关键词： adalimumab   Crohn's disease   infliximab   ulcerative colitis  

摘要： Background Inflammatory bowel disease (IBD) is often managed with anti-tumour necrosis factor-alpha therapy (anti-TNF alpha), but treatment efficacy is compromised by high annual rates of loss of response (13%-21% per patient-year). Aims To assess whether the incidence of loss of response decreases with longer treatment duration Methods This was a multicentre, retrospective cohort study of patients with ulcerative colitis (UC) or Crohn's disease (CD) who received anti-TNF alpha for at least 4 months between 2011 and 2019. We studied the incidence of loss of response as a function of treatment duration, employing parametric survival modelling. Predictors of loss of response were identified by Cox regression analysis. Secondary outcomes included overall anti-TNF alpha discontinuation and dose escalation. Results We included 844 anti-TNF alpha treatment episodes in 708 individuals. Loss of response occurred in 211 (25.0%) episodes, with anti-drug antibodies detected in 66 (31.3%). During the first year, the incidence of loss of response was three-fold higher than after four years of treatment (17.2% vs 4.8% per patient-year, P < 0.001). The incidence of anti-TNF alpha discontinuation (28.6% vs 14.0% per patient-year, P < 0.001) and dose escalations (38.0% vs 6.8% per patient-year, P < 0.001) also decreased significantly from the first year to after four years, respectively. Predictors of loss of response included UC (vs CD, adjusted hazard ratio [aHR] 1.53, 95% CI 1.10-2.15) and, among patients with CD, stricturing or penetrating disease (aHR 1.68, 95% CI 1.15-2.46) and male sex (aHR 0.55, 95% CI 0.38-0.78). Immunomodulators were protective against loss of response with anti-drug antibodies (aHR 0.42, 95% CI 0.24-0.74). Conclusions Patients with sustained benefit to anti-TNF alpha after 2 years are at low risk of subsequent loss of response.

关键词： Crohn's disease   ulcerative colitis   methotrexate   adolescence  

摘要： Objectives To evaluate quality of life (QoL) in a large cohort of pediatric patients with inflammatory bowel disease (IBD) and to identify the clinical factors that influence QoL. Study design This cross-sectional study analyzes a quality improvement initiative in 351 pediatric patients with IBD in British Columbia, Canada using the self-reported Pediatric Quality of Life Inventory (PedsQL) 4.0 generic scale. The questionnaire was completed at outpatient clinic and biologic infusion appointments. Statistical analysis included the t test, ANOVA, and multilinear regressions to evaluate the relationships between clinical factors and QoL. Results Mean (SE) QoL scores (79.95 [0.84]) fell between previously described healthy and chronically ill populations. Disease activity was the most significant predictor of QoL, with patients in remission scoring similar (84.42 [0.87]) to well established healthy norms, and those with moderately or severely active disease having some of the lowest published PedsQL scores (63.13 [3.27]), lower than most other chronic pediatric conditions. Twenty-five patients with moderately or severely active disease at the time of survey completion had follow-up surveys identified 1 year later and had a significant improvement of both their disease activity (P <.005) and their PedsQL scores (follow-up survey mean 76.13 [3.11]). Additional clinical factors independently associated with poor QoL were school nonattendance (15.5% decrease in QoL, P <.001), immune-modulator selection (methotrexate conferring a 9.5% lower mean QoL score than azathioprine, P =.005), and female gender (P =.031). Conclusion Pediatric patients with IBD experience a QoL significantly impacted by multiple clinical factors including current severity of IBD symptoms.

关键词： Crohn disease   ileal sparing   inflammatory bowel disease-unclassified   pancolitis  

摘要： Objectives: The aim of the study was to characterize epidemiology, phenotype, and clinical outcome of Inflammatory Bowel Disease (IBD) diagnosed ages 2 to 9 years, and compare age groups 2 to 5 and 6 to 9 years. Methods: A population-based retrospective cohort study of all <10-year-olds diagnosed with IBD between 2004 and 2017 in Southwest England was performed. Patients were divided into age groups at diagnosis. Demographics, investigations, and phenotype at diagnosis were collected. Treatments and outcomes were analysed at 1, 2, 5, and 10 years follow-up. Poisson regression was used for IBD incidence rate ratios;Wald test for variation by age group;parametric/nonparametric tests for phenotype. Results: There were 666 new paediatric IBD (pIBD) patients ages <= 16 years, from which 136 were 2 to 9 (2-5 years: 32;6-9 years: 104). Incidence of pIBD increased from 4 to 6 cases per 100,000 whereas in A1a group was stable around 2 cases per 100,000. Crohn Disease (CD) children were majority boys, 2- to 5-year-olds were more likely to have ileal sparing than 6 to 9-year group but had similar rates of surgery and anti-TNF therapy. Two- to 5-year-olds with ulcerative colitis were more likely to have surgery but rates for anti-TNF therapy were similar. Sixteen percent of 2- to 5-year-olds and 10% of 6- to 9-year-olds had IBD-unclassified. No significant differences in symptoms or time to diagnosis were found. Conclusions: Twenty percent of pIBD in Southwest England are 2 to 9 years old. pIBD incidence has increased but is stable in that group. In terms of phenotypic differences, ileal sparing in CD and pancolitis and surgery in UC, are more likely in 2- to 5-year-olds.

