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1.
Dig Liver Dis ; 56(1): 21-28, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37137808

RESUMO

BACKGROUND: Anti-TNF agents are the first biologic treatment option in inflammatory bowel disease (IBD). The long-term effectiveness of this strategy at the population level is poorly known, particularly in pediatric-onset IBD. METHODS: All patients diagnosed with Crohn's disease (CD) or ulcerative colitis (UC) before the age of 17 between 1988 and 2011 in the EPIMAD population-based registry were followed retrospectively until 2013. Among patients treated with anti-TNF, the cumulative probabilities of anti-TNF failure defined by primary failure, loss of response (LOR) or intolerance were evaluated. Factors associated with anti-TNF failure were investigated by a Cox model. RESULTS: Among a total of 1,007 patients with CD and 337 patients with UC, respectively 481 (48%) and 81 (24%) were treated with anti-TNF. Median age at anti-TNF initiation was 17.4 years (IQR, 15.1-20.9). Median duration of anti-TNF therapy was 20.4 months (IQR, 6.0-59.9). In CD, the probability of failure of 1st line anti-TNF at 1, 3 and 5 years was respectively 30.7%, 51.3% and 61.9% for infliximab and 25.9%, 49.3% and 57.7% for adalimumab (p = 0.740). In UC, the probability of failure of 1st line anti-TNF therapy was respectively 38.4%, 52.3% and 72.7% for infliximab and 12.5% for these 3 timepoints for adalimumab (p = 0.091). The risk of failure was maximal in the first year of treatment and LOR was the main reason for discontinuation. Female gender was associated with LOR (HR, 1.48; 95%CI 1.02-2.14) and with anti-TNF withdrawal for intolerance in CD (HR, 2.31; 95%CI 1.30-4.11) and disease duration (≥ 2 y vs. < 2 y) was associated with LOR in UC (HR, 0.37; 95%CI 0.15-0.94) in multivariate analysis. Sixty-three (13.5%) patients observed adverse events leading to termination of treatment (p = 0.57). No death, cancer or tuberculosis was observed while the patients were under anti-TNF treatment. CONCLUSION: In a population-based study of pediatric-onset IBD, about 60% in CD and 70% in UC experienced anti-TNF failure within 5 years. Loss of response account for around two-thirds of failure, both for CD and UC.


Assuntos
Colite Ulcerativa , Doença de Crohn , Doenças Inflamatórias Intestinais , Adolescente , Criança , Feminino , Humanos , Adulto Jovem , Adalimumab/efeitos adversos , Colite Ulcerativa/tratamento farmacológico , Doença de Crohn/tratamento farmacológico , Doenças Inflamatórias Intestinais/tratamento farmacológico , Infliximab/uso terapêutico , Estudos Retrospectivos , Inibidores do Fator de Necrose Tumoral/uso terapêutico , Fator de Necrose Tumoral alfa
2.
Inflamm Bowel Dis ; 29(11): 1793-1804, 2023 11 02.
Artigo em Inglês | MEDLINE | ID: mdl-37266570

RESUMO

BACKGROUND: The identification of patients at high risk of a disabling disease course would be invaluable in guiding initial therapy in Crohn's disease (CD). Our objective was to evaluate a combination of clinical, serological, and genetic factors to predict complicated disease course in pediatric-onset CD. METHODS: Data for pediatric-onset CD patients, diagnosed before 17 years of age between 1988 and 2004 and followed more than 5 years, were extracted from the population-based EPIMAD registry. The main outcome was defined by the occurrence of complicated behavior (stricturing or penetrating) and/or intestinal resection within the 5 years following diagnosis. Lasso logistic regression models were used to build a predictive model based on clinical data at diagnosis, serological data (ASCA, pANCA, anti-OmpC, anti-Cbir1, anti-Fla2, anti-Flax), and 369 candidate single nucleotide polymorphisms. RESULTS: In total, 156 children with an inflammatory (B1) disease at diagnosis were included. Among them, 35% (n = 54) progressed to a complicated behavior or an intestinal resection within the 5 years following diagnosis. The best predictive model (PREDICT-EPIMAD) included the location at diagnosis, pANCA, and 6 single nucleotide polymorphisms. This model showed good discrimination and good calibration, with an area under the curve of 0.80 after correction for optimism bias (sensitivity, 79%, specificity, 74%, positive predictive value, 61%, negative predictive value, 87%). Decision curve analysis confirmed the clinical utility of the model. CONCLUSIONS: A combination of clinical, serotypic, and genotypic variables can predict disease progression in this population-based pediatric-onset CD cohort. Independent validation is needed before it can be used in clinical practice.


Assuntos
Doença de Crohn , Criança , Humanos , Doença de Crohn/complicações , Biomarcadores , Progressão da Doença , Constrição Patológica
3.
Am J Gastroenterol ; 118(11): 1997-2004, 2023 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-37141541

RESUMO

INTRODUCTION: We evaluated the impact of immunosuppressants (IS) and antitumor necrosis factor (TNF) introduction on long-term outcomes of ulcerative colitis (UC) in a large population-based pediatric-onset cohort. METHODS: All patients included in the EPIMAD registry with a diagnosis of UC made before the age of 17 years between 1988 and 2011 were followed up retrospectively until 2013. Medication exposure and disease outcomes were compared between 3 diagnostic periods: 1988 to 1993 (period [P] 1; pre-IS era), 1994 to 2000 (P2; pre-anti-TNF era), and 2001 to 2011 (P3; anti-TNF era). RESULTS: A total of 337 patients (female, 57%) diagnosed with UC were followed up during a median duration of 7.2 years (interquartile range 3.8-13.0). The IS and anti-TNF exposure rates at 5 years increased over time from 7.8% (P1) to 63.8% (P3) and from 0% (P1) to 37.2% (P3), respectively. In parallel, the risk of colectomy at 5 years decreased significantly over time (P1, 17%; P2, 19%; and P3, 9%; P = 0.045, P -trend = 0.027) and between the pre-anti-TNF era (P1 + P2, 18%) and the anti-TNF era (P3, 9%) ( P = 0.013). The risk of disease extension at 5 years remained stable over time (P1, 36%, P2, 32%, and P3, 34%; P = 0.31, P -trend = 0.52) and between the pre-anti-TNF era (P1 + P2, 34%) and the anti-TNF era (P3, 34%) ( P = 0.92). The risk of flare-related hospitalization at 5 years significantly increased over time (P1, 16%; P2, 27%; P3, 42%; P = 0.0012, P -trend = 0.0006) and between the pre-anti-TNF era (P1 + P2, 23%) and the anti-TNF era (P3, 42%) ( P = 0.0004). DISCUSSION: In parallel with the increased use of IS and anti-TNF, an important decline in the risk of colectomy in pediatric-onset UC was observed at the population level.


