Predicting endoscopic remission in Crohn’s disease by the modified multiplier SES-CD (MM-SES-CD)

Gut ◽  
2021 ◽  
pp. gutjnl-2020-323799
Author(s):  
Neeraj Narula ◽  
Emily C L Wong ◽  
Jean-Frederic Colombel ◽  
William J Sandborn ◽  
John Kenneth Marshall ◽  
...  

Background and aimsThe Simple Endoscopic Score for Crohn’s disease (SES-CD) is the primary tool for measurement of mucosal inflammation in clinical trials but lacks prognostic potential. We set to develop and validate a modified multiplier of the SES-CD (MM-SES-CD), which takes into consideration each individual parameter’s prognostic value for achieving endoscopic remission (ER) while on active therapy.MethodsIn this posthoc analysis of three CD clinical trial programmes (n=350 patients, baseline SES-CD ≥ 3 with confirmed ulceration), data were pooled and randomly split into a 70% training and 30% testing cohort. The MM-SES-CD was designed using weights for individual parameters as determined by logistic regression modelling, with 1-year ER (SES-CD < 3) being the dependent variable. A cut point score for low and high probability of ER was determined by using the maximum Youden Index and validated in the testing cohort.ResultsBaseline ulcer size, extent of ulceration and presence of non-passable strictures had the strongest association with 1-year ER as compared with affected surface area, with differential weighting of individual parameters across disease segments being observed during logistic regression. The MM-SES-CD was generated using this weighted regression model and demonstrated strong discrimination for ER in the training dataset (area under the receiver operator curve (AUC) 0.83, 95% CI 0.78 to 0.94) and in the testing dataset (AUC 0.82, 95% CI 0.77 to 0.92). In comparison to the MM-SES-CD scoring model, the original SES-CD score lacks accuracy (AUC 0.60, 95% CI 0.55 to 0.65) for predicting the achievement of ER.ConclusionsWe developed and internally validated the MM-SES-CD as an endoscopic severity assessment tool to predict one-year ER in patients with CD on active therapy.

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S304-S304
Author(s):  
A HOLMER ◽  
B Boland ◽  
S Singh ◽  
H Le ◽  
J Neill ◽  
...  

Abstract Background The endoscopic healing index (EHI, Monitr, Prometheus Biosciences, San Diego, CA) is a serum-based biomarker panel available for identifying mucosal inflammation in Crohn’s disease.[1] We aimed to study its performance for identifying mucosal inflammation in ulcerative colitis. Methods EHI was analysed on serum samples paired with endoscopies from adult patients (≥18 years) participating in a prospective biobank (June 2014 to December 2017). Area under receiver operating characteristic curves (AUROC) were used to assess the accuracy of EHI for endoscopic improvement (EI; Mayo endoscopic sub-score [MES] 0–1) and endoscopic remission (ER; MES 0). Sensitivity for EHI was calculated using a cut-off previously identified for Crohn’s disease which optimised performance for ruling out endoscopic activity (20 points). Alternative cut-offs were explored. Results A total of 114 patients were included, with an overall prevalence of 56% and 44% for EI and ER. The AUROC was 0.79 (95% CI 0.70–0.87) for EI and 0.70 (95% CI 0.61–0.80) for ER. A cut-off of 20 points had a sensitivity of 94% (95% CI 83–99%) for ruling out moderate to severe (MES 2–3) endoscopic activity, and a sensitivity of 84% (95% CI 72–92%) for ruling out mild to severe (MES 1–3) endoscopic activity. A cut off of 40 points or higher had &gt; 90% specificity for ruling in moderate to severe (MES 2–3) or mild to severe (MES 1–3) endoscopic activity. (Table 1) Conclusion EHI has favourable accuracy in identifying the presence of mucosal inflammation in patients with ulcerative colitis. Although it was not developed and validated for ulcerative colitis, further validation is warranted. Reference


2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S192-S192
Author(s):  
L Ortega Moreno ◽  
A Sanz-Garcia ◽  
M J Fernández de la Fuente ◽  
R Arroyo Solera ◽  
M Chaparro ◽  
...  

