Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 12 de 12
Filtrar
Mais filtros










Intervalo de ano de publicação
1.
Biochem Pharmacol ; 122: 33-41, 2016 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-27664854

RESUMO

BACKGROUND: The availability of a quantitative method to measure anti-infliximab (IFX) antibodies (ATI) would facilitate the implementation of therapeutic drug monitoring in clinical decision-making. Our aim was to standardize the homogeneous mobility shift assay (HMSA) used in the measure of ATI levels. METHODS: In this prospective longitudinal multicenter study, 50 IFX-treated Crohn's disease (CD) patients were followed up for 54weeks. During this period 360 human serum samples were analysed. Monomeric ATI levels were measured by a quantitative HMSA-method using an anti-IFX calibrator. IFX trough levels measured by ELISA were correlated with ATI levels. RESULTS: Using HMSA and a pure anti-idiotypic monoclonal antibody specific for IFX (anti-IFX calibrator), we measured the levels of monomeric ATI generated in Crohn's disease patients treated with IFX. Anti-IFX calibrator allowed to quantify monomeric antibodies against IFX with a low limit of quantification (3nM). The threshold level of ATI in order to classify the immunogenicity of the patients was 10nM. We observed that 24% (12/50) of IFX-treated patients developed ATI (>10nM) during the observation period (54weeks). Serum concentration of ATI higher than 10nM dramatically increased the probability (OR=51.1; 95% CI: 20.4-128.0; p<0.0001) of presenting low levels of IFX (⩽1.5nM) in serum, as observed in some CD patients treated with standard doses of the drug. CONCLUSIONS: The HMSA-method described here allows an accurate quantification of ATI concentration in international units (IU) and therefore it could be useful in the study of the relationship between ATI concentration, infliximab level and the clinical response to the drug.


Assuntos
Anticorpos/sangue , Doença de Crohn/tratamento farmacológico , Ensaio de Desvio de Mobilidade Eletroforética/métodos , Infliximab/uso terapêutico , Doença de Crohn/sangue , Humanos , Estudos Prospectivos
2.
J Crohns Colitis ; 8(3): 234-9, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24016462

RESUMO

BACKGROUND: Phenotypic traits of familial IBD relative to sporadic cases are controversial, probably related to limited statistical power of published evidence. AIM: To know if there are phenotype differences between familial and sporadic IBD, evaluating the prospective Spanish registry (ENEIDA) with 11,983 cases. METHODS: 5783 patients (48.3%) had ulcerative colitis (UC) and 6200 (51.7%) Crohn's disease (CD). Cases with one or more 1st, 2nd or 3rd degree relatives affected by UC/CD were defined as familial case. RESULTS: In UC and CD, familial cases compared with sporadic cases had an earlier disease onset (UC: 33 years [IQR 25-44] vs 37 years [IQR 27-49]; p<0.0001); (CD: 27 years [IQR 21-35] vs 29 years [IQR 22-40]; p<0.0001), higher prevalence of extraintestinal immune-related manifestations (EIMs) (UC: 17.2% vs 14%; p=0.04); (CD: 30.1% vs 23.6%; p<0.0001). Familial CD had higher percentage of ileocolic location (42.7% vs 51.8%; p=0.0001), penetrating behavior (21% vs 17.6%; p=0.01) and perianal disease (32% vs 27.1%; p=0.003). Differences are not influenced by degree of consanguinity. CONCLUSION: When a sufficiently powered cohort is evaluated, familial aggregation in IBD is associated to an earlier disease onset, more EIMs and more severe phenotype in CD. This feature should be taken into account at establishing predictors of disease course.


Assuntos
Colite Ulcerativa/genética , Colite Ulcerativa/patologia , Doença de Crohn/genética , Doença de Crohn/patologia , Adulto , Idade de Início , Doenças do Ânus/etiologia , Colite Ulcerativa/imunologia , Colo , Doença de Crohn/imunologia , Feminino , Humanos , Íleo , Masculino , Fenótipo , Sistema de Registros , Índice de Gravidade de Doença , Espanha , Adulto Jovem
3.
Aliment Pharmacol Ther ; 38(7): 752-60, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23980933