Assuntos
Colite Ulcerativa , Criança , Humanos , Feminino , Adolescente , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/cirurgia , Colite Ulcerativa/diagnóstico , Estudos Retrospectivos , Inibidores do Fator de Necrose Tumoral/uso terapêutico , Colectomia , Imunossupressores/uso terapêutico
4.
Am J Gastroenterol ; 118(9): 1671-1678, 2023 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-37104674

RESUMO

INTRODUCTION: Anal ulcerations are frequently observed in Crohn's disease (CD). However, their natural history remains poorly known, especially in pediatric-onset CD. METHODS: All patients with a diagnosis of CD before the age of 17 years between 1988 and 2011 within the population-based registry EPIMAD were followed retrospectively until 2013. At diagnosis and during follow-up, the clinical and therapeutic features of perianal disease were recorded. An adjusted time-dependent Cox model was used to evaluate the risk of evolution of anal ulcerations toward suppurative lesions. RESULTS: Among the 1,005 included patients (females, 450 [44.8%]; median age at diagnosis 14.4 years [interquartile range 12.0-16.1]), 257 (25.6%) had an anal ulceration at diagnosis. Cumulative incidence of anal ulceration at 5 and 10 years from diagnosis was 38.4% (95% confidence interval [CI] 35.2-41.4) and 44.0% (95% CI 40.5-47.2), respectively. In multivariable analysis, the presence of extraintestinal manifestations (hazard ratio [HR] 1.46, 95% CI 1.19-1.80, P = 0.0003) and upper digestive location (HR 1.51, 95% CI 1.23-1.86, P < 0.0001) at diagnosis were associated with the occurrence of anal ulceration. Conversely, ileal location (L1) was associated with a lower risk of anal ulceration (L2 vs L1 HR 1.51, 95% CI 1.11-2.06, P = 0.0087; L3 vs L1 HR 1.42, 95% CI 1.08-1.85, P = 0.0116). The risk of fistulizing perianal CD (pCD) was doubled in patients with a history of anal ulceration (HR 2.00, 95% CI 1.45-2.74, P < 0.0001). Among the 352 patients with at least 1 episode of anal ulceration without history of fistulizing pCD, 82 (23.3%) developed fistulizing pCD after a median follow-up of 5.7 years (interquartile range 2.8-10.6). In these patients with anal ulceration, the diagnostic period (pre vs biologic era), exposure to immunosuppressants, and/or anti-tumor necrosis factor did not influence the risk of secondary anoperineal suppuration. DISCUSSION: Anal ulceration is frequent in pediatric-onset CD, with nearly half of patients presenting with at least 1 episode after 10 years of evolution. Fistulizing pCD is twice as frequent in patients with present or past anal ulceration.


Assuntos
Doença de Crohn , Fissura Anal , Fístula Retal , Feminino , Criança , Humanos , Adolescente , Doença de Crohn/complicações , Doença de Crohn/epidemiologia , Doença de Crohn/diagnóstico , Seguimentos , Estudos Retrospectivos , Fissura Anal/etiologia , Fissura Anal/complicações , Fístula Retal/etiologia
5.
J Crohns Colitis ; 17(4): 524-534, 2023 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-36316987

RESUMO

BACKGROUND AND AIMS: Paediatric-onset IBD [pIBD] is associated with an increased risk of cancer and mortality in adulthood. The aims of this study were to measure the incidence of cancer and mortality in patients with pIBD and identify factors associated with mortality and cancer. METHODS: All patients diagnosed with Crohn's disease [CD] or ulcerative colitis [UC] before the age of 17 years between 1988 and 2011 in the EPIMAD registry were retrospectively followed until 2013 for cancer and 2015 for mortality. Standardized incidence [SIR] and mortality ratios [SMR] were estimated compared to the general population. Cox regression was used to compare the effect of exposures on cancer and mortality among IBD patients. RESULTS: We included 1344 patients [52% males, 75% CD], totalling 12 957 patient-years for cancer incidence and 18 817 patient-years for mortality. There were 14 cases of cancer [median age 27.8 years] and 15 deaths [median age 28.8 years]. The incidence of cancer and of mortality were increased compared to the general population: all-cancer SIR = 2.7 (95% confidence interval [CI]: 1.5-4.8), SMR = 1.7 [95% CI: 1.0-2.8]. Colorectal cancer had the highest SIR and SMR: SIR = 41.2 [95% CI: 17.2-99.0], SMR = 70.4 [95% CI 22.7-218.2]. Cancer was associated with (hazard ratio [HR], 95% CI): active smoking at diagnosis [5.5, 1.8-16.5], p = 0.002; any exposure to anti-tumour necrosis factor [6.1, 1.7-22.3], p = 0.0065; and exposure to combination therapy [7.4, 1.8-29.7], p = 0.0047. Mortality was associated with extraintestinal manifestations (HR 4.9 [95% CI: 1.7-13.8], p = 0.003). CONCLUSIONS: In this large population-based cohort, patients with pIBD had an increased risk of both cancer [2.7-fold] and mortality [1.7-fold], particularly for colorectal cancer.


