S906 Clinical Remission Using the Patient-Reported Ulcerative Colitis Electronic Diary (UC e-Diary) in Adults With Moderate-to-Severe Ulcerative Colitis

Abstract Background Optimal management of patients with ulcerative colitis (UC) requires the accurate assessment of disease activity. Endoscopic evaluation is considered the gold standard approach, but it is invasive. We aimed to determine the operating characteristics of the Ulcerative Colitis Endoscopic Index of Severity (UCEIS), to quantify the cut off most closely correlated with clinical remission or activity and determine agreement with the Mayo endoscopic subscore (MES), Baron score, clinical scores and biomarkers. Methods 136 patients were included prospectively (age: 48 (IQR38-61) years, duration 12 (4–19)years, 63 females, 53.7% extensive disease, 40.4% on biologicals) at the time of the colonoscopy. Ulcerative Colitis Endoscopic Index of Severity (UCEIS) Mayo endoscopic subscore (MES), Baron scores were calculated, as well as the2 item patient reported outcome (PRO), partial MAYO, Simple Clinical Colitis Activity Index (SCCAI). CRP and faecal calprotectin (FCAL) was available in 58.1 and 33.8% of patients. 20.7% had clinical flare, treatment was escalated in 17.8% of patients. ROC analysis and K-statistics were performed and Spearman’s correlation was calculated. Results UCEIS was strongly associated to PRO2 SF (AUC:0.866), RBS (AUC:0.921), PRO2 combined remission (AUC:0.905), partial MAYO (AUC:0.956) and SCCAI (AUC:0.907) remission in a ROC analysis. A UCEIS of ≤3 was identified as the best cut-off to identify RBS subscore of 0, or total PRO2 remission (RBS 0 and SF ≤1), partial MAYO (≤2) and SCCAI (≤2.5) remission, while a UCEIS≥4 identified active disease frequently needing change in medical therapy. A moderate agreement was found between UCEIS and MES (K=0.451) or Baron (K=0.499) scores. Correlation between FCAL and UCEIS (coeff:0.743, p < 0.0001) was strong, while modest only with CRP (coeff:0.333, p = 0.01). Conclusion A UCEIS was strongly associated with clinical remission defined as PRO2, SF, RBS, partial Mayo or SCCAI with best agreement with RBS and partial Mayo remission. A UCEIS of ≤3 was identified as a cut-off for quiescent disease, while a UCEIS≥4 identified active disease, which can support clinical decision-making based on endoscopic findings. Agreement between UCEIS and FCAL was strong, while agreement with UCEIS and MES/Baron scores was moderate.

Download Full-text

Adalimumab Induces and Maintains Clinical Remission in Patients With Moderate-to-Severe Ulcerative Colitis

Gastroenterology ◽

10.1053/j.gastro.2012.03.055 ◽

2012 ◽

Vol 143 (1) ◽

pp. e42 ◽

Cited By ~ 5

Author(s):

Ben Warner ◽

Adam W. Harris

Keyword(s):

Ulcerative Colitis ◽

Clinical Remission ◽

Severe Ulcerative Colitis

Download Full-text

P547 Safety and efficacy of vedolizumab in the treatment of patients with moderate to severe Ulcerative Colitis: a systematic review and meta-analysis

Journal of Crohn s and Colitis ◽

10.1093/ecco-jcc/jjab076.668 ◽

2021 ◽

Vol 15 (Supplement_1) ◽

pp. S516-S517

Author(s):

M Khorshid Fasge ◽

M Alboraie ◽

W Abbas ◽

Z E Sayed ◽

M El-Nady

Keyword(s):