Abstract Background Adipose tissue wrapping the gastrointestinal tract is a risk factor for disease activity in Crohn’s disease (CD). Indeed, adipokines associated to lipid metabolism can modulate local immune responses. However, few studies have investigated the possible association between adipokines and CD. Here, we aimed to evaluate the role of serum adipokines as possible biomarkers in CD. Methods Serum samples were obtained from 18 patients with endoscopically active CD (aCD), 22 patients with endoscopically quiescent CD (qCD) and 36 non-inflamed healthy controls (HC). Serum leptin, ghrelin, resistin and adiponectin were analysed by Multiplex (Bio-Rad, Hercules, CA) in a Luminex 200 system technology. Adipokines means for each group of patients were compared and adjusted by Bonferroni or Wilcoxon tests. Receiver operating characteristic (ROC) curves and the area under the curve (AUC) were carried on to evaluate the discriminatory capacity of the adipokines levels between patients groups. Furthermore, for those adipokines that showed an AUC &gt; 0.7, a binary logistic regression adjusted by possible confounders (i.e. sex, age and BMI) was performed in order to test their possible association with CD. Results No differences were found in age, sex or BMI among aCD, qCD and HC; there was no correlation either among the adipokines analysed. Means distribution for serum resistin was different among aCD, qCD and HC (p = 0.006). However, only comparisons between HC and aCD groups showed significant differences (p = 0.02) in the post hoc test. Serum leptin, ghrelin and adiponectin did not show differences between means. ROC curve for resistin showed an AUC of 0.78, with a standard error (SE) of 0.067 when HC and aCD groups were analysed (Figure 1). Furthermore, in this case, as sensitivity and specificity for Youden index correspond to the resistin median concentration, this value was selected as a cut-off for the binary logistic regression analysis; thus, odds ratio (OR) along with their 95% confidence interval (CI) analysis of high relative resistin levels (values higher than their median) adjusted by age, sex and BMI yielded a value of 5.46 (1.34–22.14) when aCD group was compared with HC group. Comparison between qCD and aCD showed an AUC of 0.70 with an SE of 0.089. However, ROC curve did not show a good accuracy when HC and qCD groups were analysed (AUC = 0.58; SE = 0.08). ROC curves analysis for leptin, ghrelin and adiponectin did not show enough accuracy to discriminate between groups. Conclusion Resistin may modulate the inflammation state in CD and it is probably associated to activity, being this association independent of sex, age or BMI.


2020 ◽  
Vol 3 (Supplement_1) ◽  
pp. 99-100
Author(s):  
J Stone ◽  
K Witges ◽  
L Shafer ◽  
L E Targownik ◽  
L M Lix ◽  
...  