Assuntos
Colite Ulcerativa , Neoplasias Colorretais , Doença de Crohn , Doenças Inflamatórias Intestinais , Masculino , Criança , Humanos , Adulto , Adolescente , Feminino , Estudos Retrospectivos , Doenças Inflamatórias Intestinais/tratamento farmacológico , Doenças Inflamatórias Intestinais/epidemiologia , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/epidemiologia , Doença de Crohn/tratamento farmacológico , Doença de Crohn/epidemiologia , Incidência , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/etiologia
6.
Clin Gastroenterol Hepatol ; 20(11): 2588-2597.e1, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-35131345

RESUMO

BACKGROUND & AIMS: We evaluated the impact of immunosuppressants (IS) and anti-tumor necrosis factor (TNF) introduction on Crohn's disease (CD) long-term outcomes in a large population-based, pediatric-onset cohort. METHODS: All patients included in the EPIMAD registry with a diagnosis of CD occurring when they were younger than age 17 years and between 1988 and 2011 were followed up retrospectively until 2013. Three diagnostic periods were defined: 1988 to 1993 (period [P]1; pre-IS era), 1994 to 2000 (P2; pre-anti-TNF era), and 2001 to 2011 (P3; anti-TNF era). Medication exposure and disease outcomes were compared between the 3 diagnostic periods. RESULTS: A total of 1007 patients diagnosed with CD were followed up for a median duration of 8.8 years (interquartile range, 4.6-14.2 y). The IS and anti-TNF exposure rate at 5 years increased over time from 33.9% (in P1) to 76.5% (in P3) and from 0% (in P1) to 50.5% (in P3), respectively. In parallel, the risk for intestinal resection at 5 years decreased significantly over time (P1, 35%; P2, 31%; and P3, 22%; P = .0003, Ptrend < .0001), and between the pre-anti-TNF era (P1 + P2, 32%) and the anti-TNF era (P3, 22%) (P = .0007). The risk for progression from inflammatory to stricturing behavior decreased significantly over time (P1, 27%; P2, 28%; and P3, 20%; P = .11, Ptrend = .041) and between the pre-anti-TNF era (P1 + P2, 28%) and the anti-TNF era (P3, 20%) (P = .040). The risk for a CD flare-related hospitalization at 5 years remained stable over time (P1, 31%; P2, 31%; and P3, 29%; P = .76, Ptrend = .53). CONCLUSIONS: In parallel with the increased use of IS and anti-TNF, positive changes in the natural history of pediatric-onset CD were observed at the population level. A decreased risk of both intestinal resections and stricturing complications were observed during the anti-TNF era.


Assuntos
Doença de Crohn , Procedimentos Cirúrgicos do Sistema Digestório , Criança , Humanos , Adolescente , Doença de Crohn/tratamento farmacológico , Doença de Crohn/diagnóstico , Estudos Retrospectivos , Inibidores do Fator de Necrose Tumoral , Imunossupressores/uso terapêutico
7.
J Fungi (Basel) ; 7(5)2021 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-33922391

RESUMO

BACKGROUND AND AIMS: This study prompted by growing evidence of the relationship between the yeast Candida albicans and Crohn's disease (CD) was intended to assess the effect of a 6-month course of the antifungal fluconazole (FCZ) on post-operative recurrence of CD. METHODS: Mycological samples (mouth swabs and stools) and serum samples were collected from 28 CD patients randomized to receive either FCZ (n = 14) or placebo (n = 14) before surgical resection. Serological analysis focused on levels of calprotectin, anti-glycan antibodies, and antibody markers of C. albicans pathogenic transition. Levels of galectin-3 and mannose binding lectin (MBL) involved in C. albicans sensing and inflammation were also measured. RESULTS: 1, 2, 3, and 6 months after surgery, endoscopy revealed recurrence in 5/12 (41.7%) patients in the FCZ group and 5/9 (55.6%) in the placebo group, the small cohort preventing any clinical conclusions. In both groups, surgery was followed by a marked decrease in C. albicans colonization and biomarkers of C. albicans pathogenic transition decreased to non-significant levels. Anti-glycan antibodies also decreased but remained significant for CD. Galectin-3 and calprotectin also decreased. Conversely, MBL levels, which inversely correlated with anti-C. albicans antibodies before surgery, remained stable. Building biostatistical multivariate models to analyze he changes in antibody and lectin levels revealed a significant relationship between C. albicans and CD. CONCLUSION: Several combinations of biomarkers of adaptive and innate immunity targeting C. albicans were predictive of CD recurrence after surgery, with area under the curves (AUCs) as high as 0.86. FCZ had a positive effect on biomarkers evolution. ClinicalTrials.gov ID: NCT02997059, 19 December 2016. University Hospital Lille, Ministry of Health, France. Effect of Fluconazole on the Levels of Anti-Saccharomyces cerevisiae Antibodies (ASCA) After Surgical Resection for Crohn's Disease. Multicenter, Randomized, and Controlled in Two Parallel Groups Versus Placebo.

8.
J Crohns Colitis ; 14(4): 501-507, 2020 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-31637413

RESUMO

INTRODUCTION: Most studies of elderly-onset Crohn's disease [CD; diagnosed in patients aged 60 or over] have described a mild course. However, data on the natural history of perianal fistulising CD [pfCD] in this population are scarce. In a population-based cohort study, we described the prevalence, natural history, and treatment of pfCD in patients with elderly-onset CD vs patients with paediatric-onset CD. METHOD: All patients diagnosed with CD at or after the age of 60 between 1988 and 2006, were included [n = 372]. Logistic regression, Cox models, and a nested case-control method were used to identify factors associated with pfCD. RESULTS: A total of 34 elderly patients [9% of the 372] had pfCD at diagnosis. After a median follow-up of 6 years (interquartile range [IQR]: 3; 10), 59 patients [16%] had pfCD; the same prevalence [16%] was observed in paediatric-onset patients. At last follow-up, anal incontinence was more frequent in elderly patients with pfCD than in elderly patients without pfCD [22% vs 4%, respectively; p < 10-4]. Rectal CD at diagnosis was associated with pfCD: hazard ratio (95% confidence interval [CI] = 2.8 [1.6-5.0]). Although 37% of the patients received immunosuppressants and 17% received anti-tumour necrosis factor agents, 24% [14 out of 59] had a definitive stoma at last follow-up. CONCLUSION: During the first 6 years of disease, the prevalence of pfCD was similar in elderly and paediatric patients. Rectal involvement was associated with the appearance of pfCD in elderly-onset patients. Around a quarter of patients with elderly-onset CD will have a stoma. Our results suggest that treatment with biologics should be evaluated in these patients.


