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1.
Wien Klin Wochenschr ; 132(1-2): 12-18, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31915925

RESUMO

BACKGROUND: The rate of restoration of intestinal continuity after colonic resection and stoma creation in patients with Crohn's disease has not been well-documented in the era of biologics. Thus, the incidence of restoration of intestinal continuity since the introduction of biological drugs was assessed. METHODS: Consecutive patients (n = 43) who underwent colonic resection with ileostomy or colostomy formation for Crohn's disease at a single tertiary referral center between 2002 and 2014 were identified. Data from individual chart review were analyzed retrospectively. Patients were personally contacted for follow-up. RESULTS: Of the 43 patients 8 (18.4%) had a proctectomy leaving 35 patients (81.4%) with the rectum preserved. Of the 30 patients qualifying for final analysis restoration of bowel continuity was finally achieved in 10 patients (33.3%). Permanent stoma rates were comparable in the group of patients with and without biological therapy after surgery (64.3% vs. 60%). The median follow-up period was 7 years (range 3-15 years). Of the patients 20 suffered from perianal disease involvement (66.7%), which was associated with a higher rate of permanent stoma (n = 16/20, 80%) in contrast to patients without perianal disease (n = 4/10, 40%, p = 0.045). CONCLUSION: The overall incidence of stoma formation was low for patients with Crohn's disease; however, once a stoma is created the chance of ending up with a permanent stoma is high even in the era of biologics. Despite the use of new therapeutic agents perianal disease increases the risk of a permanent stoma.


Assuntos
Terapia Biológica , Doença de Crohn , Colostomia , Doença de Crohn/tratamento farmacológico , Doença de Crohn/cirurgia , Feminino , Humanos , Ileostomia , Masculino , Estudos Retrospectivos
2.
Gut ; 69(2): 274-282, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31196874

RESUMO

OBJECTIVES: To better understand the real-world impact of biologic therapy in persons with Crohn's disease (CD) and ulcerative colitis (UC), we evaluated the effect of marketplace introduction of infliximab on the population rates of hospitalisations and surgeries and public payer drug costs. DESIGN: We used health administrative data to study adult persons with CD and UC living in Ontario, Canada between 1995 and 2012. We used an interrupted time series design with segmented regression analysis to evaluate the impact of infliximab introduction on the rates of IBD-related hospitalisations, intestinal resections and public payer drug costs over 10 years among patients with CD and 5 years among patients with UC, allowing for a 1-year transition. RESULTS: Relative to what would have been expected in the absence of infliximab, marketplace introduction of infliximab did not produce significant declines in the rates of CD-related hospitalisations (OR at the last observation quarter 1.06, 95% CI 0.811 to 1.39) or intestinal resections (OR 1.10, 95% CI 0.810 to 1.50), or in the rates of UC-related hospitalisations (OR 1.22, 95% CI 1.07 to 1.39) or colectomies (OR 0.933, 95% CI 0.54 to 1.61). The findings were similar among infliximab users, except that hospitalisation rates declined substantially among UC patients following marketplace introduction of infliximab (OR 0.515, 95% CI 0.342 to 0.777). There was a threefold rise over expected trends in public payer drug cost among patients with CD following infliximab introduction (OR 2.98,95% CI 2.29 to 3.86), suggesting robust market penetration in this group, but no significant change among patients with UC (OR 1.06, 95% CI 0.955 to 1.18). CONCLUSIONS: Marketplace introduction of infliximab has not yielded anticipated reductions in the population rates of IBD-related hospitalisations or intestinal resections, despite robust market penetration among patients with CD. Misguided use of infliximab in CD patients and underuse of infliximab in UC patients may largely explain our study findings.


Assuntos
Fármacos Gastrointestinais/uso terapêutico , Hospitalização/estatística & dados numéricos , Doenças Inflamatórias Intestinais/tratamento farmacológico , /uso terapêutico , Adulto , Colectomia/estatística & dados numéricos , Colectomia/tendências , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/epidemiologia , Colite Ulcerativa/cirurgia , Doença de Crohn/tratamento farmacológico , Doença de Crohn/epidemiologia , Doença de Crohn/cirurgia , Custos de Medicamentos/estatística & dados numéricos , Custos de Medicamentos/tendências , Feminino , Hospitalização/tendências , Humanos , Doenças Inflamatórias Intestinais/epidemiologia , Doenças Inflamatórias Intestinais/cirurgia , Análise de Séries Temporais Interrompida , Masculino , Pessoa de Meia-Idade , Ontário/epidemiologia , Fatores Socioeconômicos
4.
Bratisl Lek Listy ; 120(12): 924-928, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31855052

RESUMO

OBJECTIVES: The aim of this study was to investigate the relationship between thromboxane levels and oxidative stress in children with Crohn´s disease (CD), and examine the effect of natural polyphenolic compounds on thromboxane levels. METHODS: This study involved 14 children suffering from CD and 15 healthy controls. Patients were receiving the polyphenolic extract Pycnogenol for 10 weeks. Plasma levels of the static and dynamic forms of thromboxane B2 as well as their metabolite 11-dehydro thromboxane B2 in urine were determined. RESULTS: In comparison to controls, CD patients had significantly higher levels of the static and dynamic forms of thromboxane B2. Pycnogenol decreased the level of the dynamic form of thromboxane B2 after 10 weeks of administration. CONCLUSIONS: Paediatric Crohn's disease is associated with higher thromboxane levels. Our results indicate that Pycnogenol administration reduces thromboxane levels, which may positively influence some clinical symptoms of CD such as thromboembolic episodes (Tab. 3, Ref. 49).


