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In inflammatory bowel diseases (IBDs), such as Crohn's disease (CD) and ulcerative colitis (UC), the immune system relentlessly attacks intestinal cells, causing recurrent tissue damage over the lifetime of patients. The etiology of IBD is complex and multifactorial, involving environmental, microbiota, genetic, and immunological factors that alter the molecular basis of the organism. Among these, the microbiota and immune cells play pivotal roles; the microbiota generates antigens recognized by immune cells and antibodies, while autoantibodies target and attack the intestinal membrane, exacerbating inflammation and tissue damage. Given the altered molecular framework, the analysis of multiple molecular biomarkers in patients proves exceedingly valuable for diagnosing and prognosing IBD, including markers like C reactive protein and fecal calprotectin. Upon detection and classification of patients, specific treatments are administered, ranging from conventional drugs to new biological therapies, such as antibodies to neutralize inflammatory molecules like tumor necrosis factor (TNF) and integrin. This review delves into the molecular basis and targets, biomarkers, treatment options, monitoring techniques, and, ultimately, current challenges in IBD management.
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Biomarcadores , Doenças Inflamatórias Intestinais , Humanos , Doenças Inflamatórias Intestinais/diagnóstico , Doenças Inflamatórias Intestinais/metabolismo , Doenças Inflamatórias Intestinais/terapia , Doenças Inflamatórias Intestinais/imunologia , AnimaisRESUMO
We present the clinical case of a 56-year-old former smoker female, with a family history of maternal ulcerative colitis and personal history of ankylosing spondylitis treated with Ixekizumab for 3 months, who was admitted for fever, left iliac fossa pain and diarrhea without pathological products of 2 weeks of evolution. Abdominopelvic computed tomography scan identified pancolitis. Complete colonoscopy revealed continuous involvement of the proximal colon (right and transverse colon presented deep ulcerations and mucosal friability) with preservation of the terminal ileum. After many complementary tests and according to the clinical context, the diagnosis of extensive colitis associated with IL-17 inhibitor was established.
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INTRODUCTION: The objective of this study was to assess the durability, short-term and long-term effectiveness, and safety of tofacitinib in ulcerative colitis (UC) in clinical practice. METHODS: This is a retrospective multicenter study including patients with UC who had received the first tofacitinib dose at least 8 weeks before the inclusion. Clinical effectiveness was based on partial Mayo score. RESULTS: A total of 408 patients were included. Of them, 184 (45%) withdrew tofacitinib during follow-up (mean = 18 months). The probability of maintaining tofacitinib was 67% at 6 m, 58% at 12 m, and 49% at 24 m. The main reason for tofacitinib withdrawal was primary nonresponse (44%). Older age at the start of tofacitinib and a higher severity of clinical activity were associated with tofacitinib withdrawal. The proportion of patients in remission was 38% at week 4, 45% at week 8, and 47% at week 16. Having moderate-to-severe vs mild disease activity at baseline and older age at tofacitinib start were associated with a lower and higher likelihood of remission at week 8, respectively. Of 171 patients in remission at week 8, 83 (49%) relapsed. The probability of maintaining response was 66% at 6 m and 54% at 12 m. There were 93 adverse events related to tofacitinib treatment (including 2 pulmonary thromboembolisms [in patients with risk factors] and 2 peripheral vascular thrombosis), and 29 led to tofacitinib discontinuation. DISCUSSION: Tofacitinib is effective in both short-term and long-term in patients with UC. The safety profile is similar to that previously reported.
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Colite Ulcerativa , Humanos , Colite Ulcerativa/tratamento farmacológico , Resultado do Tratamento , Indução de Remissão , Estudos RetrospectivosRESUMO
Toxic megacolon is most commonly considered as a complication of inflammatory bowel disease, especially ulcerative colitis and colonic Crohn's disease to a lesser extent. It appears in the context of moderate-to-severe disease and often requires colectomy. Currently, after an inadequate response to conventional therapy with systemic corticosteroids, the use of cyclosporine or infliximab is considered as an alternative option, prior to surgical intervention. We present a case report of toxic megacolon in a patient with a severe refractory colonic Crohn's disease, where anti-tumor necrosis factor (anti-TNF) therapies were contraindicated. Consequently, we decided to use ustekinumab as a rescue therapy, despite insufficient evidence to provide recommendations for this indication.
