RESUMO
BACKGROUND AND AIMS: Inflammatory bowel disease (IBD) is a prevalent chronic noncurable disease associated with profound metabolic changes. The discovery of novel molecular indicators for unraveling IBD etiopathogenesis and the diagnosis and prognosis of IBD is therefore pivotal. We sought to determine the distinctive metabolic signatures from the different IBD subgroups before treatment initiation. METHODS: Serum and urine samples from newly diagnosed treatment-naïve IBD patients and age and sex-matched healthy control (HC) individuals were investigated using proton nuclear magnetic resonance spectroscopy. Metabolic differences were identified based on univariate and multivariate statistical analyses. RESULTS: A total of 137 Crohn's disease patients, 202 ulcerative colitis patients, and 338 HC individuals were included. In the IBD cohort, several distinguishable metabolites were detected within each subgroup comparison. Most of the differences revealed alterations in energy and amino acid metabolism in IBD patients, with an increased demand of the body for energy mainly through the ketone bodies. As compared with HC individuals, differences in metabolites were more marked and numerous in Crohn's disease than in ulcerative colitis patients, and in serum than in urine. In addition, clustering analysis revealed 3 distinct patient profiles with notable differences among them based on the analysis of their clinical, anthropometric, and metabolomic variables. However, relevant phenotypical differences were not found among these 3 clusters. CONCLUSIONS: This study highlights the molecular alterations present within the different subgroups of newly diagnosed treatment-naïve IBD patients. The metabolomic profile of these patients may provide further understanding of pathogenic mechanisms of IBD subgroups. Serum metabotype seemed to be especially sensitive to the onset of IBD.
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Colite Ulcerativa , Doença de Crohn , Doenças Inflamatórias Intestinais , Humanos , Colite Ulcerativa/diagnóstico , Doença de Crohn/diagnóstico , Metabolômica , IntestinosRESUMO
OBJECTIVE: To study the serological response (SR) and tolerability of COVID-19 vaccine in patients with inflammatory bowel disease (IBD) and its relation with IBD treatment and type of vaccine. METHODS: Observational, cross-sectional study in patients with IBD vaccinated against COVID-19 without known previous infection. SR was analyzed by the determination of IgG antibodies against the S1 subunit. Safety was studied using a questionnaire to identify adverse effects (AE). RESULTS: 280 patients with IBD were included. Type of vaccines: Comirnaty® 68.8%; Spikevax® 10.8%, Vaxzevria® 18.3%, Ad26.COV2-S® 2.2%. 51.3% had AE, being 100% mild. 65% developed IgG antibodies after vaccination. The SR was higher for vaccines with mRNA technology (100% Spikevax®, 68.5% Comirnaty®) compared to those based on adenovirus vector (38.0% Vaxzevria®, 33.3% Ad26.COV2-S®) (P<.001). In the multivariate analysis, SR was related to age (<60 years; OR: 3.8, 95% CI 1.9-7.0; P<.001). The SR in patients with aminosalicylates was 65.4%, 61.4% with immunosuppressants, 65.8% with anti-TNF, and 68.7% with non-anti-TNF biologicals (P=.9). CONCLUSIONS: One third of patients with IBD did not develop antibodies with the initial vaccination against SARS-CoV-2. The SR to vaccines based on mRNA technology was higher, and it was related to age (higher in younger patients). Immunosuppressants and biologicals did not decrease SR. More than half of the patients presented AD, being mild in all cases.