Assuntos
Doença de Crohn/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Polifenóis/farmacologia , Tromboxanos/sangue , Adolescente , Antioxidantes/metabolismo , Biomarcadores/metabolismo , Estudos de Casos e Controles , Doença de Crohn/sangue , Doença de Crohn/diagnóstico , Doença de Crohn/tratamento farmacológico , Feminino , Flavonoides/administração & dosagem , Humanos , Masculino , Extratos Vegetais/administração & dosagem , Polifenóis/administração & dosagem
5.
Harefuah ; 158(11): 752-754, 2019 Nov.
Artigo em Hebraico | MEDLINE | ID: mdl-31721521

RESUMO

INTRODUCTION: TNFα antagonists, such as infliximab and adalimumab, are widely used for induction and maintenance of remission in pediatric patients with inflammatory bowel disease (IBD). Numerous studies in adult and pediatric patients have demonstrated that monitoring of anti-TNFα drug level improves various outcomes, especially in cases of primary non-response or loss-of-response. In this article we present the recommendations of the Israeli Pediatric Gastroenterology Association regarding measuring anti-TNFα drug and anti-drug levels in pediatric IBD patients. The recommendation to perform these studies will be provided only by a pediatric gastroenterologist based on clinical, laboratory, endoscopic or radiologic signs of active inflammation. We also recommend performing these studies once a year in patients with clinical and biochemical remission. We believe that implementing these recommendations will improve the care provided for pediatric patients with IBD.


Assuntos
Doença de Crohn , Doenças Inflamatórias Intestinais , Fator de Necrose Tumoral alfa , Criança , Doença de Crohn/tratamento farmacológico , Humanos , Doenças Inflamatórias Intestinais/tratamento farmacológico , Infliximab/uso terapêutico , Pacientes , Fator de Necrose Tumoral alfa/antagonistas & inibidores
6.
Surg Clin North Am ; 99(6): 1083-1094, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31676049

RESUMO

Patients with ulcerative colitis and Crohn's disease often present to surgery malnourished and on combination immunosuppression. These factors affect operation selection and postoperative outcomes. Corticosteroids have a well-established detrimental effect on postoperative outcomes, whereas the impact of biologic agents is more controversial. In a patient exposed to these medications, and in the presence of other risk factors, temporary intestinal diversion is likely the best choice. Enteral nutrition may help optimize malnourished patients at high risk of adverse postoperative outcomes.


Assuntos
Corticosteroides/uso terapêutico , Produtos Biológicos/uso terapêutico , Colectomia/métodos , Colite Ulcerativa/tratamento farmacológico , Doença de Crohn/tratamento farmacológico , Progressão da Doença , Tomada de Decisão Clínica , Colite Ulcerativa/diagnóstico , Colite Ulcerativa/cirurgia , Doença de Crohn/diagnóstico , Doença de Crohn/cirurgia , Nutrição Enteral/métodos , Feminino , Humanos , Imunossupressores/uso terapêutico , Doenças Inflamatórias Intestinais/tratamento farmacológico , Doenças Inflamatórias Intestinais/cirurgia , Masculino , Desnutrição/terapia , Período Pré-Operatório , Prognóstico , Resultado do Tratamento
7.
Arq Gastroenterol ; 56(3): 312-317, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31633731

RESUMO

BACKGROUND: There is scarce data regarding efficacy and safety of vedolizumab in inflammatory bowel diseases in Latin America. OBJECTIVE: To describe the first observational real-world experience with vedolizumab in Latin American inflammatory bowel diseases patients. METHODS: Retrospective observational multicentric study of patients with Crohn's disease (CD) and ulcerative colitis (UC) who used vedolizumab at any phase of their treatment. Clinical remission and response (according to Harvey-Bradshaw index for CD and Mayo score for UC), mucosal healing, need for surgery and adverse events were evaluated. RESULTS: A total of 90 patients were included (52 with CD and 38 with UC), the majority with previous exposure to anti-TNF agents (88.46% in CD and 76.31% in UC). In CD (as observed analysis) remission rates at weeks 12, 26 and 52 were 42.89% (21/49), 61.9% (26/42) and 46.15% (12/26), respectively. In UC, remission rates at weeks 12, 26 and 52 were 28.94% (11/38), 36.66% (11/30) and 41.17% (7/17). Mucosal healing rates were 36.11% in CD and 43.4% in UC. During the study period, 7/52 CD patients underwent major abdominal surgery and 4/38 UC patients needed colectomy. CONCLUSION: Vedolizumab was effective in induction and maintenance of clinical response and remission in CD and UC, with no new safety signs.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Colite Ulcerativa/tratamento farmacológico , Doença de Crohn/tratamento farmacológico , Fármacos Gastrointestinais/uso terapêutico , Adulto , Brasil , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Indução de Remissão , Estudos Retrospectivos , Resultado do Tratamento
8.
Arq Gastroenterol ; 56(3): 318-322, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31633732

