Infliximab in inflammatory bowel disease. Is premedication necessary? / Infliximab en enfermedad inflamatoria intestinal. ¿Es necesario premedicar?

BACKGROUND: The use of infliximab (IFX) in inflammatory bowel disease (IBD) has been associated with a 1-6% risk of infusion reactions. The usefulness of premedication with corticosteroids, paracetamol and /or antihistamines is controversial. AIM: The aim of this study is to assess, in IBD patients on IFX, whether there are differences in secondary reactions to the infusion between those who use premedication or not. METHODS: A retrospective cohort study was performed identifying patients with a diagnosis of IBD who received IFX at our institution between January 2009 and July 2019. Acute reactions were defined as those that occurred in the first 24 hours postinfusion and late reactions for more than 24 hours. Infusion reactions were classified as mild, moderate and severe. Descriptive and association statistics were used (χ2; p < 0.05). RESULTS: Sixty-four patients were included with 1,263 infusions in total, 52% men. Median infusions per patient was 22 (2-66). All induction infusions were administered with premedication, and in maintenance in 57% of them. Premedication was given with hydrocortisone, chlorphenamine and paracetamol. Most of reactions were acute, mild or moderate in severity and no patient needed to discontinue IFX. In the maintenance group, there were 9/718 (1.2%) infusion reactions with premedication and 4/358 (1.1%) without it (p = 0.606). In the induction group, there were 8/187 (4.3%) infusion reactions, significantly higher when compared with both maintenance groups. CONCLUSIONS: In this group, premedication use during maintenance was not effective at reducing the rate of infusion reactions. These results suggest that premedication would not be necessary.

Pregnancy in Inflammatory Bowel Disease: Experience of a Chilean cohort. / Embarazo en enfermedad inflamatoria intestinal: experiencia en una cohorte chilena.

BACKGROUND: In inflammatory bowel disease (IBD) a high percentage of women are diagnosed during their reproductive age. IBD in remission is the ideal scenario when planning a pregnancy. AIMS: To describe the clinical characteristics of pregnancy/newborn and assess disease activity at the time of conception and throughout the pregnancy in patients with IBD treated at a tertiary centre in Chile. METHODS: We retrospectively reviewed women diagnosed with IBD who were pregnant or delivered between 2017 and 2020. Demographic, clinical, obstetric and delivery data were obtained from the IBD registry, approved by the local IRB. Descriptive statistics and association tests were performed (χ2, p ≤ 0.05). RESULTS: Sixty women with IBD were included. At the beginning of pregnancy, 21 (35%) had active disease and 39 (65%) were in remission. Of those with active disease, 16 (66%) remained active and 6 had spontaneous abortions. In those who were in remission, 26 (69%) remained in this condition. Nine patients (15%) discontinued treatment, and 6 of these had inflammatory activity during pregnancy. Preconception counselling was performed in 23 of the 60 patients, being higher in the group that remained in remission during pregnancy (65% vs. 35%, p = 0.02). Patients who had a flare during pregnancy had more probability of preterm birth (<37 weeks) and newborn with lower weight compared with the group that always remained in remission (89% vs. 74%, p = 0.161) and (2.885 vs 3.370 g; p = 0.0014). CONCLUSION: Remission presents better outcomes in pregnancy and preconception counselling would allow a better IBD control during pregnancy.

Are patients with inflammatory bowel disease receiving adequate immunisation? / ¿Están recibiendo los pacientes con enfermedad inflamatoria intestinal una adecuada inmunización?