关键词： biosimilar   real world   safety   switch  

摘要： Background and Aim There are few clinical data on Adalimumab (ADA) biosimilars in inflammatory bowel disease. We aimed to perform a multicenter, observational, prospective study on safety and effectiveness of ADA biosimilar ABP 501 in patients with inflammatory bowel disease. Methods All consecutive patients from the cohort of the Sicilian Network for Inflammatory Bowel Disease treated with ADA biosimilar ABP 501 from February 2019 to February 2020 were enrolled. Patients were divided into three groups: group A, naive to ADA and naive to anti-tumor necrosis factors;group B, naive to ADA and previously exposed to anti-tumor necrosis factors;and group C: switched from ADA originator to ABP 501. Results A total of 559 patients (median age 39 years;Crohn's disease 88.0%, ulcerative colitis 12.0%) were included, with a follow-up time of 403.4 patient-years. Thirty-six serious adverse events occurred in 36 patients (6.4%;incidence rate [IR]: 8.9 per 100 person-years [PY]). The IR of serious adverse events was higher among patients in group A compared with group C (17.4 vs 4.8 per 100 PY;IR ratio = 3.61;P < 0.001) and among patients in group B compared with group C (16.4 vs 4.8 per 100 PY;IR ratio = 3.42;P = 0.041). Among ADA-naive patients (group A + B), 188 (85.8%) had a clinical response after 12 weeks, including 165 (75.3%) who achieved steroid-free remission. Higher treatment persistence estimates were reported for patients in group C compared with groups A and B (log-rank P < 0.001). Conclusions Safety and effectiveness of ABP 501 seem to be overall similar to those reported for ADA originator. Switching from originator to ABP 501 was safe and effective.

关键词： Azathioprine   Calprotectin   Deep Remission  

摘要： BACKGROUND & AIMS: There is uncertainty regarding the optimal duration of treatment with azathioprine (AZA) in ulcerative colitis (UC) and Crohn's disease (CD). We analyzed the clinical course and predictors of relapse after AZA withdrawal in patients in sustained deep remission. METHODS: A prospective study was performed on patients who stopped their treatment with AZA while being in steroid-free, extended deep remission (normal clinical, endoscopic, and histologic indexes, C-reactive protein, and fecal calprotectin [FC]). Standard biochemical tests and FC were measured at 3 and 6 months, then every 6 months. Bowel ultrasounds and ileocolonoscopy were performed every 6 and 12 months, respectively. Multivariate analysis for predictors of relapse was performed using a Cox proportional hazards model and hazard ratios were calculated. Spearman nonparametric correlation test was also used. The accuracy of significant predictors was calculated. RESULTS: Fifty-seven patients with inflammatory bowel disease stopped AZA after median 7 years (range, 5-19) and were followed up for median 50 months (range, 25-85). Twenty-six patients (18/31 UC, 8/26 CD;P = .003) relapsed, within a median 15 months (range, 2-37). FC was the only variable significantly correlated with later relapse of both diseases (UC: hazard ratio, 3.3;95% confidence interval, 1.2-10;CD: hazard ratio, 4.5;95% confidence interval, 1.4-12.5). The sensitivity, specificity, and positive and negative predictive values of FC were 50%, 100%, 100%, and 59% in UC and 50%, 94%, 80%, and 81% in CD. CONCLUSIONS: More than half patients with UC and one-third of patients with CD relapse after AZA withdrawal despite previous deep remission. FC positivity is associated with high risk of relapse, allowing early correction of the therapeutic strategy.

关键词： natural history   outcomes   primary sclerosing cholangitis   autoimmune liver disease   complications   pediatric   liver transplantation  

摘要： Objective To describe the characteristics and clinical course of children and young persons with inflammatory bowel disease (IBD) and sclerosing cholangitis (SC). Study design Retrospective analysis of clinical characteristics, management, and outcome of two separate cohorts of children and young persons with IBD-SC managed in a tertiary pediatric gastroenterology center and in a tertiary pediatric hepatology center in the UK. Results Eighty-two pediatric patients (31% female) with IBD-SC and a mean age at diagnosis of 11.9 +/- 2.8 years were followed up for a mean of 6.8 +/- 3.3 years. The most common type of IBD was ulcerative colitis (55%), followed by unclassified IBD (30%) and Crohn's disease (15%). Autoimmune SC (ASC) was diagnosed in 72%, and small duct SC was diagnosed in 28%. Complication-free and native liver survival were 96% and 100%, respectively, at 5 years after diagnosis and 75% and 88%, respectively, at 10 years after diagnosis. Patients in the gastroenterology center, who were diagnosed with liver disease sooner after diagnosis of IBD compared with the hepatology center cohort (mean, 2.7 +/- 6.1 months vs 9.3 +/- 19.4 months;P =.03), did not develop liver-related complications during follow-up. Conclusions Our data suggest that children with IBD-SC have better clinical outcomes than have been reported previously, particularly if diagnosed early. We recommend prompt assessment for SC, including liver biopsy and biliary imaging, when liver function abnormalities are detected in a children diagnosed with IBD.

