the pancreas. This case emphasizes that the evaluation of patients presenting with upper gastrointestinal bleeding due to a giant duodenal ulcer and an extrinsic mass effect noted on the duodenum should include cross-sectional images of the abdomen. In this case, the finding of a large well-encapsulated pancreatic solid and cystic mass on abdominal images was suggestive of a pancreatic neoplasm diagnosis, including an SPN.

Neoplasias sólidas pseudopapilares (NSP) são raras e representam uma minoria de todos os tumores císticos do pâncreas. Os sintomas, se presentes, geralmente são inespecíficos e a hemorragia gastrointestinal superior é extremamente incomum como apresentação inicial. Uma mulher de 31 anos sem história médica prévia apresentava a três semanas dor epigástrica, a qual ela relatava como persistente, exacerbada pela alimentação e acompanhada de astenia progressiva, fadiga e dispneia aos esforços. Além disso, um mês antes, ela teve dois episódios de melenas. Ao exame físico havia palidez cutânea, sem outras alterações. Através da investigação diagnóstica, uma esofagogastroduodenoscopia mostrou uma úlcera gigante no bulbo duodenal e a suspeita de um orifício fistuloso localizado na parede posterior do bulbo duodenal. Adicionalmente, um abaulamento sobre o bulbo duodenal, sugestivo de uma compressão extrínsica, foi notado. A tomografia computadorizada de abdome e a imagem de ressonância magnética mostraram uma lesão mista de aparência sólida e cística na cabeça do pâncreas, em proximidade direta com o duodeno, a qual continha uma imagem compatível com uma fístula. A paciente foi submetida a pancreaticoduodenectomia com sucesso. A histopatologia, incluindo análise microscópica e imunohistoquímica, foi compatível com NSP do pâncreas. Este caso enfatiza que a avaliação dos pacientes, que apresentam hemorragia gastrointestinal superior devido à úlcera duodenal gigante e um efeito de massa extrínseco notado sobre o duodeno, deve incluir imagem abdominal. Neste caso, o achado de uma grande massa pancreática sólida e cística bem encapsulada na imagem abdominal, sugeria o diagnóstico de uma neoplasia pancreática, incluindo a NSP.

Long-term effectiveness and safety of ustekinumab in bio-naïve and bio-experienced anti-tumor necrosis factor patients with Crohn's disease: a real-world multicenter Brazilian study.

BACKGROUND: The effectiveness of ustekinumab (UST) in the treatment of Crohn's disease (CD) has been demonstrated in the pivotal Phase 3 UNITI 1 and 2 and IM-UNITI studies in both anti-TNF-naïve and anti-TNF-exposed patients. Given the selective nature of pivotal trial designs, real-world effectiveness and safety studies are warranted. We report our experience with UST treatment in a large, real-world multicenter cohort of Brazilian patients with CD. METHODS: We performed a retrospective multicenter study including patients with CD, predominantly biologically refractory CD, who received UST. The primary endpoint was the proportion of patients in clinical remission at weeks 8, 24 and 56. Possible predictors of clinical and biological response/remission and safety outcomes were also assessed. RESULTS: Overall, 245 CD (mean age 39.9 [15-87]) patients were enrolled. Most patients (86.5%) had been previously exposed to biologics. According to nonresponder imputation analysis, the proportions of patients in clinical remission at weeks 8, 24 and 56 were 41.0% (n = 98/239), 64.0% (n = 153/239) and 39.3% (n = 94/239), respectively. A biological response was achieved in 55.4% of patients at week 8, and 59.3% were in steroid-free remission at the end of follow-up. No significant differences in either clinical or biological remission were noted between bio-naïve and bio-experienced patients. Forty-eight patients (19.6%) presented 60 adverse events during the follow-up, of which 8 (13.3%) were considered serious adverse events (3.2% of 245 patients). Overall, a proximal disease location, younger age, perianal involvement, and smoking were associated with lower rates of clinical remission over time. CONCLUSIONS: UST therapy was effective and safe in the long term in this large real-life cohort of Brazilian patients with refractory CD, regardless of previous exposure to other biological agents.

HIGH PREVALENCE OF NON-ADHERENCE TO ULCERATIVE COLITIS THERAPY IN REMISSION: KNOWING THE PROBLEM TO PREVENT LOSS.

BACKGROUND: Ulcerative colitis (UC) is a chronic inflammatory disease whose manifestations can drastically affect the individual's quality of life, and therefore adherence to treatment is important in order to keep it in remission. OBJECTIVE: To verify the prevalence of non-adherence and the influence of sociodemographic, clinical and pharmacotherapeutic characteristics associated with non-adherence to treatment of UC in remission. METHODS: Cross-sectional study conducted with 90 individuals diagnosed with UC in remission. The information was collected through interviews during medical consultations at Medical Clinic of Gastroenterology of Hospital Universitário da Universidade Federal de Juiz de Fora. To verify the association of the variables under study with the outcome of interest and its measure of association, Student's t-test or Pearson's chi-square non-parametric test (P<0.05) was used and prevalence ratio and confidence interval were calculated. RESULTS: A high prevalence of non-adherence (77.8%) was found among patients with UC in remission. The individuals most likely to not adhere to the treatment were those aged less than 50 years, who were not engaged in paid work, with high scores for anxiety and who used more than one medication as part of the treatment of UC. CONCLUSION: These findings reinforce that acknowledging the factors that influence the non-adherence behavior is of paramount importance for the development of strategies by health care professionals, assuring that those will be really effective to prolong, as much as possible, one of the most successful ways to maintain the UC remission period: the use of medications.