Abstract Background Medication non-adherence in IBD has previously been reported to be quite variable, ranging from 7 to 73%, and is considered to be an important contributor to disease flares. While there is currently no gold standard for medication adherence reporting in IBD, the Medication Adherence Reporting Scale 5 (MARS-5) has frequently been used in this population, but never validated. Aims This study aimed to analyze medication adherence rates in a cohort of persons with IBD in Manitoba, report predictors of medication non-adherence on self-reported symptoms, and validate the MARS-5 as a medication adherence tool. Methods 55 subjects were prospectively followed with biweekly online surveys in the Manitoba Living with IBD Study. Subjects not taking any medications for IBD or only taking as needed, missing adherence data and those lost to follow-up were excluded, leaving 112 subjects. Descriptive data on demographics, surgeries, IBD medications, medication adherence, and measures of disease activity utilizing IBDSI-SF scores were collected. Mean annual medication adherence percentage, IBDSI-SF(&gt;14=active for Crohn’s,&gt;13=active for UC) and MARS-5 scores were calculated. Logistic regression analysis was performed to determine variables associated with medication adherence and to validate the MARS-5. Results Mean age was 42.9 years (SD 12.8), with 71.4% being female. Crohn’s disease (CD) was diagnosed in 67.9%, with 37.5% having undergone at least one abdominal surgery. 70.5% of patients were on 2 or more IBD medications. Mean IBDSI score was 15.5 and mean MARS-5 score was 22.5. 20 (17.9%) patients reported a mean adherence of &lt;90% across all medications- 18 were oral medication users, 1 was on an infusion biologic and 1 on subcutaneous adalimumab. 10 (9.8%) had adherence &lt;80%, all of which were to oral medications. Multivariate regression analysis revealed only a diagnosis of Crohn’s disease (OR 4.62; 95% CI 1.37–15.7; p=0.014) to be a predictor of adherence. Disease activity as defined by IBDSI (OR 0.43, 95% CI 0.13–1.45; p=0.139) and fecal calprotectin &gt;250ug/L (OR 1.04, 95% CI 0.35–3.11; p=0.724), age &gt;55 (OR 2.37, 95% CI 0.65–8.65; p=0.476), female sex (OR 0.38, 95% CI 0.097–1.52; p=0.150) and stress (OR 0.67, 95% CI 0.19–2.32; p=0.498) were not shown to be predictors. MARS-5 was compared to percentage adherence, showing moderate correlation (Pearson r=0.46). Logistic regression analysis showed each additional MARS-5 point was associated with a 1.7 times greater odds of &gt;90% adherence. Conclusions We report a highly adherent Manitoba IBD cohort. A diagnosis of CD was the only predicitor of adherence. MARS-5 showed moderate correlation with mean percentage adherence values, suggesting it is a valid assessment tool for determining medication adherence in an IBD population. Funding Agencies None


Author(s):  
Neeraj Narula ◽  
Emily C L Wong ◽  
Parambir S Dulai ◽  
John K Marshall ◽  
Jean-Frederic Colombel ◽  
...  

Abstract Background and Aims There is paucity of evidence on the reversibility of Crohn’s disease [CD]-related strictures treated with therapies. We aimed to describe the clinical and endoscopic outcomes of CD patients with non-passable strictures. Methods This was a post-hoc analysis of three large CD clinical trial programmes examining outcomes with infliximab, ustekinumab, and azathioprine, which included data on 576 patients including 105 with non-passable strictures and 45 with passable strictures, as measured using the Simple Endoscopic Score for Crohn’s Disease [SES-CD]. The impact of non-passable strictures on achieving clinical remission [CR] and endoscopic remission [ER] was assessed using multivariate logistic regression models. CR was defined as a Crohn’s Disease Activity Index [CDAI] &lt;150, clinical response as a CDAI reduction of ≥100 points, and ER as SES-CD score &lt;3. Results After 1 year of treatment, patients with non-passable strictures demonstrated the ability to achieve passable or no strictures in 62.5% of cases, with 52.4% and 37.5% attaining CR and ER, respectively. However, patients with non-passable strictures at baseline were less likely to demonstrate symptom improvement compared with those with passable or no strictures, with reduced odds of 1-year CR (adjusted odds ratio [aOR] 0.17, 95% CI 0.03–0.99, p = 0.048). No significant differences were observed between patients with non-passable strictures at baseline and those with passable or no strictures in rates of ER [aOR 0.82, 95% CI 0.23–2.85, p = 0.751] at 1 year. Conclusions Patients with non-passable strictures can achieve symptomatic and endoscopic remission when receiving therapies used to treat CD, although they are less likely to obtain CR compared with patients without non-passable strictures. These findings support the importance of balancing the presence of non-passable strictures in trial arms.