INTRODUCTION: Inflammatory Bowel Disease (IBD) treatment may increase the risk of infections. Vaccines are part of the comprehensive IBD patient care. The aim of this study was to describe indications and adherence of immunizations in IBD and identify possible associated factors. METHODS: A cross-sectional, analytic study was conducted in patients from an IBD Program of a tertiary center in Chile, between April - June 2019. Patients were asked to answer a vaccine survey and information also was obtained from the National Immunization Registry. Descriptive and association statistic were used (χ2; p<0.05). RESULTS: A total of 243 patients were included (148 ulcerative colitis (UC), 86 Crohn's disease (CD) and 9 non-classifiable IBD). Only six patients (2%) of IBD patients received a complete immunization schedule. The highest vaccine rates were against influenza (67%), hepatitis B virus (40%), 13-valent pneumococcal (34%) and 23-polysaccharide pneumococcal (16%). The influenza vaccine rate has significantly increased, reaching 67% in 2019. The survey showed that 23% of patients have not been immunized with any vaccine, mainly due to lack of time, lack of medical prescription and high cost. CONCLUSIONS: In this cohort, although vaccination rates are higher than previously reported, adherence to IBD immunization program would be improved, being considered since diagnosis by the multidisciplinary team.

The Role of an Inflammatory Bowel Disease Nurse in the Follow-Up of Patients From a Latin American Inflammatory Bowel Disease Program.

Inflammatory bowel disease requires long-term treatment to maintain disease control. Favorable follow-up of patients indicates attention from a multidisciplinary team, in which the nurse's responsibilities have great importance. The aim of this observational, descriptive study was to describe the role of an inflammatory bowel disease nurse in the management of patients in a tertiary center in Chile, including all patients in follow-up between January 2016 and April 2017. Inflammatory bowel disease nurse contacts were recorded and classified. Demographic data, clinical variables, and patient satisfaction were also analyzed. A total of 597 patients (51%) were in follow-up over the 16-month period; 63% had ulcerative colitis, with a median age of 35 years. The inflammatory bowel disease nurse performed 760 contacts in 253 patients (42% of the follow-up patients). The most frequent nurse interventions were reinforcement of medical indications (42%), assessment of laboratory results (17%), and disease follow-up (12%); 49% related to education. Nurse interventions were focused in more severely ill patients; flares during the follow-up, biological therapy, immunomodulators, and steroids were all statistically significant. Of a sample of 107 patients surveyed, 96% perceived the inflammatory bowel disease program as excellent/good. The inflammatory bowel disease nurse plays an important role in the follow-up and management, specifically in education, of more severely ill patients.

[Environmental risk factors in the development and evolution of inflammatory bowel disease]. / Factores ambientales en el desarrollo y evolución de la enfermedad inflamatoria intestinal.

Environmental factors may influence the development of Inflammatory Bowel Disease and modify its natural history. The objective of this review is to evaluate current evidence about environmental factors associated with the disease. A better knowledge about the pathogenesis of the disease can lead to better treatment strategies and suggestions to prevent the disease.

Assessment of disease-related knowledge and possible factors associated with the knowledge level among Chilean patients with inflammatory bowel disease.

AIMS AND OBJECTIVES: To assess disease-related knowledge among patients with inflammatory bowel disease and to identify the factors that are possibly associated with the knowledge level. BACKGROUND: Disease-related knowledge can positively influence the acceptance of the disease, increase treatment compliance and improve the quality of life in patients with inflammatory bowel disease. DESIGN: An observational, cross-sectional study was conducted and prospectively included patients from the inflammatory bowel disease programme between October 2014-July 2015. METHODS: A Spanish-translated version of the 24-item Crohn's and Colitis Knowledge score was used to assess disease-related knowledge. Patients also completed a demographic and clinical questionnaire. RESULTS: A total of 203 patients were included, 62% were female, and 66% were diagnosed with ulcerative colitis; the median age was 34 years (range 18-79), and the median disease duration was four years. The median disease-related knowledge score was 9 (range 1-20). Only 29% of the patients answered more than 50% of the questions correctly. Lower disease-related knowledge was observed in questions related to pregnancy/fertility and surgery/complications. Patients older than 50 years, with ulcerative colitis, with disease durations less than five years and patients without histories of surgery exhibited lower disease-related knowledge. There was no association between the knowledge scores and the educational levels. CONCLUSIONS: The patients who attended our inflammatory bowel disease programme exhibited poor disease-related knowledge that was similar to the knowledge levels that have been observed in developed countries. It is necessary to assess patient knowledge to develop educational strategies and evaluate the influences of these strategies on patient compliance and quality of life. RELEVANCE TO CLINICAL PRACTICE: These results will allow the inflammatory bowel disease team to develop educational programmes that account for the disease-related knowledge of each patient. Inflammatory bowel disease nurses should evaluate their interventions to provide evidence that educating our patients contributes to improving their treatment outcomes and overall health statuses.

