Assuntos
Colite Ulcerativa , Piperidinas , Pirimidinas , Insuficiência Respiratória , Humanos , Piperidinas/uso terapêutico , Piperidinas/efeitos adversos , Colite Ulcerativa/tratamento farmacológico , Pirimidinas/efeitos adversos , Pirimidinas/uso terapêutico , Insuficiência Respiratória/induzido quimicamente , Pirróis/efeitos adversos , Pirróis/uso terapêutico , Masculino , Inibidores de Proteínas Quinases/efeitos adversos , Inibidores de Proteínas Quinases/uso terapêutico , Pessoa de Meia-Idade , FemininoAssuntos
Azatioprina , Colite Ulcerativa , Proteína Antagonista do Receptor de Interleucina 1 , Humanos , Azatioprina/uso terapêutico , Colite Ulcerativa/tratamento farmacológico , Imunossupressores/uso terapêutico , Proteína Antagonista do Receptor de Interleucina 1/uso terapêutico , Feminino , Adulto Jovem , Resultado do TratamentoAssuntos
Colite Ulcerativa , Terapia Biológica , Endoscopia , Fármacos Gastrointestinais , Humanos , InfliximabRESUMO
OBJECTIVES: The long-term safety of exposure to anti-tumor necrosis factor (anti-TNFα) drugs during pregnancy has received little attention. We aimed to compare the relative risk of severe infections in children of mothers with inflammatory bowel disease (IBD) who were exposed to anti-TNFα drugs in utero with that of children who were not exposed to the drugs. METHODS: Retrospective multicenter cohort study. Exposed cohort: children from mothers with IBD receiving anti-TNFα medication (with or without thiopurines) at any time during pregnancy or during the 3 months before conception. Non-exposed cohort: children from mothers with IBD not treated with anti-TNFα agents or thiopurines at any time during pregnancy or the 3 months before conception. The cumulative incidence of severe infections after birth was estimated using Kaplan-Meier curves, which were compared using the log-rank test. Cox-regression analysis was performed to identify potential predictive factors for severe infections in the offspring. RESULTS: The study population comprised 841 children, of whom 388 (46%) had been exposed to anti-TNFα agents. Median follow-up after delivery was 47 months in the exposed group and 68 months in the non-exposed group. Both univariate and multivariate analysis showed the incidence rate of severe infections to be similar in non-exposed and exposed children (1.6% vs. 2.8% per person-year, hazard ratio 1.2 (95% confidence interval 0.8-1.8)). In the multivariate analysis, preterm delivery was the only variable associated with a higher risk of severe infection (2.5% (1.5-4.3)). CONCLUSIONS: In utero exposure to anti-TNFα drugs does not seem to be associated with increased short-term or long-term risk of severe infections in children.
Assuntos
Antirreumáticos/uso terapêutico , Infecções/epidemiologia , Doenças Inflamatórias Intestinais/tratamento farmacológico , Complicações na Gravidez/tratamento farmacológico , Nascimento Prematuro/epidemiologia , Efeitos Tardios da Exposição Pré-Natal/epidemiologia , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Adalimumab/uso terapêutico , Adulto , Estudos de Casos e Controles , Certolizumab Pegol/uso terapêutico , Pré-Escolar , Estudos de Coortes , Europa (Continente)/epidemiologia , Feminino , Humanos , Incidência , Lactente , Recém-Nascido , Infliximab/uso terapêutico , Estimativa de Kaplan-Meier , Masculino , Análise Multivariada , Gravidez , Modelos de Riscos Proporcionais , Estudos RetrospectivosRESUMO
BACKGROUND: The general increased life expectancy is reflected in the age of patients with inflammatory bowel disease (IBD). The knowledge about efficacy and safety of anti-tumour necrosis factor (TNF) therapy in elderly is scarce and conflicting. AIM: To assess the efficacy and safety of anti-TNF therapy in elderly patients taking into account eventual comorbidity. METHODS: Observational and retrospective single-centred study where 66 IBD patients initiating anti-TNF treatment at age ≥65 years (cases: ≥65 anti-TNF) were compared with 112 IBD patients initiating anti-TNF <65 years (controls <65 anti-TNF) and 61 anti-TNF naïve IBD patients treated with immunosuppressants (IMS) and/or corticosteroids (CS) ≥65 years (controls ≥65 IMS/CS). Controls were matched to cases for IBD type, follow-up, disease duration and anti-TNF type. Comorbidity was assessed by using the Charlson Comorbidity Index (CCI). Both efficacy and safety of treatment were adjusted for comorbidity. RESULTS: The short-term clinical response to anti-TNF at 10 weeks was significantly lower in cases: ≥65 anti-TNF (68% vs. 89%; P < 0.001), whereas at ≥6 months, differences were not significant (79.5% vs. 82.8%; P = 0.639). The risk for any severe adverse events was higher in cases: ≥65 anti-TNF than in controls <65 anti-TNF (RR = 4.7; P < 0.001) or controls ≥65 IMS/CS (RR = 3.09; P = 0.0008). Age older than 65 and CCI > 0 were independent risk factors for malignancy and mortality regardless of the medication. CONCLUSION: Elderly patients treated with anti-TNF have a lower rate of short-term clinical response and a higher rate of severe adverse events than the younger patients under the same treatment.
