scholarly journals Predictors of Ustekinumab Failure in Crohn’s Disease After Dose Intensification

2020 ◽  
Author(s):  
Rahul S Dalal ◽  
Cheikh Njie ◽  
Jenna Marcus ◽  
Sanchit Gupta ◽  
Jessica R Allegretti
Keyword(s):  
Logistic Regression ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Cox Regression ◽  
Laboratory Data ◽  
Perianal Disease ◽  
Secondary Outcome ◽  
Opioid Use ◽  
Dose Intensification ◽  
Multivariable Logistic Regression

Abstract Background Many patients with Crohn’s disease (CD) who lose response to the standard ustekinumab dose interval of every 8 weeks (q8w) undergo dose intensification to q4w or q6w. However, baseline factors that predict success or failure after dose intensification are unknown. We sought to identify predictors of failure of ustekinumab after dose intensification for patients with CD. Methods This was a retrospective cohort study of adult CD patients undergoing ustekinumab dose intensification at a tertiary referral center between January 1, 2016, and January 31, 2019. Electronic health records were reviewed to obtain patient demographics, CD history, and laboratory data. The primary outcome was failure to achieve corticosteroid-free remission (Harvey-Bradshaw Index <5) within 12 months after intensification. The secondary outcome assessed was time to new biologic therapy after dose intensification. We used multivariable logistic regression and Cox regression to identify predictors of these outcomes. Results We included 123 patients who underwent ustekinumab dose intensification to q4w (n = 64), q5w (n = 1), q6w (n = 55), or q7w (n = 3). Multivariable logistic regression demonstrated that perianal disease, Harvey-Bradshaw Index, and opioid use at time of intensification were associated with failure to achieve remission. Cox regression demonstrated that perianal disease and corticosteroid use at time of intensification were associated with shorter time to a new biologic. Conclusion Perianal disease, Harvey-Bradshaw Index, current opioid use, and current corticosteroid use are associated with ustekinumab failure after dose intensification in CD. Larger, prospective studies are needed to corroborate these findings and guide therapeutic strategies for patients who lose response to standard ustekinumab dosing.

Clinical Factors Associated With Response to Fecal Diversion in Crohn’s Disease

2020 ◽  
Vol 86 (10) ◽  
pp. 1277-1280
Author(s):  
Hassan Buhulaigah ◽  
Adam Truong ◽  
Karen Zaghiyan ◽  
Phillip Fleshner
Keyword(s):  
Logistic Regression ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Clinical Response ◽  
Disease Duration ◽  
Binary Logistic Regression ◽  
Fecal Diversion ◽  
Age At Diagnosis ◽  
Perianal Disease ◽  
Perineal Pain

Up to 80% of Crohn’s disease (CD) patients require surgery. Fecal diversion is used selectively in CD proctocolitis refractory to medical treatment or advanced perianal disease. This study examines associations between clinical features in predicting clinical response (CR) to fecal diversion in CD. Charts of CD patients undergoing fecal diversion for medically refractory disease or perianal disease were reviewed. Clinical response was assessed focusing on improvements in urgency, abdominal and perineal pain, decreased anal fistula drainage, and weight gain. Univariate binary logistic regression and multivariate forward-stepwise modeling analysis were used to determine associations with CR. The study cohort comprised 79 patients. After a median follow-up of 36 (3-192) months, 40 (51%) patients achieved a CR. Binary logistic regression analysis revealed both age at diagnosis (hazard ratio [HR] 1.05; confidence interval [CI] 1.01-1.09; P = .007) and disease duration (HR .91; CI .86-.96; P = .001) to be significantly associated with CR. Later age of onset (HR 1.05; CI 1.01-1.10; P = .002) and shorter disease duration (HR .91; CI .86-.97; P = .02) remained significant on multivariate analysis. This largest reported series of fecal diversion for refractory CD in the biologic drug era revealed that young age at diagnosis and long disease duration are associated with a lower CR.

scholarly journals Ustekinumab Dose Intensification in Paediatric Crohn's Disease

