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INTRODUCTION: Biological therapies used for the treatment of inflammatory bowel disease (IBD) have shown to be effective and safe, although these results were obtained from studies involving mostly a young population, who are generally included in clinical trials. The aim of our study was to determine the efficacy and safety of the different biological treatments in the elderly population. METHODS: Multicenter study was carried out in the GETECCU group. Patients diagnosed with IBD and aged over 65 years at the time of initiating biological therapy (infliximab, adalimumab, golimumab, ustekinumab or vedolizumab) were retrospectively included. Among the patients included, clinical response was assessed after drug induction (12 weeks of treatment) and at 52 weeks. Patients' colonoscopy data in week 52 were assessment, where available. Regarding complications, development of oncological events during follow-up and infectious processes occurring during biological treatment were collected (excluding bowel infection by cytomegalovirus). RESULTS: A total of 1090 patients were included. After induction, at approximately 12-14 weeks of treatment, 419 patients (39.6%) were in clinical remission, 502 patients (47.4%) had responded without remission and 137 patients (12.9%) had no response. At 52 weeks of treatment 442 patients (57.1%) had achieved clinical remission, 249 patients had responded without remission (32.2%) and 53 patients had no response to the treatment (6.8%). Before 52 weeks, 129 patients (14.8%) had discontinued treatment due to inefficacy, this being significantly higher (p<0.0001) for Golimumab - 9 patients (37.5%) - compared to the other biological treatments analyzed. With respect to tumor development, an oncological event was observed in 74 patients (6.9%): 30 patients (8%) on infliximab, 23 (7.14%) on adalimumab, 3 (11.1%) on golimumab, 10 (6.4%) on ustekinumab, and 8 (3.8%) on vedolizumab. The incidence was significantly lower (p=0.04) for the vedolizumab group compared to other treatments. As regards infections, these occurred in 160 patients during treatment (14.9%), with no differences between the different biologicals used (p=0.61): 61 patients (19.4%) on infliximab, 39 (12.5%) on adalimumab, 5 (17.8%) on golimumab, 22 (14.1%) on ustekinumab, and 34 (16.5%) on vedolizumab. CONCLUSIONS: Biological drug therapies have response rates in elderly patients similar to those described in the general population, Golimumab was the drug that was discontinued most frequently due to inefficacy. In our experience, tumor development was more frequent in patients who used anti-TNF therapies compared to other targets, although its incidence was generally low and that this is in line with younger patients based on previous literature.
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INTRODUCTION: The prevalence of penetrating complications in Crohn's disease (CD) increases progressively over time, but evidence on the medical treatment in this setting is limited. The aim of this study was to evaluate the effectiveness of biologic agents in CD complicated with internal fistulizing disease. METHODS: Adult patients with CD-related fistulae who received at least 1 biologic agent for this condition from the prospectively maintained ENEIDA registry were included. Exclusion criteria involved those receiving biologics for perianal disease, enterocutaneous, rectovaginal, anastomotic, or peristomal fistulae. The primary end point was fistula-related surgery. Predictive factors associated with surgery and fistula closure were evaluated by multivariate logistic regression and survival analyses. RESULTS: A total of 760 patients from 53 hospitals (673 receiving anti-tumor necrosis factors, 69 ustekinumab, and 18 vedolizumab) were included. After a median follow-up of 56 months (interquartile range, 26-102 months), 240 patients required surgery, with surgery rates of 32%, 41%, and 24% among those under anti-tumor necrosis factor, vedolizumab, or ustekinumab, respectively. Fistula closure was observed in 24% of patients. Older patients, ileocolonic disease, entero-urinary fistulae, or an intestinal stricture distal to the origin of the fistula were associated with a higher risk of surgery, whereas nonsmokers and combination therapy with an immunomodulator reduced this risk. DISCUSSION: Biologic therapy is beneficial in approximately three-quarters of patients with fistulizing CD, achieving fistula closure in 24%. However, around one-third still undergo surgery due to refractory disease. Some patient- and lesion-related factors can identify patients who will obtain more benefit from these drugs.
