Worse outcomes and higher costs of care in fibrostenotic Crohn’s disease: a real-world propensity-matched analysis in the USA

BackgroundPatients with Crohn’s disease (CD) may develop fibrostenotic strictures. No currently available therapies prevent or treat fibrostenotic CD (FCD), making this a critical unmet need.AimTo compare health outcomes and resource utilisation between CD patients with and without fibrostenotic disease.MethodsPatients aged ≥18 years with FCD and non-FCD between 30 October 2015 and 30 September 2018 were identified in the Truven MarketScan Commercial Claims and Encounters Database. We conducted 1:3 nearest neighbour propensity score matching on age, sex, malnutrition, payer type, anti-tumour necrosis factor use, and Charlson Comorbidity Index score. Primary outcomes up to 1 year from the index claim were ≥1 hospitalisation, ≥1 procedure, ≥1 surgery, and steroid dependency (>100 day supply). Associations between FCD diagnosis and outcomes were estimated with a multivariable logistic regression model. This study was exempt from institutional review board approval.ResultsPropensity score matching yielded 11 022 patients. Compared with non-FCD, patients with FCD had increased likelihood of hospitalisations (17.1% vs 52.4%; p<0.001), endoscopic procedures (4.4% vs 8.6%; p<0.001), IBD-related surgeries (4.7% vs 9.1%; p<0.001), steroid dependency (10.0% vs 15.7%; p<0.001), and greater mean annual costs per patient ($47 575 vs $77 609; p<0.001). FCD was a significant risk factor for ≥1 hospitalisation (adjusted OR (aOR), 6.1), ≥1 procedure (aOR, 2.1), ≥1 surgery (aOR, 2.0), and steroid dependency (aOR, 1.7).ConclusionsFCD was associated with higher risk for hospitalisation, procedures, abdominal surgery, and steroid dependency. Patients with FCD had a greater mean annual cost per patient. FCD represents an ongoing unmet medical need.

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Short-term and long-term outcomes of laparoscopic vs open ileocolic resection in patients with Crohn's disease: Propensity-score matching analysis

World Journal of Gastroenterology ◽

10.3748/wjg.v27.i41.7159 ◽

2021 ◽

Vol 27 (41) ◽

pp. 7159-7172

Author(s):

Shin Jeong Pak ◽

Young Il Kim ◽

Yong Sik Yoon ◽

Jong Lyul Lee ◽

Jung Bok Lee ◽

...

Keyword(s):

Crohn’S Disease ◽

Crohn's Disease ◽

Propensity Score ◽

Propensity Score Matching ◽

Ileocolic Resection ◽

Long Term Outcomes ◽

Short Term ◽

Propensity Score Matching Analysis

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High-Risk Ileocolic Anastomoses for Crohn’s Disease: When Is Diversion Indicated?

Journal of Crohn s and Colitis ◽

10.1093/ecco-jcc/jjz004 ◽

2019 ◽

Vol 13 (7) ◽

pp. 856-863 ◽

Cited By ~ 6

Author(s):

Peter M Neary ◽

Alexandra C Aiello ◽

Luca Stocchi ◽

Sherief Shawki ◽

Tracy Hull ◽

...

Keyword(s):

