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 P484 Effectiveness and safety of ustekinumab in patients with Crohn’s disease: a real-world experience

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S426-S426
Author(s):  
D Mohammad ◽  
A Alshahrani ◽  
Y Bao ◽  
R Alramdan ◽  
A Rajani ◽  
...  
Keyword(s):  
Logistic Regression ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Adverse Events ◽  
Clinical Response ◽  
Clinical Remission ◽  
Disease Duration ◽  
Multivariate Logistic Regression ◽  
Steroid Use ◽  
Lower Likelihood

Abstract Background Ustekinumab is a monoclonal antibody against the p40 subunit of IL-12 and IL23 which has been proven efficacious and safe in clinical trials, yet, real-word effectiveness studies are lacking. We aimed to determine the effectiveness and safety of ustekinumab in Crohn’s disease patients in a usual care setting, as well as to identify factors that predict response to treatment. Methods This was a retrospective review of patients with Crohn’s disease who had received ustekinumab at McMaster University Medical Center between January 2017 and August 2019. The primary endpoints were 12-month rates of clinical response, clinical remission and endoscopic improvement (according to physician assessment). We also performed a multivariate logistic regression to determine independent predictors of treatment effectiveness. Key safety outcomes were rates of adverse events including infections. Results We included 123 patients with Crohn’s disease, 58.8% of which had ileocolonic disease. Of these patients, 79.5% had prior TNF-antagonist exposure and 17.1% had previously used vedolizumab. The 12-month rate of clinical response, clinical remission, and endoscopic improvement, were 88%, 35%, and 47% respectively. On univariable analyses, longer disease duration was associated with a lower likelihood of achieving endoscopic improvement (OR 0.91 per year of disease duration, 95% CI 0.84–0.99, p = 0.03). On multivariate logistic regression, concomitant steroid use (OR 0.34, 95% CI 0.12–0.99, p = 0.049) and previous vedolizumab exposure (OR 0.13, 95% 0.02–0.77) were significantly associated with less likelihood of achieving clinical response at 12 months. Adverse events occurred in 13% of patients and infections occurred in only 1% of patients. Conclusion Ustekinumab has been effective in our real-world experience at achieving clinical response, clinical remission and endoscopic improvement in patients with Crohn’s disease. We found that concomitant steroid use and prior vedolizumab exposure were associated with a lower likelihood of clinical response. Further prospective data are needed to understand whether these are truly predictors of lack of response, or represent confounding from patients with more refractory disease.

Is Intestinal Diversion an Effective Treatment for Distal Crohn’s Disease?

2021 ◽  
Author(s):  
Amy L Lightner ◽  
Hassan Buhulaigah ◽  
Karen Zaghiyan ◽  
Stefan D Holubar ◽  
Scott R Steele ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Clinical Response ◽  
Clinical Improvement ◽  
Fecal Diversion ◽  
Interquartile Range ◽  
Perianal Disease ◽  
Total Proctocolectomy ◽  
Factors Associated ◽  
Persistent Symptoms

Abstract Background Fecal diversion with an ileostomy is selectively used in cases of medically refractory Crohn’s proctocolitis or advanced perianal disease. The aim of this study was to evaluate clinical improvement after fecal diversion in Crohn’s disease (CD) and factors associated with clinical improvement. Methods A retrospective chart review of adult CD patients undergoing ileostomy formation for distal disease between 2000 and 2019 at 2 CD referral centers was conducted. The primary outcome was the rate of clinical improvement with diversion that allowed for successful restoration of intestinal continuity. Secondary outcomes included the rate of clinical and endoscopic improvement after fecal diversion, ileostomy morbidity, need for subsequent total proctocolectomy and end ileostomy, and factors associated with a clinical response to fecal diversion. Results A total of 132 patients with a median age of 36 years (interquartile range, 25–49) were included. Mean duration of disease was 16.2 years (10.4) years. Indication for surgery was medically refractory proctocolitis with perianal disease (n = 59; 45%), perianal disease alone (n = 24; 18%), colitis (n = 37; 28%), proctitis (n = 4; 3%), proctocolitis alone (n = 4; 3%), and ileitis with perianal disease (n = 4; 3%). Medications used before surgery included corticosteroids (n = 59; 45%), immunomodulators (n = 55; 42%) and biologics (n = 82; 62%). The clinical and endoscopic response to diversion was 43.2% (n = 57) and 23.9% (n = 16). At a median follow-up of 35.3 months (interquartile range, 10.6–74.5), 25 patients (19%) had improved and had ileostomy reversal, but 86 (65%) did not improve, with 50 (38%) undergoing total proctocolectomy for persistent symptoms. There were no significant predictors of clinical improvement. Conclusions The use of a “temporary” ileostomy is largely ineffective in achieving clinical response.