Assuntos
Anti-Inflamatórios/uso terapêutico , Imunossupressores/uso terapêutico , Doenças Inflamatórias Intestinais/tratamento farmacológico , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Corticosteroides/uso terapêutico , Adulto , Idoso , Comorbidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de RiscoRESUMO
BACKGROUND: A high proportion of patients with inflammatory bowel disease (IBD) do not achieve clinical remission with the current therapies including mesalazine (mesalamine), immunossupresants (IMS) and antibodies against tumour necrosis factor (anti-TNF). Moreover, IMS and anti-TNF involve a nonnegligible risk for infections and/or malignancies. The anti-adhesion molecules are one of the most interesting new treatments because of their gut-selectivity. AIM: To review the physiopathology of the adhesion molecules and the current drugs targeting this mechanism. METHODS: We performed a literature review in PubMed and in clinicaltrials.gov using the terms 'anti-adhesion molecules', 'inflammatory bowel disease', 'natalizumab', 'vedolizumab', 'AMG181', 'Etrolizumab', 'PF-00547659', 'AJM300', 'Alicaforsen' and 'CCX282-B' up to November 2013. RESULTS: A total of eight drugs were found including those targeting the α4ß1, α4ß7 or αEß7 integrins as well as the ICAM-1 and MAdCAM-1 addressins and the chemokine receptor 9. The rationale for these drugs is the blockade of gut-homing T lymphocytes and the ones targeting the α4ß7/MAdCAM-1 interaction presented the most promising results in luminal disease. Vedolizumab, an α4ß7 antibody, has completed phase 3 trials with very positive results especially for ulcerative colitis. However, many questions remain unanswered such as the effect of these therapies in perianal disease and extraintestinal manifestations. CONCLUSIONS: The blockade of the α4ß7/MAdCAM-1 interaction and especially vedolizumab is an effective and safe gut-specific treatment for IBD. Further studies are needed to clarify the efficacy and safety of the other anti-adhesion drugs and to define the specific indications of these therapies in the different scenarios of IBD.
Assuntos
Moléculas de Adesão Celular/antagonistas & inibidores , Colite Ulcerativa/tratamento farmacológico , Doenças Inflamatórias Intestinais/tratamento farmacológico , Animais , Colite Ulcerativa/fisiopatologia , Humanos , Doenças Inflamatórias Intestinais/fisiopatologia , Linfócitos T/imunologia , Fator de Necrose Tumoral alfa/antagonistas & inibidoresRESUMO
AIM: The management of abdominal abscesses complicating Crohn's disease is complex and involves a difficult choice between medical, radiological and surgical procedures. The long-term outcome was compared for two strategies for the management of abdominal abscess: percutaneous drainage (PD) followed by rescue surgery in the case of failure vs direct immediate surgery (IS). We also compared the results of IS with surgery performed after PD failure. METHODS: We retrospectively identified 44 patients with Crohn's disease with an abdominal abscess from January 2000 to December 2009. Therapeutic success was defined as abscess resolution and no reappearance within 1 year of follow-up. RESULTS: The first therapeutic approach was PD in 22 cases and IS in the other 22 cases. IS had a higher therapeutic success rate than PD (95.5% vs 27.2% respectively; P < 0.001). PD was the only independent variable related to treatment failure in the multivariate analysis after adjustment for possible confounders such as abscess size, multilocularity, presence of fistula and corticosteroid use (OR 88.26, 95% CI 7.38-1055.36; P < 0.001). Surgery after failure of PD (n = 16) was associated with longer total hospitalization (56.12 ± 35.89 vs 27.52 ± 15.11 days; P = 0.017) and longer postoperative stay (44.0 ± 83.7 vs 14.3 ± 30 days; P = 0.179) and needed a second operation more often (5/16, 31% vs 1/22, 4.5%; P = 0.065) than IS. CONCLUSIONS: Percutaneous drainage provided durable abscess resolution in only one-third of the patients compared with more than 90% of those treated with IS. In addition, surgery performed after PD failure results in a poorer outcome than IS.