Assuntos
Idade de Início , Doença de Crohn , Imunossupressores/uso terapêutico , Fístula Retal , Inibidores do Fator de Necrose Tumoral/uso terapêutico , Idoso , Estudos de Casos e Controles , Doença de Crohn/complicações , Doença de Crohn/epidemiologia , Doença de Crohn/fisiopatologia , Doença de Crohn/terapia , Incontinência Fecal/diagnóstico , Incontinência Fecal/etiologia , Feminino , França/epidemiologia , Humanos , Masculino , Prevalência , Fístula Retal/epidemiologia , Fístula Retal/etiologia , Fístula Retal/fisiopatologia , Fístula Retal/terapia , Sistema de Registros/estatística & dados numéricos , Estomas Cirúrgicos/estatística & dados numéricos
9.
Aliment Pharmacol Ther ; 51(1): 139-148, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31588597

RESUMO

BACKGROUND: Geographical variations in Crohn's disease (CD) suggest that the environment has a role in the pathogenesis of this condition. AIMS: To describe the spatial distribution and the clustering of CD cases in France, and to assess the relationship between the prevalence of CD and environmental risk factors. METHODS: We identified all patients with CD included in the French hospital discharge database from 2007 to 2014. Age- and gender-smoothed standardised prevalence ratios over this period were computed for 5610 spatial units. An ecological regression analysis was used to assess the relationship between the risk of CD and ecological variables (health care, latitude, socio-economic deprivation, urbanisation, proportion of agricultural surfaces and density of industries). Local spatial clusters of high-CD prevalence were searched for using elliptic spatial scan statistics and characterised in a hierarchical ascendant classification based on the same ecological variables. RESULTS: About 129 089 patients with CD were identified, yielding a crude prevalence of 203 per 100 000 inhabitants. The overall spatial heterogeneity was statistically significant (P < .001). An elevated risk of CD was found to be significantly associated with high-social deprivation (relative risk [95% confidence interval] = 1.05 [1.02-1.08]) and high urbanisation (1.09 [1.04-1.14]). Sixteen significant spatial clusters of high-CD prevalence were identified; there were no common ecological variables. CONCLUSIONS: The geographical distribution of CD prevalence in France is not uniform, and is associated with high levels of social deprivation and urbanisation. Larger ecological databases integrating more detailed environmental and clinical information are needed.


Assuntos
Doença de Crohn/epidemiologia , Meio Ambiente , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Bases de Dados Factuais , Feminino , França/epidemiologia , Geografia , História do Século XXI , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Alta do Paciente/estatística & dados numéricos , Prevalência , Fatores de Risco , Determinantes Sociais da Saúde/estatística & dados numéricos , Fatores Socioeconômicos , População Urbana/estatística & dados numéricos , Adulto Jovem
10.
Clin Transl Gastroenterol ; 10(9): e00071, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31478957

RESUMO

OBJECTIVES: Data on long-term natural history of microscopic colitis (MC), including collagenous (CC) and lymphocytic colitis (LC), are lacking. METHODS: All new cases of MC diagnosed in the Somme area, France, between January 1, 2005, and December 31, 2007, were prospectively included. Colonic biopsies from all patients were reviewed by a group of 4 gastrointestinal pathologist experts to assess the diagnosis of CC or LC. Demographic and clinical data were retrospectively collected from diagnosis to February 28, 2017. RESULTS: One hundred thirty cases of MC, 87 CC and 43 LC, were included (median age at diagnosis: 70 [interquartile range, 61-77] and 48 [IQR, 40-61] years, respectively). The median follow-up was 9.6 years (7.6; 10.6). By the end of the follow-up, 37 patients (28%) relapsed after a median time of 3.9 years (1.2; 5.0) since diagnosis, without significant difference between CC and LC (30% vs 26%; P = 0.47). Twenty patients (15%) were hospitalized for a disease flare, and 32 patients (25%) presented another autoimmune disease. Budesonide was the most widely used treatment (n = 74, 59%), followed by 5-aminosalicylic acid (n = 31, 25%). The median duration of budesonide treatment was 92 days (70; 168), and no adverse event to budesonide was reported. Sixteen patients (22%) developed steroid dependency and 4 (5%) were corticoresistant. No difference in the risk of digestive and extradigestive cancer was observed compared with the general population. None of the death (n = 25) observed during the follow-up were linked to MC. In multivariate analysis, age at diagnosis (HR, 1.03; 95% confidence interval, 1.00-1.06; P = 0.02) and budesonide exposure (HR, 2.50; 95% confidence interval, 1.11-5.55; P = 0.03) were significantly associated with relapse. DISCUSSION: This population-based study showed that after diagnosis, two-third of the patients with MC observed long-term clinical remission. Age at diagnosis and budesonide exposure were associated with a risk of relapse.