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Vacinas contra COVID-19 , COVID-19 , Doenças Inflamatórias Intestinais , Vacinas , Humanos , Pessoa de Meia-Idade , Vacina de mRNA-1273 contra 2019-nCoV , Anticorpos Antivirais , Vacina BNT162 , ChAdOx1 nCoV-19 , COVID-19/prevenção & controle , Vacinas contra COVID-19/efeitos adversos , Estudos Transversais , Imunoglobulina G , Imunossupressores , Doenças Inflamatórias Intestinais/tratamento farmacológico , RNA Mensageiro , SARS-CoV-2 , VacinaçãoRESUMO
BACKGROUND: Optimal golimumab concentration thresholds for important outcomes during maintenance are lacking. AIMS: To investigate the association of golimumab trough concentrations during maintenance with key outcomes, including endoscopic and histologic remission, and long-term event-free persistence with golimumab, in patients with UC. METHODS: This multi-centre, cross-sectional study included patients with UC on golimumab maintenance recruited either in remission or during a flare. Colonoscopy was scheduled, and study-specific rectocolonic biopsies were taken for blind central histologic reading. Samples for golimumab trough concentrations were collected close to colonoscopy. RESULTS: Fifty-two patients were included. Median golimumab trough concentrations (µg/ml) were significantly higher in patients who had clinical remission (2.01 vs. 0.72, p = 0.047), combined clinical-biochemical remission (PMS ≤2 + faecal calprotectin <250 µg/g) (2.21 vs. 1.47, p = 0.041), endoscopic healing (Mayo endoscopic subscore 0) (2.52 vs. 1.47, p = 0.003), histologic remission (Geboes index ≤2.0) (2.33 vs. 1.50, p = 0.02) and disease clearance (clinical remission endoscopic healing + histologic remission) (2.52 vs. 1.70, p = 0.009), compared with those not meeting these criteria. Golimumab concentrations were significantly higher in patients who avoided golimumab dose escalation/discontinuation during follow-up (2.24 vs. 0.98, p = 0.012). Receiver-operating characteristic analyses identified golimumab thresholds [area under the curve] of 0.85 [0.76], 1.90 [0.76], 2.29 [0.75], 1.79 [0.68], 2.29 [0.72] and 1.56 [0.71] µg/ml as associated with clinical remission, combined remission, endoscopic healing, histologic remission, disease clearance and long-term event-free persistence with golimumab, respectively. CONCLUSIONS: Golimumab trough concentrations during maintenance are associated with favourable treatment outcomes including endoscopic healing, histologic remission and long-term persistence on golimumab. We identified the optimal golimumab thresholds most closely associated with key outcomes.
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Colite Ulcerativa , Anticorpos Monoclonais , Colite Ulcerativa/diagnóstico , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/patologia , Colonoscopia , Estudos Transversais , Humanos , Complexo Antígeno L1 Leucocitário/análise , Indução de RemissãoRESUMO
Intercellular communication between monocytes/macrophages and cells involved in tissue regeneration, such as mesenchymal stromal cells (MSCs) and primary tissue cells, is essential for tissue regeneration and recovery of homeostasis. Typically, in the final phase of the inflammation-resolving process, this intercellular communication drives an anti-inflammatory immunomodulatory response. To obtain a safe and effective treatment to counteract the cytokine storm associated with a disproportionate immune response to severe infections, including that associated with COVID-19, by means of naturally balanced immunomodulation, our group has standardized the production under GMP-like conditions of a secretome by coculture of macrophages and MSCs. To characterize this proteome, we determined the expression of molecules related to cellular immune response and tissue regeneration, as well as its possible toxicity and anti-inflammatory potency. The results show a specific molecular pattern of interaction between the two cell types studied, with an anti-inflammatory and regenerative profile. In addition, the secretome is not toxic by itself on human PBMC or on THP-1 monocytes and prevents lipopolysaccharide (LPS)-induced growth effects on those cell types. Finally, PRS CK STORM prevents LPS-induced TNF-A and IL-1Β secretion from PBMC and from THP-1 cells at the same level as hydrocortisone, demonstrating its anti-inflammatory potency.
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COVID-19 , Células-Tronco Mesenquimais , Anti-Inflamatórios/metabolismo , Anti-Inflamatórios/farmacologia , Técnicas de Cocultura , Meios de Cultivo Condicionados/farmacologia , Humanos , Leucócitos Mononucleares , Lipopolissacarídeos/farmacologia , MonócitosRESUMO
BACKGROUND: A significant percentage of patients treated with ustekinumab may lose response. Our aim was to evaluate the short-term efficacy and safety of intravenous re-induction with ustekinumab in patients with Crohn's disease who have lost the response to the treatment. METHODS: This is a retrospective, observational, multicenter study. Treatment efficacy was measured at week 8 and 16; clinical remission was defined when the Harvey-Bradshaw Index was ≤4 points, and clinical response was defined as a decrease of ≥3 points in the index compared with the baseline. Adverse events and treatment decisions after re-induction were also collected. RESULTS: Fifty-three patients from 13 centers were included. Forty-nine percent had previously failed to respond to 2 biological treatments, and 24.5% had failed to respond to 3. The average exposure time to ustekinumab before re-induction was 17.7 ± 12.8 months. In 56.6% of patients, the administration interval had been shortened to every 4 to 6 weeks before re-induction. At week 8 and 16 after re-induction, 49.0% (n = 26) and 43.3% (n = 23), respectively, were in remission, whereas 64.1% (n = 34) and 52.8% (n = 28) had a clinical response. Patients who achieved remission at week 16 had lower C-reactive protein levels than those who did not respond (2.8 ± 1.6 vs 12.5 ± 9.5 mg/dL; P = 0.001). No serious adverse events related to re-induction were observed. CONCLUSION: Intravenous re-induction with ustekinumab is an effective and safe strategy that recovers the response in approximately half of the patients with refractory Crohn's disease who experience a loss of response. Re-induction can be attempted before switching out of the therapy class.