Systematic Review ◽

Ulcerative Colitis ◽

Cohort Studies ◽

Clinical Response ◽

Clinical Remission ◽

Assessment Tool ◽

Meta Analysis ◽

P Value ◽

Severe Ulcerative Colitis ◽

Significant Difference

Abstract Background To perform a systematic review and meta-analysis discussing the efficacy and safety of vedolizumab (VDZ) treatment in patients with active moderate to severe ulcerative colitis (UC). Methods Using relevant keywords, we searched PubMed, Web of Science, Scopus, and Cochrane Central databases, until June 2020. We included interventional and observational cohort studies which assessed the safety and effectiveness of VDZ 300 mg intravenous infusion, in patients with active moderate to severe UC. We used the Cochrane risk of bias assessment tool and the Newcastle-Ottawa scale to assess the quality of included interventional and cohort studies, respectively. Dichotomous outcomes were pooled as proportion, 95% Confidence interval (CI), and p-value under the random-effects model in the open meta-analyst software. Results We found 10 interventional studies and 35 cohort studies, including 4,794 patients eligible for our review. Most of the included citations were single-arm studies. Our meta-analysis showed that VDZ therapy could induce a significant clinical response in UC patients up to 54 weeks (proportion 0.516, 95% CI [0.453, 0.578], p < 0.001). VDZ was associated with clinically significantly clinical remission and steroid-free clinical remission after 54 weeks (p < 0.0001). Durable clinical remission, histological remission, and endoscopic response rates were maintained in UC patients taking VDZ at the 52nd week. There was no significant difference between VDZ and placebo regarding the incidence of drug-related serious adverse events (p = 0.113) and death rates (p = 0.085). Conclusion Our systematic review and meta-analysis showed that the use of VDZ in patients with active moderate to severe UC was associated with high percentages of clinical response and remission rates in induction and maintenance treatment stages. VDZ seems to be well tolerated in UC patients, apart from some infections and inflammations. Future RCTs should compare VDZ to active treatments for longer follow-up periods with larger sample size.

Download Full-text

DOP18 UCEIS is associated with PRO2, partial Mayo and SCCAI remission in UC: Final results from a prospective study

Journal of Crohn s and Colitis ◽

10.1093/ecco-jcc/jjab073.057 ◽

2021 ◽

Vol 15 (Supplement_1) ◽

pp. S056-S057

Author(s):

P Golovics ◽

L Gonczi ◽

J Reinglas ◽

C Verdon ◽

S Pundir ◽

...

Keyword(s):

Ulcerative Colitis ◽

Clinical Remission ◽

Roc Analysis ◽

Clinical Decision Making ◽

Activity Index ◽

Clinical Decision ◽

Operating Characteristics ◽

Patient Reported ◽

Index Of Severity ◽

Active Disease

Abstract Background Optimal management of patients with ulcerative colitis (UC) requires the accurate assessment of disease activity. Endoscopic evaluation is considered the gold standard approach, but it is invasive. We aimed to determine the operating characteristics of the Ulcerative Colitis Endoscopic Index of Severity (UCEIS), to quantify the cut off most closely correlated with clinical remission or activity and determine agreement with the Mayo endoscopic subscore (MES), Baron score, clinical scores and biomarkers. Methods 171 patients were included prospectively and consecutively (age: 49 (IQR: 38–61) years, duration 12 (4–19)years, 79 females (46.2%), 57.3% extensive disease, 42.7% on biologicals) at the time of the colonoscopy. Ulcerative Colitis Endoscopic Index of Severity (UCEIS) Mayo endoscopic subscore (MES), Baron scores were calculated, as well as the 2 item patient reported outcome (PRO), partial MAYO, Simple Clinical Colitis Activity Index (SCCAI). C reactive Protein (CRP) and fecal calprotectin (FCAL) was available in 83 and 45.6% of patients. 17.0% had clinical flare, treatment was escalated in 14.6% of patients. Sensitivity, specificity, PPV and NPV values were calculated, ROC analysis and K-statistics were performed. Results UCEIS was strongly associated to PRO2 SF (AUC:0.863), RBS (AUC:0.924), PRO2 combined (AUC:0.898), partial MAYO (AUC:0.945) and SCCAI (AUC:0.901) remission in a ROC analysis. A UCEIS of ≤3 was identified as the best cut-off to identify RBS subscore of 0, or total PRO2 remission (RBS 0 and SF ≤1), partial MAYO (≤2) and SCCAI (≤2.5) remission, while a UCEIS≥4 identified active disease frequently needing change in medical therapy. A moderate agreement was found between UCEIS <4 and MES 0 (K=0.471) or Baron 0 (K=0.414)/Baron 0–1 (K=0.353). Correlation between FCAL and UCEIS (coeff:0.701, p<0.0001) was strong, while modest only with CRP (coeff:0.248, p=0.01). Conclusion UCEIS was strongly associated with clinical remission defined as PRO2, SF, RBS, partial Mayo or SCCAI with best agreement with RBS and partial Mayo remission. A UCEIS of ≤3 was identified as a cut-off for quiescent disease, while a UCEIS≥4 identified active disease, which can support clinical decision-making based on endoscopic findings. Agreement between UCEIS and FCAL was strong, while agreement with UCEIS and MES/Baron scores was moderate.

