Cyrla Zaltman - Academia.edu (original) (raw)
Papers by Cyrla Zaltman
Journal of Crohn's and Colitis
Background There are few data on the quality-of-care for inflammatory bowel disease (IBD) in publ... more Background There are few data on the quality-of-care for inflammatory bowel disease (IBD) in public, private or mixed hospitals, especially in Latin America. The aim of the study was to evaluated clinic and quality parameters and their association with need for ICU and death in Brazilian hospitals. Methods This was a multicentre study carried out in 26 hospitals. Four hundred eighty-eight admissions of patients with IBD were analysed between June 2021 and October 2022. Results The median stay length was 6 days (0–121). The median age was 38 years (16–87), and 265 (54.6%) were female. Three hundred and thirty-nine patients (69.5%) had Crohn’s disease (CD) and 149 (30.5%) ulcerative colitis (UC). The median time between symptoms onset and hospital admission was 72 months (1-504) in CD and 49 months (1-300) in UC. In the CD group, there was structural damage in 248 cases (73.2%). UC in pancolitis form was seen in 97 (66%). The Charlson Comorbidity Index (CCI) was scored at least at one...
Journal of Clinical Medicine
This prospective, observational, open-label study aimed to provide access to ustekinumab prior to... more 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 ...
Revista de Gastroenterología de México
The Lancet Gastroenterology & Hepatology, 2021
BACKGROUND Etrolizumab is a gut-targeted anti-β7 integrin monoclonal antibody. In an earlier phas... more BACKGROUND Etrolizumab is a gut-targeted anti-β7 integrin monoclonal antibody. In an earlier phase 2 induction study, etrolizumab significantly improved clinical remission relative to placebo in patients with moderately to severely active ulcerative colitis. The HIBISCUS studies aimed to compare the efficacy and safety of etrolizumab to adalimumab and placebo for induction of remission in patients with moderately to severely active ulcerative colitis. METHODS HIBISCUS I and HIBISCUS II were identically designed, multicentre, phase 3, randomised, double-blind, placebo-controlled and active-controlled studies of etrolizumab, adalimumab, and placebo in adult (18-80 years) patients with moderately to severely active ulcerative colitis (Mayo Clinic total score [MCS] of 6-12 with an endoscopic subscore of ≥2, a rectal bleeding subscore of ≥1, and a stool frequency subscore of ≥1) who were naive to tumour necrosis factor inhibitors. All patients had an established diagnosis of ulcerative colitis for at least 3 months, corroborated by both clinical and endoscopic evidence, and evidence of disease extending at least 20 cm from the anal verge. In both studies, patients were randomly assigned (2:2:1) to receive subcutaneous etrolizumab 105 mg once every 4 weeks; subcutaneous adalimumab 160 mg on day 1, 80 mg at week 2, and 40 mg at weeks 4, 6, and 8; or placebo. Randomisation was stratified by baseline concomitant treatment with corticosteroids, concomitant treatment with immunosuppressants, and baseline disease activity. All patients and study site personnel were masked to treatment assignment. The primary endpoint was induction of remission at week 10 (defined as MCS of 2 or lower, with individual subscores of 1 or lower, and rectal bleeding subscore of 0) with etrolizumab compared with placebo. Pooled analyses of both studies comparing etrolizumab and adalimumab were examined for several clinical and endoscopic endpoints. Efficacy was analysed using a modified intent-to-treat population, defined as all randomly assigned patients who received at least one dose of study drug. These trials are registered with ClinicalTrials.gov, NCT02163759 (HIBISCUS I), NCT02171429 (HIBISCUS II). FINDINGS Between Nov 4, 2014, and May 25, 2020, each study screened 652 patients (HIBISCUS I) and 613 patients (HIBISCUS II). Each study enrolled and randomly assigned 358 patients (HIBISCUS I etrolizumab n=144, adalimumab n=142, placebo n=72; HIBISCUS II etrolizumab n=143; adalimumab n=143; placebo n=72). In HIBISCUS I, 28 (19·4%) of 144 patients in the etrolizumab group and five (6·9%) of 72 patients in the placebo group were in remission at week 10, with an adjusted treatment difference of 12·3% (95% CI 1·6 to 20·6; p=0·017) in favour of etrolizumab. In HIBISCUS II, 26 (18·2%) of 143 patients in the etrolizumab group and eight (11·1%) of 72 patients in the placebo group were in remission at week 10, with an adjusted treatment difference of 7·2% (95% CI -3·8 to 16·1; p=0·17). In the pooled analysis, etrolizumab was not superior to adalimumab for induction of remission, endoscopic improvement, clinical response, histological remission, or endoscopic remission; however, similar numerical results were observed in both groups. In HIBISCUS I, 50 (35%) of 144 patients in the etrolizumab group reported any adverse event, compared with 61 (43%) of 142 in the adalimumab group and 26 (36%) of 72 in the placebo group. In HIBISCUS II, 63 (44%) of 143 patients in the etrolizumab group reported any adverse event, as did 62 (43%) of 143 in the adalimumab group and 33 (46%) in the placebo group. The most common adverse event in all groups was ulcerative colitis flare. The incidence of serious adverse events in the pooled patient population was similar for etrolizumab (15 [5%] of 287) and placebo (seven [5%] of 144) and lower for adalimumab (six [2%] of 285). Two patients in the etrolizumab group died; neither death was deemed to be treatment related. INTERPRETATION Etrolizumab was superior to placebo for induction of remission in HIBISCUS I, but not in HIBISCUS II. Etrolizumab was well tolerated in both studies. FUNDING F Hoffmann-La Roche.