RESUMO

BACKGROUND: Recently, the notion that smoking may adversely affect Crohn's disease (CD) outcomes has been challenged by the suggestion that the widespread use of immunosuppressants and anti-TNF drugs might offset the adverse effects of tobacco. AIM: To reassess the influence of tobacco smoking on disease phenotype and complications on a time-dependent analysis, taking into account the different therapeutic interventions. METHODS: We designed a retrospective cohort study of 3224 patients with Crohn's disease. The data were collected from the Spanish national inflammatory bowel disease registry (ENEIDA), including information regarding demographics, clinical characteristics, disease complications, therapeutic interventions and smoking status. Patients were classified as nonsmokers, smokers and former smokers, according to their present and past smoking habits. RESULTS: In the univariate analysis, smokers had more strictures (22.6% vs. 19.3%, P < 0.05) and less colonic involvement (7.2% vs. 10.9%, P < 0.05), and were more frequently under treatment with steroids (91.6% vs. 85.8%, P < 0.05), immunosuppressants (73.5% vs. 63.6% P < 0.05) or anti-TNF drugs (31.4% vs. 25.1%, P < 0.05) than nonsmokers. In the time-dependent multivariate analysis, smokers were found to have a significantly decreased survival free of stricturing disease (HR: 1.5, CI 95% 1.18-1.90) or perianal complications (HR: 1.50, CI 95% 1.01-1.46), and had a higher risk for requiring thiopurine therapy (HR: 1.20, CI 95% 1.05-1.30). CONCLUSION: These results suggest that, despite the widespread use of immunosuppressants and anti-TNF drugs, smokers with Crohn's disease still have a more severe disease course, with increased therapeutic requirements when compared with nonsmokers.


Assuntos
Doença de Crohn/fisiopatologia , Fatores Imunológicos/uso terapêutico , Imunossupressores/uso terapêutico , Fumar/efeitos adversos , Adulto , Anti-Inflamatórios/uso terapêutico , Estudos de Coortes , Doença de Crohn/tratamento farmacológico , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Sistema de Registros , Estudos Retrospectivos , Risco , Índice de Gravidade de Doença , Espanha , Fator de Necrose Tumoral alfa/antagonistas & inibidores
4.
An Sist Sanit Navar ; 36(1): 63-75, 2013.
Artigo em Espanhol | MEDLINE | ID: mdl-23648494

RESUMO

The concept of inflammatory bowel disease (IBD) covers three entities: ulcerative colitis (UC), Crohn's disease (CD) and indeterminate colitis (IC). These diseases have in common a chronic and relapsing course, alternating periods marked by inflammatory activity with other quiescent periods, in which the patient is asymptomatic. For many years treatment of the disease, especially in acute phases, was based on the use of corticoids. However, in recent decades we have witnessed significant advances from the therapeutic point of view. It is estimated that during the course of the disease's evolution 80% of patients will need corticoids, 40% immunomodulators (IMM), and as many as 20% will require a biological medicine to control their disease. While all of this is accompanied by an improvement in quality of life, less hospital admissions or surgical interventions, their use also involves an increase in the risk of suffering infections, either due to germs normally found in the community or opportunistic infections. Moreover, infections are a cause of morbidity and mortality associated with IBD and some of them can be prevented with vaccinations, hence the importance that vaccination programs are acquiring in this groups of patients. We present a review of the relevant literature and propose a vaccination protocol for patients diagnosed with IBD.


Assuntos
Doenças Inflamatórias Intestinais , Vacinação , Vacinas , Humanos , Hospedeiro Imunocomprometido , Guias de Prática Clínica como Assunto
5.
An. sist. sanit. Navar ; 36(1): 63-75, ene.-abr. 2013. tab
Artigo em Espanhol | IBECS | ID: ibc-112983

RESUMO

El concepto de enfermedad inflamatoria intestinal (EII) engloba tres entidades: la colitis ulcerosa (CU), la enfermedad de Crohn (EC) y la colitis inclasificable (CI). Estas enfermedades tienen en común el curso crónico y recidivante, alternando épocas de marcada actividad inflamatoria con otras quiescentes, en las que el paciente permanece asintomático. Durante muchos años la base del tratamiento, sobre todo en las fases agudas, se basó en el uso de corticoides. Sin embargo, a lo largo de las últimas décadas hemos asistido a avances importantes desde el punto de vista terapéutico. Así se estima que, a lo largo de la evolución de la enfermedad, el 80% de los pacientes van a precisar corticoides, el 40% inmunomoduladores (IMM) y hasta un 20% necesitará un fármaco biológico para el control de su enfermedad. Si bien todo ello se acompaña de una mejora en la calidad de vida, disminuyendo la necesidad de ingresos e intervenciones quirúrgicas, su uso implica también un incremento en el riesgo de sufrir infecciones, bien por gérmenes habituales en la comunidad o por gérmenes oportunistas. Las infecciones, además, son causa de morbimortalidad asociada a EII y algunas de ellas son prevenibles con vacunas, de ahí la importancia que los programas de vacunación están adquiriendo en este grupo de pacientes. Presentamos una revisión de la literatura al respecto y proponemos unas recomendaciones de vacunación para los pacientes diagnosticados de EII (AU)