2021 ◽  
Author(s):  
Rosa Rodríguez‐Mauriz ◽  
Carlos Seguí Solanes ◽  
Isabel Masiques Mas ◽  
Nuria Rudi Sola
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Dose Intensification ◽  
Paediatric Crohn’S Disease

P007 CROHN’S DISEASE: PREDICTORS OF HOSPITAL DISPOSITION AND COSTS USING DEMOGRAPHIC, CLINICAL, AND TREATMENT DATA

2020 ◽  
Vol 26 (Supplement_1) ◽  
pp. S48-S48
Author(s):  
Hartman Brunt ◽  
Mason Adams ◽  
Michael Barker ◽  
Diana Hamer ◽  
J C Chapman
Keyword(s):  
Logistic Regression ◽  
Crohn’S Disease ◽  
Abdominal Pain ◽  
Crohn's Disease ◽  
Hospital Admission ◽  
Categorical Variables ◽  
History Of ◽  
The Difference ◽  
The Impact ◽  
Total Charges

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.

Perianal Crohn's Disease in Children and Adolescents

2020 ◽  
Vol 30 (05) ◽  
pp. 395-400
Author(s):  
Annika Mutanen ◽  
Mikko P. Pakarinen
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Children And Adolescents ◽  
Perianal Disease ◽  
Ileocecal Region ◽  
Perianal Crohn’S Disease ◽  
Perianal Sepsis ◽  
Endoscopic Assessment ◽  
Perianal Crohn's Disease

AbstractThe incidence of Crohn's disease is increasing worldwide. The clinical course of childhood onset Crohn's disease is particularly aggressive with characteristic disease localization in the ileocecal region and colon, often associated with perianal disease. Severe complications of perianal disease include recurrent perianal sepsis, chronic fistulae, fecal incontinence, and rectal strictures that impair quality of life and may require fecal diversion. Care of patients with perianal Crohn's disease requires a multidisciplinary approach with systematic clinical evaluation, endoscopic assessment, and imaging studies followed by combined medical and surgical management. In this review, we provide an update of the epidemiology, pathophysiology, diagnostics, and management of perianal Crohn's disease in children and adolescents.

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 ◽  
...  
Keyword(s):  
Logistic Regression ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Assessment Tool ◽  
Training Dataset ◽  
Mucosal Inflammation ◽  
Youden Index ◽  
Active Therapy ◽  
Testing Dataset ◽  
Endoscopic Remission

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.

Abstract 9086: Sex Differences in the Association Between Bystander CPR and Survival for Patients With Out-of-Hospital Cardiac Arrest

Circulation ◽  
2021 ◽  
Vol 144 (Suppl_2) ◽  
Author(s):  
Kiok Ahn ◽  
Bryan McNally ◽  
Paul Chan
Keyword(s):  
Logistic Regression ◽  
Cardiac Arrest ◽  
Significant Interaction ◽  
National Registry ◽  
Republic Of Korea ◽  
Secondary Outcome ◽  
Multivariable Logistic Regression ◽  
Bystander Cpr ◽  
The Republic ◽  
Hospital Cardiac Arrest

Background: Bystander cardiopulmonary resuscitation (CPR) is associated with a better survival outcome in patients with out-of-hospital cardiac arrest (OHCA). However, there may be cultural barriers in performing high-quality bystander CPR in women in some non-Western countries and the effect of bystander CPR on survival outcomes may differ by patients’ sex. Methods: Using data between 2012-2018 from a national OHCA registry from the Republic of Korea, we identified adult patients with OHCA of presumed cardiac etiology. The main exposures were bystander CPR and patients’ sex. The primary outcome was survival discharge and the secondary outcome was favorable neurological survival. Multivariable logistic regression evaluated the association between bystander CPR and survival, adjusted for patients’ age, sex, socio-economic status, year of arrest, witnessed arrest status, initial OHCA rhythm, location of arrest, urbanization level of arrest location, and type of bystander. The interaction between bystander CPR and sex was explicitly evaluated in the models. Results: Of 101,505 patients with OHCA in the cohort, 34,124 (33.6 %) were women and 67,381 (64.4 %) were men. Bystander CPR was performed on 18,481 (54.2%) women and 35,904 (53.3%) men (p=0.07). Unadjusted rates of survival discharge were 4.5% in women and 9.5 % in men (p<0.001), and rates of favorable neurological survival were 2.5% in women and 6.4% in men (p<0.001). In multivariable logistic regression models, there was a significant interaction (p=0.005) between bystander CPR and sex for survival to discharge, with an adjusted OR for bystander CPR of 1.16 (95% CI: 1.08-1.23) in men and 0.91 (95% CI: 0.80-1.02) in women. For favorable neurological survival, there was also a significant interaction (p=0.01) between sex and bystander CPR, with an adjusted OR for bystander CPR of 1.47 (95% CI: 1.36-1.60) in men and 1.16 (95% CI: 0.98- 1.37) in women. Conclusions: In a national registry of OHCA from the Republic of Korea, men who received bystander CPR were more likely to survive whereas women who received bystander CPR were not.