Journal of Crohn's and Colitis, 2022
percentage of subjects achieving clinical and endoscopic efficacy endpoints at the end of the ind... more percentage of subjects achieving clinical and endoscopic efficacy endpoints at the end of the induction increased with increasing UPA average plasma concentration (Cavg), and became mostly flat at Cavg values approximately equivalent to the, 45 mg QD (Figure, 1). For maintenance treatment, there was a trend for increasing the percentage of subjects achieving clinical remission, steroid-free remission, endoscopic improvement, and histo-endoscopic mucosal improvement within the range of UPA plasma exposures evaluated. Exposures associated with UPA, 30 mg QD were estimated to provide a, 8% to, 10% increase in the percentage of subjects achieving these endpoints compared to, 15 mg QD (Figure, 2). There was no trend for exposure-response relationships within the range of evaluated UPA exposures for any of the evaluated safety endpoints (>2 g/dL decrease in hemoglobin and >2 g/dL decrease in hemoglobin and < lower limit for normal, hemoglobin <, 8 g/dL, lymphopenia ≥ Grade, 3, neutropenia ≥ Grade, 3, Herpes Zoster infection, serious infections, and pneumonia) at the end of induction or maintenance periods. Conclusion: UPA plasma exposures associated with the, 45 mg QD induction dose maximized efficacy for clinical and endoscopic endpoints at Week, 8. Plasma exposures associated with UPA, 30 mg maintenance dose provide additional incremental benefit compared to, 15 mg QD. No trends were observed for increase in the evaluated safety events with increasing UPA plasma exposures at the end of induction or maintenance periods.
Gastroenterology, May 1, 2022
Inflammatory Bowel Diseases, Feb 1, 2017
Background: The ApaI, TaqI and FokI vitamin D receptor (VDR) gene polymorphism are associated wit... more Background: The ApaI, TaqI and FokI vitamin D receptor (VDR) gene polymorphism are associated with risk of inflammatory bowel diseases (IBD)1. These genetic variants can also determine changes in vitamin D mechanisms of action and affect the clinical course of IBD2. In Brazil, there are a lack of data concerning VDR polymorphisms in IBD patients and its use as a predictor of poor prognosis. The aim of this study was to evaluate the association of VDR gene polymorphisms, vitamin D status and the poor prognostic factors in a multiracial IBD population. Methods: A case control study recruited 107 patients with Crohn's disease (CD), 43 patients with ulcerative colitis (UC) and 81 control healthy subjects from a tertiary center in Rio de Janeiro. The VDR polymorphisms ApaI, (“Aa,” “aa”), TaqI (“Tt,” “tt”) e FokI (“Ff,” “ff”) were evaluated in IBD and non IBD groups. The genotyping was performed by polymerase chain reaction (PCR) in real time technique. Serum 25(OH)D was measured using chemiluminescence immunoassay. Demographic, clinical features and poor prognostic factors of IBD patients were obtained from the chart review. Results: The genotype “aa” (ApaI) (49.5%) and “Tt” (TaqI) (50.5%) were more frequent in CD group. The distribution of polymorphisms was similar between UC and the control group. In CD group, the “a” allele carrier status of ApaI appeared to be a protective factor against the use of immunosuppressors (OR = 0.225; 95% CI, 0.071–0.712). The “t” allele carrier status of TaqI was protective factor against the use of steroids at the time of CD diagnosis (OR = 0.242; 95% CI, 0.065–0.901) but it was associated with the need of more than 2 steroids courses in UC group (OR = 4.19; 95% CI, 1.104–15.901) The 25(OH)D level was measured in 44 IBD patients, and low levels were detected only in 38.6% of cases. No association was observed between clinical features, VDR polymorphisms and vitamin D deficiency. Conclusions: The ApaI and TaqI, but not FokI polymorphisms are associated with CD and a poor prognostic factors. Although the polymorphisms have not been associated with UC, the presence of TaqI polymorphism was associated with poor prognosis predictor in this group. No associations were detected between VDR polymorphisms and vitamin D deficiency in IBD groups.
BMC Gastroenterology, Mar 28, 2023
Background Evidence indicates that inflammation in Inflammatory Bowel Disease (IBD) is associated... more Background Evidence indicates that inflammation in Inflammatory Bowel Disease (IBD) is associated with increased systemic levels of reactive oxygen species. Systemic oxidative stress has been associated with reduced levels of plasma thiols. Less invasive tests capable of reflecting and predicting IBD activity are increasingly sought after. We sought to systematically review the evidence inherent in serum thiol levels as a marker of Crohn's Disease and Ulcerative Colitis activity (PROSPERO: CRD42021255521). Methods The highest quality documents for systematic reviews standards were used as reference. Articles were searched on Medline via PubMed, VHL, LILACS, WOS, EMBASE, SCOPUS, COCHRANE, CINAHL, OVID, CTGOV, WHO/ ICTRP, OPENGREY, BDTD and CAPES, between August, 03 and September, 03 on 2021. Descriptors were defined according to the Medical Subject Heading. Of the 11 articles selected for full reading, 8 were included in the review. It was not possible to perform a pooled analysis of the studies, as there were no combinable studies between subjects with active IBD and controls/inactive disease. Results Findings from the individual studies included in this review suggest an association between disease activity and systemic oxidation, as measured by serum thiol levels, however, there are limitations that preclude weighting the study results in a meta-analysis. Conclusions We recommend conducting better-designed and controlled studies, that include individuals of both phenotypes and at different stages of IBD, involving a larger number of participants, using the standardization of the technique for measuring serum thiols, to confirm whether thiols can be a good parameter for monitoring the clinical course of these intestinal diseases and the degree of clinical applicability.
The American Journal of Gastroenterology, Dec 1, 2020
Inflammatory Bowel Diseases, Dec 1, 2011
2009 to 2010 and was consistent across different sites-of-care (i.e., IOI, HOPD, and ASOC). While... more 2009 to 2010 and was consistent across different sites-of-care (i.e., IOI, HOPD, and ASOC). While this analysis indicated consistent IFX vial utilization per infusion across different sites-of-care, further research exploring additional measures, such as patient adherence and patient satisfaction, may provide further insight into the complete patient care experience across sites and support optimal site of care decision making.