2019 ◽  
Vol 26 (7) ◽  
pp. 1050-1058 ◽  
Author(s):  
Robert P Hirten ◽  
Ryan C Ungaro ◽  
Daniel Castaneda ◽  
Sarah Lopatin ◽  
Bruce E Sands ◽  
...  

Abstract Background Crohn’s disease recurrence after ileocolic resection is common and graded with the Rutgeerts score. There is controversy whether anastomotic ulcers represent disease recurrence and should be included in the grading system. The aim of this study was to determine the impact of anastomotic ulcers on Crohn’s disease recurrence in patients with prior ileocolic resections. Secondary aims included defining the prevalence of anastomotic ulcers, risk factors for development, and their natural history. Methods We conducted a retrospective cohort study of patients undergoing an ileocolic resection between 2008 and 2017 at a large academic center, with a postoperative colonoscopy assessing the neoterminal ileum and ileocolic anastomosis. The primary outcome was disease recurrence defined as endoscopic recurrence (&gt;5 ulcers in the neoterminal ileum) or need for another ileocolic resection among patients with or without an anastomotic ulcer in endoscopic remission. Results One hundred eighty-two subjects with Crohn’s disease and an ileocolic resection were included. Anastomotic ulcers were present in 95 (52.2%) subjects. No factors were associated with anastomotic ulcer development. One hundred eleven patients were in endoscopic remission on the first postoperative colonoscopy. On multivariable analysis, anastomotic ulcers were associated with disease recurrence (adjusted hazard ratio [aHR] 3.64; 95% CI, 1.21–10.95; P = 0.02). Sixty-six subjects with anastomotic ulcers underwent a second colonoscopy, with 31 patients (79.5%) having persistent ulcers independent of medication escalation. Conclusion Anastomotic ulcers occur in over half of Crohn’s disease patients after ileocolic resection. No factors are associated with their development. They are associated with Crohn’s disease recurrence and are persistent.


2021 ◽  
Vol 14 ◽  
pp. 175628482110066
Author(s):  
Rune Wilkens ◽  
Kerri L. Novak ◽  
Christian Maaser ◽  
Remo Panaccione ◽  
Torsten Kucharzik

Treatment targets of inflammatory bowel diseases (IBD), ulcerative colitis (UC) and Crohn’s disease (CD) have evolved over the last decade. Goals of therapy consisting of symptom control and steroid sparing have shifted to control of disease activity with endoscopic remission being an important endpoint. Unfortunately, this requires ileocolonoscopy, an invasive procedure. Biomarkers [C-reactive protein (CRP) and fecal calprotectin (FCP)] have emerged as surrogates for endoscopic remission and disease activity, but also have limitations. Despite this evolution, we must not lose sight that CD involves transmural inflammation, not fully appreciated with ileocolonoscopy. Therefore, transmural assessment of disease activity by cross-sectional imaging, in particular with magnetic resonance enterography (MRE) and intestinal ultrasonography (IUS), is vital to fully understand disease control. Bowel-wall thickness (BWT) is the cornerstone in assessment of transmural inflammation and BWT normalization, with or without bloodflow normalization, the key element demonstrating resolution of transmural inflammation, namely transmural healing (TH) or transmural remission (TR). In small studies, achievement of TR has been associated with improved long-term clinical outcomes, including reduced hospitalization, surgery, escalation of treatment, and a decrease in clinical relapse over endoscopic remission alone. This review will focus on the existing literature investigating the concept of TR or residual transmural disease and its relation to other existing treatment targets. Current data suggest that TR may be the next logical step in the evolution of treatment targets.


Digestion ◽  
2021 ◽  
pp. 1-9
Author(s):  
Akihiro Yamada ◽  
Yuga Komaki ◽  
Fukiko Komaki ◽  
Haider Haider ◽  
Dejan Micic ◽  
...  