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.

scholarly journals P329 ECCO grant recipient: preliminary results of the HOT-TOPIC trial (Hyperbaric Oxygen Therapy for the Treatment Of Perianal fistulas In Crohn’s disease)

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S318-S319
Author(s):  
C Lansdorp ◽  
K Gecse ◽  
C Buskens ◽  
M Löwenberg ◽  
J Stoker ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Adverse Events ◽  
Clinical Response ◽  
Hyperbaric Oxygen ◽  
Activity Index ◽  
Perianal Disease ◽  
Faecal Calprotectin ◽  
Preliminary Results ◽  
Patient Reported

Abstract Background Beneficial effects of hyperbaric oxygen (HBO) therapy for perianal fistulising Crohn’s disease (pCD) have been suggested in previous publications. The HOT-TOPIC study was designed to further investigate its feasibility and therapeutic effect in 20 therapy-refractory patients with pCD. Here we present the preliminary results. Methods 17 patients with pCD refractory to conventional-therapy > 6 months (medical and/or surgical, no patients with deviating stoma) were treated with 40 sessions of HBO therapy (243–253 kPa, 110 min per session throughout 8 weeks). Medical treatment remained stable from screening, seton drain(s) were removed after 30 treatment. Co-primary outcomes were clinical response as measured by the perianal disease activity index (PDAI) and MRI improvement measured by the modified van Assche index. Secondary outcomes were clinical response as assessed by fistula drainage assessment (FDA), biochemical response and patient-reported outcomes. All outcomes were assessed at baseline and 2 months after HBO. Results 17 patients (6 female, median age 34 years, median duration of disease 13 years) were treated. Median PDAI scores decreased from 8 to 4 (p < 0.001) and MRI scores from 9.4 to 7.3 (p = 0.001). Defined as PDAI of 4 or less, 11 out of 17 patients had inactive perianal disease after treatment, with 3 patients also having a predominantly fibrotic tract on MRI. Of the 45 external openings draining at baseline, 22 were clinically closed after treatment (49%, assessed by FDA). Four patients, three with one external opening and one with five openings at baseline, had no remaining openings after treatment. Median C-Reactive Protein and faecal calprotectin levels decreased from 5.0 and 416 to 2.3 and 31 (p = 0.002 and p = 0.003), respectively. Median scores of the inflammatory bowel disease questionnaire (IBDQ) increased from 169 to 185 (p = 0.001) and VAS scores from the Euroqol-5-dimensions questionnaire increased from 65 to 75 (p = 0.07), higher scores reflecting better quality of life. When asked on a validated decision regret scale if patients regretted their decision to undergo HBO, the mean score was 12.5 (0–100, higher scores indicating higher regret). During follow-up, none of the patients needed new (experimental) medication, re-interventions or stoma. Seven out of 17 patients experienced trouble equalising middle ear pressure during HBO, with four patients showing signs of barotrauma after otoscopy. Three patients needed tympanostomy tubes. No other clinically relevant adverse events occurred, and no adverse events led to discontinuation of the treatment. Conclusion Based on preliminary data, HBO treatment is associated with significant improvement in pCD, as measured by clinical and MRI endpoints.

scholarly journals DOP13 Clinical and endoscopic response to ustekinumab in Crohn’s disease: Week 16 interim analysis of the STARDUST trial

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S049-S052 ◽  
Author(s):  
S Danese ◽  
S Vermeire ◽  
G D’Haens ◽  
J Panés ◽  
A Dignass ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Clinical Response ◽  
Clinical Remission ◽  
Disease Duration ◽  
Activity Index ◽  
Standard Of Care ◽  
Treat To Target ◽  
Faecal Calprotectin ◽  
Intention To Treat