关键词： Inflammatory bowel disease   Thiopurine   NUDT15  

摘要： Background and Aims Polymorphisms in the nucleotide diphosphate-linked moiety X-type motif 15 (NUDT15) gene are associated with thiopurine-induced leukopenia in patients with inflammatory bowel disease (IBD). NUDT15-associated subcellular thiopurine metabolism has not been investigated in primary lymphocytes. We hypothesized that NUDT15 mutation increases DNA-incorporated deoxythioguanosine (dTG) and induces apoptosis in lymphocytes. Methods DNA-incorporated dTG in peripheral blood mononuclear cells (PBMCs) and 6-thioguanine nucleotides (6-TGN) in red blood cells were measured in patients with IBD undergoing thiopurine treatment. The association of a single nucleotide polymorphism for NUDT15 (rs116855232) with dTG(PBMC) was examined. The pro-apoptotic effect of DNA-incorporated dTG was examined ex vivo in association with NUDT15 genotypes by co-culturing patient-derived peripheral CD4(+) T lymphocytes with 6-thioguanine (6-TG). Results dTG(PBMC) was significantly higher in NUDT15 variants than in non-variants. dTG(PBMC), but not 6-TGN(RBC), negatively correlated with peripheral lymphocyte counts (r = - 0.31 and - 0.12, p = 0.012 and 0.173, respectively). DNA-incorporated dTG significantly accumulated to a greater extent in lymphocytes from NUDT15 variants when co-cultured with 6-TG ex vivo than in those from non-variants and was associated with decreased proliferation and increased apoptosis. Conclusion Increased DNA-incorporated dTG may be responsible for thiopurine-induced leukocytopenia through cell apoptosis in IBD patients with NUDT15 mutation.

关键词： 中药熏洗   肛肠疾病   术后恢复  

摘要： 研究中药熏洗对肛肠疾病患者术后恢复的影响。方法:选择100例肛肠疾病手术患者,将50例应用高锰酸钾配置溶液熏洗者归为对照组,50例中药熏洗者归为观察组,比较术后恢复情况及熏洗效果差异。结果:观察组术后水肿消退时间、疼痛消失时间、创面愈合时间均显著短于对照组;对照组总有效率为84%,观察组为96%。结论:中药熏洗可加速肛肠疾病术后创面愈合,缓解疼痛,具有应用价值。

关键词： Crohn’s disease   Quality of life   Stress   Ulcerative colitis  

摘要： BACKGROUND Stigmatization is the separation of an individual from a group due to aspects that make them *** may in turn influence the perception of *** with inflammatory bowel disease(IBD)are susceptible to stigma,although data are very *** To validate an Italian translation of the IBD perceived stigma scale(PSS)in relation to patients’*** Consecutive IBD outpatients were prospectively enrolled(December 2018-September 2019)in an Italian,tertiary referral,IBD *** and demographic data were *** and resilience were evaluated through the IBD-PSS and the 25-item Connor-Davidson Resilience Scale,*** International Quality of Life Assessment Project approach was followed to translate the IBD-PSS into Italian and to establish data *** scores represent greater perceived stigma and *** analysis for factors associated with greater stigma was *** Overall,126 IBD patients(mean age 46.1±16.9)were *** International Quality of Life Assessment criteria for acceptable psychometric properties of the scale were satisfied,with optimal data *** was no ceiling effect,whilst floor effect was present(7.1%).The discriminant validity and the internal consistency reliability were good(Cronbach alpha=0.87).The overall internal consistency was 95%,and the test-retest reliability was excellent *** median PSS score was 0.45(0.20-0.85).Resilience negatively correlated with perceived stigma(Spearman’s correlation=-0.18,95%confidence intervals:-0.42-0.08,P=0.03).CONCLUSION We herein validated the Italian translation of the PSS scale,also demonstrating that resilience negatively impacts perceived stigma.

关键词： 肛肠疾病   排便   穴位贴敷   神阙穴   中医护理  

摘要： 目的观察泄热通便贴脐敷促进肛肠病局部手术后排便的效果。方法选取肛肠病局部手术后患者100例为研究对象,随机分为干预组和对照组,各50例。对照组术后给予常规换药和护理,干预组在对照组基础上增加中药泄热通便贴脐敷干预。评价临床干预效果和患者不适感。结果干预组显效率为70.00%(35/50),高于对照组的22.00%(11/50),差异有统计学意义(P<0.01);干预组不适感率为16.00%(8/50),低于对照组的42.00%(21/50),差异有统计学意义(P<0.01)。结论泄热通便贴脐敷能有效促进肛肠疾病局部手术后排便,且患者易于接受,值得借鉴。