Download Full-text

A232 EFFICACY OF TOFACITINIB FOR THE TREATMENT OF MODERATE-TO-SEVERE ULCERATIVE COLITIS: REAL-WORLD DATA

Journal of the Canadian Association of Gastroenterology ◽

10.1093/jcag/gwz047.231 ◽

2020 ◽

Vol 3 (Supplement_1) ◽

pp. 108-109

Author(s):

Y Xiao ◽

P L Lakatos ◽

R Bourdages ◽

A Bitton ◽

W Afif ◽

...

Keyword(s):

Ulcerative Colitis ◽

Clinical Response ◽

Clinical Remission ◽

Preliminary Analysis ◽

Kinase Inhibitor ◽

Significant Proportion ◽

Real Life ◽

Janus Kinase ◽

Severe Ulcerative Colitis ◽

Mayo Score

Abstract Background A significant proportion of patients with moderate to severe ulcerative colitis (UC) do not respond to therapy, which includes thiopurines, glucocorticoids, and antagonists to tumour necrosis factor-α and integrin. Tofacitinib, a Janus Kinase inhibitor, has emerged as an efficacious and safe treatment for moderate to severe ulcerative colitis. However, it is not known if this efficacy translates into real-life effectiveness in a regular clinical practice. Aims We aimed to assess the rate of clinical response and clinical remission at 3 and 6 months after tofacitinib initiation. Secondary endpoints included rate of biomarker normalization, corticosteroids-free clinical remission and severe infections. Methods We conducted a multi-center retrospective observational study of adult patients with active UC started on tofacitinib from January 1, 2015 to October 1, 2019 at the McGill University Health Center and Hotel-Dieu de Lévis. A positive clinical response was defined as a decrease of ≥3 in the partial Mayo score. Clinical remission was defined as partial Mayo score of ≤2. Biomarker normalization was defined as fecal calprotectin ≤250ug/g. Severe infection was defined as an infection requiring hospitalization. Results During the study period, 40 patients with UC were started on tofacitinib. Amongst the patients, 85% (n=34) had failed ≥1 biologic and 50% (n=20) had failed ≥3 biologics. At the time of this preliminary analysis, 38 patients had undergone 3 months of treatment and 30 patients had undergone 6 months of treatment. At 3 months, a clinical response was seen in 89.5% of patients (n=34) and clinical remission occurred in 63.2% (n=24). At 6 months, clinical response occurred in 73.3% of patients (n=22) and clinical remission was sustained in 53.33% (n=16). Biochemical normalization occurred in 29.0% (n=11) and 30.0% (n=9) at 3 and 6 months, respectively. Additionally, 63.2% (n=24) and 43.3% of patients (n=13) achieved steroid-free clinical remission at 3 and 6 months, respectively. In the interim, one patient developed a serious infection requiring discontinuation of drug. Conclusions Our preliminary analysis demonstrates that in a real-life setting, tofacitinib is an effective treatment for inducing clinical remission in refractory UC patients. Further data will be complied to better assess the efficacy over a longer follow up. Funding Agencies None

Download Full-text

The Association Between Disease Activity and Patient-Reported Outcomes in Patients With Moderate-to-Severe Ulcerative Colitis in the United States

The American Journal of Gastroenterology ◽

10.14309/00000434-201810001-00621 ◽

2018 ◽

Vol 113 (Supplement) ◽

pp. S353

Author(s):

Marco DiBonaventura ◽

Danielle Bargo ◽

James Lucas ◽

Daniel Bluff ◽

Ben Hoskin ◽

...