Assuntos
Abscesso Abdominal/cirurgia , Doença de Crohn/complicações , Drenagem , Terapia de Salvação , Abscesso Abdominal/etiologia , Adulto , Feminino , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Reoperação , Estudos Retrospectivos , Fatores de Tempo , Falha de Tratamento , Adulto JovemRESUMO
BACKGROUND: Pyoderma gangrenosum is a serious cutaneous complication seen in approximately 1 % of patients with inflammatory bowel disease (IBD). Oral corticosteroids are the mainstay treatment, although the evidence supporting their use is weak. AIMS: The purpose of this study was to investigate the characteristics of pyoderma gangrenosum associated with Crohn's disease or ulcerative colitis and which treatments are prescribed in Spanish clinical practice. METHODS: In this retrospective, observational study, the medical records from all patients with IBD and a diagnosis of pyoderma gangrenosum attended by the gastroenterology departments of 12 Spanish hospitals were reviewed. Data on patient demographics and characteristics, underlying IBD and treatment, and pyoderma gangrenosum characteristics, treatment, and outcome were collected and analyzed. RESULTS: The data from 67 patients were analyzed (41 [61.2 %] women, 41 [61.2 %] with Crohn's disease, 25 [37.3 %] with ulcerative colitis, and 1 [1.5 %] with indeterminate disease). The underlying disease was in remission in approximately one-third of patients at the time of presentation of pyoderma gangrenosum. Healing was achieved in all patients (in 3 without any systemic therapy). Oral corticosteroids were taken by 51 patients (76.1 %), almost always as first-line treatment, although definitive healing was attained in 19 (28.4 %). Biologic agents such as infliximab and adalimumab were taken by 31 patients (46.3 %) at some point (first-line in 6 patients [9.0 %]), with definitive healing in 29 patients (93.5 %). CONCLUSIONS: Oral corticosteroid therapy remains the most common treatment for pyoderma gangrenosum associated with inflammatory bowel disease. Biologic therapies such as infliximab and adalimumab should also be considered.
Assuntos
Colite Ulcerativa/complicações , Doença de Crohn/complicações , Doenças Inflamatórias Intestinais/complicações , Pioderma Gangrenoso/tratamento farmacológico , Pioderma Gangrenoso/patologia , Adalimumab , Administração Oral , Administração Tópica , Corticosteroides/administração & dosagem , Corticosteroides/uso terapêutico , Adulto , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/uso terapêutico , Feminino , Humanos , Infliximab , Masculino , Pessoa de Meia-Idade , Pioderma Gangrenoso/etiologia , Estudos Retrospectivos , Espanha , Resultado do TratamentoRESUMO
BACKGROUND: The usefulness of reagent strips to check cure of spontaneous bacterial peritonitis have not been evaluated to date. AIM: To assess the usefulness of ascitic fluid analysis by means of reagent strips to check cure after a 5-day antibiotic course. METHODS: We prospectively included all cirrhotic patients diagnosed with spontaneous bacterial peritonitis. On day 5, conventional and reagent strip ascitic fluid analyses were performed. RESULTS: Fifty-three episodes of spontaneous bacterial peritonitis in 51 cirrhotic patients were included. Five patients died before the fifth day and in two patients, the control paracentesis yielded no ascitic fluid. In nine out of 46 cases (19.6%), spontaneous bacterial peritonitis had not resolved by day 5. In 32 out of 33 cases in which the ascitic fluid polymorphonuclear count was <250/microL at day five, the reagent strips was negative. The negative predictive value of the reagent strip at fifth day was 97% and the LR- 0.13. CONCLUSIONS: Almost 20% of episodes of spontaneous bacterial peritonitis do not resolve with a short-course of antibiotic treatment. In view of the high negative predictive value and low likelihood ratio for a negative test, reagent strips analysis may be an alternative to conventional cytology if a 5-day antibiotic therapy is planned.