The concept of inflammatory bowel disease (IBD) covers three entities: ulcerative colitis (UC), Crohn’s disease (CD) and indeterminate colitis (IC). These diseases have in common a chronic and relapsing course, alternating periods marked by inflammatory activity with other quiescent periods, in which the patient is asymptomatic. For many years treatment of the disease, especially in acute phases, was based on the use of corticoids. However, in recent decades we have witnessed significant advances from the therapeutic point of view. It is estimated that during the course of the disease’s evolution 80% of patients will need corticoids, 40% immunomodulators (IMM), and as many as 20% will require a biological medicine to control their disease. While all of this is accompanied by an improvement in quality of life, less hospital admissions or surgical interventions, their use also involves an increase in the risk of suffering infections, either due to germs normally found in the community or opportunistic infections. Moreover, infections are a cause of morbidity and mortality associated with IBD and some of them can be prevented with vaccinations, hence the importance that vaccination programs are acquiring in this groups of patients. We present a review of the relevant literature and propose a vaccination protocol for patients diagnosed with IBD (AU)


Assuntos
Humanos , Doenças Inflamatórias Intestinais/imunologia , Fatores Imunológicos/uso terapêutico , Corticosteroides/uso terapêutico , Vacinação , Hospedeiro Imunocomprometido/imunologia , Padrões de Prática Médica
6.
Aliment Pharmacol Ther ; 35(8): 941-7, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22372560

RESUMO

BACKGROUND: In some cases, Helicobacter pylori infection persists even after three eradication treatments. AIM: To evaluate the efficacy of an empirical fourth-line rescue regimen with rifabutin in patients with three eradication failures. DESIGN: Multicentre, prospective study. PATIENTS: In whom the following three treatments had consecutively failed: first (PPI + clarithromycin + amoxicillin); second (PPI + bismuth + tetracycline + metronidazole); third (PPI + amoxicillin + levofloxacin). INTERVENTION: A fourth regimen with rifabutin (150 mg b.d.), amoxicillin (1 g b.d.) and a PPI (standard dose b.d.) was prescribed for 10 days. OUTCOME: Eradication was confirmed by (13) C-urea breath test 4-8 weeks after therapy. Compliance and tolerance: Compliance was determined through questioning and recovery of empty medication envelopes. Adverse effects were evaluated using a questionnaire. RESULTS: One-hundred patients (mean age 50 years, 39% men, 31% peptic ulcer/69% functional dyspepsia) were included. Eight patients did not take the medication correctly (in six cases due to adverse effects). Per-protocol and intention-to-treat eradication rates were 52% (95% CI = 41-63%) and 50% (40-60%). Adverse effects were reported in 30 (30%) patients: nausea/vomiting (13 patients), asthenia/anorexia (8), abdominal pain (7), diarrhoea (5), fever (4), metallic taste (4), myalgia (4), hypertransaminasemia (2), leucopenia (<1,500 neutrophils) (2), thrombopenia (<150,000 platelets) (2), headache (1) and aphthous stomatitis (1). Myelotoxicity resolved spontaneously in all cases. CONCLUSIONS: Even after three previous H. pylori eradication failures, an empirical fourth-line rescue treatment with rifabutin may be effective in approximately 50% of the cases. Therefore, rifabutin-based rescue therapy constitutes a valid strategy after multiple previous eradication failures with key antibiotics, such as clarithromycin, metronidazole, tetracycline and levofloxacin.


Assuntos
Antibacterianos/uso terapêutico , Dispepsia/tratamento farmacológico , Infecções por Helicobacter/tratamento farmacológico , Helicobacter pylori/isolamento & purificação , Úlcera Péptica/tratamento farmacológico , Rifabutina/uso terapêutico , Adulto , Antibacterianos/efeitos adversos , Quimioterapia Combinada , Dispepsia/microbiologia , Feminino , Seguimentos , Infecções por Helicobacter/microbiologia , Humanos , Masculino , Pessoa de Meia-Idade , Cooperação do Paciente , Úlcera Péptica/microbiologia , Estudos Prospectivos , Rifabutina/efeitos adversos , Inquéritos e Questionários , Falha de Tratamento , Resultado do Tratamento
7.
Inflamm Bowel Dis ; 18(4): 685-90, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21618353