Risk Factors ◽

Crohn’S Disease ◽

Crohn's Disease ◽

Propensity Score ◽

Propensity Score Matching ◽

Anastomotic Leak ◽

Primary Anastomosis ◽

Leak Rate ◽

Ileocolic Resection ◽

Diverting Ileostomy

Abstract Background and Aims Patients with Crohn’s disease undergoing ileocolectomy and primary anastomosis are often at increased risk of anastomotic leak. We aimed to determine whether diverting ileostomy was protective against anastomotic leak after ileocolic resection for Crohn’s disease using a large international registry. Methods We analysed the National Surgical Quality Improvement Program Colectomy Module from 2012 to 2016. Multivariable logistic regression analysis and propensity-score matching were used to identify independent risk factors for leak, and to test the hypothesis that diverting ileostomy was protective against anastomotic leakage. Results A total of 4172 [92%] patients underwent primary anastomosis, and 365 [8%] underwent anastomosis plus ileostomy. The leak rates in the two groups were 4.5% and 2.7%, [p = 0.12], respectively. Multivariate analysis indicated ileostomy omission, emergency surgery, smoking, inpatient status, wound classification 3 or 4, weight loss, steroid use, and prolonged operative time were independently associated with leak. Patients with 0–6 risk factors had leak rates of 1.6%, 2.7%, 4.3%, 6.7%, 8.8%, 11.5%, and 14.3% [p ≤ 0.001], respectively. Following propensity-score matching, ileostomy reduced the risk of leak rate by 55% [p = 0.005]. Patients with primary anastomosis who leaked most frequently required reoperation [57.8%], but anastomosis plus ileostomy patients who leaked most frequently were managed by percutaneous drainage [70%], p = 0.04. Conclusions After ileocolic resection for Crohn’s disease, anastomotic leak may be predicted by simple addition of risk factors. We found that diverting ileostomy mitigated against leak, reducing both the leak rate and the likelihood of unplanned reoperations. Faecal diversion should be considered when ≥3 risk factors are present.

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DOP77 Ustekinumab is associated with better effectiveness outcomes when compared with vedolizumab in Crohn’s disease patients with prior anti-TNF failure: comparative effectiveness study from the ICC Registry

Journal of Crohn s and Colitis ◽

10.1093/ecco-jcc/jjz203.116 ◽

2020 ◽

Vol 14 (Supplement_1) ◽

pp. S114-S116 ◽

Cited By ~ 1

Author(s):

V Biemans drs ◽

J van der Woude ◽

G Dijkstra ◽

A van der Meulen- de Jong ◽

M Löwenberg ◽

...

Keyword(s):

Logistic Regression ◽

Crohn’S Disease ◽

Crohn's Disease ◽

Propensity Score ◽

Propensity Score Matching ◽

Clinical Remission ◽

Current Smoker ◽

Faecal Calprotectin ◽

Safety Outcomes ◽

Biochemical Remission

Abstract Background Both vedolizumab and ustekinumab can be considered for the treatment of Crohn’s disease (CD) when anti-TNF treatment fails. However, head-to-head trials are currently not available or planned in the near future. The aim of this study was to compare vedolizumab and ustekinumab in CD patients using a quasi-experimental study design in a prospective registry specifically developed for comparative studies. Methods CD patients who failed anti-TNF treatment and started vedolizumab or ustekinumab in standard care as second-line biological and naïve to the latter two therapies, were identified in the observational prospective ICC Registry. Corticosteroid-free clinical remission (Harvey Bradshaw Index ≤4), biochemical remission (C-reactive protein ≤5 mg/l and faecal calprotectin ≤250 µg/g), combined corticosteroid-free clinical and biochemical remission, and safety outcomes were compared after 52 weeks of treatment. To adjust for confounding and selection bias, we used multiple logistic regression (correcting for current smoker, disease duration, complicated disease (stricturing or penetrating behaviour), prior CD-related surgery, number of prior anti-TNF treatments, HBI at baseline and biochemical disease at baseline) and propensity score matching (variables include the same variables as logistic regression analysis with addition of disease location and behaviour, corticosteroid and immunosuppressant use at baseline). Results In total, 128 vedolizumab- and 85 ustekinumab-treated patients fulfilled the inclusion criteria. By using propensity score matching, 69 vedolizumab-treated patients were matched with 69 ustekinumab-treated patients. After adjusting for confounders, ustekinumab-treated patients were more likely to achieve corticosteroid-free clinical remission (OR: 2.56, 95% CI: 1.35–4.87, p = 0.004), biochemical remission (OR: 2.22, 95% CI: 1.04–4.74, p = 0.040), and combined corticosteroid-free clinical and biochemical remission (OR: 2.58, 95% CI: 1.15–5.78, p = 0.022), while safety outcomes (infections: OR: 1.26, 95% CI: 0.63–2.54, p = 0.517; adverse events: OR: 1.33, 95% CI: 0.62–2.81, p = 0.464; hospitalisations: OR: 0.67, 95% CI: 0.32–1.39, p = 0.282) were comparable between the two groups. The propensity score matched cohort showed comparable results. Conclusion In this prospective, comparative analysis ustekinumab was associated with higher effectiveness outcomes of ustekinumab when compared with vedolizumab. Safety outcomes were comparable after 52 weeks of treatment in CD patients who have failed anti-TNF treatment.