Assuntos
Colite Microscópica/diagnóstico , Adulto , Idoso , Estudos de Coortes , Colite Microscópica/complicações , Colite Microscópica/terapia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Recidiva , Fatores de Tempo
11.
Dig Liver Dis ; 51(4): 496-502, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30611597

RESUMO

BACKGROUND: Pediatric-onset Crohn's disease (CD) may represent a more severe form of disease. The aim of this study was to describe long-term outcome and identify associated risk factors of complicated behavior in a large population-based pediatric-onset CD cohort. PATIENTS AND METHODS: Cases included all patients recorded in the EPIMAD registry diagnosed with definite or probable CD between January 1988 and December 2004, under the age of 17 years at the time of diagnosis, with at least two years of follow-up. RESULTS: Five hundred and thirty-five patients were included. Median follow-up was 11.1 years [IQR, 7.3-15.0]. At the end of follow-up, 8% (n = 44) of patients had pure ileal disease (L1), 8% (n = 44) had pure colonic disease (L2), and 83% (n = 439) had ileocolonic disease (L3). L4 disease and perianal disease were observed in 42% (n = 227) and 16% (n = 85) of patients, respectively. At the end of follow-up, 58% (n = 308) of patients presented complicated disease behavior (B2, 39% and B3, 19%), and 42% (n = 163) of patients with inflammatory behavior at diagnosis had evolved to complicated behavior. During follow-up, 86% of patients (n = 466) received at least one course of corticosteroids, 67% (n = 357) of patients had been exposed to immunosuppressants and 35% (n = 187) of patients received at least one anti-TNF agent. Forty-three percent (n = 230) of patients underwent at least one intestinal resection. The overall mortality rate was 0.93% and the SMR was 1.6 [0.5-3.8] (p = 0.20). Five cancers were reported with a crude cancer incidence rate of 1.1% and an SIR of 3.3 [1.2-7.0] (p = 0.01). In a multivariate Cox model, ileal (HR, 1.87 [1.09-3.21], p = 0.022) or ileocolonic (HR, 1.54 [1.01-2.34], p = 0.042) and perianal lesions at diagnosis (HR, 1.81 [1.13- 2.89], p = 0.013) were significantly associated with complicated behavior. CONCLUSION: About 80% of patients with pediatric-onset CD presented extensive ileocolonic disease during follow-up. The majority of patients evolved to complicated behavior. Surgery, cancer and mortality were observed in 43%, 0.9% and 0.9% of patients, respectively.


Assuntos
Doença de Crohn/diagnóstico , Doença de Crohn/mortalidade , Adolescente , Corticosteroides/uso terapêutico , Idade de Início , Criança , Doença de Crohn/terapia , Progressão da Doença , Feminino , Seguimentos , França/epidemiologia , Humanos , Imunossupressores/uso terapêutico , Masculino , Análise Multivariada , Neoplasias/complicações , Modelos de Riscos Proporcionais , Sistema de Registros , Fatores de Risco , Índice de Gravidade de Doença
12.
Inflamm Bowel Dis ; 25(2): 394-402, 2019 01 10.
Artigo em Inglês | MEDLINE | ID: mdl-30085159

RESUMO

Background: Extraintestinal manifestations (EIM) have been associated with more severe course of inflammatory bowel disease. The aim was to study the frequency of EIM in pediatric- and elderly-onset Crohn's disease (CD) and the factors associated with EIM and their impact on long-term disease outcome. Methods: Pediatric- (age at diagnosis younger than 17 years) and elderly-onset CD patients (age at diagnosis 60 years or older) from a prospective population-based registry (EPIMAD) were recruited. Data on EIM and clinical factors at diagnosis and at maximal follow-up were collected. Results: We included 535 pediatric- and 370 elderly-onset patients (median age 14.5 and 69.9 years; median follow-up 11.1 and 5.9 years). Extraintestinal manifestations presented in 23.5% of childhood-onset and 4.9% of elderly-onset individuals at diagnosis, while in 29.8% and 5.9% of patients, EIM developed newly during the follow-up (hazard ration [HR] 4.4, 95% CI, 2.7-7.0, P < 0.001). The most frequently involved organ in both age cohorts, either at diagnosis or during disease course, were joints (pediatric: 11.2% and 22.6%; elderly: 3.2% and 3.5%, respectively) followed by skin (pediatric: 15.9% and 13.6%; elderly: 2.7% and 2.7%, respectively). Extraintestinal manifestations at diagnosis were associated with increased risk for corticosteroids (HR 1.42, 95% CI, 1.14-1.78 and HR 3.38, 95% CI, 1.88-6.08) and immunosuppressive therapy (HR 1.30, 95% CI, 1.02-1.65 and HR 4.24, 95% CI, 1.91-9.42), in both age populations. Conclusions: Extraintestinal manifestations occurred at lower frequency in elderly-onset compared with pediatric-onset patients. In both age populations, presence of EIM at diagnosis independently increased the need for corticosteroid and immunosuppressive treatment.


Assuntos
Doença de Crohn/tratamento farmacológico , Doença de Crohn/epidemiologia , Oftalmopatias/fisiopatologia , Artropatias/fisiopatologia , Dermatopatias/fisiopatologia , Adolescente , Idade de Início , Idoso , Criança , Doença de Crohn/diagnóstico , Feminino , Seguimentos , França/epidemiologia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Estudos Retrospectivos , Fatores de Risco
13.
Dig Liver Dis ; 50(9): 903-909, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29739650

RESUMO

BACKGROUND: Recent population-based study of elderly-onset Crohn's disease patients reported age-related differences in disease phenotype and outcome. AIMS: The aim was to assess the impact of age at diagnosis on natural history of elderly-onset ulcerative colitis patients with emphasis on disease presentation, phenotype and treatment. METHODS: Elderly-onset patients with ulcerative colitis (≥60 years at diagnosis) registered in a French population-based Registry EPIMAD (1988-2006) were included. Demographic and clinical data at diagnosis and at maximal follow-up were collected using predefined questionnaire. RESULTS: Four-hundred and sixty-five elderly-onset ulcerative colitis patients were included (median follow-up 6.2 years); 276 (59%) were <70 and 189 (41%) ≥70 years at diagnosis. Patients aged <70 years presented with more rectal bleeding (86% vs. 79%, p = .06) and abdominal pain (44% vs. 34%, p = .04) while those ≥70 years had higher rate of left-sided colitis (62% vs. 49%; p = .02). Cumulative exposure to 5-ASA, corticosteroids and immunosuppressants was similar between the groups as well as surgery rate. However, patients <70 years were significantly more steroid-resistant than older individuals (12% vs. 3%, p < .05) while no significant difference in steroid-dependency was observed. CONCLUSION: Patients with elderly-onset ulcerative colitis differed in presentation, disease phenotype and response to medication with respect to age at diagnosis.


