RESUMO
Therapy with anti-tumor necrosis factor (TNF) has dramatically changed the natural history of Crohn's disease (CD). However, these drugs are not without adverse events, and up to 40% of patients could lose efficacy in the long term. We aimed to identify reliable markers of response to anti-TNF drugs in patients with CD. A consecutive cohort of 113 anti-TNF naive patients with CD was stratified according to clinical response as short-term remission (STR) or non-STR (NSTR) at 12 weeks of treatment. We compared the protein expression profiles of plasma samples in a subset of patients from both groups prior to anti-TNF therapy by SWATH proteomics. We identified 18 differentially expressed proteins (p ≤ 0.01, fold change ≥ 2.4) involved in the organization of the cytoskeleton and cell junction, hemostasis/platelet function, carbohydrate metabolism, and immune response as candidate biomarkers of STR. Among them, vinculin was one of the most deregulated proteins (p < 0.001), whose differential expression was confirmed by ELISA (p = 0.054). In the multivariate analysis, plasma vinculin levels along with basal CD Activity Index, corticosteroids induction, and bowel resection were factors predicting NSTR.
Assuntos
Antineoplásicos , Doença de Crohn , Humanos , Doença de Crohn/tratamento farmacológico , Inibidores do Fator de Necrose Tumoral/uso terapêutico , Vinculina , Fator de Necrose Tumoral alfa/uso terapêutico , Antineoplásicos/uso terapêutico , Indução de Remissão , Infliximab/uso terapêuticoRESUMO
OBJECTIVE: To evaluate the impact of magnetic resonance enterography (MRE) diagnosis on clinical decision-making regarding treatment choice and maintenance of treatment over time in patients with inflammatory bowel disease (IBD). METHODS: A cohort of patients who underwent MRE for IBD assessment between 2011 and 2014 was analyzed. From clinical records, we retrospectively retrieved their demographic data and clinical data on their IBD at the time of MRE, the results of MRE and the patient's clinical course. Medical management decisions made during the three months following MRE and at the 15-month follow-up were assessed. RESULTS: In total, 474 MREs were reviewed. In the first three-month period, MRE results led to changes in the medical management of 266 patients (56.1%). Of those, maintenance therapy was altered in 140 patients (68.3%) (90.7% step-up and 9.3% top-down strategy), 65 (24.4%) were prescribed a course of steroids and 61 (22.9%) underwent surgery. MRE confirmed a CD diagnosis in 14/41 patients (34.1%) previously diagnosed with indeterminate colitis or ulcerative colitis and in 4/18 patients (22.2%) with suspected IBD. At the 15-month follow-up, treatment remained unchanged in 289 patients (65.8%). CONCLUSIONS: These results suggest that MRE is a diagnostic tool that provides valid information for the clinical-decision making process for patients with CD.
Assuntos
Tomada de Decisão Clínica/métodos , Doenças Inflamatórias Intestinais/diagnóstico por imagem , Imageamento por Ressonância Magnética , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
PURPOSE: Nivolumab, a monoclonal antibody-targeting programmed cell death protein-1, is being increasingly used for the treatment of some advanced neoplasms. Several of its adverse effects are a result of the upregulation of T cells, with colitis as one of the most severe, and a challenging differential diagnosis with ulcerative colitis. However, few real-life clinical practice cases have been reported beyond trials. Our aim was to report a series of new cases, reviewing previously communicated endoscopic-proven nivolumab-induced colitis. METHOD: All patients treated with nivolumab in three university centers were identified and those who developed immune-mediated colitis (defined as the presence of diarrhea and evidence of colitis demonstrated by colonoscopy) were described. Additionally, a review of case reports of nivolumab-induced colitis reported in the literature up to March 2018 was performed. RESULTS: Six new cases of nivolumab-induced colitis and 13 previously reported cases out of randomized clinical trials are described. Colonoscopy showed a mucosal pattern mimicking ulcerative colitis in a large proportion of patients. Clostridium difficile superinfection was observed in two out of 19 cases. All but three patients definitively discontinued nivolumab therapy. Most patients were initially managed with oral or intravenous corticosteroids, but five of them required rescue therapy with infliximab. CONCLUSIONS: Nivolumab-induced colitis may mimic ulcerative colitis. Steroid therapy (oral or intravenously) is often efficient, but one-fourth of patients need rescue therapy with anti-TNF. Intestinal superinfection with Clostridium difficile or cytomegalovirus should be ruled out before starting immunosuppressive therapy.
