Clinical predictors for a complicated course of disease in an inception cohort of patients with ulcerative colitis: results from the prospective, observational EPICOL study.
Ontology highlight
ABSTRACT: Purpose
The clinical course of ulcerative colitis (UC) is highly heterogeneous, with 20 to 30% of patients experiencing chronic disease activity requiring immunosuppressive or biologic therapies. The aim of this study was to identify predictors for a complicated disease course in an inception cohort of patients with UC.Methods
EPICOL was a prospective, observational, inception cohort (UC diagnosis, ≤ 6 months) study in 311 patients with UC who were naive to immunosuppressants (IS)/biologics. A complicated course of disease was defined as the need for IS and/or biologic treatment (here therapy with a TNF-α antagonist) and/or UC-related hospitalisation. Patients were followed up for 24 months.Results
Of the 307 out of 311 participants (4 patients did not meet the inclusion criteria "confirmed diagnosis of active UC within the last 6 months" (n = 2) and "immunosuppressive-naïve" (n = 2), analysis population), 209 (68.1%) versus 98 (31.9%) had an uncomplicated versus a complicated disease course, respectively. In a multivariate regression analysis, prior use of corticosteroids and prior anaemia were associated with a significantly increased risk for a complicated disease course (2.3- and 1.9-fold increase, respectively; p < 0.001 and p = 0.002). Based on these parameters, a risk model for patient stratification was developed.Conclusion
Our study identifies anaemia and an early need for corticosteroids as predictors for a complicated course of disease in an inception cohort of patients with UC. By determining these parameters in routine clinical practice, our results may support the identification of patients who might benefit from early escalation of therapy.
SUBMITTER: Schmidt C
PROVIDER: S-EPMC8803753 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:IntroductionUlcerative colitis (UC) is a chronic inflammatory disease that mainly affects the colon in young patients. Typical symptoms of UC are bloody diarrhoea and faecal urgency, which disturb the quality of life (QOL) of patients, and intractable UC leads to hospitalisation and colectomy. To improve relevant outcomes such as symptoms, QOL and colectomy, many clinical questions need to be resolved regarding what the ideal lifestyle, psychosocial burden and optimal practice patterns are. In this YOu and Ulcerative colitis: Registry and Social network (YOURS) study, we will investigate the effect of lifestyle, psychosocial factors and practice patterns on patient-reported outcomes (PRO), hospitalisation rate and colectomy rate in Japanese patients with UC.Methods and analysisFor this prospective cohort study, we recruited 2006 patients from five hospitals (Tokyo and Chiba; May 2018-January 2019). Patients will be able to access their own data and compare them with summarised data from all patients on the website beyond the YOURS study. At baseline, patients will answer a questionnaire regarding lifestyle (diet, exercise, sleep and work), psychosocial factors (stress, depression and social support) and PRO (symptoms and QOL). Information on practice patterns (eg, medications, endoscopy frequency) will be collected from electronic medical records. Gaps between patients' needs and healthcare professionals' practice will be identified. Follow-up surveys will be conducted periodically for approximately 3 years. Research questions suggested by patients and healthcare professionals may be used in subsequent surveys. Results from the YOURS study will demonstrate optimal UC management strategies to improve relevant outcomes.The study was approved by the ethics committees of five investigational sites before starting the study. The results will be submitted to journals.UMIN000031995.
| S-EPMC6738732 | biostudies-literature
Project description:Background Optimization of treatment with biologics is currently an unmet need for patients with ulcerative colitis (UC). Real-world studies provide neutral estimates of drug efficacy and safety within unselected patient populations and allow for the recognition of specific characteristics that affect response to therapy. Aims We aimed to depict the efficacy of vedolizumab in patients with UC in a real-world setting and identify prognosticators of improved outcomes. Methods Patients with active UC who commenced treatment with vedolizumab were prospectively followed up. Patient-reported outcomes (PROs) and clinical/endoscopic-reported outcomes were recorded at baseline and at weeks 14 and 54. Predefined endpoints of early and persistent efficacy were analyzed against clinical characteristics to identify prognostic factors for response. Results We included 96 patients (anti-TNF-exposed?=?38.5%). At week 14, 73 patients (76%) had clinical response and 54 (56.3%) clinical remission. At week 54, the primary endpoint of vedolizumab persistence was met by 72 patients (75%), whereas steroid-free clinical remission by 59.4%. Among patients who had endoscopy, rates for mucosal healing (Mayo endoscopic score of 0) were 29.8% at week 14 and 44.6% at week 54, respectively. Vedolizumab treatment led to significant improvements in quality of life. Corticosteroid-refractory or anti-TNF-refractory disease, articular manifestations, and high baseline UC-PRO2 were associated with decreased efficacy of vedolizumab in the primary and secondary outcomes. Conclusions Vedolizumab is characterized by high efficacy and long-term treatment persistence in UC. More aggressive disease, as indicated by refractoriness to steroids or anti-TNFs and elevated baseline PROs, may predict suboptimal response and help pre-treatment prognostic stratification of patients. Supplementary Information The online version contains supplementary material available at 10.1007/s10620-021-06907-5.