<b><i>Background and Aims:</i></b> Vitamin D deficiency has been associated with disease activity in Crohn’s disease (CD). We assessed whether there is a correlation between vitamin D levels and the risk of postoperative recurrence in CD. <b><i>Methods:</i></b> CD patients who underwent surgery were identified from a prospectively maintained database at the University of Chicago. The primary endpoint was the correlation of serum 25-hydroxy vitamin D levels measured at 6–12 months after surgery and the proportion of patients in endoscopic remission, defined as a simple endoscopic score for CD of 0. Clinical, biological (C-reactive protein), and histologic recurrences were also studied. <b><i>Results:</i></b> Among a total of 89 patients, 17, 46, and 26 patients had vitamin D levels of &#x3c;15, 15–30, and &#x3e;30 ng/mL, respectively. Patients with higher vitamin D levels were significantly more likely to be in endoscopic remission compared to those with lower levels (23, 42, and 67% in ascending tertile order; <i>p</i> = 0.028). On multivariate analysis, vitamin D &#x3e;30 ng/mL (odds ratio [OR] 0.22, 95% confidence interval [CI] 0.07–0.66, <i>p</i> = 0.006) and anti-tumor necrosis factor agent treatment (OR 0.25, 95% CI 0.08–0.83, <i>p</i> = 0.01) were associated with reduced risk of endoscopic recurrence. Rates of clinical, biological, and histologic remission trended to be higher in patients with higher vitamin D levels (<i>p</i> = 0.17, 0.55, 0.062, respectively). <b><i>Conclusion:</i></b> In the present study, higher vitamin D level was associated with lower risk of postoperative endoscopic CD recurrence. Further, studies are warranted to assess the role of vitamin D in postoperative CD recurrence.


2020 ◽  
Vol 26 (Supplement_1) ◽  
pp. S75-S75
Author(s):  
Scott D Lee ◽  
Anand Singla ◽  
Caitlin Kerwin ◽  
Kindra Clark-Snustad

Abstract Background Vedolizumab (VDZ) is an effective treatment for Crohn’s disease (CD); however, inadequate and loss of response is common. Pivotal VDZ trials evaluated alternative dosing intervals, demonstrating numeric but not statistical superiority in efficacy as compared to FDA-approved dosing. The safety and effectiveness of FDA-approved and modified-dosing schedules in a real-world population are unknown. We aimed to evaluate clinical and endoscopic effectiveness & safety of standard and modified maintenance VDZ dosing in a real world cohort. Methods We retrospectively reviewed CD patients (pts) treated with &gt;3 months VDZ, assessing Harvey Bradshaw Index (HBI), Simple Endoscopic Score for Crohn’s disease (SESCD), Short Inflammatory Bowel Disease Questionnaire (SIBDQ), C-reactive protein (CRP), albumin and hematocrit prior to and following standard VDZ dosing, and prior to and following modified VDZ maintenance dosing. We measured duration on therapy and adverse events. Results We identified 226 eligible pts, mean age 41.5 years, 55.3% female, median disease duration 10 years, 88.9% with prior biologic exposure. Mean duration on VDZ was 28.3 months. Standard VDZ dosing: 61.5% of pts with active clinical disease and adequate follow up data achieved clinical response after 3–12 months; 41.0% had clinical remission. 51.9% of pts with active endoscopic disease and adequate follow up data achieved mucosal improvement; 42.3% had endoscopic remission; 26.0% had mucosal healing after 3–24 months. 50.0% of pts with elevated CRP and adequate follow up data normalized CRP after 3–12 months. Modified maintenance dosing: 72 non-remitters to standard VDZ dosing received modified VDZ maintenance dosing. 51.5% of pts with active clinical disease prior to starting dose modification and adequate follow up data achieved clinical response after 3–12 months of modified maintenance dosing; 42.4% had clinical remission. 22.2% of pts with SESCD ≥3 prior to starting dose modification achieved mucosal improvement after 3–24 months; 22.2% had mucosal healing. 26.7% of pts with SESCD ≥4 prior to starting modified dosing had endoscopic remission after 3–24 months. 50.0% of pts with elevated CRP and adequate follow up data normalized their CRP after 3–12 months. Safety: 82.7% of pts reported ≥1 adverse events, most commonly infection and worsening CD symptoms. Discussion Standard VDZ dosing resulted in clinical and endoscopic improvement in pts with moderate-severe CD, with prior exposure to multiple advanced therapies. For non-remitters to standard dosing, modified VDZ maintenance dosing improved clinical disease activity in ∼50% of pts and improved endoscopic disease activity in ∼20% of pts, suggesting that for pts who did not achieve remission with standard VDZ dosing, modified VDZ dosing may result in clinical and endoscopic improvement.