Assuntos
Doença de Crohn , Ustekinumab , Administração Intravenosa , Doença de Crohn/terapia , Humanos , Indução de Remissão , Resultado do Tratamento , Ustekinumab/efeitos adversosRESUMO
BACKGROUND: Crohn's disease (CD) with upper gastrointestinal involvement (UGI) may have a more aggressive and refractory course. However, evidence on this phenotype of patients is scarce. AIMS: To identify the clinical characteristics, therapeutic requirements and complications associated with UGI in CD METHODS: Nationwide study of cases (UGI, UGI plus ileal/ileocolonic involvement) paired with controls (ileal/ileocolonic involvement) from the ENEIDA registry. Cases were matched to 2 controls by year of diagnosis ± 2.5 years. Patients with exclusive/predominant colonic location or complex perianal fistula were excluded. RESULTS: Of 24 738 patients with CD in the ENEIDA registry, we identified 4058 with UGI (16% of the total CD cohort). Finally, 854 cases and 1708 controls were included. Cases were independently associated to extensive involvement (OR 2.7 [2.2-3.3], P < 0.0001), strictures [OR 1.8 (1.5-2.2), P < 0.0001], chronic iron deficiency anaemia [OR 2.2 (1.3-3.2), P < 0.001] and use of second-line biologics [OR 1.7 (1.1-2.6), P = 0.021]. The median stricture-free time was 14 years (95% CI, 12-16) for cases vs 21 years (95% CI, 19-23) for controls (P < 0.0001). Cases with isolated UGI compared to UGI plus ileal/ileocolonic more frequently had localised disease [OR 0.5(0.3-0.8), P = 0.003] and underwent more endoscopic stricture dilations [OR 2.7(1.3-5.4), P = 0.006]. CONCLUSIONS: The largest cohort of patients with CD and UGI provides information on the natural history of this particular phenotype. Increased awareness of the clinical picture and therapeutic requirements of these patients could lead to earlier diagnosis and treatment of upper gastrointestinal lesions, preventing the structural damage frequently seen in these patients at diagnosis and during follow-up.
Assuntos
Doença de Crohn , Fístula Retal , Trato Gastrointestinal Superior , Colo , Doença de Crohn/tratamento farmacológico , Humanos , ÍleoRESUMO
Iron deficiency anemia (IDA) is a common manifestation of Inflammatory Bowel Disease (IBD). Oral iron supplements are the treatment of choice, but are not always well tolerated. Sucrosomial® iron (SI) may represent an alternative. This prospective study assessed the tolerability and effectiveness of SI, and quality of life (QoL) of IDA-IBD patients who were intolerant to oral iron salts. The study included 52 individuals treated with 1 capsule/day for 12 weeks. Tolerability was assessed through a gastrointestinal symptom severity questionnaire. Hemoglobin (Hb) levels and clinical symptoms of IDA were analyzed. QoL was assessed using IBDQ-9 and EuroQoL questionnaires. The percentage of patients with excellent/good health increased from 42.9% to 94.3%. Mean Hb concentration significantly increased at all follow-up visits (p < 0.05). Almost all participants (96.9%) were adherent to the study medication. Patients' QoL improved (IBDQ-9: from 60.9 to 65.5). Patients also improved in mobility (71.8% to 78.1%), usual activities (51.3% to 68.7%), pain/discomfort (41.0% to 53.1%), and extreme depression/anxiety problems (7.7% to 3.2%); they worsened in self-care (100% to 90.6%), but perceived an enhancement in their global health [EQ-VAS score: 61.9 (±26.1) to 66.9 (±20.3)]. SI was well tolerated and improved IDA symptoms, IBD activity, and patients' QoL. In conclusion, SI should be considered in IDA-IBD patients.