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OP26 Risankizumab induces early clinical remission and response in patients with Moderate-to-Severe Crohn’s Disease: Results from the phase 3 ADVANCE and MOTIVATE studies

Journal of Crohn s and Colitis ◽

10.1093/ecco-jcc/jjab075.025 ◽

2021 ◽

Vol 15 (Supplement_1) ◽

pp. S026-S027

Author(s):

S W Schreiber ◽

M Ferrante ◽

R Panaccione ◽

J F Colombel ◽

T Hisamatsu ◽

...

Keyword(s):

Crohn’S Disease ◽

Crohn's Disease ◽

Clinical Response ◽

Induction Therapy ◽

Clinical Remission ◽

Activity Index ◽

Unmet Need ◽

Inadequate Response ◽

Biologic Treatment ◽

Double Blind

Abstract Background Present therapies leave an unmet need for early and effective treatment for patients with Crohn’s disease (CD). Risankizumab (RZB), a humanized immunoglobulin G1 monoclonal antibody against the p19 subunit of interleukin-23, was evaluated as an induction therapy to induce early clinical remission and response in patients with moderate-to-severe CD in two double-blind, randomized, placebo (PBO)-controlled studies (ADVANCE [NCT03104413] and MOTIVATE [NCT03105128]). Methods Patients with moderate-to-severe CD (CD Activity Index [CDAI] of 220–450, Simple Endoscopic Score for CD [SES-CD] ≥ 6 [≥ 4 for isolated ileal disease] excluding the narrowing component, and average daily [liquid/very soft] stool frequency [SF] ≥ 4 and/or average daily abdominal pain [AP] score ≥ 2) who had inadequate response or intolerance to conventional and/or biologic treatment (ADVANCE), or biologic treatment only (MOTIVATE) were randomised 2:2:1 (ADVANCE) or 1:1:1 (MOTIVATE) to receive intravenous RZB 600 mg, RZB 1200 mg, or PBO as induction therapy at weeks 0, 4, and 8. Clinical remission (per either CDAI or a composite of SF and AP criteria), clinical response (per CDAI criterion), and enhanced clinical response (per a composite of SF and AP criteria) were evaluated at weeks 4, 8, and 12 (endpoints defined in Figure 1 footnotes). Safety was assessed throughout the studies. Results A total of 1419 patients from ADVANCE (N = 850) and MOTIVATE (N = 569) respectively, were randomised and included in the intention-to-treat population. In both studies, starting at week 4 (the first prespecified measurement), greater proportions of RZB 600 mg or RZB 1200 mg- vs PBO-treated patients achieved clinical remission per either CDAI (P = .01/P < .05) or SF/AP criteria (P < .01/P < .01), clinical response per CDAI criterion (P = .001/P < .01), and enhanced clinical response per SF/AP criteria (P < .01/P = .14) (Figure 1). For both RZB 600 mg and RZB 1200 mg, the efficacy and treatment effect increased through week 12 (P ≤ .001/P ≤ .001) (Figure 1). Treatment with RZB 600 mg or 1200 mg was well tolerated, and no new safety risks were identified.1,2 Conclusion Induction therapy with both RZB 600 mg and 1200 mg intravenous resulted in significantly greater clinical remission and response vs PBO as early as week 4 and sustained through week 12 in patients with moderate-to-severe CD who had inadequate response or intolerance to conventional and/or biologic treatment. References