Assuntos
Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/imunologia , Nivolumabe/efeitos adversos , Idoso , Idoso de 80 Anos ou mais , Colite Ulcerativa/patologia , Colonoscopia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do TratamentoRESUMO
BACKGROUND: Effectiveness of vedolizumab in real world clinical practice is unknown. AIM: To evaluate the short and long-term effectiveness of vedolizumab in patients with inflammatory bowel disease (IBD). METHODS: Patients who received at least 1 induction dose of vedolizumab were included. Effectiveness was defined based on Harvey-Bradshaw index (HBI) in Crohn's disease (CD) and Partial Mayo Score (PMS) in ulcerative colitis (UC). Short-term response was assessed at week 14. Variables associated with short-term remission were identified by logistic regression analysis. The Kaplan-Meier method was used to evaluate the long-term durability of vedolizumab treatment. Cox model was used to identify factors associated with discontinuation of treatment and loss of response. RESULTS: 521 patients were included (median follow-up 10 months [interquartile range 5-18 months]). At week 14, 46.8% had remission and 15.7% clinical response. CD (vs UC), previous surgery, higher CRP concentration and disease severity at baseline were significantly associated with impaired response. The rate of vedolizumab discontinuation was 37% per patient-year of follow-up (27.6% in UC and 45.3% in CD, P < 0.01). CD (vs UC), anaemia at baseline, steroids during induction and CRP concentration were associated with lower durability of treatment. Seven per cent of patients developed adverse events, infections being the most frequent. CONCLUSIONS: Over 60% of IBD patients respond to vedolizumab. Many patients discontinue treatment over time. CD and disease burden impair both short- and long-term response. Vedolizumab seems to be safe in clinical practice.
Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Fármacos Gastrointestinais/uso terapêutico , Doenças Inflamatórias Intestinais/diagnóstico , Doenças Inflamatórias Intestinais/tratamento farmacológico , Sistema de Registros , Adulto , Anticorpos Monoclonais Humanizados/efeitos adversos , Colite Ulcerativa/diagnóstico , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/epidemiologia , Doenças Transmissíveis/induzido quimicamente , Doenças Transmissíveis/diagnóstico , Doenças Transmissíveis/epidemiologia , Doença de Crohn/diagnóstico , Doença de Crohn/tratamento farmacológico , Doença de Crohn/epidemiologia , Feminino , Seguimentos , Fármacos Gastrointestinais/efeitos adversos , Humanos , Doenças Inflamatórias Intestinais/epidemiologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Indução de Remissão , Espanha/epidemiologia , Resultado do TratamentoRESUMO
BACKGROUND: In conditions associated with inflammation, biochemical parameters alone could be inadequate for assessing iron status. We investigated the potential utility of mean reticulocyte hemoglobin content (MCHr) in the assessment of the erythropoiesis status in inflammatory bowel disease (IBD). METHODS: We recruited 124 anemic outpatients with IBD. Serum iron, transferrin and ferritin were tested. Complete blood counts were performed on a CELL-DYN Sapphire analyzer (Abbott Diagnostics). Differences among groups were assessed using analysis of variance, considering Pâ¯<â¯0.05 to be significant. Receiver operating characteristic analysis was used to assess the diagnostic performance of MCHr for detecting iron deficient erythropoiesis. The reference used as an indicator of insufficient iron availability was transferrin saturation <20%. RESULTS: Overall, 47.6% of the patients had iron deficiency anemia (IDA) and 31.5% anemia of chronic disease (ACD), while the others (20.9%) had mixed anemia. Patients with ACD or mixed anemia showed functional iron deficiency: normal or high ferritin and low MCHr. The area under curve was 0.858 (95% CI 0.742-0.942), considering a cut off 30.3â¯pg, the sensitivity was 82.2%, specificity 83.3%. CONCLUSIONS: MCHr provides information on iron availability in IBD patients. It is a reliable test to assess iron supply for erythropoiesis.