[Acute severe ulcerative colitis treated with accelerated infliximab induction. Case report]. / Terapia de inducción acelerada con infliximab en paciente con colitis ulcerosa grave refractaria a corticoides. Caso clínico.

Acute severe ulcerative colitis (ASUC) is a potentially life-threatening condition that requires early recognition, hospitalization and adequate treatment. Currently, the use of infliximab in ulcerative colitis (UC) is recommended in the case of severe disease refractory to corticosteroids, once that superimposed bacterial or viral infections (such as cytomegalovirus or Clostridium difficile) have been excluded. However, conventional weight-based regimens of infliximab might be insufficient for patients with ASUC. Accelerated infliximab induction regimen may increase its serum concentration levels and efficacy by reducing early colectomy rates in these patients. We report a 34 year old female presenting with an ASUC. She was initially treated with hydrocortisone 300 mg/day and mesalazine enemas 4 g/day with an unfavorable clinical response. At the fifth day of therapy, an accelerated induction therapy with infliximab was started in doses of 10 mg/kg at weeks 0, 1 and 4. After the second dose, there was a favorable response with reduction of abdominal pain, stool frequency and hematochezia. She was discharged with prednisone and azathioprine. After a year of starting infliximab, the patient remains in clinical remission.

[Natalizumab for the treatment of Crohn’s disease: Report of three cases]. / Experiencia local con natalizumab en pacientes con enfermedad de Crohn refractaria a anti-TNF: Casos clínicos.

Anti-tumor necrosis factor-α (TNF) agents have dramatically changed the management of Crohn’s Disease (CD). However, a significant number of these patients do not respond at all or cease to respond to antibodies against TNF. In this clinical situation, the options include intensification of anti-TNF therapy by either increasing the dose or by shortening the administration interval, the use of a second anti-TNF or medications with a different mechanism of action. Among the later, Natalizumab, a humanized IgG4 monoclonal antibody against α4ß1 and α4ß7 integrins, is safe and effective in inducing and maintaining remission in active CD patient’s refractory to anti-TNF. In spite of this, Natalizumab use has been limited because of an increased risk of progressive multifocal leukoencephalophaty which results from reactivation of the John Cunningham (JC) virus. However, the presence of antibodies against JC virus in serum can be used to reduce the risk for this complication. We report three patients with Crohn’s disease refractory to treatment with infliximab, who responded successfully to the use of Natalizumab.

[Benign multicystic peritoneal mesothelioma in a patient with Crohn disease]. / Mesotelioma benigno como causa de dolor abdominal inespecífico en un paciente con Enfermedad de Crohn.

Benign multicystic peritoneal mesothelioma is an uncommon lesion arising from the peritoneal mesothelium. It is asymptomatic or presents with unspecific symptoms. Imaging techniques may reveal it, however the final diagnosis can only be made by histopathology. Surgery is the only effective treatment considering its high recurrence rate. We report a 19 years old male with Crohn’s disease. Due to persistent abdominal pain, an abdominal magnetic resonance imaging was performed, showing a complex cystic mass in the lower abdomen. The patient underwent surgery and the lesion was completely resected. The pathological study reported a benign multicystic peritoneal mesothelioma.

[Differences by age in clinical features of inflammatory bowel disease]. / Enfermedad inflamatoria intestinal en pacientes mayores de 60 años: ¿es una enfermedad diferente?