Arquivos De Gastroenterologia, Dec 1, 2009
Context-Although endoscopic esophageal variceal sclerotherapy has been largely supplanted by vari... more Context-Although endoscopic esophageal variceal sclerotherapy has been largely supplanted by variceal band ligation, it is still performed routinely in many institutions, especially in developing countries. Intramural esophageal hematoma has been described as a rare complication of sclerotherapy. Risk factors have not been completely established. Objective-To demonstrate the incidence of post-sclerotherapy intramural esophageal hematoma in our hospital and discuss the possible factors involved. Methods-This is a retrospective observational study made at the "Hospital Universitário Clementino Fraga Filho", Rio de Janeiro, RJ, Brazil, reviewing the medical records of all esophageal variceal sclerotherapy procedures performed from April 2000 to November 2005. The evaluation of the clinical, laboratorial and endoscopic features in our patients and those reported in the literature was also done. Review of literature was performed through MEDLINE search. Results-A total of 1,433 esophageal variceal sclerotherapy procedures were performed in 397 patients, with an intramural esophageal hematoma incidence of 4 cases (0.28%). Three of our patients developed additional complications, and one death was a direct consequence of a rupture of the hematoma. Nineteen well described cases were reported in the literature. Intramural esophageal hematoma occurred mostly after the forth esophageal variceal sclerotherapy session. Coagulation disturbances were present in the majority of cases. Conclusion-Intramural esophageal hematoma is a rare complication of esophageal variceal sclerotherapy and its incidence in our institution was similar to those observed in the literature. Our study suggests that this complication occurs as a result of a fragile esophageal mucosa after previous esophageal variceal sclerotherapy sessions. Impaired coagulation, although not essential, could contribute to hematoma formation and extension through esophageal submucosa. HEADINGS-Esophageal diseases. Hematoma. Sclerotherapy.
River Publishers eBooks, Sep 1, 2022
The American Journal of Gastroenterology, Feb 1, 2018
This article discusses the various meanings ascribed to the concept of Complementary and Alternat... more This article discusses the various meanings ascribed to the concept of Complementary and Alternative Medicine (CAM) in Brazil, where research on this theme has a limited tradition in terms of influences from anthropology, sociology of knowledge and epistemology, and sociology of CAM and clinical medicine. By means of the concepts identified in the literature, we elaborated a table with types of meanings. The terms Alternative Medicine and Complementary Medicine were found in more than one of the types in the table. Alternative Medicine identifies a model of medical practice influenced by the social, political, and economic context and by the logic of scientific production based on opposing pairs. Beginning in the 1980s, the important volume of reflections on official medical practice and the search for other forms of knowledge production led to the creation of the concept of Complementary Medicine. Its meaning is that of a new epistemological form of knowledge production between the official and alternative poles, a set of therapeutic practices, and confusion with the nomenclature for ancillary medical diagnostic tests, referred to in Portuguese as "complementary exams".
Arquivos De Gastroenterologia, Sep 1, 2022
Background-The conventional treatment of inflammatory bowel disease (IBD) is based on drug therap... more Background-The conventional treatment of inflammatory bowel disease (IBD) is based on drug therapy, but different studies have shown a progressive increase in the use of complementary and alternative medicine (CAM). The most used CAM comprises of acupuncture, traditional Chinese medicine, Ayurvedic medicine, homeopathy, and herbal medicine, as well as more modern practices, including aromatherapy and reflexology. Data from CAM use in Brazil has previously been scarce and there are no studies among Brazilian patients with IBD. Objective-The aim of the study was to evaluate the frequency of, and factors associated with the use of CAM among IBD patients in Brazil, in addition to estimating the satisfaction with CAM use. Methods-A cross-sectional study was performed in adult IBD outpatients from two Southeastern Brazilian referral centers, with a total a sample of 227 individuals. A semi-structured questionnaire was used containing CAM products-tea, probiotics, omega 3 or glutamine, homeopathy, and herbal therapy, and factors associated with CAM use and patient satisfaction. We used descriptive statistics, association tests (P<0.05) and logistic regression for statistical analyses. Results-In total, 126 patients with Crohn's disease and 101 with ulcerative colitis were included. The mean age was 41.19±14.49 years and 57.27% were female. The time since diagnosis was 10.58±7.5 years, and most patients were in clinical remission. Twenty-nine patients (12.8%) reported having used CAM for IBD treatment, such as tea (5.29%), probiotics (5.29%), omega-3 or glutamine (1.76%), homeopathy (0.88%), and herbal therapies (0.44%). Despite the low frequency, patients were satisfied (>50%). There was no difference between CAM use in Crohn's disease as compared to ulcerative colitis patients (P=0.1171). The factors associated with the use of CAM were regular or poor quality of life (odds ratio 2.084; 95% confidence interval 1.147-3.786, P=0.0159) and a shorter time since diagnosis (odds ratio 0.956; 95% confidence interval 0.918-0.995; P=0.0260). Conclusion-The prevalence of CAM use was low, but satisfactory among Brazilian IBD patients. The application of CAM has been associated with poor quality of life and shorter disease duration compared to patients with no use of CAM.
American Journal of Gastroenterology, 2020
American Journal of Gastroenterology, 2020
Folha méd, 1987
... Id: 47124. Autor: Elia, Celeste Carvalho Siqueira; Zaltman, Cyrla; Fogaça, Homero Soares;Moço... more ... Id: 47124. Autor: Elia, Celeste Carvalho Siqueira; Zaltman, Cyrla; Fogaça, Homero Soares;Moço, Márcio R. S; Carneiro, Antônio José de Vasconcelos; Vieira, Kátia Regina Machado; Ribeiro, Marcos Byrro; Frossard, Marília Costa; Denecke, Claúdia Ellen. ...