RESUMO

BACKGROUND: The introduction of anti-TNF agents represented a landmark in the management of both Crohn's disease (CD) and ulcerative colitis (UC), with improved efficacy and safety when compared with conventional treatment. However, significant challenges still exist in Latin America to facilitate the access of biological agents for physicians and patients. OBJECTIVE: The aim of this review was to summarize current evidence on penetration of biological agents for CD and UC in Latin America. METHODS: Data are derived from a previous complete systematic review that explored different characteristics of inflammatory bowel diseases (IBD) in Latin America. The studies fully included in this previous systematic review which contained detailed descriptions of the percentage of use of biological agents in different cohorts throughout Latin American and Caribbean countries were included, and descriptive findings were compiled, describing CD and UC penetration of these drugs in different patient cohorts from different countries. RESULTS: From the 61 studies included in the original systematic review, only 19 included data of the percentage of patients treated with biological agents. Anti-TNF use in CD varied from 1.51% in Mexico up to 46.9% in Colombia, with most of the studies describing anti-TNF use in approximately 20%-40% of CD patients. On the other side, the frequency of the use of biologics was clearly lower in UC, varying from 0% in 2009 to up 16.2% in 2018, according to two different Mexican studies. Only two studies described the penetration of anti-TNF agents in IBD overall: 13.4% in a Colombian and 37.93% in a Brazilian study. No studies described percentage of use of new biologic agents (vedolizumab and ustekinumab). CONCLUSION: Penetration of anti-TNF agents in Latin America is comparable to the rest of the world in CD, but lower in UC. With the increase in the incidence and prevalence of IBD, specific strategies to increase access to anti-TNF agents in UC and new biological agents overall are warranted.


Assuntos
Doenças Inflamatórias Intestinais/tratamento farmacológico , Fator de Necrose Tumoral alfa/uso terapêutico , Terapia Biológica , Colite Ulcerativa/tratamento farmacológico , Doença de Crohn/tratamento farmacológico , Humanos , América Latina , Revisão Sistemática como Assunto
9.
Z Gastroenterol ; 57(10): 1218-1225, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31610585

RESUMO

INTRODUCTION: Response to anti-TNF therapy is crucial for life expectancy and life quality in patients with severe Crohn's disease. We investigated if a previously reported gene expression profile predictive for infliximab response could be also applied to adalimumab response in an independent cohort. METHODS: Forty-seven Slovene Crohn's disease patients indicated for adalimumab therapy were enrolled in the study. Inflamed and non-inflamed colon biopsy samples were obtained during routine colonoscopy prior to adalimumab treatment. Response to adalimumab was measured with IBDQ. Gene expression in inflamed and non-inflamed colon biopsy samples was measured with RT-qPCR. Genotypes were extracted from previously available genotype data. Statistical analysis was performed with SPSS software. The R package e1071 was used to train bootstrap aggregated support vector machines (SVM). RESULTS: SVM prediction model analysis was used to analyze pooled, non-inflamed, and inflamed colon tissue datasets using IBDQ response after 4, 12, 20 and 30 weeks of adalimumab treatment. The bagging approach was used in an endeavor to obtain 100 % accuracy using 10 × 100 or 100 × 100 iterations. Average adalimumab response prediction accuracy is 75.5 % for pooled samples, 90.5 % for inflamed samples, and 100 % for non-inflamed samples. Moreover, models trained on selected SNPs from analyzed genes had an average accuracy of 92.8 %, confirming the involvement of genetic regions mapping the reported genes. Finally, using combined gene expression and SNP data we observed 100 % adalimumab response prediction accuracy for pooled, inflamed, and non-inflamed datasets. DISCUSSION: Our study supports the reported genetic anti-TNF response profile and extends it for adalimumab prediction.


Assuntos
Adalimumab , Doença de Crohn , Marcadores Genéticos , Adalimumab/uso terapêutico , Adulto , Anti-Inflamatórios/uso terapêutico , Doença de Crohn/tratamento farmacológico , Doença de Crohn/genética , Feminino , Perfilação da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Farmacogenética , Eslovênia
11.
Dis Colon Rectum ; 62(11): 1352-1362, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31567927