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Anemia Ferropriva/tratamento farmacológico , Doenças Inflamatórias Intestinais/tratamento farmacológico , Ferro/administração & dosagem , Qualidade de Vida , Administração Oral , Adulto , Idoso , Idoso de 80 Anos ou mais , Anemia Ferropriva/complicações , Suplementos Nutricionais , Feminino , Compostos Férricos , Hemoglobinas/análise , Humanos , Doenças Inflamatórias Intestinais/complicações , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Inquéritos e Questionários , Oligoelementos/administração & dosagem , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: Idiopathic acute pancreatitis (IAP) in patients with inflammatory bowel disease (IBD) is not well characterized. Our purpose was to better understand this condition and its natural history. METHODS: Retrospective cohort study conducted at nine Spanish IBD referral centers. Patients with IBD and a first episode of acute pancreatitis (AP) between 1998 and 2018 were included. Patients with a previous episode of AP or a diagnosis of chronic pancreatitis were excluded. IAP and non-IAP were compared by multivariate logistic regression and survival analysis. RESULTS: We identified 185 patients with IBD (68.7% Crohn's disease) and a first episode of AP. Thirty-eight of those 185 (20.6%) fulfilled criteria for IAP. There were no severe cases of IAP. On multivariate analysis, AP before IBD diagnosis (21.1% vs. 3.4%, p = 0.04) and ulcerative colitis (52.6% vs. 23.1%, p = 0.002) were significantly more common in IAP. Further work-up was performed in 16/38 (42%) IAP patients, and a cause was identified in 6/16 (37.5%). Median time from AP to the end of follow-up was 6.3 years (3.1-10). Five-year risk of AP recurrence was significantly higher in IAP group (28% vs. 5.1%, log-rank p = 0.001), with a median time to first recurrence of 4.4 months (2.9-12.2). CONCLUSIONS: IAP represents the second cause of AP in patients with IBD. It is more frequent in ulcerative colitis, and presents a high risk of recurrence. Additional imaging work-up after a first episode of IAP in IBD patients is highly advisable, as it identifies a cause in more than one-third of cases.
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Doenças Inflamatórias Intestinais/etiologia , Pancreatite/complicações , Adulto , Estudos de Coortes , Colite Ulcerativa/complicações , Colite Ulcerativa/epidemiologia , Doença de Crohn/complicações , Doença de Crohn/epidemiologia , Determinação de Ponto Final , Feminino , Seguimentos , Humanos , Doenças Inflamatórias Intestinais/epidemiologia , Masculino , Pessoa de Meia-Idade , Pancreatite/epidemiologia , Recidiva , Estudos Retrospectivos , Espanha/epidemiologiaRESUMO
INTRODUCTION: Faecal calprotectin is a useful technique for detecting activity in patients with ulcerative colitis. However, there may be high levels due to factors other than the activity of ulcerative colitis. Our aim was to analyse possible false positive results of calprotectin for the activity of ulcerative colitis owing to the presence of inflammatory polyps. PATIENTS AND METHODS: Retrospective, observational, descriptive study. Data was collected from patients monitored for 2 years in whom a colonoscopy had been requested within 3 months after detecting high calprotectin values (>150µg/g) and before modifying the treatment. RESULTS: We reviewed 39 patients and in 5 of them, with previous diagnosis of extensive ulcerative colitis, inflammatory polyps were detected. Three patients were on treatment with mesalazine, one with azathioprine and other with infliximab. All of them were asymptomatic and the endoscopy did not show macroscopic activity (endoscopic Mayo score=0) or histological activity. The median values of calprotectin were 422µg/g (IQR: 298-2,408) and they remained elevated in a second measurement. In 4 of the patients the inflammatory polyps were multiple and small in size. The other patient had a polyp measuring 4cm. DISCUSSION: In clinical practice we can find high faecal calprotectin levels not due to the presence of ulcerative colitis activity, but due to other lesions such as inflammatory polyps. This fact must be taken into account before carrying out relevant changes such as step-up therapy to immunosuppressive drugs or biological drugs in patients with confirmed high calprotectin levels.
Assuntos
Colite Ulcerativa/diagnóstico , Fezes/química , Inflamação/diagnóstico , Pólipos Intestinais/diagnóstico , Complexo Antígeno L1 Leucocitário/análise , Adulto , Colite Ulcerativa/metabolismo , Diagnóstico Diferencial , Reações Falso-Positivas , Feminino , Humanos , Inflamação/complicações , Inflamação/metabolismo , Pólipos Intestinais/complicações , Pólipos Intestinais/metabolismo , Complexo Antígeno L1 Leucocitário/metabolismo , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
BACKGROUND: the safety and diagnostic accuracy of colonoscopies depends on the quality of colon cleansing. Several factors have been reported that affect the quality of bowel cleansing, hospitalization being one of them. AIMS: the aim of the study was to investigate whether a visual educational leaflet improved the level of cleanliness achieved in hospitalized patients undergoing a colonoscopy and to identify predictors of a poor bowel preparation. METHODS: a prospective, single-center, endoscopist-blinded, randomized controlled trial was performed. The intervention group was given a visual educational leaflet and both groups received four liters of polyethylene glycol solution. Demographic data, personal history, reason for admission and indication for colonoscopy, work shift during which the procedure was performed and endoscopy findings were collected. The Boston Bowel Preparation Scale (BBPS) was used to assess the bowel preparation. RESULTS: one hundred and thirty-six patients were included in the study; 51.5% were male, with a mean age of 64.3 ± 17.6 years. The educational leaflet did not result in a difference in the total BBPS obtained between the standard group and the intervention group (7 [6-9] vs 6 [5.7-9]; p = 0.17). According to the multivariable analysis, the only factors associated with a poor bowel cleansing were heart disease (OR 3.37 [1.34-8.46]; p = 0.010) and colorectal cancer (OR 3.82 [1.26-11.61]; p = 0.018). CONCLUSION: the use of a visual educational leaflet for the preparation of colonoscopies did not provide a significant improvement in hospitalized patients in our health area. Heart disease was identified as the only predictor of poor preparation for colonoscopy.