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Doença de Crohn , Fístula , Fístula Retal , Adulto , Humanos , Doença de Crohn/complicações , Doença de Crohn/tratamento farmacológico , Doença de Crohn/cirurgia , Ustekinumab/uso terapêutico , Resultado do Tratamento , Terapia Biológica , Necrose , Estudos Retrospectivos , Fístula Retal/etiologia , Fístula Retal/terapiaRESUMO
INTRODUCTION: COVID-19 has altered the usual practice of medicine and the state of emergency declared in Spain on March 14th has considerably changed the activity of inflammatory bowel disease (IBD) units. The aim of this study was to evaluate the consequences of COVID-19 on the IBD Unit's activity and provide information on restructuring with available resources. METHODS: an observational study was performed in a referral hospital in Madrid (Spain). Type of appointment, loss of follow-up, hospital admission, treatment changes, endoscopic activity, surgeries and blood tests were evaluated between March 15th and May 15th, 2020. This data was compared with the usual activity a year before. RESULTS: among the 510 patients included, 476 (93.33 %) received had a remote consultation, representing an increase of 92.38 % compared with the previous year (0.95 %). There was a loss of follow-up in 26 patients (5.1 %) vs 15 (3.58 %) the previous year. A total of 60 (35.09 %) blood tests, 64 (76.19 %) endoscopies and all scheduled surgeries were suspended. Besides, 484 (94.9 %) patients remained adherent vs 417/419 (99.5 %) in the pre-pandemic period and 48 (9.41 %) reported symptoms of an IBD flare. Thirty-nine (7.6 %) patients developed symptoms suggestive of COVID-19. CONCLUSION: a large number of tests and on-site outpatient visit consultations were suspended. However, a rapid adaptation to telemedicine allowed these patients to be closely followed up. Although it was possible to maintain therapeutic compliance, with a loss to follow-up slightly higher than the previous year, suspensions and delays of tests could have significant negative consequences in the long term.
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COVID-19 , Doenças Inflamatórias Intestinais/terapia , Adulto , COVID-19/epidemiologia , Atenção à Saúde , Feminino , Unidades Hospitalares , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Espanha/epidemiologiaRESUMO
BACKGROUND: Thiopurines are classically used in Crohn's disease (CD). Treatment fails in a proportion of patients either due to adverse events (AE) or lack of efficacy. Increasing use of anti-TNFα biologic drugs may have had impact on thiopurines usage. AIM: To evaluate the evolving use of azathioprine (AZA) monotherapy in the era of biologics. METHODS: The study retrospectively analyzed clinical records of all CD patients who started treatment with AZA monotherapy at our center since 1990. Dates of starting AZA and treatment failure (TF) were collected. We defined AZA TF if it was withdrawn due to lack of efficacy or AE, or biologics were added. RESULTS: A total of 383 patients were included: 46.5% were males and mean age was 31 (range 17-84) years. Median follow-up was 43 (range 0.2-289) months. Overall, 147 patients (38%) experienced TF. Median cumulative survival time of AZA was 126 (95% CI 105-147) months. Proportion of patients with AZA TF increased along time: 7 patients in 1990-1995 (4.7% of all TF); 8 in 1996-2000 (5.4%); 22 in 2001-2005(15%); 41 in 2006-2010 (28%); 69 in 2011-2014 (47%) (p = 0.04). 7%, 21%, 4%, 45%, and 33.3% of patients moved to biologics in each period, respectively (χ2 = 13.07; p < 0.05). Seventy-four patients (18.4%) stopped AZA due to AE, and 73(19%) due to lack of efficacy. Regarding AZA indication, prevention of postoperative recurrence obtained better results than steroid dependency (p = 0.001); perianal fistulizing CD predicted poorer outcomes (p = 0.002). CONCLUSION: An important proportion of CD patients under AZA monotherapy experienced TF in our experience. Although AZA monotherapy remains useful for CD in the era of biologics, current clinical practice is shifting to anti-TNFα biologic drugs in an increasing proportion of patients.