The Lancet Gastroenterology & Hepatology, 2021
BACKGROUND Etrolizumab is a gut-targeted, anti-β7 integrin, monoclonal antibody. In an earlier ph... more BACKGROUND Etrolizumab is a gut-targeted, anti-β7 integrin, monoclonal antibody. In an earlier phase 2 induction study, etrolizumab significantly improved clinical remission compared with placebo in patients with moderately to severely active ulcerative colitis. We aimed to evaluate the efficacy and safety of etrolizumab in patients with moderately to severely active ulcerative colitis who had been previously treated with anti-tumour necrosis factor (TNF) agents. METHODS HICKORY was a multicentre, phase 3, double-blind, placebo-controlled study in adult (18-80 years) patients with moderately to severely active ulcerative colitis (Mayo Clinic total score [MCS] of 6-12 with an endoscopic subscore of ≥2, a rectal bleeding subscore of ≥1, and a stool frequency subscore of ≥1) previously treated with TNF inhibitors. Patients were recruited from 184 treatment centres across 24 countries in North America, South America, Europe, Asia, Oceania, and the Middle East. Patients needed to have an established diagnosis of ulcerative colitis for at least 3 months, corroborated by both clinical and endoscopic evidence, and evidence of disease extending at least 20 cm from the anal verge. In cohort 1, patients received open-label etrolizumab 105 mg every 4 weeks for a 14-week induction period. In cohort 2, patients were randomly assigned (4:1) to receive subcutaneous etrolizumab 105 mg or placebo every 4 weeks for the 14-week induction phase. Patients in either cohort achieving clinical response to etrolizumab induction were eligible for the maintenance phase, in which they were randomly assigned (1:1) to receive subcutaneous etrolizumab 105 mg or placebo every 4 weeks through to week 66. Randomisation was stratified by baseline concomitant treatment with corticosteroids, concomitant treatment with immunosuppressants (induction randomisation only), baseline disease activity, week 14 MCS remission status (maintenance randomisation only), and induction cohort (maintenance randomisation only). All patients and study site personnel were masked to treatment assignment. Primary endpoints were remission (Mayo Clinic total score [MCS] ≤2, with individual subscores of ≤1 and a rectal bleeding subscore of 0) at week 14, and remission at week 66 among patients with a clinical response (MCS with ≥3-point decrease and ≥30% reduction from baseline, plus ≥1 point decrease in rectal bleeding subscore or absolute rectal bleeding score of 0 or 1) at week 14. Efficacy was analysed using a modified intent-to-treat population. Safety analyses included all patients who received at least one dose of study drug during the induction phase. This study is registered at ClinicalTrials.gov, NCT02100696. FINDINGS HICKORY was conducted from May 21, 2014, to April 16, 2020, during which time 1081 patients were screened, and 609 deemed eligible for inclusion. 130 patients were included in cohort 1. In cohort 2,479 patients were randomly assigned to the induction phase (etrolizumab n=384, placebo n=95). 232 patients were randomly assigned to the maintenance phase (etrolizumab to etrolizumab n=117, etrolizumab to placebo n=115). At week 14, 71 (18·5%) of 384 patients in the etrolizumab group and six (6·3%) of 95 patients in the placebo group achieved the primary induction endpoint of remission (p=0·0033). No significant difference between etrolizumab and placebo was observed for the primary maintenance endpoint of remission at week 66 among patients with a clinical response at week 14 (27 [24·1%] of 112 vs 23 [20·2%] of 114; p=0·50). Four patients in the etrolizumab group reported treatment-related adverse events leading to treatment discontinuation. The proportion of patients reporting at least adverse event was similar between treatment groups for induction (etrolizumab 253 [66%] of 384; placebo 63 [66%] of 95) and maintenance (etrolizumab to etrolizumab 98 [88%] of 112; etrolizumab to placebo 97 [85%] of 114). The most common adverse event in both groups was ulcerative colitis flare. Most adverse events were mild or moderate. During induction, the most common serious adverse event was ulcerative colitis flare (etrolizumab ten [3%] of 384; placebo: two [2%] of 95). During maintenance, the most common serious adverse event in the etrolizumab to etrolizumab group was appendicitis (two [2%] of 112) and the most common serious adverse events in the etrolizumab to placebo group were ulcerative colitis flare (two [2%] of 114) and anaemia (two [2%] of 114). INTERPRETATION HICKORY demonstrated that a significantly higher proportion of patients with moderately to severely active ulcerative colitis who had been previously treated with anti-TNF agent were able to achieve remission at week 14 when treated with etrolizumab compared with placebo; however, there was no significant difference between groups in remission at week 66 among patients with a clinical response at week 14. FUNDING F Hoffmann-La Roche.
Journal of Crohn's and Colitis
Background Brazil has shown an increase in Inflammatory Bowel Disease (IBD) cases. GEDIIB (Brazil... more Background Brazil has shown an increase in Inflammatory Bowel Disease (IBD) cases. GEDIIB (Brazilian Organization of Crohn's Disease and Colitis) established a data platform to create a national registry of IBD patients. The study aimed to characterize the profile of IBD patients and identify clinical factors associated with IBD severity. Methods A cohort study was conducted between Jul/20 and Aug/22. Data obtained from medical records and/or directly from patients were registered via REDCap. Local institutional review boards approved the study protocol. We designed a population-based risk model aimed at stratifying severe disease based on one or more outcome variables: previous hospitalization, surgery, and biologics. Univariate and bivariate analyses and Poisson modeling were used. Results A total of 1,179 patients were included: 600 (51%) with ulcerative colitis (UC), 568 (48%) with Crohn's Disease (CD), and 11 (0.9%) with indeterminate colitis. The mean age was 34.4±14.7...