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Colonoscopia/educação , Pacientes Internados/educação , Folhetos , Educação de Pacientes como Assunto/métodos , Cuidados Pré-Operatórios/educação , Idoso , Análise de Variância , Recursos Audiovisuais , Catárticos , Colo/diagnóstico por imagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Polietilenoglicóis , Estudos Prospectivos , Método Simples-Cego , Estatísticas não ParamétricasRESUMO
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 SobrevidaRESUMO
OBJECTIVE: To study the multidisciplinary management of patients with Crohn's disease (CD) and perianal disease (perianal Crohn's disease, PCD), as well as to analyse a possible relationship between the recurrence of perianal symptoms, the type of fistula and the treatment used. PATIENTS AND METHODS: Descriptive, retrospective study of patients with PCD who were treated in the Inflammatory Bowel Disease Unit. Epidemiological, clinical, diagnostic and therapeutic variables were collected, as well as clinical outcome and response to treatment. RESULTS: Of the 300 patients who attended the outpatient clinic at a university hospital, 65 had PCD. Sixteen simple fistulas (24.6%) and 49 complex fistulas (75.4%) were diagnosed. The most commonly used diagnostic technique was the endoanal ultrasound (45%). Antibiotics were used in 77.4% of patients, and 70% needed anti-TNF therapy to manage the PCD. Surgery was performed on 75.4% of the patients overall. PCD recurred in 41.5% of cases, requiring a change of the biological drugs administered and/or surgery. Complex fistulas were more likely to require surgery (P=.012) and recurrence of PCD was also more common with complex fistulas (P=.036). CONCLUSION: Management of PCD must be multidisciplinary and combined. Most patients with complex PCD require treatment based on biological drugs. Despite therapy, remission of perianal symptoms is not achieved in a percentage of patients, supporting the need to develop new therapies for refractory cases.
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Doença de Crohn/terapia , Fístula Retal/terapia , Adolescente , Adulto , Terapia Combinada , Doença de Crohn/complicações , Feminino , Recursos em Saúde , Humanos , Masculino , Fístula Retal/etiologia , Recidiva , Estudos Retrospectivos , Resultado do Tratamento , Adulto JovemRESUMO
Perianal localization of Crohn's disease involves significant morbidity, affects quality of life and results in an increased use of healthcare resources. Medical and surgical therapies contribute to its management. The objective of this review is to address the current understanding in the management of perianal Crohn's disease, with the main focus in reviewing pharmacological therapies, including stem cells. In complex fistulas, once local sepsis has been controlled by surgical drainage and/or antibiotics, anti-TNF drugs (infliximab, adalimumab) are the first-line therapy, with or without associated immunomodulators. Combining surgery and anti-TNF therapy has additional benefits for healing. However, response is inadequate in up to half of cases. A possible role of new biological drugs in this context (vedolizumab, ustekinumab) is an area of ongoing investigation, as is the local application of autologous or allogeneic mesenchymal stem cells. These are non-hematopoietic multipotent cells with anti-inflammatory and immunomodulatory properties, the use of which may successfully treat refractory patients, and seem to be a promising and safe alternative to achieving fistula healing in Crohn's disease, without known systemic effects.