Elevada prevalência de não adesão ao tratamento da colite ulcerativa em remissão: conhecer o problema para prevenir o prejuízo / High prevalence of non-adherence to ulcerative colitis therapy in remission: knowing the problem to prevent loss

ABSTRACT Background Ulcerative colitis (UC) is a chronic inflammatory disease whose manifestations can drastically affect the individual's quality of life, and therefore adherence to treatment is important in order to keep it in remission. Objective To verify the prevalence of non-adherence and the influence of sociodemographic, clinical and pharmacotherapeutic characteristics associated with non-adherence to treatment of UC in remission. Methods Cross-sectional study conducted with 90 individuals diagnosed with UC in remission. The information was collected through interviews during medical consultations at Medical Clinic of Gastroenterology of Hospital Universitário da Universidade Federal de Juiz de Fora. To verify the association of the variables under study with the outcome of interest and its measure of association, Student's t-test or Pearson's chi-square non-parametric test (P<0.05) was used and prevalence ratio and confidence interval were calculated. Results A high prevalence of non-adherence (77.8%) was found among patients with UC in remission. The individuals most likely to not adhere to the treatment were those aged less than 50 years, who were not engaged in paid work, with high scores for anxiety and who used more than one medication as part of the treatment of UC. Conclusion These findings reinforce that acknowledging the factors that influence the non-adherence behavior is of paramount importance for the development of strategies by health care professionals, assuring that those will be really effective to prolong, as much as possible, one of the most successful ways to maintain the UC remission period: the use of medications.

RESUMO Contexto Colite ulcerativa é uma doença inflamatória crônica que pode apresentar manifestações graves que afetam drasticamente a qualidade de vida do indivíduo e, dessa maneira, a adesão ao tratamento é importante a fim de manter a doença em remissão. Objetivo Verificar a prevalência de não adesão e a influência de características sociodemográficas, clínicas e farmacoterapêuticas associadas a não adesão ao tratamento da colite ulcerativa em remissão. Métodos Estudo transversal envolvendo 90 indivíduos diagnosticados com colite ulcerativa em remissão. As entrevistas foram conduzidas durante as consultas médicas realizadas na Clínica Médica de Gastroenterologia do Hospital Universitário da Universidade Federal de Juiz de Fora. Para verificar a associação entre as variáveis com o desfecho de interesse, foi aplicado teste-t de Student ou teste não-paramétrico qui-quadrado de Pearson (P<0,05) e também razão de prevelência e intervalos de confiança foram calculados. Resultados Uma elevada prevalência de não adesão (77,8%) foi encontrada dentre os pacientes com colite ulcerativa em remissão. Os indivíduos mais propensos ao comportamento em questão foram aqueles com menos de 50 anos, sem trabalho remumerado, com escores mais elevados no teste de ansiedade e que utilizavam mais de um medicamento para o tratamento da colite ulcerativa. Conclusão Estes achados reforçam que o conhecimento de fatores que influenciam o comportamento de não adesão é de grande importância para o desenvolvimento de estratégias para a equipe de saúde, garantindo que estas sejam realmente eficazes para prolongar, tanto quanto possível, uma das formas mais bem-sucedidas de manter o período de remissão da colite ulcerativa: o uso de medicamentos.

Simultaneous Monitoring of Azathioprine Metabolites in Erythrocytes of Crohn's Disease Patients by HPLC-UV.

The conversion of azathioprine (AZA) to active 6-thioguanine nucleotides (6-TGN) is essential for its clinical efficacy; however, another metabolite formed, 6-methylmercaptopurine (6-MMP), is related to hepatotoxicity. Blood samples were collected from 37 patients under AZA's treatment, and a new HPLC-UV method was validated and applied for simultaneous quantification of 6-TGN and 6-MMP in erythrocytes of Crohn's disease (CD) patients. The concentration of 6-TGN and 6-MMP found ranged from 4.5 to 2,456 ρmol/8 × 108 red blood cells (RBCs) for 6-TGN and from 170 to 53,951 ρmol/8 × 108 RBCs for 6-MMP. Reduced levels of 6-MMP in patients into combo therapy with AZA and allopurinol (2,031 ρmol/8 × 108 RBCs) have been observed when compared to patients undergoing monotherapy with AZA (9,098 ρmol/8 × 108 RBCs). Additionally, there was a negative correlation (r = -83.7%, P < 0.05) between lymphocyte count and 6-TGN levels. The method developed is reliable, accurate and reproducible and can be used as an important tool in the monitoring routine of patients with CD under AZA treatment, allowing the individualization of the dose, monitoring adherence to the treatment and the evaluation of the clinical outcome of these patients.

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.