Journal of Crohn's and Colitis
Background There are few data on the quality-of-care for inflammatory bowel disease (IBD) in publ... more Background There are few data on the quality-of-care for inflammatory bowel disease (IBD) in public, private or mixed hospitals, especially in Latin America. The aim of the study was to evaluated clinic and quality parameters and their association with need for ICU and death in Brazilian hospitals. Methods This was a multicentre study carried out in 26 hospitals. Four hundred eighty-eight admissions of patients with IBD were analysed between June 2021 and October 2022. Results The median stay length was 6 days (0–121). The median age was 38 years (16–87), and 265 (54.6%) were female. Three hundred and thirty-nine patients (69.5%) had Crohn’s disease (CD) and 149 (30.5%) ulcerative colitis (UC). The median time between symptoms onset and hospital admission was 72 months (1-504) in CD and 49 months (1-300) in UC. In the CD group, there was structural damage in 248 cases (73.2%). UC in pancolitis form was seen in 97 (66%). The Charlson Comorbidity Index (CCI) was scored at least at one...
Journal of Clinical Medicine
This prospective, observational, open-label study aimed to provide access to ustekinumab prior to... more 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 ...
Revista de Gastroenterología de México
The Lancet Gastroenterology & Hepatology, 2021
BACKGROUND Etrolizumab is a gut-targeted anti-β7 integrin monoclonal antibody. In an earlier phas... more BACKGROUND Etrolizumab is a gut-targeted anti-β7 integrin monoclonal antibody. In an earlier phase 2 induction study, etrolizumab significantly improved clinical remission relative to placebo in patients with moderately to severely active ulcerative colitis. The HIBISCUS studies aimed to compare the efficacy and safety of etrolizumab to adalimumab and placebo for induction of remission in patients with moderately to severely active ulcerative colitis. METHODS HIBISCUS I and HIBISCUS II were identically designed, multicentre, phase 3, randomised, double-blind, placebo-controlled and active-controlled studies of etrolizumab, adalimumab, and placebo in adult (18-80 years) patients with moderately to severely active ulcerative colitis (Mayo Clinic total score [MCS] of 6-12 with an endoscopic subscore of ≥2, a rectal bleeding subscore of ≥1, and a stool frequency subscore of ≥1) who were naive to tumour necrosis factor inhibitors. All patients had an established diagnosis of ulcerative colitis for at least 3 months, corroborated by both clinical and endoscopic evidence, and evidence of disease extending at least 20 cm from the anal verge. In both studies, patients were randomly assigned (2:2:1) to receive subcutaneous etrolizumab 105 mg once every 4 weeks; subcutaneous adalimumab 160 mg on day 1, 80 mg at week 2, and 40 mg at weeks 4, 6, and 8; or placebo. Randomisation was stratified by baseline concomitant treatment with corticosteroids, concomitant treatment with immunosuppressants, and baseline disease activity. All patients and study site personnel were masked to treatment assignment. The primary endpoint was induction of remission at week 10 (defined as MCS of 2 or lower, with individual subscores of 1 or lower, and rectal bleeding subscore of 0) with etrolizumab compared with placebo. Pooled analyses of both studies comparing etrolizumab and adalimumab were examined for several clinical and endoscopic endpoints. Efficacy was analysed using a modified intent-to-treat population, defined as all randomly assigned patients who received at least one dose of study drug. These trials are registered with ClinicalTrials.gov, NCT02163759 (HIBISCUS I), NCT02171429 (HIBISCUS II). FINDINGS Between Nov 4, 2014, and May 25, 2020, each study screened 652 patients (HIBISCUS I) and 613 patients (HIBISCUS II). Each study enrolled and randomly assigned 358 patients (HIBISCUS I etrolizumab n=144, adalimumab n=142, placebo n=72; HIBISCUS II etrolizumab n=143; adalimumab n=143; placebo n=72). In HIBISCUS I, 28 (19·4%) of 144 patients in the etrolizumab group and five (6·9%) of 72 patients in the placebo group were in remission at week 10, with an adjusted treatment difference of 12·3% (95% CI 1·6 to 20·6; p=0·017) in favour of etrolizumab. In HIBISCUS II, 26 (18·2%) of 143 patients in the etrolizumab group and eight (11·1%) of 72 patients in the placebo group were in remission at week 10, with an adjusted treatment difference of 7·2% (95% CI -3·8 to 16·1; p=0·17). In the pooled analysis, etrolizumab was not superior to adalimumab for induction of remission, endoscopic improvement, clinical response, histological remission, or endoscopic remission; however, similar numerical results were observed in both groups. In HIBISCUS I, 50 (35%) of 144 patients in the etrolizumab group reported any adverse event, compared with 61 (43%) of 142 in the adalimumab group and 26 (36%) of 72 in the placebo group. In HIBISCUS II, 63 (44%) of 143 patients in the etrolizumab group reported any adverse event, as did 62 (43%) of 143 in the adalimumab group and 33 (46%) in the placebo group. The most common adverse event in all groups was ulcerative colitis flare. The incidence of serious adverse events in the pooled patient population was similar for etrolizumab (15 [5%] of 287) and placebo (seven [5%] of 144) and lower for adalimumab (six [2%] of 285). Two patients in the etrolizumab group died; neither death was deemed to be treatment related. INTERPRETATION Etrolizumab was superior to placebo for induction of remission in HIBISCUS I, but not in HIBISCUS II. Etrolizumab was well tolerated in both studies. FUNDING F Hoffmann-La Roche.