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Edoxaban versus warfarin on stroke risk in patients with atrial fibrillation: a territory-wide cohort study

10.1101/2021.01.04.21249209 ◽

2021 ◽

Author(s):

Dicken Kong ◽

Jiandong Zhou ◽

Sharen Lee ◽

Keith Sai Kit Leung ◽

Tong Liu ◽

...

Keyword(s):

Atrial Fibrillation ◽

Cohort Study ◽

Ischemic Stroke ◽

Propensity Score ◽

Ischaemic Stroke ◽

Propensity Score Matching ◽

Lower Risk ◽

Cox Regression ◽

Significant Risk ◽

Risk Predictors

AbstractBackgroundIn this territory-wide, observational, propensity score-matched cohort study, we evaluate the development of transient ischaemic attack and ischaemic stroke (TIA/Ischaemic stroke) in patients with AF treated with edoxaban or warfarin.MethodsThis was an observational, territory-wide cohort study of patients between January 1st, 2016 and December 31st, 2019, in Hong Kong. The inclusion were patients with i) atrial fibrillation, and ii) edoxaban or warfarin prescription. 1:2 propensity score matching was performed between edoxaban and warfarin users. Univariate Cox regression identifies significant risk predictors of the primary, secondary and safety outcomes. Hazard ratios (HRs) with corresponding 95% confidence interval [CI] and p values were reported.ResultsThis cohort included 3464 patients (54.18% males, median baseline age: 72 years old, IQR: 63-80, max: 100 years old), 664 (19.17%) with edoxaban use and 2800 (80.83%) with warfarin use. After a median follow-up of 606 days (IQR: 306-1044, max: 1520 days), 91(incidence rate: 2.62%) developed TIA/ischaemic stroke: 1.51% (10/664) in the edoxaban group and 2.89% (81/2800) in the warfarin group. Edoxaban was associated with a lower risk of TIA or ischemic stroke when compared to warfarin.ConclusionsEdoxaban use was associated with a lower risk of TIA or ischemic stroke after propensity score matching for demographics, comorbidities and medication use.

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The New Proactive Approach and Precision Medicine in Crohn’s Disease

Biomedicines ◽

10.3390/biomedicines8070193 ◽

2020 ◽

Vol 8 (7) ◽

pp. 193

Author(s):

Eran Zittan ◽

Ian M. Gralnek ◽

Marc S. Berns

Keyword(s):

Crohn’S Disease ◽

Crohn's Disease ◽

Personalized Medicine ◽

Precision Medicine ◽

Unmet Need ◽

Fecal Calprotectin ◽

Mucosal Inflammation ◽

Remission Induction ◽

Clinical Relapse ◽

Proactive Approach

The proactive approach to Crohn’s disease (CD) management advocates moving toward algorithmic tight-control scenarios that are designed for each CD phenotype to guide remission induction, maintenance therapy, active monitoring, and multidisciplinary care to manage the complexities of each inflammatory bowel disease (IBD) patient. This requires accurate initial clinical, laboratory, radiological, endoscopic, and/or tissue diagnosis for proper phenotypic stratification of each CD patient. A substantial proportion of patients in symptomatic remission have been reported to demonstrate evidence of active disease, with elevated fecal calprotectin(FC) and C-reactive protein (CRP) levels as a hallmark for mucosal inflammation. Active mucosal inflammation, and elevated CRP and fecal calprotectin (FC) have been shown to be good predictors of clinical relapse, disease progression, and complications in IBD patients. The next frontier of treatment is personalized medicine or precision medicine to help solve the problem of IBD heterogeneity and variable responses to treatment. Personalized medicine has the potential to increase the efficacy and/or reduce potential adverse effects of treatment for each CD phenotype. However, there is currently an unmet need for better elucidation of the inflammatory biopathways and genetic signatures of each IBD phenotype, so personalized medicine can specifically target the underlying cause of the disease and provide maximal efficacy to each patient.