| S-EPMC7942521 | biostudies-literature
Project description:To determine the prognostic potential of classic and novel serologic antibodies regarding unfavorable disease course in a prospective ulcerative colitis (UC) patient cohort, since few and conflicting data are available in the literature regarding this matter.187 consecutive patients were studied prospectively (median follow-up: 135 months) from a single referral IBD center in Hungary. Sera were tested for different IgA/IgG type autoantibodies (anti-neutrophil cytoplasmic [ANCA], anti-DNA-bound-lactoferrin [anti-LFS], anti-goblet cell [anti-GAB] and anti-pancreatic [PAB: anti-CUZD1 and anti-GP2)]) by indirect immunofluorescence technique and for anti-microbial (anti-Saccharomyces cerevisiae [ASCA] IgG/IgA and anti-OMP Plus™ IgA) antibodies by enzyme-linked immunosorbent assays.A total of 73.6%, 62.4% and 11.2% of UC patients were positive for IgA/IgG type of atypical perinuclear-ANCA, anti-LFS and anti-GAB, respectively. Occurrences of PABs were 9.6%, while ASCA IgA/IgG and anti-OMP IgA were 17.6% and 19.8%, respectively. Antibody status was stable over time. IgA type PABs were more prevalent in patients with primary sclerosing cholangitis (37.5% vs. 4.7% for anti-CUZD1 and 12.5% vs. 0% for anti-GP2, p<0.001 for both). IgA type ASCA and anti-CUZD1 antibodies were associated with higher risk of requirement for long-term immunosuppressant therapy in Kaplan-Meier analysis (pLogRank <0.01 for both). However, in multivariate Cox-regression analysis only ASCA IgA (HR: 2.74, 95%CI: 1.46-5.14, p<0.01) remained independent predictor. UC-related hospitalization due to disease activity was only associated with multiple antibody positivity (for 3 or more; HR 2.03 [95% CI: 1.16-3.56]; p = 0.013). None of the individual antibodies or their combination was associated with the risk of development of extensive disease or colectomy.Even with low prevalence rates, present study gives further evidence to the role of certain antibodies as markers for distinct phenotype and disease outcome in UC. Considering the result of the multivariate analysis the novel antibodies investigated do not seem to be associated with poor clinical outcome in UC, only a classic antibody, IgA subtype ASCA remained an independent predictor of long-term immunosuppressive therapy.
| S-EPMC5874003 | biostudies-literature
Project description:BACKGROUND:Stricturing and penetrating complications account for substantial morbidity and health-care costs in paediatric and adult onset Crohn's disease. Validated models to predict risk for complications are not available, and the effect of treatment on risk is unknown. METHODS:We did a prospective inception cohort study of paediatric patients with newly diagnosed Crohn's disease at 28 sites in the USA and Canada. Genotypes, antimicrobial serologies, ileal gene expression, and ileal, rectal, and faecal microbiota were assessed. A competing-risk model for disease complications was derived and validated in independent groups. Propensity-score matching tested the effect of anti-tumour necrosis factor ? (TNF?) therapy exposure within 90 days of diagnosis on complication risk. FINDINGS:Between Nov 1, 2008, and June 30, 2012, we enrolled 913 patients, 78 (9%) of whom experienced Crohn's disease complications. The validated competing-risk model included age, race, disease location, and antimicrobial serologies and provided a sensitivity of 66% (95% CI 51-82) and specificity of 63% (55-71), with a negative predictive value of 95% (94-97). Patients who received early anti-TNF? therapy were less likely to have penetrating complications (hazard ratio [HR] 0·30, 95% CI 0·10-0·89; p=0·0296) but not stricturing complication (1·13, 0·51-2·51; 0·76) than were those who did not receive early anti-TNF? therapy. Ruminococcus was implicated in stricturing complications and Veillonella in penetrating complications. Ileal genes controlling extracellular matrix production were upregulated at diagnosis, and this gene signature was associated with stricturing in the risk model (HR 1·70, 95% CI 1·12-2·57; p=0·0120). When this gene signature was included, the model's specificity improved to 71%. INTERPRETATION:Our findings support the usefulness of risk stratification of paediatric patients with Crohn's disease at diagnosis, and selection of anti-TNF? therapy. FUNDING:Crohn's and Colitis Foundation of America, Cincinnati Children's Hospital Research Foundation Digestive Health Center.