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Azatioprina/uso terapêutico , Doença de Crohn/tratamento farmacológico , Fármacos Gastrointestinais/uso terapêutico , Imunossupressores/uso terapêutico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Azatioprina/efeitos adversos , Produtos Biológicos/uso terapêutico , Doença de Crohn/diagnóstico , Doença de Crohn/imunologia , Feminino , Fármacos Gastrointestinais/efeitos adversos , Humanos , Imunossupressores/efeitos adversos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Espanha , Fatores de Tempo , Falha de Tratamento , Adulto JovemRESUMO
Malignant bile duct obstruction is a common entity in clinical practice and is infrequently caused by non-biliopancreatic neoplasms. We report the case of a male admitted with malignant obstruction of the biliary tract, showing after numerous studies that this obstruction was the initial presentation of a stage IV adenocarcinoma of the lung. Pulmonary neoplasms have variable behaviors being often spread at time of diagnosis, especially in the more aggressive subtypes. However, it is uncommon its manifestation as obstructive jaundice and when this happens it is usually due to liver damage and not to metastases to periampullary region that are extremely infrequent. In this case, the role of pathological anatomy and immunohistochemistry was essential in identifying the origin of the tumor and starting targeted treatment, since the clinical presentation and usual laboratory and image tests did not allow to differentiate it from a primary cholangiocarcinoma.
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Adenocarcinoma/complicações , Icterícia Obstrutiva/etiologia , Neoplasias Pulmonares/complicações , Adenocarcinoma/diagnóstico por imagem , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma de Pulmão , Colangiopancreatografia Retrógrada Endoscópica , Diagnóstico Precoce , Humanos , Icterícia Obstrutiva/diagnóstico por imagem , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Tomografia Computadorizada por Raios XRESUMO
Chronic complications of acute appendicitis managed in a conservative manner are not frequent. We present a case of acute lower gastrointestinal hemorrhage in a young patient with a previous acute appendicitis without surgical intervention. The colonoscopy detected an appendicular bleeding which was surgically treated. The anatomopathological diagnosis was granulomatous appendicitis. The clinical evolution of the patient was favorable without bleeding recurrence. Appendicular hemorrhage can be an unusual complication-however potentially severe-of acute appendicitis not treated surgically.
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Apendicite/complicações , Hemorragia Gastrointestinal/etiologia , Angiografia , Apendicectomia , Apendicite/diagnóstico por imagem , Apendicite/patologia , Apêndice/diagnóstico por imagem , Apêndice/patologia , Colonoscopia , Hemorragia Gastrointestinal/diagnóstico por imagem , Hemorragia Gastrointestinal/patologia , Humanos , Masculino , Tomografia Computadorizada por Raios X , Adulto JovemRESUMO
INTRODUCTION: The possibility of developing idiopathic portal hypertension has been described with thiopurine treatment despite compromises the prognosis of these patients, the fact its true prevalence is unknown. MATERIAL AND METHODS: A cross-sectional study was conducted in a cohort of inflammatory bowel disease (IBD) patients followed at our unit, to determine the prevalence of diagnosis of idiopathic portal hypertension (IPH) and its relationship with thiopurine treatment. RESULTS: At the time of the analysis, 927/1,419 patients were under treatment with thiopurine drugs (65%). A total of 4 patients with IBD type Crohn's disease with idiopathic portal hypertension probably related to the thiopurine treatment were identified (incidence of 4.3 cases per 1,000). Seventy-five percent of patients started with signs or symptoms of portal hypertension. Only one patient was asymptomatic but the diagnosis of IPH because of isolated thrombocytopenia is suspected. However, note that all patients had thrombocytopenia previously. Abdominal ultrasound with fibroscan, hepatic vein catheterization and liver biopsy were performed on all of them as part of the etiology of portal hypertension. In the abdominal ultrasound, indirect portal hypertension data were observed in all patients (as splenomegaly) cirrhosis was also ruled out. The fibroscan data showed significant liver fibrosis (F2-F3). CONCLUSION: Idiopathic portal hypertension following thiopurine treatment in IBD patients is a rare occurrence, but it must be borne in mind in the differential diagnosis for early diagnosis, especially in patients undergoing thiopurine treatment over a long period. The presence of thrombocytopenia is often the only predictor of its development in the preclinical stage.