RESUMO

BACKGROUND: Adalimumab is an effective treatment for Crohn's disease (CD), but may also be associated with loss of response. Few reports provide insight into the durability of treatment of CD with adalimumab for periods longer than 12 months in clinical practice. AIMS: To evaluate the long-term durability of adalimumab maintenance treatment and to identify predictive factors associated with loss of response. METHODS: CD patients who initially responded to adalimumab were evaluated in a historical cohort study. Maintenance of long-term response was estimated using Kaplan-Meier analysis. Cox regression analysis was performed to identify potential predictive factors for loss of efficacy. RESULTS: In all, 380 CD patients were included (mean age, 38 years; 52% female). Of these, 43% had ileocolic CD, 50% inflammatory CD, and 41% perianal CD. Median follow-up with adalimumab was 8 months (range, 4-75 months). The annual risk of loss of response to adalimumab was 18% per patient-year of follow-up. Twenty-eight percent of patients were anti-TNF-naïve and 72% anti-TNF-experienced. The loss of efficacy was 8% per patient-year of follow-up in the anti-TNF-naïve patients and 22% in the anti-TNF-experienced group (P < 0.01). In the multivariate analysis, the presence of extraintestinal manifestations (hazard ratio [HR] = 1.7; 95% confidence interval [CI] = 1.02-2.9) and previous experience with other anti-TNF agents (HR = 2.5,95% CI = 1.2-5.3) were associated with higher risk of loss of efficacy. CONCLUSIONS: A relevant proportion of CD patients on long-term adalimumab lost response. The risk of loss of response was higher (more than 2-fold) in anti-TNF-experienced than in anti-TNF-naïve patients (22% vs. 8% per patient-year of treatment). Having extraintestinal manifestations seems to increase the risk of loss of efficacy.


Assuntos
Anti-Inflamatórios/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Doença de Crohn/tratamento farmacológico , Adalimumab , Adolescente , Adulto , Idoso , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Adulto Jovem
8.
J Gastroenterol ; 47(4): 359-65, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22105230

RESUMO

BACKGROUND: Several small, prospective, open studies suggest that leukocytapheresis might be efficient in patients with steroid-dependent ulcerative colitis (UC). AIM: To evaluate the short- and long-term effectiveness of leukocytapheresis for the management of steroid-dependent UC in clinical practice. METHODS: A Web-based, nationwide database specifically designed to record the efficacy and safety data of leukocytapheresis therapy in UC was available from September 2007 in Spain. Clinical data were collected at treatment baseline, 1 month after the last apheresis session (initial efficacy), and 6 and 12 months thereafter (long-term efficacy). Remission was defined as a Mayo Clinic index ≤2 together with complete steroid withdrawal and response as a decrease of ≥3 from the baseline score. RESULTS: A total of 142 steroid-dependent UC patients were included in the registry, most of them treated with the Adacolumn™ system. In 69% of patients thiopurine therapy failed to achieve steroid-free clinical remission. Initial clinical remission was obtained in 37% of cases. The initial corticosteroid dose, the number and frequency of apheresis sessions, or the previous failure of thiopurines and/or infliximab did not influence the initial remission rate, but a greater decrease in CRP levels was associated with a higher probability to obtain initial remission. At 6 and 12 months, 41 and 36% of patients were in clinical remission, respectively. Only one serious adverse effect was recorded. CONCLUSIONS: In clinical practice, apheresis allows long-term steroid-free clinical remission in up to one third of steroid-dependent UC patients, even in those with prior failure of thiopurines.


Assuntos
Colite Ulcerativa/terapia , Leucaférese/métodos , Esteroides/uso terapêutico , Adulto , Colite Ulcerativa/tratamento farmacológico , Bases de Dados Factuais , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Masculino , Indução de Remissão , Espanha , Resultado do Tratamento
9.
Aliment Pharmacol Ther ; 34(5): 544-54, 2011 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-21722149