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Doenças do Ânus/terapia , Doença de Crohn/terapia , Antibacterianos/imunologia , Antibacterianos/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Anticorpos Monoclonais/imunologia , Anticorpos Monoclonais/uso terapêutico , Doenças do Ânus/complicações , Terapia Combinada , Doença de Crohn/complicações , Feminino , Humanos , Fatores Imunológicos/uso terapêutico , Transplante de Células-Tronco Mesenquimais , Fator de Necrose Tumoral alfa/imunologiaRESUMO
BACKGROUND AND AIMS: This study sought to determine the prevalence of malnutrition in patients with inflammatory bowel disease, to analyse the dietary beliefs and behaviours of these patients, to study their body composition, to evaluate their muscular strength and to identify the factors associated with malnutrition in these patients. METHODS: This was a prospective, multicentre study. Crohn's disease and ulcerative colitis patients from 30 Spanish centres, from the outpatient clinics, were included. A questionnaire of 11 items was applied to obtain data from patients' dietary behaviour and beliefs. Patients who accepted were evaluated to assess their nutritional status using Subjective Global Assessment and body mass index. Body composition was evaluated through bioelectrical impedance. RESULTS: A total of 1271 patients were included [51% women, median age 45 years, 60% Crohn's disease]. Of these, 333 patients underwent the nutritional evaluation. A total of 77% of patients declared that they avoided some foods to prevent disease relapse. Eighty-six per cent of patients avoided some foods when they had disease activity because of fear of worsening the flare. Sixty-seven per cent of patients modified their dietary habits after disease diagnosis. The prevalence of malnutrition was 16% [95% confidence interval = 12-20%]. In the multivariate analysis, history of abdominal surgery, active disease and avoidance of some foods during flares were associated with higher risk of malnutrition. CONCLUSIONS: The prevalence of malnutrition in inflammatory bowel disease patients was high. We identified some predictive factors of malnutrition. Most of the patients had self-imposed food restrictions, based on their beliefs.
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Dieta , Comportamento Alimentar , Conhecimentos, Atitudes e Prática em Saúde , Doenças Inflamatórias Intestinais/fisiopatologia , Desnutrição/epidemiologia , Desnutrição/fisiopatologia , Estado Nutricional , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Composição Corporal , Índice de Massa Corporal , Doença de Crohn , Impedância Elétrica , Feminino , Alimentos , Força da Mão , Humanos , Doenças Inflamatórias Intestinais/complicações , Masculino , Pessoa de Meia-Idade , Avaliação Nutricional , Prevalência , Estudos Prospectivos , Fatores de Risco , Espanha/epidemiologia , Exacerbação dos Sintomas , Adulto JovemRESUMO
BACKGROUND: Data supporting a role of female hormones and/or their receptors in inflammatory bowel disease (IBD) are increasing, but most of them are derived from animal models. Estrogen receptors alpha (ERα) and beta (ERß) participate in immune and inflammatory response, among a variety of biological processes. Their effects are antagonistic, and the net action of estrogens may depend on their relative proportions. AIM: To determine the possible association between the balance of circulating ERß and ERα (ERß/ERα) and IBD risk and activity. METHODS: Serum samples from 145 patients with IBD (79 Crohn's disease [CD] and 66 ulcerative colitis [UC]) and 39 controls were retrospectively studied. Circulating ERα and ERß were measured by ELISA. Disease activities were assessed by clinical and endoscopic indices specific for CD and UC. RESULTS: Low values of ERß/ERα ratio were directly associated with clinical (p = 0.019) and endoscopic (p = 0.002) disease activity. Further analyses by type of IBD confirmed a strong association between low ERß/ERα ratio and CD clinical (p = 0.011) and endoscopic activity (p = 0.002). The receiver operating curve (ROC) analysis showed that an ERß/ERα ratio under 0.85 was a good marker of CD endoscopic activity (area under the curve [AUC]: 0.84; p = 0.002; sensitivity: 70%; specificity: 91%). ERß/ERα ratio was not useful to predict UC activity. CONCLUSIONS: An ERß/ERα ratio under 0.85 indicated CD endoscopic activity. The determination of serum ERß/ERα might be a useful noninvasive screening tool for CD endoscopic activity.
Assuntos
Colite Ulcerativa/sangue , Doença de Crohn/sangue , Doença de Crohn/diagnóstico , Endoscopia Gastrointestinal , Receptor alfa de Estrogênio/sangue , Receptor beta de Estrogênio/sangue , Adolescente , Adulto , Idoso , Área Sob a Curva , Biomarcadores/sangue , Colite Ulcerativa/diagnóstico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Curva ROC , Estudos Retrospectivos , Índice de Gravidade de Doença , Adulto JovemRESUMO
BACKGROUND: Golimumab efficacy data in ulcerative colitis (UC) are limited to anti-tumor necrosis factor α (TNF)-naive patients. The aim of this study was to assess the short-term and long-term efficacy of golimumab used as first, second, or third anti-TNF in UC in a real-life clinical setting. METHODS: This retrospective multicenter cohort study included patients with moderate-to-severe UC treated with golimumab. The primary efficacy endpoints were short-term partial Mayo score response, long-term golimumab failure-free survival, and colectomy-free survival. RESULTS: In 142 patients with UC, golimumab was administered as first (40%), second (23%), or third anti-TNF (37%). Ninety-two patients (65%, 95% confidence interval 56.6-73) achieved short-term clinical response. Forty-five patients (32%, 95% confidence interval 23.7-39.7) achieved clinical remission. Response rates for golimumab were 75% as first anti-TNF, 70% as second anti-TNF (ns versus first anti-TNF), and 50% as third anti-TNF (P = 0.007 versus first anti-TNF). After 12 months median follow-up (interquartile range 6-18), 60 patients (42%, 95% confidence interval 34-51) had golimumab failure, and 15 patients (11%) needed colectomy. Thirty-one patients (22%) needed golimumab dose escalation, and 71% of these regained response after escalation. Starting maintenance with 100 mg golimumab doses and short-term nonresponse were independent predictors of golimumab failure. CONCLUSIONS: In this real-life cohort of patients with UC, golimumab therapy was effective for inducing and maintaining clinical response. Although anti-TNF-naive patients had better outcomes, golimumab was also effective in anti-TNF-experienced patients. Only the patients given golimumab after previous failure of 2 anti-TNF agents had significantly worse outcomes. Golimumab dose escalation was beneficial and safe.