Assuntos
Anemia Ferropriva/diagnóstico , Eritropoese , Hemoglobinas/análise , Doenças Inflamatórias Intestinais/complicações , Reticulócitos/química , Adulto , Idoso , Anemia Ferropriva/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Curva ROCRESUMO
BACKGROUND: Data regarding the effectiveness of adalimumab (ADA) in the treatment of perianal fistula in patients with Crohn's disease (CD) naive to antitumor necrosis factor (TNF) therapy are scarce. AIM: : To assess the effectiveness of ADA in the treatment of perianal fistulas in CD patients naive to anti-TNF therapy. METHODS: A retrospective multicenter study was designed. The Fistula Drainage Assessment Index was used to assess the clinical response, and the Van Assche and Ng indexes to classify radiologic response (magnetic resonance imaging). RESULTS: A total of 46 patients (83% women, 83% complex fistula) were included. At 6 months, 72% of patients responded to ADA (54% remission, 18% partial response) and at 12 months 49% responded (41% remission, 8% partial response). Among patients with complex fistula, the response rate was 66% at 6 months and 39% at 12 months. Nine patients escalated the ADA dose to 40 mg weekly, 6 for partial response and 3 for absence of response. Thirty-three percent of these patients achieved remission after dose escalation. There was a good correlation between clinical and radiologic assessment of response (κ=0.68). In the multivariate analysis, complex fistula was the only predictor of a worse response (hazard ratio 0.083; 95% confidence interval, 0.0009-0.764; P=0.028). Adverse effects were recorded in 11% of patients. CONCLUSIONS: ADA was effective for the treatment of perianal fistulas in CD patients naive to anti-TNF drugs. We found a good correlation between clinical and radiologic assessment of therapy response.
Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Doença de Crohn/tratamento farmacológico , Fístula Cutânea/tratamento farmacológico , Fístula Retal/tratamento farmacológico , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Adalimumab , Adulto , Anti-Inflamatórios não Esteroides/efeitos adversos , Anticorpos Monoclonais Humanizados/efeitos adversos , Doença de Crohn/complicações , Doença de Crohn/cirurgia , Fístula Cutânea/etiologia , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Fístula Retal/etiologia , Estudos Retrospectivos , Índice de Gravidade de Doença , Adulto JovemRESUMO
BACKGROUND & AIMS: Disease outcome has been found to be poorer in familial inflammatory bowel disease (IBD) than in sporadic forms, but assessment of phenotypic concordance in familial IBD provided controversial results. We assessed the concordance for disease type and phenotypic features in IBD families. METHODS: Patients with familial IBD were identified from the IBD Spanish database ENEIDA. Families in whom at least two members were in the database were selected for concordance analysis (κ index). Concordance for type of IBD [Crohn's disease (CD) vs. ulcerative colitis (UC)], as well as for disease extent, localization and behaviour, perianal disease, extraintestinal manifestations, and indicators of severe disease (i.e., need for immunosuppressors, biological agents, and surgery) for those pairs concordant for IBD type, were analyzed. RESULTS: 798 out of 11,905 IBD patients (7%) in ENEIDA had familial history of IBD. Complete data of 107 families (231 patients and 144 consanguineous pairs) were available for concordance analyses. The youngest members of the pairs were diagnosed with IBD at a significantly younger age (p<0.001) than the oldest ones. Seventy-six percent of pairs matched up for the IBD type (κ=0.58; 95%CI: 0.42-0.73, moderate concordance). There was no relevant concordance for any of the phenotypic items assessed in both diseases. CONCLUSIONS: Familial IBD is associated with diagnostic anticipation in younger individuals. Familial history does not allow predicting any phenotypic feature other than IBD type.
Assuntos
Colite Ulcerativa/epidemiologia , Colite Ulcerativa/genética , Doença de Crohn/epidemiologia , Doença de Crohn/genética , Fenótipo , Adolescente , Adulto , Idade de Início , Colite Ulcerativa/patologia , Constrição Patológica/epidemiologia , Doença de Crohn/patologia , Feminino , Predisposição Genética para Doença/epidemiologia , Humanos , Fístula Intestinal/epidemiologia , Masculino , Pessoa de Meia-Idade , Linhagem , Prevalência , Espanha/epidemiologia , Adulto JovemRESUMO
BACKGROUND: To evaluate the safety of thiopurines in patients with inflammatory bowel disease. To identify predictive factors associated with the development of thiopurine-induced adverse events. METHODS: Long-term incidence of adverse events was estimated in patients from a prospectively maintained Spanish nationwide database using Kaplan-Meier analysis. Cox regression analysis was performed to identify potential predictive factors of adverse events. RESULTS: Three thousand nine hundred and thirty-one patients were included. Ninety-five percent of patients were on azathioprine. The median follow-up with thiopurines was 44 months (range, 0-420). Adverse events occurred at a median of 1 month after starting treatment. The cumulative incidence of adverse events was 26%, with an annual risk of 7% per patient-year of treatment. Most frequent adverse events were nausea (8%), hepatotoxicity (4%), myelotoxicity (4%), and pancreatitis (4%). Four patients had lymphoma. Female and Crohn's disease increased the risk of having nausea. The risk of hepatotoxicity was lower in females and higher in Crohn's disease. The risk of myelotoxicity was significantly higher in patients treated with mercaptopurine and in females. The risk of pancreatitis was higher in Crohn's disease. Overall, 17% of patients discontinued thiopurine treatment due to adverse events. Thirty-seven percent of these patients started thiopurines again and 40% of them had adverse events again. CONCLUSIONS: As many as 1 of 4 patients on thiopurine therapy had adverse events during follow-up. A relatively high proportion of patients (17%) had to discontinue the treatment with thiopurines due to adverse events. However, more than half of patients that restarted thiopurine treatment after its discontinuation due to adverse events tolerated it. Several predictive factors for some adverse events have been identified.