Journal of Crohn's and Colitis, 2022
percentage of subjects achieving clinical and endoscopic efficacy endpoints at the end of the ind... more percentage of subjects achieving clinical and endoscopic efficacy endpoints at the end of the induction increased with increasing UPA average plasma concentration (Cavg), and became mostly flat at Cavg values approximately equivalent to the, 45 mg QD (Figure, 1). For maintenance treatment, there was a trend for increasing the percentage of subjects achieving clinical remission, steroid-free remission, endoscopic improvement, and histo-endoscopic mucosal improvement within the range of UPA plasma exposures evaluated. Exposures associated with UPA, 30 mg QD were estimated to provide a, 8% to, 10% increase in the percentage of subjects achieving these endpoints compared to, 15 mg QD (Figure, 2). There was no trend for exposure-response relationships within the range of evaluated UPA exposures for any of the evaluated safety endpoints (>2 g/dL decrease in hemoglobin and >2 g/dL decrease in hemoglobin and < lower limit for normal, hemoglobin <, 8 g/dL, lymphopenia ≥ Grade, 3, neutropenia ≥ Grade, 3, Herpes Zoster infection, serious infections, and pneumonia) at the end of induction or maintenance periods. Conclusion: UPA plasma exposures associated with the, 45 mg QD induction dose maximized efficacy for clinical and endoscopic endpoints at Week, 8. Plasma exposures associated with UPA, 30 mg maintenance dose provide additional incremental benefit compared to, 15 mg QD. No trends were observed for increase in the evaluated safety events with increasing UPA plasma exposures at the end of induction or maintenance periods.
Gastroenterology, May 1, 2022
Inflammatory Bowel Diseases, Feb 1, 2017
Background: The ApaI, TaqI and FokI vitamin D receptor (VDR) gene polymorphism are associated wit... more Background: The ApaI, TaqI and FokI vitamin D receptor (VDR) gene polymorphism are associated with risk of inflammatory bowel diseases (IBD)1. These genetic variants can also determine changes in vitamin D mechanisms of action and affect the clinical course of IBD2. In Brazil, there are a lack of data concerning VDR polymorphisms in IBD patients and its use as a predictor of poor prognosis. The aim of this study was to evaluate the association of VDR gene polymorphisms, vitamin D status and the poor prognostic factors in a multiracial IBD population. Methods: A case control study recruited 107 patients with Crohn's disease (CD), 43 patients with ulcerative colitis (UC) and 81 control healthy subjects from a tertiary center in Rio de Janeiro. The VDR polymorphisms ApaI, (“Aa,” “aa”), TaqI (“Tt,” “tt”) e FokI (“Ff,” “ff”) were evaluated in IBD and non IBD groups. The genotyping was performed by polymerase chain reaction (PCR) in real time technique. Serum 25(OH)D was measured using chemiluminescence immunoassay. Demographic, clinical features and poor prognostic factors of IBD patients were obtained from the chart review. Results: The genotype “aa” (ApaI) (49.5%) and “Tt” (TaqI) (50.5%) were more frequent in CD group. The distribution of polymorphisms was similar between UC and the control group. In CD group, the “a” allele carrier status of ApaI appeared to be a protective factor against the use of immunosuppressors (OR = 0.225; 95% CI, 0.071–0.712). The “t” allele carrier status of TaqI was protective factor against the use of steroids at the time of CD diagnosis (OR = 0.242; 95% CI, 0.065–0.901) but it was associated with the need of more than 2 steroids courses in UC group (OR = 4.19; 95% CI, 1.104–15.901) The 25(OH)D level was measured in 44 IBD patients, and low levels were detected only in 38.6% of cases. No association was observed between clinical features, VDR polymorphisms and vitamin D deficiency. Conclusions: The ApaI and TaqI, but not FokI polymorphisms are associated with CD and a poor prognostic factors. Although the polymorphisms have not been associated with UC, the presence of TaqI polymorphism was associated with poor prognosis predictor in this group. No associations were detected between VDR polymorphisms and vitamin D deficiency in IBD groups.
BMC Gastroenterology, Mar 28, 2023
Background Evidence indicates that inflammation in Inflammatory Bowel Disease (IBD) is associated... more Background Evidence indicates that inflammation in Inflammatory Bowel Disease (IBD) is associated with increased systemic levels of reactive oxygen species. Systemic oxidative stress has been associated with reduced levels of plasma thiols. Less invasive tests capable of reflecting and predicting IBD activity are increasingly sought after. We sought to systematically review the evidence inherent in serum thiol levels as a marker of Crohn's Disease and Ulcerative Colitis activity (PROSPERO: CRD42021255521). Methods The highest quality documents for systematic reviews standards were used as reference. Articles were searched on Medline via PubMed, VHL, LILACS, WOS, EMBASE, SCOPUS, COCHRANE, CINAHL, OVID, CTGOV, WHO/ ICTRP, OPENGREY, BDTD and CAPES, between August, 03 and September, 03 on 2021. Descriptors were defined according to the Medical Subject Heading. Of the 11 articles selected for full reading, 8 were included in the review. It was not possible to perform a pooled analysis of the studies, as there were no combinable studies between subjects with active IBD and controls/inactive disease. Results Findings from the individual studies included in this review suggest an association between disease activity and systemic oxidation, as measured by serum thiol levels, however, there are limitations that preclude weighting the study results in a meta-analysis. Conclusions We recommend conducting better-designed and controlled studies, that include individuals of both phenotypes and at different stages of IBD, involving a larger number of participants, using the standardization of the technique for measuring serum thiols, to confirm whether thiols can be a good parameter for monitoring the clinical course of these intestinal diseases and the degree of clinical applicability.
The American Journal of Gastroenterology, Dec 1, 2020
Inflammatory Bowel Diseases, Dec 1, 2011
2009 to 2010 and was consistent across different sites-of-care (i.e., IOI, HOPD, and ASOC). While... more 2009 to 2010 and was consistent across different sites-of-care (i.e., IOI, HOPD, and ASOC). While this analysis indicated consistent IFX vial utilization per infusion across different sites-of-care, further research exploring additional measures, such as patient adherence and patient satisfaction, may provide further insight into the complete patient care experience across sites and support optimal site of care decision making.