Assuntos
Idade de Início , Colite Ulcerativa , Progressão da Doença , Corticosteroides/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Colite Ulcerativa/complicações , Colite Ulcerativa/diagnóstico , Colite Ulcerativa/tratamento farmacológico , Feminino , França , Humanos , Imunossupressores/uso terapêutico , Masculino , Pessoa de Meia-Idade , Vigilância da População , Estudos Prospectivos , Recidiva , Sistema de Registros , Estudos Retrospectivos
14.
Am J Gastroenterol ; 113(2): 265-272, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-28809388

RESUMO

OBJECTIVES: Few data are available to describe the changes in incidence of pediatric-onset inflammatory bowel disease (IBD). The aim of this study was to describe changes in incidence and phenotypic presentation of pediatric-onset IBD in northern France during a 24-year period. METHODS: Pediatric-onset IBD (<17 years) was issued from a population-based IBD study in France between 1988 and 2011. Age groups and digestive location were defined according to the Paris classification. RESULTS: 1,350 incident cases were recorded (8.3% of all IBD) including 990 Crohn's disease (CD), 326 ulcerative colitis (UC) and 34 IBD unclassified (IBDU). Median age at diagnosis was similar in CD (14.4 years (Q1=11.8-Q3=16.0)) and UC (14.0 years (11.0-16.0)) and did not change over time. There were significantly more males with CD (females/males=0.82) than UC (females/males=1.25) (P=0.0042). Median time between onset of symptoms and IBD diagnosis was consistently 3 months (1-6). Mean incidence was 4.4/105 for IBD overall (3.2 for CD, 1.1 for UC and 0.1 for IBDU). From 1988-1990 to 2009-2011, a dramatic increase in incidences of both CD and UC were observed in adolescents (10-16 years): for CD from 4.2 to 9.5/105 (+126%; P<0.001) and for UC, from 1.6 to 4.1/105 (+156%; P<0.001). No modification in age or location at diagnosis was observed in either CD or UC. CONCLUSIONS: In this population-based study, CD and UC incidences increased dramatically in adolescents across a 24-year span, suggesting that one or more strong environmental factors may predispose this population to IBD.


Assuntos
Colite Ulcerativa/epidemiologia , Doença de Crohn/epidemiologia , Adolescente , Criança , Feminino , França/epidemiologia , Humanos , Incidência , Doenças Inflamatórias Intestinais/epidemiologia , Masculino
15.
J Crohns Colitis ; 11(11): 1326-1334, 2017 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-28981648

RESUMO

BACKGROUND AND AIMS: Data on extra-intestinal manifestations [EIM] and their impact on the disease course of ulcerative colitis [UC] in population-based cohorts are scarce, particularly in paediatric- and elderly-onset UC patients. The aims of this population-based study were to assess: 1] the occurrence of EIM in paediatric- and elderly-onset UC; 2] the factors associated with EIM; and 3] their impact on long-term disease outcome. METHODS: Paediatric-onset [< 17 years at diagnosis] and elderly-onset UC patients [> 60 years at diagnosis] from a French prospective population-based registry [EPIMAD] were included. Data on EIM and other clinical factors at diagnosis and at maximal follow-up were collected. RESULTS: In all, 158 paediatric- and 470 elderly-onset patients were included [median age at diagnosis 14.5 and 68.8 years, median follow-up 11.2 and 6.2 years, respectively]. EIM occurred in 8.9% of childhood- and 3% of elderly-onset patients at diagnosis and in 16.7% and 2.2% of individuals during follow-up [p < 0.01], respectively. The most frequent EIM was joint involvement [15.8% of paediatric onset and 2.6% of elderly-onset]. Presence of EIM at diagnosis was associated with more severe disease course [need for immunosuppressants or biologic therapy or colectomy] in both paediatric- and elderly-onset UC (hazard ratio [HR] = 2.0, 95% confidence interval [CI]: 1.0-4.2; and HR = 2.8, 0.9-7.9, respectively). Extensive colitis was another independent risk factor in both age groups. CONCLUSIONS: Elderly-onset UC patients had lower risk of EIM either at diagnosis or during follow-up than paediatric-onset individuals. EIM at diagnosis predicted more severe disease outcome, including need for immunosuppressive or biologic therapy or surgery, in both paediatric- and elderly-onset UC.


Assuntos
Colite Ulcerativa/patologia , Adolescente , Fatores Etários , Idade de Início , Idoso , Colite Ulcerativa/diagnóstico , Feminino , Humanos , Masculino , Fatores de Risco , Resultado do Tratamento
16.
Langenbecks Arch Surg ; 402(7): 1063-1069, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28840372

RESUMO

BACKGROUND AND AIMS: Persistent perineal sinus (PPS) defined as a perineal wound remaining unhealed more than 6 months after abdominoperineal resection (APR) is a well-known complication. The aim of our study was (1) to evaluate the incidence of PPS after APR for Crohn's disease (CD) in the era of biotherapy, (2) to determine long-term outcome of PPS, (3) to study risk factors associated with delayed perineal healing, and (4) to compare the results in this CD patient group with patients without CD. METHODS: From 1997 to 2013, the records of patients who underwent APR for CD and for non-CD rectal cancer with or without radiochemotherapy at two French university hospitals were studied retrospectively. Perineal healing was evaluated by clinical examination at 1, 6, and 12 months after surgery. RESULTS: The cumulative probability of perineal wound unhealed at 6 and 12 months after surgery was 85 and 48%, respectively, for 81 patients who underwent APR for CD patients in contrast to 21 and 13%, respectively, for 25 non-CD patients with rectal cancer. Eight patients with CD (10%) remained with PPS after a median follow up of 4 years and spontaneous perineal healing occurred with time for all non-CD patients. Factors associated with delayed perineal healing in CD included age at surgery < 49 years (p = 0.001) and colonic-only Crohn's disease location (p = 0.045). Medical treatments had no significant impact on perineal healing. CONCLUSIONS: PPS beyond 6 months post-APR remains a frequent complication but mostly resolves over time. CD is a risk factor for developing PPS and factors associated with higher incidence of PPS were age at surgery < 49 years and colonic-only Crohn's disease location. Prevention of PPS in this population with muscle flap during APR deserves to be evaluated.