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Hipertensão Portal/induzido quimicamente , Imunossupressores/efeitos adversos , Doenças Inflamatórias Intestinais/tratamento farmacológico , Cirrose Hepática/induzido quimicamente , Mercaptopurina/efeitos adversos , Pancitopenia/induzido quimicamente , Esplenomegalia/induzido quimicamente , Adulto , Idoso , Azatioprina/efeitos adversos , Azatioprina/uso terapêutico , Estudos Transversais , Feminino , Humanos , Hipertensão Portal/diagnóstico , Hipertensão Portal/epidemiologia , Imunossupressores/uso terapêutico , Cirrose Hepática/diagnóstico , Cirrose Hepática/epidemiologia , Masculino , Mercaptopurina/uso terapêutico , Pessoa de Meia-Idade , Pancitopenia/diagnóstico , Pancitopenia/epidemiologia , Esplenomegalia/diagnóstico , Esplenomegalia/epidemiologia , Resultado do Tratamento , Hipertensão Portal não Cirrótica IdiopáticaRESUMO
BACKGROUND: Despite the growing incidence of Clostridium difficile diarrhea (CCD) in patients with inflammatory bowel disease (IBD), little is known about the associated risk factors. METHOD: A retrospective study comparing cases of CCD in patients with IBD to IBD carriers who did not develop CCD. A comparison was also made with patients who developed CCD but did not suffer IBD. RESULTS: Three cases (20%) with IBD and CCD had received antibiotics during the previous three months versus none of the controls (IBD without CCD, p = 0.22). Ten cases (67%) received treatment with proton pump inhibitors (PPIs) versus 2 (13%) in the control group (IBD without CCD, p = 0.001). Seven cases underwent colonoscopy and pseudomembranes were seen in one (14%). Fourteen (93%) patients demonstrated a favourable response to metronidazole. Patients with IBD and CCD presented with younger age (36 ± 10 years), a higher degree of community-acquired infection (13 patients, 87%), immunosuppressive treatment (7 patients, 47%) and less patients had received previous antibiotic treatment (3 patients, 20%) than those with CCD without IBD. The proportion of patients who received treatment with PPIs was similar (66% and 80%, respectively p = 0.266). CONCLUSIONS: CCD in IBD carriers affects younger patients, the majority are community acquired (less nosocomial) and it is more related to previous treatment with PPIs than with the antibiotic treatment. Clinical evolution is also favourable.
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Clostridioides difficile , Diarreia/microbiologia , Enterocolite Pseudomembranosa/microbiologia , Doenças Inflamatórias Intestinais/microbiologia , Adulto , Fatores Etários , Infecções Comunitárias Adquiridas , Infecção Hospitalar , Diarreia/tratamento farmacológico , Diarreia/etiologia , Enterocolite Pseudomembranosa/complicações , Enterocolite Pseudomembranosa/tratamento farmacológico , Feminino , Humanos , Doenças Inflamatórias Intestinais/complicações , Doenças Inflamatórias Intestinais/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Inibidores da Bomba de Prótons/uso terapêutico , Fatores de RiscoRESUMO
Background: Loss of response to anti-tumor necrosis factor drugs in patients with inflammatory bowel disease (IBD) is frequent and, in case of low drug levels, treatment intensification is recommended. In addition, in cases in which clinical response without attainment of remission (clinical, endoscopic, or radiological), intensification could be justified since higher drug levels are associated with better outcomes. For adalimumab (ADA), the standard intensification regimen is 40 mg every week (ew). Availability of ADA 80 mg prefilled pens has enabled every other week (eow) intensification. We assessed the clinical efficacy of intensification with ADA 80 mg eow. Methods: This retrospective study was conducted at a tertiary hospital in Spain. Patients with IBD receiving maintenance ADA 80 mg eow with clinical, biomarker, and drug-level assessments were included. Demographics and clinical, biological, and endoscopic evaluation of the disease before and after ADA intensification, and pharmacokinetic assessments, were collected. Results: Eighty-seven patients (72 Crohn's disease, 15 ulcerative colitis; average age 50 years) were included. Reasons for ADA intensification were: low ADA levels-<5 µg mL-1-(17%), low ADA levels-<5 µg mL-1-without clinical response (63%), clinical response without clinical remission (15%) and active disease on objective evaluation (including colonoscopy, magnetic resonance imaging, capsule endoscopy, and/or intestinal ultrasound; 5%). Following treatment intensification to ADA 80 mg eow, 75 patients (86%) were in clinical remission and 69 (79.3%) were in biologic remission (clinical remission and normalization of biomarkers). After a median follow-up of 19 months (interquartile range 13-25), 63 patients (72%) remained on treatment and in clinical remission. There were no serious infections, hospitalizations, or deaths. Drug costs did not increase with the 80 mg eow regimen versus a standard intensification regimen. Conclusions: ADA intensification to 80 mg eow was safe, effective, and did not increase drug costs versus standard intensification to 40 mg ew in our experience.