RESUMO

BACKGROUND: The evidence regarding the association of preoperative biologic exposure and postoperative outcomes remains controversial for both antitumor necrosis factor agents and vedolizumab and largely unknown for ustekinumab. OBJECTIVE: The purpose of this study was to determine differences in the rates of 30-day postoperative overall infectious complications and intra-abdominal septic complications among the 3 classes of biologic therapies as compared with no biologic therapy. DESIGN: This was a retrospective review. SETTINGS: The study was conducted at an IBD referral center. PATIENTS: Adult patients with Crohn's disease who received an antitumor necrosis factor, vedolizumab, ustekinumab, or no biologic therapy within 12 weeks of a major abdominal operation between May 20, 2014, and December 31, 2017, were included. MAIN OUTCOMES MEASURES: Thirty-day overall postoperative infectious complications and intra-abdominal septic complications were measured. RESULTS: A total of 712 patients with Crohn's disease were included; 272 patients were exposed to an antitumor necrosis factor agents, 127 to vedolizumab, 38 to ustekinumab, and 275 to no biologic therapy within the 12 weeks before an abdominal operation. Patients exposed to a biologic were more likely to be taking a concurrent immunomodulator, but there was no difference in concurrent corticosteroid usage. The particular class of biologic was not independently associated with total overall infectious complications. Vedolizumab was associated with an increased rate of intra-abdominal sepsis on univariate analysis but not on multivariable analysis. Combination immunosuppression was associated with both an increased rate of overall postoperative infectious complications and intra-abdominal sepsis. LIMITATIONS: The study was limited by its retrospective design and single-center data. CONCLUSIONS: The overall rate of total infectious complications or intra-abdominal septic complications was not increased based on preoperative exposure to a particular class of biologic. Rates increased with combination immunosuppression of biologic therapy with corticosteroids and previous abdominal resection. See Video Abstract at http://links.lww.com/DCR/B24. BIOLÓGICOS Y COMPLICACIONES POSTOPERATORIAS DE 30 DÍAS DESPUÉS DE LAS OPERACIONES ABDOMINALES PARA LA ENFERMEDAD DE CROHN: ¿EXISTEN DIFERENCIAS EN LOS PERFILES DE SEGURIDAD?:: La evidencia sobre la asociación de la exposición biológica preoperatoria y los resultados postoperatorios sigue siendo controvertida controversial tanto para los agentes del factor de necrosis tumoral (anti-TNF) como para el vedolizumab, y en gran parte desconocida para el ustekinumab.Determinar las diferencias en las tasas de complicaciones infecciosas generales postoperatorias de 30 días y complicaciones sépticas intraabdominales entre las tres clases de terapias biológicas en comparación con ninguna terapia biológica.Revisión retrospectiva.centro de referencia de la enfermedad inflamatoria intestinal.Pacientes adultos con enfermedad de Crohn que recibieron un factor de necrosis antitumoral, vedolizumab, ustekinumab o ningún tratamiento biológico dentro de las 12 semanas de una operación abdominal mayor entre el 5/20/2014 y el 12/31/2017.Complicaciones infecciosas postoperatorias generales de 30 días, complicaciones sépticas intraabdominales.Se incluyeron setecientos doce pacientes con enfermedad de Crohn; 272 pacientes fueron expuestos a un anti-TNF, 127 a vedolizumab, 38 a ustekinumab y 275 a ninguna terapia biológica dentro de las 12 semanas previas a una operación abdominal. Los pacientes expuestos a un producto biológico tenían más probabilidades de tomar un inmunomodulador concurrente, pero no hubo diferencias en el uso simultáneo de corticosteroides. La clase particular de productos biológicos no se asoció de forma independiente con las complicaciones infecciosas totales. Vedolizumab se asoció con una mayor tasa de sepsis intraabdominal en el análisis univariable, pero no en el análisis multivariable. La inmunosupresión combinada se asoció tanto con una mayor tasa de complicaciones infecciosas postoperatorias generales como con sepsis intraabdominal.Diseño retrospectivo, datos de centro único.La tasa general de complicaciones infecciosas totales o complicaciones sépticas intraabdominales no aumentó en función de la exposición preoperatoria a una clase particular de productos biológicos. Las tasas aumentaron con la combinación de inmunosupresión de la terapia biológica con corticosteroides y resección abdominal previa. Vea el Resumen del Video en http://links.lww.com/DCR/B24.


Assuntos
Anticorpos Monoclonais Humanizados , Colectomia , Doença de Crohn , Infecções Intra-Abdominais , Complicações Pós-Operatórias , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Ustekinumab , Adulto , Anti-Inflamatórios/efeitos adversos , Anti-Inflamatórios/uso terapêutico , Anticorpos Monoclonais Humanizados/efeitos adversos , Anticorpos Monoclonais Humanizados/uso terapêutico , Produtos Biológicos/efeitos adversos , Produtos Biológicos/uso terapêutico , Colectomia/efeitos adversos , Colectomia/métodos , Doença de Crohn/tratamento farmacológico , Doença de Crohn/imunologia , Doença de Crohn/cirurgia , Monitoramento de Medicamentos/métodos , Feminino , Seguimentos , Humanos , Interleucina-12/antagonistas & inibidores , Interleucina-23/antagonistas & inibidores , Infecções Intra-Abdominais/diagnóstico , Infecções Intra-Abdominais/epidemiologia , Infecções Intra-Abdominais/etiologia , Masculino , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/epidemiologia , Período Pré-Operatório , Estados Unidos , Ustekinumab/efeitos adversos , Ustekinumab/uso terapêutico
12.
Arq Gastroenterol ; 56(4): 351-356, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31618395

RESUMO

BACKGROUND: Physical activity in daily life and exercise capacity have not been assessed in patients with Crohn's disease to date. OBJECTIVE: To evaluate the physical activity in daily life, exercise capacity, quality of life, and prevalence of mood disorders in patients with moderate-to-severe Crohn's disease on infliximab-induced remission and the possible associations among variables. METHODS: A cross-sectional preliminary study was conducted. Twenty-six patients with Crohn's disease and 20 controls were selected. Participants underwent evaluation of physical activity in daily life (triaxial accelerometer), exercise capacity (shuttle walk test), handgrip strength, quality of life, and presence of mood disorders. RESULTS: The number of steps taken (7446±3081 vs 7898±2487), active time (80.6±42 vs 89.7±24.3min), shuttle walk test distance [665 (405) vs 710 (409) m] and handgrip strength [31 (15) vs 29 (20) kgf did not show any difference between the patients with Crohn's disease and the controls. The time spent lying down [95.8 (68.8) vs 60.9 (74.7) min] was greater and some domains of the quality of life were superior in the patients with Crohn's disease. No correlation was observed between the physical activity in daily life and quality of life or presence of mood disorders in patients with Crohn's disease. CONCLUSION: Patients with Crohn's disease on infliximab-induced remission, despite to more time spent lying down, they have the same level of physical activity in daily life and exercise capacity min compared with the controls.


