P168 BACTEROIDETES SPECIES ARE USEFUL BIOMARKER OF CLINICAL ACTIVITY IN ULCERATIVE COLITIS

2020 ◽  
Vol 158 (3) ◽  
pp. S64-S65
Author(s):  
Kei Nomura ◽  
Dai Ishikawa ◽  
Koki Okahara ◽  
Shoko Ito ◽  
Masahito Takahashi ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Clinical Activity

scholarly journals Fecal calprotectin is a useful biomarker for predicting the clinical outcome of granulocyte and monocyte adsorptive apheresis in ulcerative colitis patients: a prospective observation study

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Nobuhiro Ueno ◽  
Yuya Sugiyama ◽  
Yu Kobayashi ◽  
Yuki Murakami ◽  
Takuya Iwama ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Clinical Outcome ◽  
Sensitivity And Specificity ◽  
Reduction Rate ◽  
Fecal Calprotectin ◽  
Remission Induction ◽  
Clinical Activity ◽  
Observation Study ◽  
Mayo Score ◽  
Adsorptive Apheresis

Abstract Background Granulocyte and monocyte adsorptive apheresis (GMA) is widely used as a remission induction therapy for active ulcerative colitis (UC) patients. However, there are no available biomarkers for predicting the clinical outcome of GMA. We investigated the utility of Fecal calprotectin (FC) as a biomarker for predicting the clinical outcome during GMA therapy in active UC patients. Methods In this multicenter prospective observation study, all patients received 10 sessions of GMA, twice a week, for 5 consecutive weeks. FC was measured at entry, one week, two weeks, and at the end of GMA. Colonoscopy was performed at entry and after GMA. The clinical activity was assessed based on the partial Mayo score when FC was measured. Clinical remission (CR) was defined as a partial Mayo score of ≤ 2 and endoscopic remission (ER) was defined as Mayo endoscopic subscore of either 0 or 1. We analyzed the relationships between the clinical outcome (CR and ER) and the change in FC concentration. Result Twenty-six patients were included in this study. The overall CR and ER rates were 50.0% and 19.2%, respectively. After GMA, the median FC concentration in patients with ER was significantly lower than that in patients without ER (469 mg/kg vs. 3107 mg/kg, p = 0.03). When the cut-off value of FC concentration was set at 1150 mg/kg for assessing ER after GMA, the sensitivity and specificity were 0.8 and 0.81, respectively. The FC concentration had significantly decreased by one week. An ROC analysis demonstrated that the reduction rate of FC (ΔFC) at 1 week was the most accurate predictor of CR at the end of GMA (AUC = 0.852, P = 0.002). When the cut-off value of ΔFC was set at ≤ 40% at 1 week for predicting CR at the end of GMA, the sensitivity and specificity were 76.9% and 84.6%, respectively. Conclusion We evaluated the utility of FC as a biomarker for assessing ER after GMA and predicting CR in the early phase during GMA in patients with active UC. Our findings will benefit patients with active UC by allowing them to avoid unnecessary invasive procedures and will help establish new strategies for GMA.

scholarly journals Machine learning using clinical data at baseline predicts the efficacy of vedolizumab at week 22 in patients with ulcerative colitis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jun Miyoshi ◽  
Tsubasa Maeda ◽  
Katsuyoshi Matsuoka ◽  
Daisuke Saito ◽  
Sawako Miyoshi ◽  
...  
Keyword(s):  
Machine Learning ◽  
Ulcerative Colitis ◽  
Prediction Model ◽  
Clinical Features ◽  
Unmet Need ◽  
Patient Treatment ◽  
Clinical Activity ◽  
Prediction Tool ◽  
Real World Data ◽  
Predictive Values

AbstractPredicting the response of patients with ulcerative colitis (UC) to a biologic such as vedolizumab (VDZ) before administration is an unmet need for optimizing individual patient treatment. We hypothesized that the machine-learning approach with daily clinical information can be a new, promising strategy for developing a drug-efficacy prediction tool. Random forest with grid search and cross-validation was employed in Cohort 1 to determine the contribution of clinical features at baseline (week 0) to steroid-free clinical remission (SFCR) with VDZ at week 22. Among 49 clinical features including sex, age, height, body weight, BMI, disease duration/phenotype, treatment history, clinical activity, endoscopic activity, and blood test items, the top eight features (partial Mayo score, MCH, BMI, BUN, concomitant use of AZA, lymphocyte fraction, height, and CRP) were selected for logistic regression to develop a prediction model for SFCR at week 22. In the validation using the external Cohort 2, the positive and negative predictive values of the prediction model were 54.5% and 92.3%, respectively. The prediction tool appeared useful for identifying patients with UC who would not achieve SFCR at week 22 during VDZ therapy. This study provides a proof-of-concept that machine learning using real-world data could permit personalized treatment for UC.