Assuntos
Anticorpos Monoclonais/uso terapêutico , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/mortalidade , Índice de Gravidade de Doença , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Colite Ulcerativa/patologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Indução de Remissão , Estudos Retrospectivos , Taxa de Sobrevida , Adulto JovemRESUMO
BACKGROUND: Data on fertility rates and medication safety in men with inflammatory bowel disease (IBD) are limited. The aim of this study was to evaluate whether there is a seminal alteration in patients with IBD and, if so, to evaluate the mechanisms that may play a role according to what has been described in the literature. Its secondary aim was to evaluate the impact on male sexual function of IBD. METHODS: Multicenter, cross-sectional, case series study comparing men with IBD and control subjects. Semen analysis was performed according to the recommendations of World Health Organization. The impact on male sexual function was evaluated with the International Index of Erectile Function questionnaire. RESULTS: On multivariate analysis, patients with Crohn's disease had lower sperm concentrations compared with those with ulcerative colitis (median [interquartile range], 34.5 [19.2-48] versus 70 [34.5-127.5], P = 0.02) and lower seminal zinc levels (mean ± SD, 1475 ± 235 µmol/L versus 2221 ± 1123 µmol/L, P = 0.04). Patients with Crohn's disease on anti-tumor necrosis factor treatment had better progressive motility (mean ± SD, 56.7 ± 17.7 versus 35.1 ± 22.1, P = 0.01) and sperm morphology (14.4 ± 7.1 versus 7.6 ± 4.9, P = 0.04) than those who were not on anti-tumor necrosis factor. Regarding sexual function, no significant differences were found across patients with IBD and control subjects. CONCLUSIONS: Men with Crohn's disease showed a trend toward poorer semen quality than those with ulcerative colitis. Treatment with anti-tumor necrosis factor drugs does not seem to be associated with poor sperm quality. In patients in clinical remission, male sexual function is not affected by IBD.
Assuntos
Doenças Inflamatórias Intestinais/fisiopatologia , Qualidade de Vida , Sêmen/química , Disfunções Sexuais Fisiológicas/epidemiologia , Sexualidade/fisiologia , Adulto , Estudos de Casos e Controles , Estudos Transversais , Seguimentos , Humanos , Incidência , Masculino , Prognóstico , Espanha/epidemiologiaRESUMO
BACKGROUND: Data about use and effectiveness of mercaptopurine in inflammatory bowel disease are relatively limited. AIMS: To assess the possible therapeutic indications, efficacy and safety of mercaptopurine as an alternative to azathioprine in inflammatory bowel disease. METHODS: Retrospective observational study in patients treated with mercaptopurine in a total cohort of 1,574 patients with inflammatory bowel disease. RESULTS: One hundred and fifty-two patients received mercaptopurine, 15.7% of these patients as an initial thiopurine, 5.3% after azathioprine failure, and 79% after azathioprine intolerance. In 52.6% of patients (n = 80), adverse effects of mercaptopurine occurred, resulting in withdrawal in 49 of them. Mercaptopurine was effective in 39% of cases (95% CI 31-48%). In the remaining patients, failure was due mainly to withdrawal due to side effects (55.1%) and therapeutic step-up (33.7%). The average total time of mercaptopurine exposure was 36 months (IQR: 2-60). Myelotoxicity with mercaptopurine was more common in patients with intermediate TPMT activity than in those with normal activity (p = 0.046). CONCLUSIONS: In our setting, mercaptopurine is primarily used as a rescue therapy in patients with azathioprine adverse effects. This could explain its modest efficacy and the high rate of adverse effects. However, this drug is still an alternative in this group of patients, before a therapeutic step-up to biologics is considered.