The Incidence and Disease Course of Perianal Crohn’s Disease: A Danish Nationwide Cohort Study, 1997–2015

2020 ◽  
Author(s):  
M D Wewer ◽  
M Zhao ◽  
A Nordholm-Carstensen ◽  
P Weimers ◽  
J B Seidelin ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Cox Regression ◽  
Major Surgery ◽  
Disease Course ◽  
Cox Regression Analysis ◽  
Perianal Crohn’S Disease ◽  
Increased Risk ◽  
Perianal Crohn's Disease

Abstract Background and Aims Perianal Crohn’s disease [CD] places a considerable burden on patients’ quality of life and is complex to treat. Despite its impact and high frequency, few studies have investigated the incidence and disease course of perianal CD. The aim of this study was to assess the incidence and disease course of perianal CD in adult patients throughout a 19-year period. Methods The cohort comprised all individuals aged 18 years or older who were diagnosed with CD in Denmark between January 1, 1997, and December 31, 2015, according to the National Patient Registry [NPR]. Results A total of 1812 [19%] out of 9739 patients with CD were found to have perianal CD. Perianal fistulas were the most common manifestation, accounting for 943 [52%] cases. The incidence of perianal CD remained stable over time. Patients with perianal CD were found to have an increased risk of undergoing major abdominal surgery compared with patients without perianal CD (hazard ratio: 1.51, 95% confidence interval [CI]: 1.40 to 1.64, p &lt;0.001) in a multivariate Cox regression analysis. The incidence rate ratios of anal and rectal cancer in perianal CD patients were 11.45 [95% CI: 4.70 to 27.91, p &lt;0.001] and 2.29 [95% CI: 1.25 to 4.20, p = 0.006], respectively, as compared with non-IBD matched controls. Conclusions In this nationwide study, 19% of CD patients developed perianal disease. Patients with perianal CD were at increased risk of undergoing major surgery compared with non-perianal CD patients. The risk of anal and rectal cancer was increased in patients with perianal CD compared with non-IBD matched controls. Podcast This article has an associated podcast which can be accessed at https://academic.oup.com/ecco-jcc/pages/podcast

scholarly journals Nomogram to predict primary non-response to infliximab in patients with Crohn’s disease: a multicenter study

2020 ◽  
Author(s):  
Xiao-Qi Ye ◽  
Jing Cai ◽  
Qiao Yu ◽  
Xiao-Cang Cao ◽  
Yan Chen ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Validation Cohort ◽  
Characteristic Curve ◽  
Mucosal Healing ◽  
Clinical Usefulness ◽  
Secondary Outcome ◽  
Training Cohort ◽  
Graphical Tool ◽  
Therapeutic Decision Making