2020 ◽  
Vol 26 (Supplement_1) ◽  
pp. S48-S48
Author(s):  
Hartman Brunt ◽  
Mason Adams ◽  
Michael Barker ◽  
Diana Hamer ◽  
J C Chapman

Abstract Purpose Crohn’s disease (CD) is an inflammatory bowel disease (IBD) caused by an abnormal immune response to intestinal microbes in a genetically susceptible host. The objective of this cohort analysis is to compare demographic characteristics, cost difference, and treatment modalities between patients who were discharged from the Emergency Department (ED) and those who were admitted to the hospital. Methods This study is a retrospective chart review of adult patients diagnosed with CD who were discharged from the ED and those who were admitted to the hospital between January 1, 2014 and January 1, 2017. We compared demographic and clinical characteristics as well as total charges incurred by these patients. A chi square test of independence and a Mann Whitney U-Test were used to compare categorical variables. Linear and logistic regression analyses were utilized to identify predictors of hospitalization and total charges. Results Of a total 195 patients, 97 were discharged from the ED and 98 were admitted to the hospital (Table 1). Patients who presented with fever, nausea/vomiting, or abdominal pain or who had a history of a fistula or stenosis were more likely to be hospitalized, as were patients who presented on steroids, 5-ASA compounds, or narcotics (Table 2). A logistic regression adjusted for these factors showed patients presenting with abdominal pain (OR=0.239, 95% CI 0.07 – 0.77) are less likely, while patients presenting with fever (OR=7.0, 95% CI 1.9 – 24.5) and history of stenosis (OR=17.8, 95% CI 5.7 – 55.9) are more likely to have a hospital admission. An increase in age and white blood cell count was associated with an increase in likelihood of admission (OR=1.04, 95% CI 1.01 – 1.07 and OR=1.2, 95% CI 1.1 – 1.4), while an increase in HGB was associated with a decrease in likelihood of admission (OR=0.682, 95% CI 0.55 – 0.83). Patients on 5-ASA compounds had the strongest association with hospital admission (OR=4.5, 95% CI 1.03 – 20.4). A linear regression analysis predicting total charges of hospitalization identified an increase of $37,500 (95% CI 6,600 – 68,489) for obese patients and of $29,000 (95% CI 20 – 57,000) for patients on narcotics prior to hospitalization. Notably, blacks were on average 6 years younger than whites (μ=36.2, st.d.=13.2 v μ=42.7, st.d.=18.2, p=0.031, respectively). No other differences in presentation or outcomes of CD were identified between these races. Conclusion This study describes the difference between CD patients who were admitted to the hospital compared to those who were discharged from the ED. The impact that 5-ASA compound, steroid, and narcotic use prior to presentation has on hospital admission and charges highlights the need for consistent outpatient care to manage the symptoms and disease progression in patients with CD in Baton Rouge. The difference in age at presentation between blacks and whites should also be considered in future research.


2014 ◽  
Vol 48 (6) ◽  
pp. 513-523 ◽  
Author(s):  
Qiurong Li ◽  
Chenyang Wang ◽  
Chun Tang ◽  
Qin He ◽  
Ning Li ◽  
...  

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