RESUMO

BACKGROUND: Low thiopurine-methyl-transferase (TPMT) activity and high 6-thioguanine-nucleotide (6TGN) concentrations have been linked to therapeutic success in inflammatory bowel disease patients treated with thiopurines; however, this has not been implemented in clinical practice. AIM: To identify a therapeutic threshold value for TPMT or 6TGN concentrations, and their capability to predict treatment safety and efficacy. METHODS: Prospective multicentre study including steroid-resistant/dependent patients starting thiopurines. The TPMT activity was determined at inclusion (>5 U/mL required). Azathioprine metabolites [6TGN, 6-methyl-mercaptopurine ribonucleotides (6MMP), and 6TGN/6MMP and 6TGN/TPMT ratios] were periodically monitored during steroid tapering and after withdrawal for 6 months or until a new flare occurred. RESULTS: A total of 113 patients were analysed (62% clinical response). Areas under the receiver operating characteristic (ROC) curve (AUC) relating clinical response and metabolite levels at 2, 4 and 6 months after steroid withdrawal were less than 0.7. The AUCs relating final response and initial TPMT activity or metabolite concentrations at 2, 4, 8 and 16 weeks after starting thiopurines were less than 0.7. No cut-off point with worthwhile sensitivity/specificity was found. Eight (7%) patients developed thiopurine-related toxicity that could not be linked to TPMT activity or 6TGN levels. CONCLUSIONS: Our results do not support determination of TPMT activity or 6TGN concentrations to predict treatment outcome, and no useful serum metabolites threshold value to adjust the drug's dose was identified.


Assuntos
Azatioprina/sangue , Imunossupressores/uso terapêutico , Doenças Inflamatórias Intestinais/tratamento farmacológico , Mercaptopurina/análogos & derivados , Mercaptopurina/administração & dosagem , Metiltransferases/sangue , Adolescente , Adulto , Idoso , Área Sob a Curva , Biomarcadores/metabolismo , Relação Dose-Resposta a Droga , Feminino , Nucleotídeos de Guanina/sangue , Humanos , Doenças Inflamatórias Intestinais/enzimologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Curva ROC , Tionucleotídeos/sangue , Resultado do Tratamento , Adulto Jovem
10.
Aliment Pharmacol Ther ; 25(4): 409-18, 2007 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-17269996

RESUMO

BACKGROUND: The use of tumour necrosis factor antagonists has changed the therapeutic approach to Crohn's disease. AIM: To determine response and remission rates associated with the 4-week induction phase of adalimumab treatment in patients with luminal and/or fistulizing Crohn's disease, who have lost response to or become intolerant of infliximab. METHODS: In this multicentre, prospective, open-label, observational, 52-week study, 50 adults received an induction dose of adalimumab (160 mg at baseline followed by 80 mg at week 2). RESULTS: Of the 36 patients with luminal Crohn's disease, 83% achieved clinical response [> or =70-point reduction in the Crohn's Disease Activity Index (CDAI) score] and 42% achieved clinical remission (CDAI score <150) at week 4. Of the 22 patients with fistulizing disease, five (23%) experienced fistula remission (complete closure of all fistulas that were draining at baseline), and nine (41%) experienced fistula improvement (> or =50% decrease in the number of fistulas that were draining at baseline) at week 4. Of the 19 adverse events, most [13 (68%)] were mild, and no serious or infectious adverse events occurred. CONCLUSIONS: Adalimumab may be an effective alternative in patients with luminal and/or fistulizing Crohn's disease who have lost response to or become intolerant of infliximab.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Doença de Crohn/tratamento farmacológico , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Fator de Necrose Tumoral alfa/uso terapêutico , Adalimumab , Adulto , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais Humanizados , Tolerância a Medicamentos , Feminino , Fármacos Gastrointestinais/uso terapêutico , Humanos , Infliximab , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
12.
Gastrointest Endosc ; 54(4): 511-3, 2001 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-11577321

RESUMO

BACKGROUND: The rendezvous technique combines endoscopy with percutaneous transhepatic cholangiography to facilitate cannulation of the bile duct when previous attempts have failed. METHODS: Over a 7-year period, a total of 1753 ERCPs were performed. Twelve of these patients with a diagnosis of choledocholithiasis were poor candidates for surgery. Percutaneous transhepatic cholangiography as well as ERCP with precut papillotomy failed to resolve biliary obstruction. In a further 2 cases the percutaneous approach was used by means of a T-tube positioned at a prior cholecystectomy. OBSERVATIONS: The combined procedure was successful in 13 patients (93%). It was unsuccessful in 1 patient because of a stone lodged distally near the papilla. There was only 1 complication (7%), a retroperitoneal perforation that occurred during papillotomy; no mortality was directly attributable to the technique. CONCLUSIONS: The rendezvous technique is recommended for patients who are not eligible for surgery when ERCP is unsuccessful and when it is impossible to resolve biliary obstruction by percutaneous transhepatic cholangiography.


Assuntos
Colangiopancreatografia Retrógrada Endoscópica , Cálculos Biliares/terapia , Idoso , Cateterismo/métodos , Colangiografia , Feminino , Humanos , Intubação/métodos , Masculino
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...