scholarly journals Pharmacokinetics, Pharmacodynamics, and Safety of Etrolizumab in Children With Moderately to Severely Active Ulcerative Colitis or Crohn’s Disease: Results from a Phase 1 Randomized Trial

2021 ◽  
Author(s):  
Wenhui Zhang ◽  
Astrid Scalori ◽  
Franklin Fuh ◽  
Jacqueline McBride ◽  
Gaohong She ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Phase 1 ◽  
Receptor Occupancy ◽  
Clinical Activity ◽  
Active Ulcerative Colitis ◽  
Open Label ◽  
Proportional Increase ◽  
Dose Proportional

Abstract Background Etrolizumab, a humanized anti-β7 antibody, has not been studied in children. Here, we evaluate the pharmacokinetics, pharmacodynamics, and safety of etrolizumab in children with inflammatory bowel disease. Methods Patients age 4 to 17 years with moderately to severely active ulcerative colitis or Crohn’s disease were randomized 1:1 to receive 1.5mg/kg of etrolizumab subcutaneously every 4 weeks (q4w) or 3.0mg/kg every 8 weeks (q8w) for 16 weeks in this open-label phase 1 trial. Pharmacokinetics, pharmacodynamics, safety, and efficacy were assessed. Results Of the 24 patients treated, 21 completed the study. In the groups of 1.5mg/kg q4w and 3.0mg/kg q8w, respectively, mean (SD) maximum concentration (Cmax) was 9.8 (4.86) µg/mL and 18.1 (6.25) µg/mL; and mean (SD) area under the curve within a dosing interval (AUCtau) was 167 (86.9) and 521 (306) μg·day/mL after the last dose. The Cmax increased dose proportionally. The AUC over an 8-week period was slightly higher in the 3.0mg/kg q8w dose group. Median half-life was similar for both dosing regimens. Median numbers of free β7high gut-homing T and B cell subsets declined below 10% of baseline, confirming β7 target engagement and complete/near-complete receptor occupancy. Adverse events were consistent with the safety profile in adults. Approximately 60% of patients achieved a clinical response. Conclusions Etrolizumab showed a dose-proportional increase in Cmax and a slightly greater than dose-proportional increase in AUCtau. Both regimens achieved complete/near-complete β7 receptor occupancy, with a similar relationship to concentration as adults. Etrolizumab was well tolerated and demonstrated clinical activity in children.

Psychologic Stress in Crohn's Disease an Ulcerative Colitis: Role of Gender and Clinical Activity of the Disease

2011 ◽  
Vol 140 (5) ◽  
pp. S-787
Author(s):  
Marta Iglesias-Rey ◽  
Manuel Barreiro-de Acosta ◽  
Isabel Vazquez ◽  
Maria Piñeiro ◽  
Adolfo Figueiras ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Clinical Activity ◽  
Psychologic Stress

scholarly journals P187 The significance of netrin-1 level in the clinical activity of ulcerative colitis, its association between TNF-α and IL-6

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S232-S232
Author(s):  
H Korkmaz ◽  
K Fidan
Keyword(s):  
Ulcerative Colitis ◽  
Proinflammatory Cytokines ◽  
Activity Index ◽  
Enzyme Linked Immunosorbent Assay ◽  
Control Group ◽  
Clinical Activity ◽  
Tnf Α ◽  
Significant Difference ◽  
And Control ◽  
Control Study

Abstract Background In this study, we investigated the importance of netrin-1 levels in ulcerative colitis (UC) in clinical activity of the disease, and its association with other proinflammatory cytokines IL-6 and TNF-α. Methods This study is a type of case–control study. Sixty-seven patients with UC (36 of them activation, 31 of remission) and 50 healthy controls were included in the study. UC patients; ‘Truelove Witts clinical activity index by remission (n = 31), mild activation (n = 21), moderate activation (n = 6) and severe activation (n = 9) were divided into groups. Netrin, IL-6 and TNF-α measurements in plasma samples were performed using enzyme-linked immunosorbent assay kit. Results Between the patient group and the control group; there was a statistically significant difference between netrin-1, IL-6, TNF-α, neutrophil, platelet (p < 0.05 for all). The plasma netrin-1 mean of UC with severe activation group (139.21 ± 48.09 pg/ml) was statistically significantly higher than that of the mild activation (p = 0,037), remission group (p = 0,001) and control group(p = 0,011). The plasma netrin-1 mean of UC with moderate activation group was statistically significantly higher than that of the mild activation(p = 0,045) and remission group(p = 0,004). Conclusion Our results reveal that plasma netrin-1 levels have been shown to be associated with UC activation, similar to proinflammatory cytokines such as TNF-α and IL-6, in UC.

scholarly journals P476 Effectiveness and safety of ustekinumab in ulcerative colitis: Real-world evidence from the ENEIDA registry