Assuntos
Doença de Crohn/tratamento farmacológico , Doença de Crohn/psicologia , Exercício/psicologia , Fármacos Gastrointestinais/administração & dosagem , Infliximab/administração & dosagem , Transtornos do Humor/psicologia , Qualidade de Vida/psicologia , Adulto , Estudos de Casos e Controles , Doença de Crohn/radioterapia , Estudos Transversais , Tolerância ao Exercício , Feminino , Humanos , Masculino , Prevalência , Índice de Gravidade de Doença
13.
Expert Opin Pharmacother ; 20(17): 2161-2168, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31574236

RESUMO

Introduction: Crohn's disease (CD) is a chronic inflammatory condition that can occur throughout the gastrointestinal tract. The aims of treatment of children with CD are to induce and maintain clinical remission of disease, optimize nutrition and growth, minimize adverse effects of therapies, and if possible, achieve mucosal healing.Areas covered: This review summarizes evidence for the various therapeutic options in the treatment of children with CD. Exclusive enteral nutrition, corticosteroids, and biologics may be used for induction of remission. Immunomodulators (thiopurines, methotrexate) and biologics (infliximab, adalimumab) may be employed for maintenance of remission to prevent flares of disease and avoid chronic steroid use. In cases of fibrotic disease, intestinal perforations, or medically refractory, surgery may be the best therapeutic option.Expert opinion: Exclusive enteral nutrition, corticosteroids, and biologics (including anti-TNF inhibitors) may be used for induction of remission in patients with active flare of their disease. Immunomodulators and TNF inhibitors may be used for maintenance of remission. Early use of anti-TNF inhibitors in patients with moderate to severe CD may improve efficacy and prevent penetrating complications of disease. While pediatric data is limited, newer biologics, such as vedolizumab and ustekinumab, are used off-label in anti-TNF refractory disease.


Assuntos
Adalimumab/uso terapêutico , Doença de Crohn/tratamento farmacológico , Fatores Imunológicos/uso terapêutico , Infliximab/uso terapêutico , Adalimumab/efeitos adversos , Corticosteroides/efeitos adversos , Corticosteroides/uso terapêutico , Criança , Ensaios Clínicos como Assunto , Humanos , Fatores Imunológicos/efeitos adversos , Infliximab/efeitos adversos , Indução de Remissão
15.
Cochrane Database Syst Rev ; 9: CD013210, 2019 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-31513295

RESUMO

BACKGROUND: Crohn's disease (CD) is a chronic disease of the gut. About 75% of people with CD undergo surgery at least once in their lifetime to induce remission. However, as there is no known cure for the disease, patients usually experience a recurrence even after surgery. Different interventions are routinely used in maintaining postsurgical remission. There is currently no consensus on which treatment is the most effective. OBJECTIVES: To assess the effects and harms of interventions for the maintenance of surgically induced remission in Crohn's disease and rank the treatments in order of effectiveness. SEARCH METHODS: We searched the Cochrane IBD Group Specialized Register, CENTRAL, MEDLINE, and Embase from inception to 15 January 2019. We also searched reference lists of relevant articles, abstracts from major gastroenterology meetings, ClinicalTrials.gov, and the WHO ICTRP. There was no restriction on language, date, or publication status. SELECTION CRITERIA: We considered for inclusion randomised controlled trials (RCTs) that compared different interventions used for maintaining surgically induced remission in people with CD who were in postsurgical remission. Participants had to have received maintenance treatment for at least three months. We excluded studies assessing enteral diet, diet manipulation, herbal medicine, and nutritional supplementation. DATA COLLECTION AND ANALYSIS: Two review authors independently selected relevant studies, extracted data, and assessed the risk of bias. Any disagreements were resolved by discussion or by arbitration of a third review author when necessary. We conducted a network meta-analysis (NMA) using a Bayesian approach through Markov Chain Monte Carlo (MCMC) simulation. For the pairwise comparisons carried out in Review Manager 5, we calculated risk ratios (RR) with their corresponding 95% confidence intervals (95% CI). For the NMA, we presented hazard ratios (HR) with corresponding 95% credible intervals (95% CrI) and reported ranking probabilities for each intervention. For the NMA, we focused on three main outcomes: clinical relapse, endoscopic relapse, and withdrawals due to adverse events. Data were insufficient to assess time to relapse and histologic relapse. Adverse events and serious adverse events were not sufficiently or objectively reported to permit an NMA. We used CINeMA (Confidence in Network Meta-Analysis) methods to evaluate our confidence in the findings within networks, and GRADE for entire networks. MAIN RESULTS: We included 35 RCTs (3249 participants) in the review. The average age of study participants ranged between 33.6 and 38.8 years. Risk of bias was high in 18 studies, low in four studies, and unclear in 13 studies. Of the 35 included RCTs, 26 studies (2581 participants; 9 interventions) were considered eligible for inclusion in the NMA. The interventions studied included 5-aminosalicylic acid (5-ASA), adalimumab, antibiotics, budesonide, infliximab, probiotics, purine analogues, sulfasalazine, and a combination of sulfasalazine and prednisolone. This resulted in 30 direct contrasts, which informed 102 mixed-treatment contrasts.The evidence for the clinical relapse network (21 studies; 2245 participants) and endoscopic relapse (12 studies; 1128 participants) were of low certainty while the evidence for withdrawal due to adverse events (15 studies; 1498 participants) was of very low certainty. This assessment was due to high risk of bias in most of the studies, inconsistency, and imprecision across networks. We mainly judged individual contrasts as of low or very low certainty, except 5-ASA versus placebo, the evidence for which was judged as of moderate certainty.We ranked the treatments based on effectiveness and the certainty of the evidence. For clinical relapse, the five most highly ranked treatments were adalimumab, infliximab, budesonide, 5-ASA, and purine analogues. We found some evidence that adalimumab (HR 0.11, 95% Crl 0.02 to 0.33; low-certainty evidence) and 5-ASA may reduce the probability of clinical relapse compared to placebo (HR 0.69, 95% Crl 0.53 to 0.87; moderate-certainty evidence). However, budesonide may not be effective in preventing clinical relapse (HR 0.66, 95% CrI 0.27 to 1.34; low-certainty evidence). We are less confident about the effectiveness of infliximab (HR 0.36, 95% CrI 0.02 to 1.74; very low-certainty evidence) and purine analogues (HR 0.75, 95% CrI 0.55 to 1.00; low-certainty evidence). It was unclear whether the other interventions reduced the probability of a clinical relapse, as the certainty of the evidence was very low.Due to high risk of bias and limited data across the network, we are uncertain about the effectiveness of interventions for preventing endoscopic relapse. Whilst there might be some evidence of prevention of endoscopic relapse with adalimumab (HR 0.10, 95% CrI 0.01 to 0.32; low-certainty evidence), no other intervention studied appeared to be effective.Due to high risk of bias and limited data across the network, we are uncertain about the effectiveness of interventions for preventing withdrawal due to adverse events. Withdrawal due to adverse events appeared to be least likely with sulfasalazine (HR 1.96, 95% Crl 0.00 to 8.90; very low-certainty evidence) and most likely with antibiotics (HR 53.92, 95% Crl 0.43 to 259.80; very low-certainty evidence). When considering the network as a whole, two adverse events leading to study withdrawal (i.e. pancreatitis and leukopenia) occurred in more than 1% of participants treated with an intervention. Pancreatitis occurred in 2.8% (11/399) of purine analogue participants compared to 0.17% (2/1210) of all other groups studied. Leukopenia occurred in 2.5% (10/399) of purine analogue participants compared to 0.08% (1/1210) of all other groups studied. AUTHORS' CONCLUSIONS: Due to low-certainty evidence in the networks, we are unable to draw conclusions on which treatment is most effective for preventing clinical relapse and endoscopic relapse. Evidence on the safety of the interventions was inconclusive, however cases of pancreatitis and leukopenia from purine analogues were evident in the studies. Larger trials are needed to further understand the effect of the interventions on endoscopic relapse.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Doença de Crohn/prevenção & controle , Quimioterapia de Manutenção/métodos , Anti-Inflamatórios não Esteroides/uso terapêutico , Antimetabólitos/uso terapêutico , Doença de Crohn/tratamento farmacológico , Doença de Crohn/cirurgia , Humanos , Imunossupressores/uso terapêutico , Meta-Análise em Rede , Ensaios Clínicos Controlados Aleatórios como Assunto , Recidiva , Indução de Remissão , Prevenção Secundária
16.
Internist (Berl) ; 60(10): 1043-1058, 2019 Oct.
Artigo em Alemão | MEDLINE | ID: mdl-31501913