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Colite Ulcerativa , Doença de Crohn , Megacolo Tóxico , Doença de Crohn/complicações , Doença de Crohn/tratamento farmacológico , Humanos , Infliximab , Megacolo Tóxico/tratamento farmacológico , Megacolo Tóxico/etiologia , Megacolo Tóxico/cirurgia , Inibidores do Fator de Necrose Tumoral , Ustekinumab/uso terapêuticoRESUMO
INTRODUCTION: Infliximab (IFX) is effective in treating ulcerative colitis (UC) and in achieving mucosal healing (MH). Little is known about the role of mucosal healing (MH) in the subsequent evolution of the disease and the consequences of discontinuing treatment. AIMS: To evaluate the characteristics and evolution of patients with UC treated with IFX who discontinued treatment after disease remission. METHODS: Observational, prospective study of patients with moderate to severe UC, corticosteroid-resistant/corticosteroid-dependent, naïve to anti-TNF. IFX administration regimen: 5 mg/kg at 0-2-6 weeks and every 8 weeks thereafter until week 54. In patients achieving MH, IFX was discontinued and the patients were followed-up for at least 20 months. Clinical remission (CR): mayo score <2; Clinical response: decrease in mayo score of 3 points; MH: mayo score 0-1; Deep remission: patient with CR and MH. RESULTS: Of the 21 patients enrolled, 19 completed the study (colectomy, n = 1; non-responder, n = 1). Mean age: 47.8 years. UC: severe (n = 13) and moderate (n = 6); most patients (n = 11) were steroid-resistant; 57.8% received combined treatment with immunosuppressants, and 31.5% intensified treatment. Week 54: 16 patients (84.2%) showed clinical response, 13 (68.4%) showed CR, and 12 (63.2%) deep remission. Of these, 6 (25%) presented a new episode of UC, and in 3 (25%) IFX was restarted within 12 weeks of discontinuation, with all patients responding. Of the total sample, 91.7% remained IFX-free at week 8, and 75% at week 12, with no remission during follow-up. None of the patients required hospitalization or surgery. CONCLUSIONS: Half of patients with deep remission of UC with IFX therapy presented a new episode after treatment discontinuation, and in 25% IFX therapy was restarted.
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Terapia Biológica , Colite Ulcerativa/tratamento farmacológico , Infliximab/uso terapêutico , Corticosteroides/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Colite Ulcerativa/fisiopatologia , Resistência a Medicamentos , Feminino , Seguimentos , Humanos , Imunossupressores/uso terapêutico , Infliximab/administração & dosagem , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Recidiva , Indução de Remissão , Índice de Gravidade de Doença , Suspensão de TratamentoRESUMO
Markers that allow for the selection of tailored treatments for individual patients with inflammatory bowel diseases (IBD) are yet to be identified. Our aim was to describe trends in real-life treatment usage. For this purpose, patients from the ENEIDA registry who received their first targeted IBD treatment (biologics or tofacitinib) between 2015 and 2021 were included. A subsequent analysis with Machine Learning models was performed. The study included 10,009 patients [71% with Crohn's disease (CD) and 29% with ulcerative colitis (UC)]. In CD, anti-TNF (predominantly adalimumab) were the main agents in the 1st line of treatment (LoT), although their use declined over time. In UC, anti-TNF (mainly infliximab) use was predominant in 1st LoT, remaining stable over time. Ustekinumab and vedolizumab were the most prescribed drugs in 2nd and 3rd LoT in CD and UC, respectively. Overall, the use of biosimilars increased over time. Machine Learning failed to identify a model capable of predicting treatment patterns. In conclusion, drug positioning is different in CD and UC. Anti-TNF were the most used drugs in IBD 1st LoT, being adalimumab predominant in CD and infliximab in UC. Ustekinumab and vedolizumab have gained importance in CD and UC, respectively. The approval of biosimilars had a significant impact on treatment.