Abstract Background Infliximab (IFX) is effective at inducing and maintaining clinical remission and mucosal healing in patients with Crohn’s disease (CD); however, 9%–40% of patients do not respond to primary IFX treatment. This study aimed to construct and validate nomograms to predict IFX response in CD patients. Methods A total of 343 patients diagnosed with CD who had received IFX induction from four tertiary centers between September 2008 and September 2019 were enrolled in this study and randomly classified into a training cohort (n = 240) and a validation cohort (n = 103). The primary outcome was primary non-response (PNR) and the secondary outcome was mucosal healing (MH). Nomograms were constructed from the training cohort using multivariate logistic regression. Performance of nomograms was evaluated by area under the receiver-operating characteristic curve (AUC) and calibration curve. The clinical usefulness of nomograms was evaluated by decision-curve analysis. Results The nomogram for PNR was developed based on four independent predictors: age, C-reactive protein (CRP) at week 2, body mass index, and non-stricturing, non-penetrating behavior (B1). AUC was 0.77 in the training cohort and 0.76 in the validation cohort. The nomogram for MH included four independent factors: baseline Crohn’s Disease Endoscopic Index of Severity, CRP at week 2, B1, and disease duration. AUC was 0.79 and 0.72 in the training and validation cohorts, respectively. The two nomograms showed good calibration in both cohorts and were superior to single factors and an existing matrix model. The decision curve indicated the clinical usefulness of the PNR nomogram. Conclusions We established and validated nomograms for the prediction of PNR to IFX and MH in CD patients. This graphical tool is easy to use and will assist physicians in therapeutic decision-making.

scholarly journals P549 A virtual clinic enhances the quality use of anti-TNF dose intensification and rates of treatment success using a treat-to-target approach compared with standard outpatient care in Crohn’s disease

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S467-S467
Author(s):  
A Srinivasan ◽  
D R van Langenberg ◽  
R Little ◽  
M P Sparrow ◽  
P De Cruz ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Disease Activity ◽  
Outpatient Care ◽  
Inactive Disease ◽  
Treat To Target ◽  
Model Of Care ◽  
Dose Intensification ◽  
Trough Levels

Abstract Background Virtual clinics (VC) represent a novel model-of-care which promote quality use of biologics and facilitate a treat-to-target (T2T) approach. We aimed to evaluate the clinical and process-driven outcomes of intensified anti-TNF therapy for secondary loss of response (SLoR) in a VC compared with standard outpatient care (SoC). Methods A retrospective multicenter, parallel observational cohort study of patients with Crohn’s disease (CD) who underwent anti-TNF dose intensification to address SLoR with up to 2-years of follow-up was undertaken. Objective assessments of disease activity and anti-TNF trough levels at SLoR then during subsequent 6-month semesters were compared longitudinally between VC and SoC groups. ‘Anti-TNF escalation success’ was the primary endpoint, defined as achieved when two consecutive 6-month semesters of objective assessment demonstrated inactive disease. Dose intensification was defined as ‘appropriate’ if there was both objective evidence of disease activity, plus anti-TNF trough levels at or below the lower limit of the therapeutic range prior to intensification. ‘Treatment escalation failure’ was defined by the occurrence of one or more of biologic switching, discontinuation or further intensification; recommencement of corticosteroids, or IBD-related surgery. Results 149 patients (69 VC vs. 80 SoC) underwent infliximab (n = 94) or adalimumab (n = 55) dose intensification with similar baseline patient, disease and treatment characteristics between cohorts. The median duration of follow-up post dose-intensification was 1.9 and 1.5 years for the SoC and VC cohorts respectively (p = 0.37). There were higher rates of appropriate dose intensification (82.6 vs. 40.0%, p &lt; 0.01) across the VC cohort. Higher proportions of anti-TNF escalation success (60.9 v 35.0%, p &lt; 0.01), biomarker remission (i.e., C-Reactive Protein (&lt;5mg/l) and faecal calprotectin (&lt;150 μg/ml) normalisation, log-rank tests, p = 0.06 and p &lt; 0.01 respectively), tight disease monitoring (84.1 vs. 28.8%, p &lt; 0.01) and de-escalation of intensified therapy (21.3 vs. 10.0%, p = 0.03) were also achieved by the VC cohort following dose-intensification. Conclusion This study favoured a VC-led model of care over standard outpatient-based IBD care in facilitating an effective T2T approach to CD management. A VC model of care improved quality use of intensified anti-TNF therapy through processes that promoted appropriate dose intensification and encouraged more frequent anti-TNF dose de-escalation. Moreover, tight semester-based monitoring using a T2T-based strategy facilitated by the VC was associated with improved treatment outcomes.

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