| S-EPMC5719489 | biostudies-literature
Project description:BackgroundApproximately 80% of patients with ulcerative colitis (UC) have intermittently active disease and up to 20% will require a colectomy, but little data available on predictors of poor disease course. The aim of this study was to identify clinical and genetic markers that can predict prognosis.MethodsMedical records of patients with UC with ≥5 years of follow-up and available DNA and serum were retrospectively assessed. Immunochip was used to genotype loci associated with immune mediated inflammatory disorders (IMIDs), inflammatory bowel diseases, and other single nucleotide polypmorphisms previously associated with disease severity. Serum levels of pANCA, ASCA, CBir1, and OmpC were also evaluated. Requirement for colectomy, medication, and hospitalization were used to group patients into 3 prognostic groups.ResultsSix hundred one patients with UC were classified as mild (n = 78), moderate (n = 273), or severe disease (n = 250). Proximal disease location frequencies at diagnosis were 13%, 21%, and 30% for mild, moderate, and severe UC, respectively (P = 0.001). Disease severity was associated with greater proximal extension rates on follow-up (P < 0.0001) and with shorter time to extension (P = 0.03) and to prednisone initiation (P = 0.0004). When comparing severe UC with mild and moderate UC together, diagnosis age >40 and proximal disease location were associated with severe UC (odds ratios = 1.94 and 2.12, respectively). None of the single nucleotide polypmorphisms or serum markers tested was associated with severe UC, proximal disease extension or colectomy.ConclusionsOlder age and proximal disease location at diagnosis, but not genetic and serum markers, were associated with a more severe course. Further work is required to identify biomarkers that will predict outcomes in UC.
| S-EPMC8157811 | biostudies-literature
Project description:Background/aimsAdalimumab has been shown to induce and maintain clinical remission in patients with moderate to severe ulcerative colitis (UC). However, no large-scale population-based studies have been performed in Japan. This study was conducted to evaluate the safety and effectiveness of adalimumab in clinical practice in Japanese patients with UC.MethodsIn this 52-week, prospective, multicenter, single-cohort, noninterventional, observational, postmarketing surveillance study, patients with moderate to severe UC received an initial subcutaneous injection of adalimumab 160 mg, followed by 80 mg at 2 weeks, and then 40 mg every other week. Safety assessments were the incidence of adverse drug reactions (ADRs) and serious ADRs. Effectiveness assessments were clinical remission, corticosteroid-free remission, mucosal healing, and change in C-reactive protein (CRP) levels from baseline.ResultsOf 1,593 registered patients, 1,523 (male, 57.6%; mean age, 41.8 years) and 1,241 patients were included in the safety and effectiveness populations, respectively. ADRs were reported in 18.1% and serious ADRs in 4.9% of patients. Clinical remission was achieved in 49.7% of patients at week 4, increasing to 74.4% at week 52. Corticosteroid-free remission rates increased over time, from 10.4% at week 4 to 53.1% at week 52. More than 60% of patients demonstrated mucosal healing at weeks 24 and 52. Mean CRP levels (mg/dL) decreased from 1.2 at baseline to 0.6 at week 4 and 0.3 at week 52.ConclusionsThis large real-world study confirmed the safety and effectiveness of adalimumab in patients with UC in Japan. No new safety concerns were identified.