RESUMO

Therapeutic regimens using monoclonal antibodies have been implemented in clinical daily practice for various gastroenterological diseases, for therapeutic strategies in gastrointestinal (GI) oncology, and infectious diseases of the gastrointestinal tract. The main indications remain the therapy of chronic inflammatory bowel disease and in GI oncology. A new field has opened for targeted therapy with monoclonal antibodies of recurrent Clostridium difficile infection. In the nomenclature of monoclonal antibodies, the endings of the substances indicate the production or degree of "humanization" of the respective antibodies ("umab": fully human, recombinant antibody; "ximab": chimeric antibody with variable murine domain). For chronic inflammatory bowel disease, monoclonal antibodies has been developed to interfere with molecular targets of the inflammatory cascade in the underlying pathogenesis (tumor necrosis factor­α, interleukin-12 and -23; α4ß7-integrins). The development of targeted therapies in the treatment of GI malignancies, monoclonal antibodies has been developed to interfere with substantial pathways of proliferation and apoptosis as well as neoplastic vascularization and neovascularization (e.g., vascular endothelial growth factor [VEGF] and VEGF receptor antibodies, epidermal growth factor receptor antibodies, HER2/neu antibodies). In the current review, we provide a summary of the current applications of monoclonal antibodies in the therapeutic treatment of gastroenterological diseases.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Gastroenteropatias/tratamento farmacológico , Fatores Imunológicos/uso terapêutico , Doenças Inflamatórias Intestinais/tratamento farmacológico , Terapia de Alvo Molecular/métodos , Animais , Anticorpos Monoclonais/farmacologia , Antineoplásicos Imunológicos , Colite Ulcerativa/tratamento farmacológico , Neoplasias Colorretais/tratamento farmacológico , Doença de Crohn/tratamento farmacológico , Receptores ErbB/efeitos dos fármacos , Gastroenterologia , Humanos , Fatores Imunológicos/farmacologia , Camundongos , Receptores de Fatores de Crescimento do Endotélio Vascular/efeitos dos fármacos , Neoplasias Gástricas/tratamento farmacológico , Fator A de Crescimento do Endotélio Vascular
17.
Cochrane Database Syst Rev ; 8: CD012893, 2019 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-31476018