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DOP06 Non-invasive identification of adherent-invasive E. coli in patients with Crohn’s disease

Journal of Crohn s and Colitis ◽

10.1093/ecco-jcc/jjz203.045 ◽

2020 ◽

Vol 14 (Supplement_1) ◽

pp. S044-S045 ◽

Cited By ~ 1

Author(s):

A Buisson ◽

E Vazeille ◽

X Hébuterne ◽

M Fumery ◽

B Pariente ◽

...

Keyword(s):

Crohn’S Disease ◽

Crohn's Disease ◽

Unmet Need ◽

Inhibition Test ◽

Invasive Ability ◽

Ileal Mucosa ◽

Multi Centre Study ◽

E Coli ◽

Non Invasive ◽

Adhesion Inhibition

Abstract Background Medications limiting the adhesion of ‘adherent and invasive E. coli’ (AIEC) represent potential strategies to treat Crohn’s disease (CD). However, the ileal AIEC identification is a time-consuming procedure, and the number of AIEC strains which colonise ileal CD mucosa remains unknown. There is an unmet need for non-invasive biomarkers to identify patients colonised by AIEC. We aimed to evaluate non-invasive biomarker of ileal AIEC colonisation in patients with CD. Methods This prospective and multi-centre study included CD patients requiring ileocoloscopy. Saliva, serum, stools and ileal biopsies were collected. Abundance and global invasive ability of ileal or faecal E. coli were performed. Isolated E. coli were characterised as AIEC or non-AIEC on I407 epithelial cells and THP1 macrophages. The ERIC-PCR profiles of ileal E. coli were performed. Ileal E. coli/CEACAM6 interaction was analysed by a yeast aggregation test and T84 assays (CEACAM6 protein expression, adhesion inhibition test with D-mannose). Quantification of serum anti-E. coli and ileal or salivary CEACAM6 was realised by ELISA. Results Overall, 102 CD patients were enrolled in this study and 25.8% of them exhibited ileal AIEC colonisation (AIEC+). The abundance and global invasive ability of ileal mucosa-associated E. coli were higher in AIEC+ CD patients compared with CD patients without AIEC (AIEC−) (p = 0.0065 and p = 0.0007, respectively). There was no difference between faecal abundance and invasive ability of E. coli between AIEC+ and AIEC− patients. The ERIC-PCR profiles of ileal E. coli showed that CD AIEC+ were for 78% of them colonised by not more than 2 clonal AIEC strains. In addition, AIEC were able to interact with CEACAM6 by binding D-mannose residues and to induce CEACAM6 expression in T84 cells (p = 0.0009 and p = 0.0185, vs. non-AIEC; respectively). This was also supported by adhesion inhibition test. Serum anti-E. coli level was higher for CD AIEC+ (vs. CD AIEC-). Ileal CEACAM6 level were positively correlated with abundance of ileal associated E. coli in AIEC+ patients (r = 0.4000; p = 0.0362) and with salivary CEACAM6 level (r = 0.4690; p < 0.0001). The non-invasive biomarker ‘serum anti-E.coli/salivary CEACAM6’ index was higher for CD AIEC+ (p = 0.0174; vs. CD AIEC-). A cut-off value < 1.34 × 10−6 eliminated the presence of ileal AIEC with a high negative predictive value (90% CI95% [69%–95%]). Conclusion Our study reported that identification of faecal AIEC cannot replace identification of AIEC from ileal biopsies, most of AIEC infection are mono or bi-clonal (≤ 2 strains) and that non-invasive biomarker such as ‘serum anti-E.coli/salivary CEACAM6’ index could be helpful to screen CD patients for AIEC infection.

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