BACKGROUND: Approximately, 15% of patients with Inflammatory Bowel Disease (IBD) are diagnosed at 60 years of age or more. AIM: To characterize and compare clinical variables between patients with IBD aged 60 years or more and their younger counterparts. MATERIAL AND METHODS: Retrospective study based on a registry of IBD patients diagnosed between the years 1976 and 2014. RESULTS: Four hundred and nine IBD patients were included. Among them, 294 had Ulcerative Colitis (UC), 104 had Crohn's Disease (CD) and eleven had an indeterminate IBD. Forty-six patients (11.2%) were older than 60 years and 16 (3.9%) had been diagnosed after this age. When comparing patients by age, those aged 60 years or more had a higher frequency of CD and indeterminate IBD (p < 0.01) and a lower ileocolic location in CD (p = 0.02). Both groups were similar in terms of hospitalization due to IBD flare, surgery, use of steroids, immunosuppressive or biological therapies and drug-related adverse events. When analyzing age at diagnosis of IBD, patients diagnosed at ages of 60 years or more had a lower frequency of UC (p < 0.01), a higher frequency of exclusive colonic involvement (p = 0.01), and lower use of mesalamine (p < 0.01). There were no differences in drug-related adverse events, hospitalizations due to IBD flares and surgery according to age at diagnosis. CONCLUSIONS: In this population, clinical features of IBD in older patients were similar to those in younger patients.

[Adverse events associated with the treatment of inflammatory bowel disease]. / Eventos adversos en la terapia farmacológica de la enfermedad inflamatoria intestinal.

BACKGROUND: The purpose of inflammatory bowel disease (IBD) treatment is to achieve resolution of symptoms and remission of disease with a minimum of adverse events (AE). AIM: To report AE of different prescriptions used for the treatment of IBD. MATERIAL AND METHODS: Analysis of a registry of patients with IBD held at a private clinic from 1976 to 2013. All used medications, the occurrence and severity of AE were recorded. RESULTS: The records of 346 patients aged 16 to 86 years, 74% with ulcerative colitis, were analyzed. The most commonly type of medications prescribed were 5-aminosalicylates (5-ASAs) in 329 patients (92%), followed by adrenal steroids in 218 (61%). Forty nine AE were recorded in the same number of patents (14%). These were more common in patients with Crohn disease (n = 19, 21%). An univariate analysis, demonstrated that extra-intestinal manifestations, hospitalizations secondary to IBD crisis, requirement of surgery and treatment with steroids, immunosuppressants or biologic agents were significantly associated with the presence of AE. AEs were more common with immunosuppressants, followed by 5-ASAs and steroids. Discontinuation of therapy was required in 79, 100 and 43% of patients taking these medications, respectively. Twenty percent of AEs were severe. Leukopenia and pancytopenia along with alopecia were the most common AEs attributable to azathioprine. CONCLUSIONS: The occurrence of AEs in patients with IBD is uncommon. Even inmunosuppressants or biologic agents have a low rate of AE and most of them mild.

[Development of malignant tumors in patients with inflammatory bowel disease]. / Desarrollo de neoplasia en pacientes con enfermedad inflamatoria intestinal.

BACKGROUND: The chronic inflammation of the intestinal mucosa, the extra-intestinal manifestations of the disease and the immunosuppressive treatment of inflammatory bowel disease may increase cancer risk. AIM: To report the demographic and clinical features of patients with IBD who developed a malignant tumor. MATERIAL AND METHODS: Retrospective analysis of an IBD patient registry of a private clinic, diagnosed between 1976 and 2014. RESULTS: 437 subjects were included, aged 15-88 years (58% women). Seventy two percent of patients had ulcerative colitis. The median time of follow up was 6 years. Ten patients (2.3%) developed a malignant tumor. In four, the tumor could be related to IBD (two colorectal cancers, one cholangiocarcinoma and one chronic myeloid leukemia (CML)). Two of 45 patients treated with biological therapy developed a tumor (CML and hypernephroma). Three of 170 patients on immunosuppressive treatment developed tumors. Only one had a tumor possibly related with the use of azathioprine (non-melanoma skin cancer). In only two patients, the treatment was changed at the time of their cancer diagnosis, from immunosuppressive medications to mesalamine. CONCLUSIONS: Only a small proportion of these patients with IBD developed a malignant tumor. The treatment of IBD has to be determined by the severity of the disease and not by the fear of developing a neoplasia. Following recommendations is fundamental to decrease the possibility of developing this complication.