| S-EPMC8566831 | biostudies-literature
Project description:BackgroundPrevious retrospective studies of paediatric ulcerative colitis have had limited ability to describe disease progression and identify predictors of treatment response. In this study, we aimed to identify characteristics associated with outcomes following standardised therapy after initial diagnosis.MethodsThe PROTECT multicentre inception cohort study was based at 29 centres in the USA and Canada and included paediatric patients aged 4-17 years who were newly diagnosed with ulcerative colitis. Guided by the Pediatric Ulcerative Colitis Activity Index (PUCAI), patients received initial standardised treatment with mesalazine (PUCAI 10-30) oral corticosteroids (PUCAI 35-60), or intravenous corticosteroids (PUCAI ≥65). The key outcomes for this analysis were week 12 corticosteroid-free remission, defined as PUCAI less than 10 and taking only mesalazine, and treatment escalation during the 12 study weeks to anti-tumour necrosis factor α (TNFα) agents, immunomodulators, or colectomy among those initially treated with intravenous corticosteroids. We identified independent predictors of outcome through multivariable logistic regression using a per-protocol approach. This study is registered with ClinicalTrials.gov, number NCT01536535.FindingsPatients were recruited between July 10, 2012, and April 21, 2015. 428 children initiated mesalazine (n=136), oral corticosteroids (n=144), or intravenous corticosteroids (n=148). Initial mean PUCAI was 31·1 (SD 13·3) in children initiating with mesalazine, 50·4 (13·8) in those initiating oral corticosteroids, and 66·9 (13·7) in those initiating intravenous corticosteroids (p<0·0001 for between-group comparison). Week 12 outcome data were available for 132 patients who initiated with mesalazine, 141 with oral corticosteroids, and 143 with intravenous corticosteroids. Corticosteroid-free remission with the patient receiving mesalazine treatment only at 12 weeks was achieved by 64 (48%) patients in the mesalazine group, 47 (33%) in the oral corticosteroid group, and 30 (21%) in the intravenous corticosteroid group (p<0·0001). Treatment escalation was required by nine (7%) patients in the mesalazine group, 21 (15%) in the oral corticosteroid group, and 52 (36%) in the intravenous corticosteroid group (p<0·0001). Eight patients, all of whom were initially treated with intravenous corticosteroids, underwent colectomy. Predictors of week 12 corticosteroid-free remission were baseline PUCAI less than 35 (odds ratio 2·44, 95% CI 1·41-4·22; p=0·0015), higher baseline albumin by 1 g/dL increments among children younger than 12 years (4·05, 1·90-8·64; p=0·00030), and week 4 remission (6·26, 3·79-10·35; p<0·0001). Predictors of treatment escalation by week 12 in patients initially treated with intravenous corticosteroids included baseline total Mayo score of 11 or higher (2·59, 0·93-7·21; p=0·068 [retained in model due to clinical relevance]), rectal biopsy eosinophil count less than or equal to 32 cells per high power field (4·55, 1·62-12·78; p=0·0040), rectal biopsy surface villiform changes (3·05, 1·09-8·56; p=0·034), and not achieving week 4 remission (30·28, 6·36-144·20; p<0·0001).InterpretationOur findings provide guidelines to assess the response of children newly diagnosed with ulcerative colitis to standardised initial therapy and identify predictors of treatment response and failure. These data suggest that additional therapeutic interventions might be warranted to improve early outcomes, especially in patients presenting with severe disease and requiring intravenous corticosteroids.FundingNational Institutes of Health.
| S-EPMC5695708 | biostudies-literature
Project description:BACKGROUND:Lack of evidence-based outcomes data leads to uncertainty in developing treatment regimens in children who are newly diagnosed with ulcerative colitis. We hypothesised that pretreatment clinical, transcriptomic, and microbial factors predict disease course. METHODS:In this inception cohort study, we recruited paediatric patients aged 4-17 years with newly diagnosed ulcerative colitis from 29 centres in the USA and Canada. Patients initially received standardised mesalazine or corticosteroids, with pre-established criteria for escalation to immunomodulators (ie, thiopurines) or anti-tumor necrosis factor-? (TNF?) therapy. We used RNA sequencing to define rectal gene expression before treatment, and 16S sequencing to characterise rectal and faecal microbiota. The primary outcome was week 52 corticosteroid-free remission with no therapy beyond mesalazine. We assessed factors associated with the primary outcome using logistic regression models of the per-protocol population. This study is registered with ClinicalTrials.gov, number NCT01536535. FINDINGS:Between July 10, 2012, and April 21, 2015, of 467 patients recruited, 428 started medical therapy, of whom 400 (93%) were evaluable at 52 weeks and 386 (90%) completed the study period with no protocol violations. 150 (38%) of 400 participants achieved week 52 corticosteroid-free remission, of whom 147 (98%) were taking mesalazine and three (2%) were taking no medication. 74 (19%) of 400 were escalated to immunomodulators alone, 123 (31%) anti-TNF? therapy, and 25 (6%) colectomy. Low baseline clinical severity, high baseline haemoglobin, and week 4 clinical remission were associated with achieving week 52 corticosteroid-free remission (n=386, logistic model area under the curve [AUC] 0·70, 95% CI 0·65-0·75; specificity 77%, 95% CI 71-82). Baseline severity and remission by week 4 were validated in an independent cohort of 274 paediatric patients with newly diagnosed ulcerative colitis. After adjusting for clinical predictors, an antimicrobial peptide gene signature (odds ratio [OR] 0·57, 95% CI 0·39-0·81; p=0·002) and abundance of Ruminococcaceae (OR 1·43, 1·02-2·00; p=0·04), and Sutterella (OR 0·81, 0·65-1·00; p=0·05) were independently associated with week 52 corticosteroid-free remission. INTERPRETATION:Our findings support the utility of initial clinical activity and treatment response by 4 weeks to predict week 52 corticosteroid-free remission with mesalazine alone in children who are newly diagnosed with ulcerative colitis. The development of personalised clinical and biological signatures holds the promise of informing ulcerative colitis therapeutic decisions. FUNDING:US National Institutes of Health.