Assuntos
Azatioprina/efeitos adversos , Colite Ulcerativa/complicações , Doença de Crohn/complicações , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Imunossupressores/efeitos adversos , Adulto , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/mortalidade , Doença de Crohn/tratamento farmacológico , Doença de Crohn/mortalidade , Feminino , Seguimentos , Humanos , Masculino , Prognóstico , Estudos Prospectivos , Fatores de Risco , Taxa de SobrevidaRESUMO
BACKGROUND: Information on efficacy and predictors of response to adalimumab in ulcerative colitis (UC) clinical practice is limited. AIM: Assessment of response to adalimumab and its predictors in an observational cohort study. METHODS: Retrospective cohort study based on data obtained from ENEIDA registry. All patients diagnosed with UC treated with adalimumab were included. Response to adalimumab was evaluated at weeks 12, 28, and 54 according to the partial Mayo score, and requirement of colectomy until end of follow-up. RESULTS: 48 patients with UC treated with adalimumab were included; 39 (81.3%) had previously received infliximab. Response rates at weeks 12, 28 and 54 were 70.8%, 43.2% and 35% respectively. Response to prior treatment with infliximab was the only predictive factor of response to adalimumab at week 12, which was obtained in 90% of infliximab remitters, 53.8% of responders and 33.3% of primary non-responders (p=0.01). Colectomy was required in 11 patients (22.9%), after a mean time of 205 days. The only clinical independent predictor of colectomy was non-response to adalimumab at week 12: colectomy rates were 5/34 (14.7%) in responders and 6/14 (42.9%) in non-responders (p=0.035), time free of colectomy was significantly reduced in non-responders (p=0.01). Adalimumab withdrawal due to adverse events occurred in 4.2% of patients. CONCLUSION: This study shows that adalimumab is an effective treatment in patients with UC. If used as a second anti-TNF, previous achievement of remission with the first anti-TNF predicts response, and failure to achieve response at week 12 predicts colectomy.
Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Colite Ulcerativa/tratamento farmacológico , Adalimumab , Adulto , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais Humanizados/efeitos adversos , Colectomia , Colite Ulcerativa/cirurgia , Feminino , Humanos , Infliximab , Masculino , Indução de Remissão , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: Leukocytapheresis (LAP) could be an alternative treatment for steroid-dependent ulcerative colitis (UC). AIMS: To assess the duration of response at 1 year after this treatment. PATIENTS AND METHODS: A prospective study in 18 patients with steroid-dependent UC treated with LAP plus steroids after failure or intolerance to immunomodulators. Clinical and endoscopic (Mayo Clinic index) examinations were performed at 1 month after the last apheresis and at 12 months. The clinical, endoscopic remission and the relapse during the 1-year follow-up were evaluated based on standard parameters. RESULTS: Induction of remission: clinical remission: 10/18 (55%). Partial response: 4. Endoscopic remission: 9 (50%), always accompanied by clinical remission. A significant correlation was observed between clinical remission and endoscopic remission (r(s)=0.894; p< or =0.001). At 1 year: sustained steroid-free clinical remission in 9 (50%), all of whom presented initial endoscopic remission. Remission and relapse before 1 year in 17%. A tendency for sustained remission at 1 year was observed when initial endoscopic remission was achieved. CONCLUSIONS: Initial remission can be maintained at 1 year in half of the patients without the need for additional steroids. Complete remission and endoscopic mucosal healing is proposed as an objective for achieving a lasting response.