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BACKGROUND: Thromboembolic events are frequent among patients with inflammatory bowel disease (IBD). However, there is little information on the prevalence, features and outcomes of splanchnic vein thrombosis (SVT) in patients with IBD. AIMS: To describe the clinical features and outcomes of SVT in patients with IBD and to perform a systematic review of these data with published cases and series. METHODS: A retrospective observational study from the Spanish nationwide ENEIDA registry was performed. A systematic search of the literature was performed to identify studies with at least one case of SVT in IBD patients. RESULTS: A new cohort of 49 episodes of SVT from the Eneida registry and 318 IBD patients with IBD identified from the literature review (sixty studies: two multicentre, six single-centre and fifty-two case reports or case series) were analysed. There was a mild predominance of Crohn's disease and the most frequent clinical presentation was abdominal pain with or without fever followed by the incidental finding in cross-sectional imaging techniques. The most frequent SVT location was the main portal trunk in two-thirds of the cases, followed by the superior mesenteric vein. Anticoagulation therapy was prescribed in almost 90% of the cases, with a high rate of radiologic resolution of SVT. Thrombophilic conditions other than IBD itself were found in at least one-fifth of patients. CONCLUSIONS: SVT seems to be a rare (or underdiagnosed) complication in IBD patients. SVT is mostly associated with disease activity and evolves suitably when anticoagulation therapy is started.
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BACKGROUND AIMS: Current therapeutic goals in ulcerative colitis (UC) include clinical and endoscopic remission, named mucosal healing (MH). Despite MH, a proportion of patients suffer a clinical relapse, which has been related to histological inflammation. We aimed to identify which histopathological features or histopathological index cut-off was associated with endoscopic relapse (ER) in UC patients with MH. METHODS: Retrospective analysis of UC patients who underwent surveillance colonoscopy showing complete MH (endoscopic Mayo subscore=0) with random biopsies, and at least one more endoscopy along the follow-up. After a consensus meeting, expert pathologist performed histological assessment according to Simplified Geboes Score (SGS), Nancy Index (NI) and Robarts Histopathological Index (RHI). Other histopathological features were also evaluated. Patients were followed until ER or last endoscopy performed showing persistence of MH. RESULTS: A total of 95 patients (150 colonoscopies) were included. After mean follow-up of 31.2 months (SD 21.7), 33 patients (34.7%) suffered ER. Neutrophils in lamina propria (OR 2.6; P = 0.037), within the epithelium (OR 2.6; P = 0.03), SGS ≥3.1 (OR 2.6; P = 0.037), NI ≥2 (OR 2.6; P = 0.03) and RHI ≥5 (OR 2.6; P = 0.037) were associated with ER in univariate analysis. In multivariate analysis, eosinophils in the lamina propria (HR 2.5; P = 0.01) and clinical remission<12 months (HR 3.2; P = 0.002) were associated with ER. CONCLUSIONS: Histopathological findings in UC patients who have achieved endoscopic MH may predict ER. Standardized histopathology reports according to the presence of neutrophils, eosinophils or to defined cut-off of validated histopathologic indexes may represent a useful tool to predict ER and should be considered at therapeutic and surveillance decision process.