Assuntos
Imunossupressores/uso terapêutico , Doenças Inflamatórias Intestinais/tratamento farmacológico , Mercaptopurina/uso terapêutico , Adulto , Idoso , Azatioprina/efeitos adversos , Azatioprina/uso terapêutico , Estudos de Coortes , Doença de Crohn/tratamento farmacológico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Falha de TratamentoRESUMO
BACKGROUND: Psoriasis induced by anti-tumor necrosis factor-α (TNF) therapy has been described as a paradoxical side effect. AIM: To determine the incidence, clinical characteristics, and management of psoriasis induced by anti-TNF therapy in a large nationwide cohort of inflammatory bowel disease patients. METHODS: Patients with inflammatory bowel disease were identified from the Spanish prospectively maintained Estudio Nacional en Enfermedad Inflamatoria Intestinal sobre Determinantes genéticos y Ambientales registry of Grupo Español de Trabajo en Enfermedad de Croh y Colitis Ulcerosa. Patients who developed psoriasis by anti-TNF drugs were the cases, whereas patients treated with anti-TNFs without psoriasis were controls. Cox regression analysis was performed to identify predictive factors. RESULTS: Anti-TNF-induced psoriasis was reported in 125 of 7415 patients treated with anti-TNFs (1.7%; 95% CI, 1.4-2). The incidence rate of psoriasis is 0.5% (95% CI, 0.4-0.6) per patient-year. In the multivariate analysis, the female sex (HR 1.9; 95% CI, 1.3-2.9) and being a smoker/former smoker (HR 2.1; 95% CI, 1.4-3.3) were associated with an increased risk of psoriasis. The age at start of anti-TNF therapy, type of inflammatory bowel disease, Montreal Classification, and first anti-TNF drug used were not associated with the risk of psoriasis. Topical steroids were the most frequent treatment (70%), achieving clinical response in 78% of patients. Patients switching to another anti-TNF agent resulted in 60% presenting recurrence of psoriasis. In 45 patients (37%), the anti-TNF therapy had to be definitely withdrawn. CONCLUSIONS: The incidence rate of psoriasis induced by anti-TNF therapy is higher in women and in smokers/former smokers. In most patients, skin lesions were controlled with topical steroids. More than half of patients switching to another anti-TNF agent had recurrence of psoriasis. In most patients, the anti-TNF therapy could be maintained.
Assuntos
Adalimumab/efeitos adversos , Colite Ulcerativa/tratamento farmacológico , Doença de Crohn/tratamento farmacológico , Infliximab/efeitos adversos , Psoríase/epidemiologia , Psoríase/prevenção & controle , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Adolescente , Adulto , Anti-Inflamatórios/efeitos adversos , Estudos de Casos e Controles , Estudos de Coortes , Feminino , Seguimentos , Fármacos Gastrointestinais/efeitos adversos , Humanos , Incidência , Masculino , Prognóstico , Psoríase/patologia , Espanha/epidemiologia , Suspensão de TratamentoRESUMO
BACKGROUND AND AIMS: Patients with inflammatory bowel disease [IBD] are at increased risk for developing some types of neoplasia. Our aims were to determin the risk for cancer in patients with IBD and to describe the relationship with immunosuppressive therapies and clinical management after tumor diagnosis. METHODS: Retrospective, multicenter, observational, 5-year follow-up, cohort study. Relative risk [RR] of cancer in the IBD cohort and the background population, therapeutic strategies, and cancer evolution were analyzed. RESULTS: A total of 145 cancers were diagnosed in 133 of 9100 patients with IBD (global cumulative incidence 1.6% vs 2.4% in local population; RR = 0.67; 95% confidence interval [CI]: 0.57-0.78). Patients with IBD had a significantly increased RR of non-melanoma skin cancer [RR = 3.85; 2.53-5.80] and small bowel cancer [RR = 3.70; 1.23-11.13]. After cancer diagnosis, IBD treatment was maintained in 13 of 27 [48.1%] patients on thiopurines, in 2 of 3 on methotrexate [66.6%], none on anti-TNF-α monotherapy [n = 6] and 4 of 12 [33.3%] patients on combined therapy. Rate of death and cancer remission during follow-up did not differ [p > 0.05] between patients who maintained the treatment compared with patients who withdrew [5% vs 8% and 95% vs 74%, respectively]. An association between thiopurines [p = 0.20] or anti-TNF-α drugs [p = 0.77] and cancer was not found. CONCLUSIONS: Patients with IBD have an increased risk for non-melanoma skin cancer and small bowel cancer. Immunosuppresive therapy is not related to a higher overall risk for cancer or worse tumor evolution in patients who maintain these drugs after cancer diagnosis.