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Imunodeficiência de Variável Comum/complicações , Infecções por Citomegalovirus/complicações , Fármacos Gastrointestinais/uso terapêutico , Infliximab/uso terapêutico , Enteropatias/tratamento farmacológico , Enteropatias/etiologia , Adulto , Feminino , Humanos , Índice de Gravidade de DoençaRESUMO
BACKGROUND: Previous studies comparing immigrant ethnic groups and native patients with IBD have yielded clinical and phenotypic differences. To date, no study has focused on the immigrant IBD population in Spain. METHODS: Prospective, observational, multicenter study comparing cohorts of IBD patients from ENEIDA-registry who were born outside Spain with a cohort of native patients. RESULTS: We included 13,524 patients (1,864 immigrant and 11,660 native). The immigrants were younger (45 ± 12 vs. 54 ± 16 years, p < 0.001), had been diagnosed younger (31 ± 12 vs. 36 ± 15 years, p < 0.001), and had a shorter disease duration (14 ± 7 vs. 18 ± 8 years, p < 0.001) than native patients. Family history of IBD (9 vs. 14%, p < 0.001) and smoking (30 vs. 40%, p < 0.001) were more frequent among native patients. The most prevalent ethnic groups among immigrants were Caucasian (41.5%), followed by Latin American (30.8%), Arab (18.3%), and Asian (6.7%). Extraintestinal manifestations, mainly musculoskeletal affections, were more frequent in immigrants (19 vs. 11%, p < 0.001). Use of biologics, mainly anti-TNF, was greater in immigrants (36 vs. 29%, p < 0.001). The risk of having extraintestinal manifestations [OR: 2.23 (1.92-2.58, p < 0.001)] and using biologics [OR: 1.13 (1.0-1.26, p = 0.042)] was independently associated with immigrant status in the multivariate analyses. CONCLUSIONS: Compared with native-born patients, first-generation-immigrant IBD patients in Spain were younger at disease onset and showed an increased risk of having extraintestinal manifestations and using biologics. Our study suggests a featured phenotype of immigrant IBD patients in Spain, and constitutes a new landmark in the epidemiological characterization of immigrant IBD populations in Southern Europe.
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Falso Aneurisma/diagnóstico por imagem , Colecistite/complicações , Duodenopatias/etiologia , Vesícula Biliar/irrigação sanguínea , Hemorragia Gastrointestinal/etiologia , Xantomatose/complicações , Idoso , Falso Aneurisma/complicações , Artérias/diagnóstico por imagem , Duodenopatias/diagnóstico por imagem , Vesícula Biliar/diagnóstico por imagem , Hemorragia Gastrointestinal/diagnóstico por imagem , Gastroscopia , Humanos , Imageamento por Ressonância Magnética , Masculino , Tomografia Computadorizada MultidetectoresRESUMO
BACKGROUND AND AIMS: Primary sclerosing cholangitis [PSC] is usually associated with inflammatory bowel disease [IBD]. An increased risk of malignancies, mainly colorectal cancer [CRC] and cholangiocarcinoma [CCA], has been reported in PSC-IBD patients. Our aim was to determine the clinical characteristics and management of PSC in IBD patients, and the factors associated with malignancies. METHODS: PSC-IBD patients were identified from the Spanish ENEIDA registry of GETECCU. Additional data were collected using the AEG-REDCap electronic data capture tool. RESULTS: In total, 277 PSC-IBD patients were included, with an incidence rate of 61 PSC cases per 100 000 IBD patient-years, 69.7% men, 67.5% ulcerative colitis and mean age at PSC diagnosis of 40 ± 16 years. Most patients [85.2%] were treated with ursodeoxycholic acid. Liver transplantation was required in 35 patients [12.6%] after 79 months (interquartile range [IQR] 50-139). It was more common in intra- and extrahepatic PSC compared with small-duct PSC (16.3% vs 3.3%; odds ratio [OR] 5.7: 95% confidence interval [CI] = 1.7-19.3). The incidence rate of CRC since PSC diagnosis was 3.3 cases per 1000 patient-years [95% CI = 1.9-5.6]. Having symptoms of PSC at PSC diagnosis was the only factor related to an increased risk of CRC after IBD diagnosis [hazard ratio= 3.3: 95% CI = 1.1-9.9]. CCA was detected in seven patients [2.5%] with intra- and extrahepatic PSC, with median age of 42 years [IQR 39-53], and presented a lower life expectancy compared with patients without CCA and patients with or without CRC. CONCLUSIONS: PSC-IBD patients with symptoms of PSC at PSC diagnosis have an increased risk of CRC. CCA was only diagnosed in patients with intra- and extrahepatic PSC and was associated with poor survival.