[Inflammatory bowel disease. Experience in 316 patients]. / Enfermedad inflamatoria intestinal a partir de una experiencia local.

BACKGROUND: The incidence and prevalence of Inflammatory Bowel Disease (IBD) has increased. AIM: To determine demographic and clinical characteristics of patients with IBD in a Chilean private hospital. PATIENTS AND METHODS: Review of a prospective registry of patients with IBD, started on 2012. It includes clinical, imaging, endoscopical and pathological information of patients. RESULTS: Data of 316 patients with IBD, aged 16 to 86 years (56% females), were analyzed. Ulcerative Colitis (UC), Crohn´s and non-classifiable IBD were diagnosed in 230, 77 and 9 patients, respectively. The disease was diagnosed in 82% of patients in the period between 2002 and 2012. There was a peak in the diagnosis of both UC and CD between 20 and 39 years of age, without gender differences. The disease switched from UC to CD in six patients. In four, there was a change in disease behavior. Thirty eight patients were treated with biological therapy. The median lapse between the diagnosis and the use of biological therapy was 1 year in patients diagnosed after 2007, compared with 5.5 years among those patients diagnosed before 2007 (p = 0.001). There was a trend towards a higher requirement of surgery until 2006. Subsequently there was a stabilization of the requirement, concomitant with the incorporation of biological therapy. CONCLUSIONS: An adequate registry of IBD patients is necessary to improve demographic and clinical characteristics. A national registry is needed to assess the epidemiological changes of IBD in Chile.

[Treatment of inflammatory bowel disease with infliximab: experience in 25 patients]. / Rol de infliximab en enfermedad inflamatoria intestinal: Experiencia local.

BACKGROUND: Biological therapy has an important role in the treatment of Inflammatory Bowel Disease (IBD). However, the use of these drugs is resisted due to fears about their side effects. AIM: To report the experience with the use of Infliximab in patients with IBD. MATERIAL AND METHODS: Descriptive study of a historical cohort of patients with IBD treated between 2007 and 2012 with Infliximab. A favorable clinical response was considered when general, intestinal and extra-intestinal symptoms subsided after the second or third dose of the drug. Endoscopic or imaging response was evaluated between three and six months of treatment. RESULTS: Twenty five patients aged 18 to 61 years (12 women) were included. Sixteen had Cohn's Disease and 9 had Ulcerative Colitis. Treatment was indicated due to refractory disease in 13 patients, perianal involvement in nine, stenosis in two and pyoderma gangrenosum in one. Ten patients initiated Infliximab within less than two years of diagnosis. Twenty-two patients received combined treatment with immunosuppressive medications and the other three patients were treated exclusively with Infliximab. A favorable clinical response was observed in 88% after the second dose and 64% had endoscopic or imaging remission after 3-6 months. Twelve patients discontinued Infliximab, due to bad response to treatment in three patients, economic cost in three patients, and patient/doctor decision in six. Only three patients had side effects (herpes zoster and sinusitis). None of these motivated the discontinuation of treatment. CONCLUSIONS: In this cohort of patients with IBD, the use of Infliximab was associated with endoscopic or imaging remission in 64% of cases after 3-6 months of treatment with no major side effects.

[A screening program for colorectal cancer in Chilean subjects aged fifty years or more]. / Programa de detección de neoplasias colorrectales en población mayor de 50 años.