2021 ◽  
Vol 15 (Supplement_1) ◽  
pp. S465-S466
Author(s):  
M Chaparro ◽  
A Garre ◽  
M Iborra ◽  
M Sierra ◽  
M Barreiro-de Acosta ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Clinical Practice ◽  
Elevated Serum ◽  
Real Life ◽  
Development Program ◽  
Lower Probability ◽  
Clinical Activity ◽  
Mayo Score

Abstract Background The development program (UNIFI) has shown promising results of ustekinumab in ulcerative colitis (UC) treatment that should be confirmed in clinical practice. Aims Primary: to evaluate the durability of ustekinumab treatment in UC patients in clinical practice. Secondary: to assess the short-term response (at week 16) and the long-term effectiveness (at maximum follow-up) and to assess the safety of ustekinumab in clinical practice. Methods Patients included in the prospectively maintained ENEIDA registry who received at least one intravenous dose of ustekinumab due to active UC [Partial Mayo Score (PMS) >2] were included. Clinical activity and effectiveness were defined based on PMS. Results 95 patients were included (table 1). At week 16, 53% of patients had clinical response (including 35% of patients in remission) (figure 1). In the multivariate analysis, elevated serum C-reactive protein was the only variable significantly associated with clinical remission. Long-term remission is represented in figure 2. 36% of patients discontinued the treatment with ustekinumab during a median follow-up of 31 weeks. The probability of maintaining ustekinumab treatment was 87% at week 16, 63% at week 56, and 59% at week 72 (figure 3); primary failure was the main reason for ustekinumab discontinuation. No variable was associated with risk of discontinuation. Three patients reported adverse events; one of them had a fatal severe SARS-CoV-2 infection. Conclusion Ustekinumab is effective both in the short and the long-term in real-life, even in a highly refractory cohort. Higher inflammatory burden at baseline correlated with lower probability of achieving remission. Safety was consistent with the known profile of ustekinumab.

scholarly journals P434 Effectiveness and safety of ustekinumab in ulcerative colitis: real-world evidence from Eneida Registry

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S394-S395
Author(s):  
M Chaparro ◽  
A Garre ◽  
M Iborra ◽  
M Barreiro-de Acosta ◽  
M J Casanova ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Real Life ◽  
Development Program ◽  
Analysis Data ◽  
Lower Probability ◽  
Clinical Activity ◽  
Short Term ◽  
Mayo Score ◽  
Patient Status ◽  
Probability Of Response

Abstract Background Ustekinumab has shown promising results in ulcerative colitis (UC) in the development program (UNIFI) that should be confirmed in clinical practice. Our aim was to evaluate the effectiveness and safety of ustekinumab in UC in real life. Methods Patients included in the prospectively maintained ENEIDA registry that received at least 1 dose of ustekinumab intravenously due to active UC were included. Clinical activity and effectiveness were defined based on Partial Mayo Score (PMS). The short-term response was assessed at week 8 and 16. The last-observation-carried-forward method was used in patients that stopped ustekinumab treatment before week 8 or 16. Variables associated with short-term remission were identified by logistic regression analysis. Data quality was assessed by remote monitoring. Results Forty-seven patients were included (Table 1); all of them had been previously exposed to biologic agents (70% to >2): 100% to anti-TNF and 83% to vedolizumab. A total of 26% had been exposed to tofacitinib. Seventeen patients (36%) had response at week 8 [3 of them (6%) had remission]; 16 patients (34%) had response at week 16 [5 of them (11%) had remission] (Figure 1). There was a statistically significant decrease in C-reactive protein (CRP) concentration during the induction only in patients with a response at week 16 (Figure 2). The proportion of patients with CRP elevated at baseline and at week 8 was higher among non-responders at week 16 (Table 2). In the multivariate analysis, higher PMS at week 8 [odds ratio (OR) = 0.5; 95% confidence interval (CI) = 0.3–0.9)] and CRP over the upper normal limit at week 8 (OR = 0.1; 95% CI = 0.01–0.8) were associated with lower probability of response at week 16; steroids during induction increased the probability of response at week 16 (OR = 8; 95% CI = 1–71). Of patients without response at week 8, only 7% achieved response at week 16. Seventeen out of 31 patients continued ustekinumab beyond week 16, despite being non-responders. Of these 17 patients, 4 reached remission after the third dose, 1 after the fifth and 1 after the seventh one. There were 2 infections, one of them with fatal consequences (in a patient under steroids and tacrolimus due to renal transplant). Conclusion Ustekinumab shows benefit in some UC patients in real practice, even in a very refractory cohort in which the drug was prescribed as last resort. Patient status at week 8 seems to be a good predictor of response after the induction. Safety was consistent with the known profile of ustekinumab.

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