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Colangiocarcinoma , Colangite Esclerosante , Neoplasias Colorretais , Doenças Inflamatórias Intestinais , Adulto , Ductos Biliares Extra-Hepáticos/patologia , Ductos Biliares Intra-Hepáticos/patologia , Colangiocarcinoma/diagnóstico , Colangiocarcinoma/mortalidade , Colangite Esclerosante/diagnóstico , Colangite Esclerosante/epidemiologia , Colangite Esclerosante/fisiopatologia , Colangite Esclerosante/terapia , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/mortalidade , Feminino , Humanos , Doenças Inflamatórias Intestinais/diagnóstico , Doenças Inflamatórias Intestinais/epidemiologia , Doenças Inflamatórias Intestinais/fisiopatologia , Doenças Inflamatórias Intestinais/terapia , Masculino , Pessoa de Meia-Idade , Administração dos Cuidados ao Paciente/métodos , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Espanha/epidemiologia , Análise de SobrevidaAssuntos
Anticorpos Monoclonais Humanizados/efeitos adversos , Doença de Crohn/tratamento farmacológico , Imunossupressores/efeitos adversos , Vasculite Leucocitoclástica Cutânea/induzido quimicamente , Adalimumab , Corticosteroides/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Quimioterapia Combinada , Feminino , Humanos , Imunossupressores/uso terapêutico , Mercaptopurina/uso terapêutico , Metotrexato/uso terapêutico , Pessoa de Meia-Idade , Púrpura/induzido quimicamente , Fator de Necrose Tumoral alfa/antagonistas & inibidoresRESUMO
BACKGROUND: Adalimumab is the second tumour necrosis factor antagonist (anti-TNF) adopted for the treatment of ulcerative colitis. Clinical data from naïve patients are scarce. AIM: Examine the response to adalimumab in TNF-antagonist-naïve patients. METHODS: This multicentre, observational, prospective study was conducted using a cohort of consecutive patients with ulcerative colitis. Clinical remission, mucosal healing and deep remission were examined employing the Mayo Score and Mayo Endoscopic Score. Clinical response was assessed using the Partial Mayo Score. RESULTS: Of 53 individuals included in this study, 49.1% of patients were in clinical remission at week 8 and 60.3%, at week 52. Clinical response was observed in 84.9% and 69.8%, respectively. Mucosal healing was found in 62.3% and 67.9% of the patients, and 43.4% and 58.4% showed deep remission at week 8 and 52, respectively. After a year, 71.7% of the patients continued the adalimumab treatment. Adverse effects were observed in 28.3% of patients. Multivariate analysis showed that the long-term factor predictive of response at week 52 was the response in week 8 (expressed as Mayo Score; OR 0.66; 95% IC 0.1-0.67, pâ¯<â¯0.006). CONCLUSIONS: Adalimumab treatment of ulcerative colitis is effective; the results are better in clinical practice and in patients naïve to anti-TNF.