| S-EPMC6501846 | biostudies-literature
Project description:BACKGROUND:Acute severe ulcerative colitis (UC) remains a significant clinical challenge and the ability to predict, at an early stage, those individuals at risk of colectomy for medically refractory UC (MR-UC) would be a major clinical advance. The aim of this study was to use a genome-wide association study (GWAS) in a well-characterized cohort of UC patients to identify genetic variation that contributes to MR-UC. METHODS:A GWAS comparing 324 MR-UC patients with 537 non-MR-UC patients was analyzed using logistic regression and Cox proportional hazards methods. In addition, the MR-UC patients were compared with 2601 healthy controls. RESULTS:MR-UC was associated with more extensive disease (P = 2.7 × 10(-6)) and a positive family history of UC (P = 0.004). A risk score based on the combination of 46 single nucleotide polymorphisms (SNPs) associated with MR-UC explained 48% of the variance for colectomy risk in our cohort. Risk scores divided into quarters showed the risk of colectomy to be 0%, 17%, 74%, and 100% in the four groups. Comparison of the MR-UC subjects with healthy controls confirmed the contribution of the major histocompatibility complex to severe UC (peak association: rs17207986, P = 1.4 × 10(-16)) and provided genome-wide suggestive association at the TNFSF15 (TL1A) locus (peak association: rs11554257, P = 1.4 × 10(-6)). CONCLUSIONS:A SNP-based risk scoring system, identified here by GWAS analyses, may provide a useful adjunct to clinical parameters for predicting the natural history of UC. Furthermore, discovery of genetic processes underlying disease severity may help to identify pathways for novel therapeutic intervention in severe UC.
| S-EPMC2959149 | biostudies-literature
Project description:Background/aimsLimited data are available regarding psychosocial distress at the time of diagnosis of ulcerative colitis (UC). We investigated the psychosocial burden and factors related to poor health-related quality of life (HRQL) among patients newly diagnosed with moderate-to-severe UC who were affiliated with the nationwide prospective cohort study.MethodsWithin the first 4 weeks of UC diagnosis, all patients were assessed using the Hospital Anxiety and Depression Scale (HADS), Work Productivity and Activity Impairment questionnaire, Inflammatory Bowel Disease Questionnaire (IBDQ), and 12-Item Short Form (SF-12) health survey. A multiple linear regression model was used to identify factors associated with HRQL.ResultsBetween August 2014 and February 2017, 355 patients completed questionnaires. Significant mood disorders requiring psychological interventions, defined by a HADS score ≥11, were identified in 16.7% (anxiety) and 20.6% (depression) of patients. Patients with severe disease were more likely to have presenteeism, loss of work productivity, and activity loss than those with moderate disease (all p<0.05). Significant mood disorders had the strongest negative relationship with total IBDQ score, which indicates disease-specific HRQL (β coefficient: -22.1 for depression and -40.0 for anxiety, p<0.001). The scores of all SF-12 dimensions, which indicate general HRQL, were remarkably decreased in the study population compared indirectly with previously reported scores in the general population. The Mayo score, C-reactive protein level, and white blood cell count showed significant negative associations with the IBDQ score (p<0.05).ConclusionsPsychosocial screening and timely interventions should be incorporated into the initial care of patients newly diagnosed with UC.
| S-EPMC7366148 | biostudies-literature