RESUMO

BACKGROUND: Crohn's disease (CD) is a chronic inflammatory disease of the gastrointestinal tract, and immune response modulation is the main treatment strategy to induce remission in active CD. Certolizumab pegol (CZP) is a tumor necrosis factor-alfa (TNF-α) inhibitor which regulates impaired immune response. OBJECTIVES: The primary objectives were to evaluate the efficacy and safety of CZP for the induction of remission in CD. SEARCH METHODS: We searched MEDLINE, Embase, CENTRAL, the Cochrane IBD group specialized register, trials registers and other sources from inception to 28 January 2019. Moreover, we contacted the pharmaceutical company that manufactures CZP. SELECTION CRITERIA: We included randomized controlled trials comparing CZP with placebo or no treatment in active CD patients. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methodological procedures. The main outcomes selected for GRADE analysis were clinical remission at week 8 (Crohn's Disease Activity Index [CDAI] ≤150), clinical response at week 8 (CDAI reduction ≥ 100 or clinical remission), and serious adverse events. The Mantel-Haenszel random-effects method was applied for the statistical analyses. For dichotomous outcomes, we calculated the risk ratio (RR) and corresponding 95% confidence interval (95% CI). MAIN RESULTS: Four studies involving 1485 participants with moderate to severe CD met the inclusion criteria and were used in the meta-analyses. All studies included active CD patients with CDAI ranging from 220 to 450. Most patients were adults over 18 years of age. One study was identified as high risk of bias due to a non-identical placebo while the other studies were judged to be at low risk of bias.CZP (100 mg to 400 mg every 2 to 4 weeks) was shown to be superior to placebo for achieving clinical remission at week 8 (RR 1.36, 95% CI 1.11 to 1.66; moderate certainty evidence). The raw numbers of participants achieving clinical remission at week 8 were 26.9% (225/835) and 19.8% (129/650) in the CZP and the placebo groups, respectively.CZP was shown to be superior to placebo for achieving clinical response at week 8 (RR 1.29, 95% CI 1.09 to 1.53; moderate certainty evidence). In raw numbers, clinical response at week 8 was achieved in 40.2% (336/835) and 30.9% (201/650) of participants in the CZP and the placebo groups, respectively.In raw numbers, serious adverse events were observed in 8.7% (73/835) and 6.2% (40/650) of participants in the CZP and the placebo groups, respectively (RR 1.35, 95% CI 0.93 to 1.97; moderate certainty evidence). Serious adverse events included worsening Crohn's disease, infections, and malignancy. AUTHORS' CONCLUSIONS: Moderate certainty evidence suggests that CZP is effective for induction of clinical remission and clinical response in participants with active CD patients. It is uncertain whether the risk of serious adverse events differs between CZP and placebo as the 95% CI includes the possibility of a small decrease or doubling of events. Future studies are needed to evaluate the long-term efficacy and safety of CZP in CD patients.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Certolizumab Pegol/uso terapêutico , Doença de Crohn/tratamento farmacológico , Humanos , Fatores Imunológicos/uso terapêutico , Quimioterapia de Indução , Ensaios Clínicos Controlados Aleatórios como Assunto , Indução de Remissão
18.
Medicine (Baltimore) ; 98(33): e16622, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31415355

RESUMO

OBJECTIVE: This study aimed to investigate the correlation of serum Jun-amino-terminal kinase (JNK) pathway-associated phosphatase (JKAP) level with disease risk, severity, inflammation, and treatment response to tumor necrosis factor (TNF)-α inhibitor in Crohn disease (CD) patients. METHOD: Ninety-six active CD patients and 90 healthy controls (HCs) were consecutively enrolled. Serum JKAP level of participants was determined via enzyme-linked immunosorbent assay (ELISA). In CD patients, C-reactive protein (CRP), erythrocyte sedimentation rate, Crohn disease activity index (CDAI), and inflammatory cytokine levels (determined by ELISA) were recorded. All CD patients underwent infliximab (IFX) treatment for 12 weeks, then treatment response (defined as decrement of CDAI ≥70) was assessed at week 12 (W12). RESULTS: Serum JKAP level in CD patients was lower compared to HCs, and it disclosed a good predictive value for decreased CD risk; meanwhile, it was negatively correlated with CRP level, CDAI score, TNF-α, interleukin (IL)-6, and IL-17 levels in CD patients. Sixty-eight (70.8%) patients achieved treatment response to IFX at W12, and JKAP level was increased at W12 compared to baseline. Interestingly, baseline JKAP level in response patients was decreased compared to nonresponse patients, and it exhibited a good predictive value for decreased treatment response to IFX, multivariate logistic regression revealed that JKAP was an independent factor for predicting reduced IFX response. CONCLUSION: Circulating JKAP expression correlates with decreased disease risk, activity, and inflammation level, and it could be served as a novel biomarker for predicting reduced clinical response to TNF-α inhibitor in CD patients.


Assuntos
Doença de Crohn/tratamento farmacológico , Fármacos Gastrointestinais/uso terapêutico , Sistema de Sinalização das MAP Quinases/fisiologia , Monoéster Fosfórico Hidrolases/sangue , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Adulto , Biomarcadores/sangue , Sedimentação Sanguínea , Proteína C-Reativa/metabolismo , Doença de Crohn/sangue , Citocinas/sangue , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Inflamação , Infliximab/uso terapêutico , Masculino , Fatores de Risco , Resultado do Tratamento
19.
Pediatr Neonatol ; 60(4): 396-404, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31409456