Keyword(s):

United States ◽

Ulcerative Colitis ◽

Disease Activity ◽

Patient Reported Outcomes ◽

The United States ◽

Severe Ulcerative Colitis ◽

Patient Reported

Download Full-text

ANTI-TNF PHARMACOKINETICS AND RESPONSE TO THERAPY IN PEDIATRIC ACUTE SEVERE ULCERATIVE COLITIS (THE ARCH STUDY)

Inflammatory Bowel Diseases ◽

10.1093/ibd/izaa347.132 ◽

2021 ◽

Vol 27 (Supplement_1) ◽

pp. S55-S56

Author(s):

Kaitlin Whaley ◽

Vivian Xiong ◽

Rebekah Karns ◽

Jeffrey Hyams ◽

Subra Kugathasan ◽

...

Keyword(s):

Ulcerative Colitis ◽

Clinical Remission ◽

Pediatric Population ◽

Controlled Trial ◽

Positive Association ◽

Volume Of Distribution ◽

Response To Therapy ◽

Parameter Estimates ◽

Time Curve ◽

Severe Ulcerative Colitis

Abstract Background and Aims 25% of children hospitalized with acute severe ulcerative colitis (ASUC) rescued with infliximab (IFX) at labeled dosing undergo a colectomy prior to discharge. Our aim was to determine whether IFX pharmacokinetics (PK) are associated with treatment response in pediatric ASUC. Methods We prospectively enrolled hospitalized pediatric patients initiating IFX for ASUC or IBD-U (PUCAI ≥65) at 7 North American centers and followed for 26 weeks in this pilot and feasibility cohort study. Serial IFX levels (Prometheus Biosciences, Inc.) were obtained and individual PK parameter estimates, such as volume of distribution, clearance (CL), elimination half-life (T1/2) and IFX exposure (area under the concentration-time curve) were estimated using Bayesian methodology. The primary outcome was Day 7 clinical response (CR-D7, PUCAI <35). Key secondary outcomes were Week 8 clinical remission (CR-W8, PUCAI <10) and Week 26 corticosteroid-free clinical remission (CFR-W26). Results 38 participants (mean age 14.5 years, 50% female, 95% UC, 87% extensive/pancolitis) were treated with IFX at a mean higher than labeled dosing of 9.9 [9.3,10.3] mg/kg, and 16% received an early second dose 4–6 days after the first infusion. CR-D7, CR-W8, and CFR-W26 were achieved in 71%, 55%, and 41%, respectively. Only one participant (2.7%) underwent colectomy by week 26. Using 304 IFX level measurements, we developed a novel pediatric population PK model for IFX in ASUC that incorporated albumin, antibodies to IFX, CRP, and height to characterize the PK profile for participants. The median IFX T1/2 was 5.8 [4.2,7.0] days at Day 7 and lengthened to 7.4 [5.4,8.4] days by Week 26 (P=0.014), but notably remained below the median 10.8 [8.6, 15.4] days reported in a randomized controlled trial of IFX for moderate to severe pediatric UC (Fig. 1). IFX exposure was not associated with CR-D7, CR-W8, or CSR-W26. More rapid IFX CL at Week 26 was significantly associated with inability to achieve CFR-W26 (P=.013). This finding was in line with a higher, but not statistically significant, median trough IFX level nearest Week 26 in those with (19.5 [13.6, 30.3]) versus without (14.2 [6.0, 21.3] μg/ml) CFR-W26 (P=.13) (Fig. 2). Conclusion At the higher than standard IFX dosing used to treated children with ASUC in this observational study, we observed a lower colectomy rate compared to prior studies but did not observe a positive association between IFX exposure and clinical outcomes. Albumin, CRP, height, and ATI were associated with IFX PK and incorporated into a new pediatric ASUC PK model. Initial 10 mg/kg IFX dosing may be sufficient to optimize early outcomes in pediatric ASUC. Additional studies are needed to determine if sustained intensification of maintenance IFX regimens can overcome persistent rapid clearance and improve later outcomes in pediatric ASUC.

Download Full-text