Assuntos
Doença de Crohn/cirurgia , Complicações Pós-Operatórias/epidemiologia , Neoplasias Retais/cirurgia , Estudos de Casos e Controles , Humanos , Incidência , Períneo , Complicações Pós-Operatórias/patologia , Fatores de Risco , Cicatrização
17.
J Crohns Colitis ; 11(2): 165-174, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27516406

RESUMO

BACKGROUND: Patient reported-outcomes [PROs] are a major therapeutic goal in inflammatory bowel disease [IBD]. METHODS: Between January and June 2014, patients affiliated with the French national IBD association filled out six self-questionnaires: quality of life 9QoL, according to the Short Inflammatory Bowel Disease Questionnaire [SIBDQ] and the Short-Form-36 Questionnaire [SF-36] v2); fatigue (the Functional Assessment of Chronic Illness Therapy-Fatigue [FACIT-F]); work productivity (the Work Productivity and Activity Impairment [WPAI] questionnaire); disability [the I nflammatory Bowel Disease Disability Index]; and anxiety/depression (the Hospital Anxiety and Depression scale [HADS]). Associated factors were identified by univariate and multivariate logistic regression analyses. RESULTS: Datasets were obtained from 1185 IBD patients. Around half of patients reported poor QoL [SIBDQ <45: 53.3%], severe fatigue [FACIT-F <30: 47.4%] and/or depression [HAD-D >7: 49.4%]. One-third of the patients reported anxiety [HAD-A >7: 30.3%] and/or moderate [22.4%] or severe [11.9%] disability. About half of them reported presenteeism and moderate-to-severe loss of work productivity and loss of activity. Poor QoL, severe fatigue, severe disease-related disability, and/or high WPAI were all associated with female gender, unemployment, and disease activity. Poor QoL, severe fatigue, and high WPAI were also associated with the use of tumour necrosis factor antagonists. A history of surgery was associated with poor QoL, whereas age was associated with severe fatigue. Severe depression was associated with female gender and disease activity. CONCLUSIONS: The disease burden is very high in IBD, with poor QoL, fatigue, work impairment, and depression in half of patients. Marked disability and anxiety were reported by one-third of patients.


Assuntos
Efeitos Psicossociais da Doença , Doenças Inflamatórias Intestinais , Qualidade de Vida , Adulto , Sintomas Comportamentais/etiologia , Sintomas Comportamentais/fisiopatologia , Estudos Transversais , Avaliação da Deficiência , Fadiga/etiologia , Fadiga/fisiopatologia , Feminino , França/epidemiologia , Humanos , Doenças Inflamatórias Intestinais/diagnóstico , Doenças Inflamatórias Intestinais/epidemiologia , Doenças Inflamatórias Intestinais/fisiopatologia , Doenças Inflamatórias Intestinais/psicologia , Avaliação de Estado de Karnofsky/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Gravidade do Paciente , Medidas de Resultados Relatados pelo Paciente , Desempenho Profissional/estatística & dados numéricos
18.
J Crohns Colitis ; 11(3): 281-288, 2017 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-27578800

RESUMO

BACKGROUND AND AIMS: Infliximab and adalimumab are increasingly used to prevent postoperative recurrence in Crohn's disease patients. The impact of previous exposure to one or more anti-tumour necrosis factor [TNF] agents before surgery on the efficacy of anti-TNF therapy on postoperative recurrence is unknown. METHODS: We performed a retrospective analysis of Crohn's disease patients who underwent surgical bowel resection with anastomosis and prophylactic treatment with anti-TNF therapy between January 2005 and June 2013. RESULTS: A total of 57 consecutive Crohn's disease patients with bowel resection and anastomosis followed by prophylactic treatment with anti-TNF were included; 21 [37%] and 24 [42%] patients had a previous exposure to one and more than one anti-TNF agents, respectively; 39 patients [68%] had a surveillance colonoscopy. Cumulative rates of postoperative endoscopic recurrence at 2 years were 45.5% [26.6-69.6%] in patients exposed to two or more anti-TNFα as compared with 29.1% [11.5-48.1%] in patients exposed to one or to zero anti-TNFα before surgery [p = 0.07]. Cumulative rates of clinical recurrence at 1 year were 21.6% [9.6-44.4%] in patients exposed to two or more anti-TNFα as compared with 6.9% [1.8-25.1%] in patients exposed to zero or one anti-TNFα before surgery [p = 0.02]. Multivariable analysis identified smoking and previous exposure to two or more anti-TNFα as risk factors for Crohn's disease clinical or endoscopic postoperative recurrence (hazard ratio [HR] = 3.17; 95% confidence interval [CI]: 1.3-7.8, p = 0.01 and HR = 4.2; 95% CI: 1.8-10.2, p = 0.001, respectively). CONCLUSIONS: Previous exposure to two or more anti-TNF agents was associated with a higher risk of postoperative recurrence in Crohn's disease patients.