Assuntos
Colite Ulcerativa/terapia , Glucocorticoides/uso terapêutico , Leucaférese/métodos , Colite Ulcerativa/diagnóstico , Colonoscopia , Feminino , Seguimentos , Humanos , Mucosa Intestinal/patologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Indução de Remissão , Fatores de Tempo , Resultado do TratamentoRESUMO
Postoperative biliary tract lesions are becoming increasingly common. The diagnosis is made by direct cholangiography via endoscopic retrograde cholangiopancreatography (ERCP) or percutaneous transhepatic cholangiography (PTC). The present comparative study evaluates the diagnostic efficacy of magnetic resonance cholangiopancreatography (MRCP) in application to iatrogenic bile duct injury. A prospective blind study was performed, contrasting MRCP and ERCP in 10 patients with suspected postoperative biliary tract lesions. MRCP was performed less than 72 h before ERCP. Final diagnosis was made on the basis of findings at surgery and ERCP. The presence of biliary dilatation, excision injury, stricture, fluid collection and free fluid was analyzed. The mean patient age was 66.5 years. There were three males and seven females. The type of postoperative lesion (Bergman classification) are five patients type C, three type D, one type B and one type A. Diagnostic failure was recorded in two cases with ERCP, while in five patients it was unable to define a therapeutic approach. In contrast, MRCP correctly diagnosed all patients. MRCP is effective in diagnosing postoperative biliary tract lesions, and can help decide the best therapeutic approach.
Assuntos
Doenças dos Ductos Biliares/diagnóstico , Ductos Biliares/lesões , Colecistectomia Laparoscópica/efeitos adversos , Imageamento por Ressonância Magnética/métodos , Idoso , Doenças dos Ductos Biliares/etiologia , Feminino , Humanos , Doença Iatrogênica , Masculino , Reprodutibilidade dos Testes , Sensibilidade e EspecificidadeRESUMO
OBJECTIVES: To investigate the diagnostic efficacy of magnetic resonance cholangiopancreatography (MRCP) in choledocholithiasis and to determine whether use of MRCP may eliminate the need for purely diagnostic endoscopic retrograde cholangiopancreatography (ERCP). PATIENTS AND METHODS: A total of 116 patients with suspected biliopancreatic pathology were studied prospectively between November 1996 and February 1998. Choledocholithiasis was initially suspected in 61 patients and rated before ERCP and MRCP as being of low, intermediate, or high probability based on clinical, laboratory, and/or imaging findings (Cotton criteria). RESULTS: The sensitivity of choledocholithiasis diagnosis was 91%, with a global efficacy of 90%. The level of duct stone obstruction was visualized in all patients. Suprastenotic dilatation also showed a good correlation to ERCP. Choledocholithiasis was found in 32 patients (65%) and 3 patients (33%) in the high- and intermediate-probability groups, respectively. None of the low-probability patients had choledocholithiasis. Endoscopic retrograde cholangiopancreatography was performed for only a diagnostic (not therapeutic) purpose in 3 patients (6%) and 2 patients (22%) of the high- and intermediate-probability cases, respectively. CONCLUSIONS: Magnetic resonance cholangiopancreatography seems to be effective in diagnosing choledocholithiasis. It plays a fundamental role in patients with a low or intermediate risk of choledocholithiasis, contributing to the avoidance of purely diagnostic ERCP.
Assuntos
Neoplasias dos Ductos Biliares/diagnóstico , Colangiopancreatografia Retrógrada Endoscópica , Cálculos Biliares/diagnóstico , Imageamento por Ressonância Magnética/métodos , Idoso , Ampola Hepatopancreática/patologia , Neoplasias dos Ductos Biliares/patologia , Colestase/diagnóstico , Feminino , Humanos , Masculino , Valor Preditivo dos Testes , Sensibilidade e EspecificidadeRESUMO
OBJECTIVE: To date, ERCP has been the reference technique in the diagnosis of pancreatic duct pathology. The aim of the present study was to evaluate the accuracy of magnetic resonance cholangiopancreatography (MRCP), a relatively new, noninvasive diagnostic method, in studying the pancreatic duct. METHODS: A prospective 15-month study was done of 78 patients with suspected biliopancreatic pathology and indications for ERCP. In all cases, MRCP was performed <72 h before ERCP. Both techniques were used to assess the size of the pancreatic tract (normal or dilated), the presence or absence of obstruction, the level of obstruction where present, and its etiology. RESULTS: Both techniques found the pancreatic tract to be normal and nondilated in 60 patients. The specificity and sensitivity of MRCP in evaluating the normal pancreatic duct were 98% and 94%, respectively. In nine cases, a stenotic duct of Wirsung was detected (seven at the head of the pancreas and two in the body), with the same correlation being shown by ERCP (sensitivity 100%). The sensitivity and specificity of MRCP relating to diffuse irregular and dilated morphologies of the entire pancreatic duct was 86% and 100%, respectively. Nine patients were diagnosed with pancreatic neoplasms by both techniques, with an accuracy of 100%. Four patients presented chronic pancreatitis, which was correctly diagnosed by MRCP in each case. CONCLUSIONS: MRCP is an effective technique for evaluating both the normal and diseased duct of Wirsung, and for establishing the underlying pathology.