Arquivos De Gastroenterologia, Dec 1, 2009
Context-Although endoscopic esophageal variceal sclerotherapy has been largely supplanted by vari... more Context-Although endoscopic esophageal variceal sclerotherapy has been largely supplanted by variceal band ligation, it is still performed routinely in many institutions, especially in developing countries. Intramural esophageal hematoma has been described as a rare complication of sclerotherapy. Risk factors have not been completely established. Objective-To demonstrate the incidence of post-sclerotherapy intramural esophageal hematoma in our hospital and discuss the possible factors involved. Methods-This is a retrospective observational study made at the "Hospital Universitário Clementino Fraga Filho", Rio de Janeiro, RJ, Brazil, reviewing the medical records of all esophageal variceal sclerotherapy procedures performed from April 2000 to November 2005. The evaluation of the clinical, laboratorial and endoscopic features in our patients and those reported in the literature was also done. Review of literature was performed through MEDLINE search. Results-A total of 1,433 esophageal variceal sclerotherapy procedures were performed in 397 patients, with an intramural esophageal hematoma incidence of 4 cases (0.28%). Three of our patients developed additional complications, and one death was a direct consequence of a rupture of the hematoma. Nineteen well described cases were reported in the literature. Intramural esophageal hematoma occurred mostly after the forth esophageal variceal sclerotherapy session. Coagulation disturbances were present in the majority of cases. Conclusion-Intramural esophageal hematoma is a rare complication of esophageal variceal sclerotherapy and its incidence in our institution was similar to those observed in the literature. Our study suggests that this complication occurs as a result of a fragile esophageal mucosa after previous esophageal variceal sclerotherapy sessions. Impaired coagulation, although not essential, could contribute to hematoma formation and extension through esophageal submucosa. HEADINGS-Esophageal diseases. Hematoma. Sclerotherapy.
River Publishers eBooks, Sep 1, 2022
The American Journal of Gastroenterology, Feb 1, 2018
This article discusses the various meanings ascribed to the concept of Complementary and Alternat... more This article discusses the various meanings ascribed to the concept of Complementary and Alternative Medicine (CAM) in Brazil, where research on this theme has a limited tradition in terms of influences from anthropology, sociology of knowledge and epistemology, and sociology of CAM and clinical medicine. By means of the concepts identified in the literature, we elaborated a table with types of meanings. The terms Alternative Medicine and Complementary Medicine were found in more than one of the types in the table. Alternative Medicine identifies a model of medical practice influenced by the social, political, and economic context and by the logic of scientific production based on opposing pairs. Beginning in the 1980s, the important volume of reflections on official medical practice and the search for other forms of knowledge production led to the creation of the concept of Complementary Medicine. Its meaning is that of a new epistemological form of knowledge production between the official and alternative poles, a set of therapeutic practices, and confusion with the nomenclature for ancillary medical diagnostic tests, referred to in Portuguese as "complementary exams".
Arquivos De Gastroenterologia, Sep 1, 2022
Background-The conventional treatment of inflammatory bowel disease (IBD) is based on drug therap... more Background-The conventional treatment of inflammatory bowel disease (IBD) is based on drug therapy, but different studies have shown a progressive increase in the use of complementary and alternative medicine (CAM). The most used CAM comprises of acupuncture, traditional Chinese medicine, Ayurvedic medicine, homeopathy, and herbal medicine, as well as more modern practices, including aromatherapy and reflexology. Data from CAM use in Brazil has previously been scarce and there are no studies among Brazilian patients with IBD. Objective-The aim of the study was to evaluate the frequency of, and factors associated with the use of CAM among IBD patients in Brazil, in addition to estimating the satisfaction with CAM use. Methods-A cross-sectional study was performed in adult IBD outpatients from two Southeastern Brazilian referral centers, with a total a sample of 227 individuals. A semi-structured questionnaire was used containing CAM products-tea, probiotics, omega 3 or glutamine, homeopathy, and herbal therapy, and factors associated with CAM use and patient satisfaction. We used descriptive statistics, association tests (P<0.05) and logistic regression for statistical analyses. Results-In total, 126 patients with Crohn's disease and 101 with ulcerative colitis were included. The mean age was 41.19±14.49 years and 57.27% were female. The time since diagnosis was 10.58±7.5 years, and most patients were in clinical remission. Twenty-nine patients (12.8%) reported having used CAM for IBD treatment, such as tea (5.29%), probiotics (5.29%), omega-3 or glutamine (1.76%), homeopathy (0.88%), and herbal therapies (0.44%). Despite the low frequency, patients were satisfied (>50%). There was no difference between CAM use in Crohn's disease as compared to ulcerative colitis patients (P=0.1171). The factors associated with the use of CAM were regular or poor quality of life (odds ratio 2.084; 95% confidence interval 1.147-3.786, P=0.0159) and a shorter time since diagnosis (odds ratio 0.956; 95% confidence interval 0.918-0.995; P=0.0260). Conclusion-The prevalence of CAM use was low, but satisfactory among Brazilian IBD patients. The application of CAM has been associated with poor quality of life and shorter disease duration compared to patients with no use of CAM.
American Journal of Gastroenterology, 2020
American Journal of Gastroenterology, 2020
Folha méd, 1987
... Id: 47124. Autor: Elia, Celeste Carvalho Siqueira; Zaltman, Cyrla; Fogaça, Homero Soares;Moço... more ... Id: 47124. Autor: Elia, Celeste Carvalho Siqueira; Zaltman, Cyrla; Fogaça, Homero Soares;Moço, Márcio R. S; Carneiro, Antônio José de Vasconcelos; Vieira, Kátia Regina Machado; Ribeiro, Marcos Byrro; Frossard, Marília Costa; Denecke, Claúdia Ellen. ...