Assuntos
Adalimumab/uso terapêutico , Doença de Crohn/prevenção & controle , Doença de Crohn/cirurgia , Fármacos Gastrointestinais/uso terapêutico , Infliximab/uso terapêutico , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Adolescente , Adulto , Colonoscopia , Doença de Crohn/diagnóstico por imagem , Feminino , Humanos , Masculino , Período Pós-Operatório , Período Pré-Operatório , Recidiva , Estudos Retrospectivos , Fatores de Risco , Prevenção Secundária , Fumar/efeitos adversos , Adulto Jovem
19.
Gut ; 66(4): 588-596, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-26646934

RESUMO

BACKGROUND: IBDs are chronic destructive disorders that negatively affect the functional status of patients. Recently, the Inflammatory Bowel Disease Disability Index (IBD-DI) was developed according to standard WHO processes. The aims of the current study were to validate the IBD-DI in an independent patient cohort, to develop an index-specific scoring system and to describe the disability status of a well-defined population-based cohort of French patients with IBD. METHODS: From February 2012 to March 2014, the IBD-DI questionnaire was administered to a random sample of adult patients with an established diagnosis of IBD issued from a French population-based registry. The IBD-DI consists of 28 items that evaluate the four domains of body functions, activity participation, body structures and environmental factors. Validation included item reduction and data structure, construct validity, internal consistency, interobserver and intraobserver reliability evaluations. RESULTS: 150 patients with Crohn's disease (CD) and 50 patients with UC completed the IBD-DI validation phase. The intraclass correlation coefficient for interobserver reliability was 0.91 and 0.54 for intraobserver reliability. Cronbach's α of internal consistency was 0.86. IBD-DI scores varied from 0 to 100 with a mean of 35.3 (Q1=19.6; Q3=51.8). IBD-DI scores were highly correlated with Inflammatory Bowel Disease Questionnaire (-0.82; p<0.001) and SF-36 (-0.61; p<0.05) scores. Female gender (p<0.001), clinical disease activity (p<0.0001) and disease duration (p=0.02) were associated with higher IBD-DI scores. CONCLUSIONS: The IBD-DI has been validated for use in clinical trials and epidemiological studies. The IBD-DI showed high internal consistency, interobserver reliability and construct validity, and a moderate intraobserver reliability. It comprises 14 questions and ranges from 0 to 100. The mean IBD-DI score was 35.3 and was associated with gender, clinical disease activity and disease duration. Further research is needed to confirm the structural validity and to assess the responsiveness of IBD-DI. TRIAL REGISTRATION NUMBER: 2011-A00877-34.


Assuntos
Colite Ulcerativa , Doença de Crohn , Avaliação da Deficiência , Índice de Gravidade de Doença , Inquéritos e Questionários , Adulto , Colite Ulcerativa/complicações , Doença de Crohn/complicações , Feminino , Humanos , Masculino , Estudos Prospectivos , Reprodutibilidade dos Testes , Fatores Sexuais , Fatores de Tempo , Adulto Jovem
20.
Inflamm Bowel Dis ; 22(7): 1698-707, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-27206018

RESUMO

INTRODUCTION: Elderly onset (>60 yrs at diagnosis) Crohn's disease (CD) seems to be associated with a better outcome than when diagnosed earlier in life. The aim of this study was to compare the natural history of patients with CD older than 70 years at diagnosis with that of elderly patients diagnosed between 60 and 70 years in the EPIMAD population-based registry. METHODS: Three hundred seventy patients with elderly onset CD diagnosed between January 1988 and December 2006 were identified. Among them, 188 (63%) were older than 70 years at diagnosis (≥70 yrs). Clinical presentation, disease location, and behavior at diagnosis and also natural history, surgery needs, and drug exposure were recorded, with a median follow-up of 4.5 years (1.1; 8.3) in CD diagnosed after 70 years and of 7.8 years (3.3; 12.1) in CD diagnosed between 60 and 70 years, respectively. RESULTS: CD incidence in elderly patients diagnosed ≥70 years was 2.3/100,000 inhabitants, compared with 2.6/100,000 in elderly patients diagnosed below the age of 70 (60-69 yrs). The proportion of males was lower in patients ≥70 years than in patients aged 60 to 69 (31% versus 45%, P = 0.006). Clinical presentation at diagnosis was similar in both groups. Pure colonic location (L2) was more frequent among patients >70 years both at diagnosis (73% versus 57%, P = 0.004) and maximal follow-up (70% versus 47%, P < 0.0001). Disease extension (from L1 or L2 to L3) was not significantly different among patients >70 years and patients aged 60 to 69 years (hazard ratio [HR] = 2.0 [0.9; 4.5] for 60 to 69 yrs, P = 0.09). The most frequent behavior in the 2 groups was inflammatory, both at diagnosis (75% versus 80%, P = 0.43) and at maximal follow-up (69% versus 70%, P = 0.55). There was no significant difference in patients >70 years compared with patients aged 60 to 69 years regarding treatment with 5-aminosalicylic acid (P = 0.72), oral corticosteroids (P = 0.83), and anti-tumor necrosis factor therapies (P = 0.37). However, the use of immunosuppressants was significantly less frequent in patients >70 years (HR = 2.1 [1.3; 3.5] for 60 to 69 yrs, P = 0.003). Risk of surgery was similar in both groups (P = 0.72). Extraintestinal manifestations at diagnosis were significantly associated with an evolution to complicated behavior (HR = 2.7 [1.0; 7.0], P = 0.045), immunosuppressant treatment (HR = 2.9 [1.4; 6.0], P = 0.006), and corticosteroid use (HR = 3.3 [1.8; 6.1], P < 0.0001). CONCLUSIONS: The natural history of CD in elderly patients diagnosed over the age of 70 is mild with low disease extension and complicated behavior. This needs to be taken into account when establishing therapeutic strategies.


Assuntos
Doença de Crohn/epidemiologia , Doença de Crohn/patologia , Corticosteroides/uso terapêutico , Idade de Início , Idoso , Anti-Inflamatórios não Esteroides/uso terapêutico , Colectomia , Colo/patologia , Doença de Crohn/diagnóstico , Doença de Crohn/terapia , Progressão da Doença , Feminino , Seguimentos , Humanos , Íleo/cirurgia , Imunossupressores/uso terapêutico , Incidência , Masculino , Mesalamina/uso terapêutico , Pessoa de Meia-Idade , Fenótipo , Distribuição por Sexo , Fator de Necrose Tumoral alfa/antagonistas & inibidores
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