RESUMO

BACKGROUND: Current knowledge on the clinical features and natural history of childhood primary sclerosing cholangitis - inflammatory bowel disease in Asia is limited. We described the presenting features and natural history of primary sclerosing cholangitis-inflammatory bowel disease seen in a cohort of Southeast Asian children. METHODS: We conducted a retrospective review of childhood primary sclerosing cholangitis-inflammatory bowel disease from three tertiary centers in Singapore and Malaysia. RESULTS: Of 24 patients (boys, 58%; median age at diagnosis: 6.3 years) with primary sclerosing cholangitis-inflammatory bowel disease (ulcerative colitis, n = 21; Crohn's disease, n = 1; undifferentiated, n = 2), 63% (n = 15) were diagnosed during follow-up for colitis, and 21% (n = 5) presented with acute or chronic hepatitis, 17% (n = 4) presented simultaneously. Disease phenotype of liver involvement showed 79% had sclerosing cholangitis-autoimmune hepatitis overlap, 54% large duct disease, and 46% small duct disease. All patients received immunosuppression therapy. At final review after a median [±S.D.] duration follow-up of 4.7 [±3.8] years, 12.5% patients had normal liver enzymes, 75% persistent disease, and 12.5% liver failure. The proportion of patients with liver cirrhosis increased from 13% at diagnosis to 29%; 21% had portal hypertension, and 17% had liver dysfunction. One patient required liver transplant. Transplant-free survival was 95%. For colitis, 95% had pancolitis, 27% rectal sparing, and 11% backwash ileitis at initial presentation. At final review, 67% patients had quiescent bowel disease with immunosuppression. One patient who had UC with pancolitis which was diagnosed at 3 years old developed colorectal cancer at 22 years of age. All patients survived. CONCLUSIONS: Liver disease in primary sclerosing cholangitis-inflammatory bowel disease in Asian children has variable severity. With immunosuppression, two-thirds of patients have quiescent bowel disease but the majority have persistent cholangitis and progressive liver disease.


Assuntos
Colagogos e Coleréticos/uso terapêutico , Colangite Esclerosante/tratamento farmacológico , Hepatite Autoimune/tratamento farmacológico , Imunossupressores/uso terapêutico , Doenças Inflamatórias Intestinais/tratamento farmacológico , Cirrose Hepática Biliar/etiologia , Adolescente , Grupo com Ancestrais do Continente Asiático , Criança , Pré-Escolar , Colangite Esclerosante/complicações , Colangite Esclerosante/fisiopatologia , Estudos de Coortes , Colite Ulcerativa/complicações , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/fisiopatologia , Doença de Crohn/complicações , Doença de Crohn/tratamento farmacológico , Doença de Crohn/fisiopatologia , Progressão da Doença , Feminino , Hepatite Autoimune/complicações , Hepatite Autoimune/fisiopatologia , Humanos , Hipertensão Portal/etiologia , Doenças Inflamatórias Intestinais/complicações , Doenças Inflamatórias Intestinais/fisiopatologia , Hepatopatias/etiologia , Transplante de Fígado , Malásia , Masculino , Estudos Retrospectivos , Singapura , Adulto Jovem
20.
Medicine (Baltimore) ; 98(32): e16750, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31393390

RESUMO

RATIONALE: Crohn disease includes 3 phenotypes, inflammatory, stricturing, and penetrating. In cases where corticosteroids and immunosuppressive agents are not suitable treatment options, enteral nutrition (EN) can be used to reduce disease severity and enhance barrier defense with fewer potential adverse effects. PATIENT CONCERNS: A 23-year-old man with abdominal pain and diarrhea presented at our hospital in 2014. The frequency of defecation was 3 or 4 times a day without mucus or blood in the stool. His body mass index was 15.8, and in laboratory tests the erythrocyte sedimentation rate was 42.4 mm/h, serum C reactive protein was 65.2 mg/L, the leukocyte count was 11.64 × 109/L, and hemoglobin was 111 g/L. DIAGNOSIS: In computed tomography (CT) enterography the ascending colon was thickened, and there was effusion and enlarged lymph nodes around the colon. Colonoscopy revealed ulcer, polypoid proliferation, and bowel stenosis in many segments. Chronic inflammation was evident in multiple biopsies. Crohn disease was diagnosed based on the above observations. INTERVENTIONS: Mesalazine was administered at a dose of 4 g daily for 2 years. The patient was hospitalized again due to severe abdominal pain and ongoing fever. Intestinal perforation was detected via CT. Percutaneous drainage was performed followed by administration of intravenous metronidazole (0.5 g) and ciprofloxacin (0.2 g) twice a day. Peptison liquid was used as exclusive EN. After 2 weeks the antibiotics regimen was changed to metronidazole 0.4 g twice a day and ciprofloxacin 0.25 g 3 times a day, both administered orally. OUTCOMES: CT revealed that the infection was eliminated and the fistula was healed after 10 weeks, at which point antibiotics and exclusive EN was discontinued. Azathioprine was prescribed at a dose of 2 mg/kg daily to maintain clinical remission. The patient did not report any pain or diarrhea at a 1-year follow-up visit. LESSONS: The present case suggests that exclusive EN combined with antibiotics is useful in inducing remission in Crohn disease patients with active disease and penetrating complications.


Assuntos
Doença de Crohn/complicações , Doença de Crohn/terapia , Nutrição Enteral/métodos , Perfuração Intestinal/etiologia , Perfuração Intestinal/terapia , Adulto , Antibacterianos/uso terapêutico , Doença de Crohn/tratamento farmacológico , Humanos , Perfuração Intestinal/tratamento farmacológico , Masculino , Indução de Remissão , Índice de Gravidade de Doença , Tomografia Computadorizada por Raios X
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