Abstract Background Treat-to-target (T2T) strategy may optimise IBD disease management. We describe interim clinical and endoscopic results of the STARDUST trial in Crohn’s disease (CD) patients, following 16 weeks (W) of ustekinumab (UST) induction. Methods STARDUST, an ongoing phase 3b randomised strategy trial, enrolled adults with moderate–severely active CD (CD activity index [CDAI] 220–450) and simple endoscopic index for CD [SES-CD] ≥3) who failed conventional therapy ±1 biologic. At W0, patients received intravenous, weight-based UST of ~6mg/kg (approved label) and at W8, subcutaneous UST 90mg. At W16, patients with CDAI reduction ≥70 points were randomised (1:1) to T2T or standard of care. Key endpoints (intention-to-treat [ITT] set, as observed) were analysed at W8 and W16: % patients in clinical remission (CDAI score <150); % patients with a clinical response (CDAI <150 or decrease vs. baseline [BL] ≥100 points); faecal calprotectin (FCal) and C-reactive protein (CRP) levels: normalisation of FCal or/and CRP; improvement ≥50% vs. BL (patients with elevated FCal and CRP subpopulations); change vs. BL in CDAI and Inflammatory Bowel Disease Questionnaire (IBDQ) total scores. Patients randomised to T2T underwent colonoscopy at W16 and were analysed for change in SES-CD score vs. BL, endoscopic response (decrease in SES-CD score ≥50% vs. BL) and endoscopic remission (SES-CD score ≤2) (central reading). Results The ITT full set included 500 patients with BL mean (SD) CDAI score 282.3 (65.8), SES-CD 13.1 (8.1), CRP 15.7 (23.4) mg/l, FCal 1741.9 (2932.1) mg/g and disease duration 9.4 (8.7) years; 58.4% previously failed 1 biologic. At W16, 79.4% of patients had a clinical response and 66.6% were in clinical remission. About half of the patients showed ≥50% improvement in FCal and CRP levels, which normalised in about 1/3 of patients. Results were similar irrespective of previous biologic (Table 1); 84% of patients in response at W16 were in clinical remission. Statistically significant changes from BL in CDAI, FCal, and CRP were observed at W8, and in IBDQ scores at W16 (Table 2). In the T2T set (n = 220; CDAI 70 responders), BL characteristics were similar to the full analysis set; SES-CD score was 13.4 (8.8). At W16, 36.8% and 11.4% of patients in the T2T set achieved endoscopic response and remission, respectively. The endoscopic response was independent of BL SES-CD score and disease duration, but numerically better for colonic vs. ileal disease. No new safety signals were reported. Conclusion STARDUST is the first T2T trial in CD patients. After 16 W following induction with UST, 2/3 of patients achieved clinical remission. Thirty-seven per cent of those randomised to the T2T arm (CDAI 70 responders) showed endoscopic response by central reading at W16. Results were similar irrespective of being bio-naïve or failing 1 biologic.

scholarly journals S0731 Does Fecal Diversion Induce Clinical Response for Crohn’s Disease of the Colorectum?

2020 ◽  
Vol 115 (1) ◽  
pp. S367-S367
Author(s):  
Amy L. Lightner ◽  
Hassan Buhulaigah ◽  
Karen Zhaghiyan ◽  
Prashansha Vaidya ◽  
Miguel Regueiro ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Clinical Response ◽  
Fecal Diversion

scholarly journals P113 Serum adipokines as non-invasive biomarker in Crohn’s disease

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 ◽  
...  
Keyword(s):  
Logistic Regression ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Roc Curve ◽  
Binary Logistic Regression ◽  
Roc Curves ◽  
Youden Index ◽  
Binary Logistic Regression Analysis ◽  
Serum Samples ◽  
Serum Leptin

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 > 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.

scholarly journals Infliximab Preferentially Induces Clinical Remission and Mucosal Healing in Short Course Crohn’s Disease with Luminal Lesions through Balancing Abnormal Immune Response in Gut Mucosa

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Lijuan Yu ◽  
Xuehua Yang ◽  
Lu Xia ◽  
Jie Zhong ◽  
Wensong Ge ◽  
...  
Keyword(s):  
Immune Response ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Clinical Response ◽  
Clinical Remission ◽  
Disease Duration ◽  
Activity Index ◽  
Mucosal Healing ◽  
Short Course ◽  
Short Disease Duration

This study was undertaken to evaluate the efficacy of infliximab (IFX) in treatment of Crohn’s disease (CD) patients. 106 CD patients were undergoing treatment with IFX from five hospitals in Shanghai, China. Clinical remission to IFX induction therapy was defined as Crohn’s disease activity index (CDAI) < 150. Clinical response was assessed by a decrease in CDAI ≥ 70, and the failure as a CDAI was not significantly changed or increased. Ten weeks after therapy, 61 (57.5%) patients achieved clinical remission, 17 (16.0%) had clinical response, and the remaining 28 (26.4%) were failed. In remission group, significant changes were observed in CDAI, the Simple Endoscopic Score for Crohn’s Disease (SES-CD), and serum indexes. Patients with short disease duration (22.2 ± 23.2 months) and luminal lesions showed better effects compared to those with long disease duration (71.0 ± 58.2 months) or stricturing and penetrating lesions. IFX markedly downregulated Th1/Th17-mediated immune response but promoted IL-25 production in intestinal mucosa from remission group. No serious adverse events occurred to terminate treatment. Taken together, our studies demonstrated that IFX is efficacious and safe in inducing clinical remission, promoting mucosal healing, and downregulating Th1/Th17-mediated immune response in short course CD patients with luminal lesions.

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