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Colite Ulcerativa , Colite Ulcerativa/tratamento farmacológico , Colonoscopia , Humanos , Mucosa Intestinal/diagnóstico por imagem , Mucosa Intestinal/patologia , Mucosa/patologia , Recidiva , Indução de Remissão , Estudos Retrospectivos , Índice de Gravidade de DoençaRESUMO
BACKGROUND: The impact of biologics on the risk of postoperative complications (PC) in inflammatory bowel disease (IBD) is still an ongoing debate. This lack of evidence is more relevant for ustekinumab and vedolizumab. AIMS: To evaluate the impact of biologics on the risk of PC. METHODS: A retrospective study was performed in 37 centres. Patients treated with biologics within 12 weeks before surgery were considered "exposed". The impact of the exposure on the risk of 30-day PC and the risk of infections was assessed by logistic regression and propensity score-matched analysis. RESULTS: A total of 1535 surgeries were performed on 1370 patients. Of them, 711 surgeries were conducted in the exposed cohort (584 anti-TNF, 58 vedolizumab and 69 ustekinumab). In the multivariate analysis, male gender (OR: 1.5; 95% CI: 1.2-2.0), urgent surgery (OR: 1.6; 95% CI: 1.2-2.2), laparotomy approach (OR: 1.5; 95% CI: 1.1-1.9) and severe anaemia (OR: 1.8; 95% CI: 1.3-2.6) had higher risk of PC, while academic hospitals had significantly lower risk. Exposure to biologics (either anti-TNF, vedolizumab or ustekinumab) did not increase the risk of PC (OR: 1.2; 95% CI: 0.97-1.58), although it could be a risk factor for postoperative infections (OR 1.5; 95% CI: 1.03-2.27). CONCLUSIONS: Preoperative administration of biologics does not seem to be a risk factor for overall PC, although it may be so for postoperative infections.
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Encefalopatia Hepática/etiologia , Veias Mesentéricas/anormalidades , Fístula Vascular/diagnóstico por imagem , Veia Cava Inferior/anormalidades , Idoso , Feminino , Encefalopatia Hepática/diagnóstico , Humanos , Veias Mesentéricas/diagnóstico por imagem , Fístula Vascular/complicações , Veia Cava Inferior/diagnóstico por imagemRESUMO
INTRODUCTION: Early stages of Crohn's disease [CD] are predominantly inflammatory and early treatment could be useful to change the natural history of CD. We aimed to evaluate the impact of early treatment in our cohort of CD patients. METHODS: We retrospectively reviewed clinical records of all CD patients at our centre who have received immunomodulators. Time from diagnosis to first CD-related major abdominal surgery or end of follow-up was considered. Dates of diagnosis, of starting immunomodulators (thiopurines / anti-tumour necrosis factor [TNF]), and of the first CD-related surgery when appropriate were collected. RESULTS: Of 422 patients who received thiopurines, 189 operated patients started thiopurines after a median of 117 months (interquartile range [IQR] 44-196) since diagnosis; non-operated patients, after a median of 30 months [IQR 6-128], p < 0,005. Odds ratio [OR] for surgery was 1.006 (95% confidence interval [CI]1.004-1008) for each month of delay in starting thiopurines. Among 272 patients who received anti-TNFs, 137 operated patients started anti-TNFs after a median of 166 months [IQR 90-233] since diagnosis; non-operated patients after a median of 59 months [IQR 14-162]; p < 0,005. OR for surgery was 1.008 [95% CI 1.005-1.010] for each month of delay in starting anti-TNFs. Among 467 patients who received thiopurines and/or anti-TNF, 210 operated patients started any immunomodulator after a median of 120 months [IQR 48-197] since diagnosis and non-operated patients after a median of 30 months [IQR 6-126], p < 0,005. OR for surgery was 1.008 [95% CI 1.005-1.010] for each month of delay in starting immunomodulators. CONCLUSIONS: In our experience, time between diagnosis and thiopurine or anti-TNF initiation was associated with the risk of major abdominal surgery in Crohn's disease.