BACKGROUND: Mortality from colorectal cancer (CCR) in Chile has nearly doubled over the past 15 years. International studies have shown that CCR screening programs based on fecal occult blood test (FOBT) reduce CCR mortality. AIM: To analyze the results from a CCR screening model in people over 50 years. MATERIAL AND METHODS: Between 2007 and 2009, a prospective multicenter study was performed in seven major Chilean cities. FOBT using an immunological method, was measured in asymptomatic subjects aged 50 years or more, without risk factors. In patients with a positive FOBT, with symptoms or with family risk factors, a colonoscopy was indicated. RESULTS: A total of 6348 subjects were assessed, FOBT was performed in 4938 of them, with a compliance of 77%. The result was positive in 9.6%. A total of 2359 colonoscopies were ordered, with an overall compliance of 50.1%. Of the 1184 colonoscopies performed, adenomas and high risk adenomas were found in 304 (26%) and 75 (6%) patients, respectively. Thirteen patients were diagnosed with stage I and IICCR. Three of these lesions were excised endoscopically and 10 surgically. The detection rate of polyps, high risk adenomas and cancer was 75, 12 and 2 per 1000 screened individuals, respectively. CONCLUSIONS: This program allowed the early detection of an important number of high risk colon lesions, and all patients with CCR were diagnosed at early stages.

Regulation of the Intestinal Extra-Adrenal Steroidogenic Pathway Component LRH-1 by Glucocorticoids in Ulcerative Colitis.

Ulcerative colitis (UC) is an inflammatory bowel disease (IBD) and can be treated with glucocorticoids (GC), although some patients are unresponsive to this therapy. The transcription factor LRH-1/NR5A2 is critical to intestinal cortisol production (intestinal steroidogenesis), being reduced in UC patients. However, the relationship between LRH-1 expression and distribution with altered corticosteroid responses is unknown. To address this, we categorized UC patients by their steroid response. Here, we found that steroid-dependent and refractory patients presented reduced glucocorticoid receptor (GR)-mediated intestinal steroidogenesis compared to healthy individuals and responder patients, possibly related to increased colonic mucosa GR isoform beta (GRß) content and cytoplasmic LRH-1 levels in epithelial and lamina propria cells. Interestingly, an intestinal epithelium-specific GR-induced knockout (GRiKO) dextran sodium sulfate (DSS)-colitis mice model presented decreased epithelial LRH-1 expression, whilst it increased in the lamina propria compared to DSS-treated control mice. Mechanistically, GR directly induced NR5A2 gene expression in CCD841CoN cells and human colonic organoids. Furthermore, GR bound to two glucocorticoid-response elements within the NR5A2 promoter in dexamethasone-stimulated CCD841CoN cells. We conclude that GR contributes to intestinal steroidogenesis by inducing LRH-1 in epithelial cells, suggesting LRH-1 as a potential marker for glucocorticoid-impaired response in UC. However, further studies with a larger patient cohort will be necessary to confirm role of LRH-1 as a therapeutic biomarker.

Complementary and alternative medicine in patients with inflammatory bowel disease: A survey performed in a tertiary center in Chile.

OBJECTIVES: The aim of this study was to assess the type and prevalence of complementary and alternative medicine (CAM) use in patients with inflammatory bowel disease (IBD) who are treated at our center. DESIGN: Observational, cross-sectional questionnaire-based study that included patients from the IBD program of our center. SETTING: Tertiary clinical center in Santiago, Chile. MAIN OUTCOME MEASURES: Types of CAM being used by patients with IBD. RESULTS: A total of 200 patients were included, 68% ulcerative colitis, 29% Crohn's disease, and 3% non-classifiable IBD. Overall, 25% of the patients reported current use of CAM, 30% reported using in it the past, and 45% indicated that they had never used it before. The use of CAM was recommended in 20% of the patients by other healthcare professionals and in 10% of the patients by the gastroenterologist. Forty-nine percent of the patients informed the gastroenterologist that they were using CAM. Overall, 86% of the patients did not modify the conventional medical treatment (CMT). None of the patients who were using curcumin, homeopathic medicine, acupuncture or biomagnetism modified the CMT. CONCLUSIONS: The type of CAM being used plays an important role when the patient makes the decision to inform the gastroenterologist. Other healthcare professionals play an important role in providing the advice to start CAM. Gastroenterologists must be aware of the high prevalence of CAM use in IBD patients, actively ask about CAM use and guide the patients who want to use CAM in a responsible and safe manner.