The Lancet Gastroenterology & Hepatology, 2021
BACKGROUND Etrolizumab is a gut-targeted, anti-β7 integrin, monoclonal antibody. In an earlier ph... more BACKGROUND Etrolizumab is a gut-targeted, anti-β7 integrin, monoclonal antibody. In an earlier phase 2 induction study, etrolizumab significantly improved clinical remission compared with placebo in patients with moderately to severely active ulcerative colitis. We aimed to evaluate the efficacy and safety of etrolizumab in patients with moderately to severely active ulcerative colitis who had been previously treated with anti-tumour necrosis factor (TNF) agents. METHODS HICKORY was a multicentre, phase 3, double-blind, placebo-controlled study in adult (18-80 years) patients with moderately to severely active ulcerative colitis (Mayo Clinic total score [MCS] of 6-12 with an endoscopic subscore of ≥2, a rectal bleeding subscore of ≥1, and a stool frequency subscore of ≥1) previously treated with TNF inhibitors. Patients were recruited from 184 treatment centres across 24 countries in North America, South America, Europe, Asia, Oceania, and the Middle East. Patients needed to have an established diagnosis of ulcerative colitis for at least 3 months, corroborated by both clinical and endoscopic evidence, and evidence of disease extending at least 20 cm from the anal verge. In cohort 1, patients received open-label etrolizumab 105 mg every 4 weeks for a 14-week induction period. In cohort 2, patients were randomly assigned (4:1) to receive subcutaneous etrolizumab 105 mg or placebo every 4 weeks for the 14-week induction phase. Patients in either cohort achieving clinical response to etrolizumab induction were eligible for the maintenance phase, in which they were randomly assigned (1:1) to receive subcutaneous etrolizumab 105 mg or placebo every 4 weeks through to week 66. Randomisation was stratified by baseline concomitant treatment with corticosteroids, concomitant treatment with immunosuppressants (induction randomisation only), baseline disease activity, week 14 MCS remission status (maintenance randomisation only), and induction cohort (maintenance randomisation only). All patients and study site personnel were masked to treatment assignment. Primary endpoints were remission (Mayo Clinic total score [MCS] ≤2, with individual subscores of ≤1 and a rectal bleeding subscore of 0) at week 14, and remission at week 66 among patients with a clinical response (MCS with ≥3-point decrease and ≥30% reduction from baseline, plus ≥1 point decrease in rectal bleeding subscore or absolute rectal bleeding score of 0 or 1) at week 14. Efficacy was analysed using a modified intent-to-treat population. Safety analyses included all patients who received at least one dose of study drug during the induction phase. This study is registered at ClinicalTrials.gov, NCT02100696. FINDINGS HICKORY was conducted from May 21, 2014, to April 16, 2020, during which time 1081 patients were screened, and 609 deemed eligible for inclusion. 130 patients were included in cohort 1. In cohort 2,479 patients were randomly assigned to the induction phase (etrolizumab n=384, placebo n=95). 232 patients were randomly assigned to the maintenance phase (etrolizumab to etrolizumab n=117, etrolizumab to placebo n=115). At week 14, 71 (18·5%) of 384 patients in the etrolizumab group and six (6·3%) of 95 patients in the placebo group achieved the primary induction endpoint of remission (p=0·0033). No significant difference between etrolizumab and placebo was observed for the primary maintenance endpoint of remission at week 66 among patients with a clinical response at week 14 (27 [24·1%] of 112 vs 23 [20·2%] of 114; p=0·50). Four patients in the etrolizumab group reported treatment-related adverse events leading to treatment discontinuation. The proportion of patients reporting at least adverse event was similar between treatment groups for induction (etrolizumab 253 [66%] of 384; placebo 63 [66%] of 95) and maintenance (etrolizumab to etrolizumab 98 [88%] of 112; etrolizumab to placebo 97 [85%] of 114). The most common adverse event in both groups was ulcerative colitis flare. Most adverse events were mild or moderate. During induction, the most common serious adverse event was ulcerative colitis flare (etrolizumab ten [3%] of 384; placebo: two [2%] of 95). During maintenance, the most common serious adverse event in the etrolizumab to etrolizumab group was appendicitis (two [2%] of 112) and the most common serious adverse events in the etrolizumab to placebo group were ulcerative colitis flare (two [2%] of 114) and anaemia (two [2%] of 114). INTERPRETATION HICKORY demonstrated that a significantly higher proportion of patients with moderately to severely active ulcerative colitis who had been previously treated with anti-TNF agent were able to achieve remission at week 14 when treated with etrolizumab compared with placebo; however, there was no significant difference between groups in remission at week 66 among patients with a clinical response at week 14. FUNDING F Hoffmann-La Roche.
Journal of Crohn's and Colitis
Background Brazil has shown an increase in Inflammatory Bowel Disease (IBD) cases. GEDIIB (Brazil... more Background Brazil has shown an increase in Inflammatory Bowel Disease (IBD) cases. GEDIIB (Brazilian Organization of Crohn's Disease and Colitis) established a data platform to create a national registry of IBD patients. The study aimed to characterize the profile of IBD patients and identify clinical factors associated with IBD severity. Methods A cohort study was conducted between Jul/20 and Aug/22. Data obtained from medical records and/or directly from patients were registered via REDCap. Local institutional review boards approved the study protocol. We designed a population-based risk model aimed at stratifying severe disease based on one or more outcome variables: previous hospitalization, surgery, and biologics. Univariate and bivariate analyses and Poisson modeling were used. Results A total of 1,179 patients were included: 600 (51%) with ulcerative colitis (UC), 568 (48%) with Crohn's Disease (CD), and 11 (0.9%) with indeterminate colitis. The mean age was 34.4±14.7...