Faculty Opinions recommendation of Ustekinumab exposure-outcome analysis in Crohn's disease only in part explains limited endoscopic remission rates.

2019 ◽  
Author(s):  
Sara McCartney
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Outcome Analysis ◽  
Endoscopic Remission ◽  
Remission Rates

scholarly journals Ustekinumab Exposure-outcome Analysis in Crohn’s Disease Only in Part Explains Limited Endoscopic Remission Rates

2019 ◽  
Vol 13 (7) ◽  
pp. 864-872 ◽  
Author(s):  
Bram Verstockt ◽  
Erwin Dreesen ◽  
Maja Noman ◽  
An Outtier ◽  
Nathalie Van den Berghe ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Clinical Remission ◽  
Real Life ◽  
Outcome Analysis ◽  
Faecal Calprotectin ◽  
Exposure Response ◽  
Patient Reported ◽  
Endoscopic Remission ◽  
Remission Rates

Abstract Background and Aims Ustekinumab, an anti-IL12/23p40 monoclonal antibody, has been approved for Crohn’s disease [CD]. Real-life data in CD patients receiving ustekinumab intravenously [IV] during induction, followed by subcutaneous [SC] maintenance, are lacking. We assessed efficacy of ustekinumab and studied exposure-response correlations. Methods We performed a prospective study in 86 CD patients predominantly refractory or intolerant to anti-tumour necrosis factor agents and/or vedolizumab. All received ustekinumab 6 mg/kg IV induction, with 90 mg SC every 8 weeks thereafter. Endoscopic response (50% decrease in Simple Endoscopic Score for CD [SES-CD] at Week 24), endoscopic remission [SES-CD ≤2], and clinical remission [daily stool frequency ≤2.8 and abdominal pain score ≤1] were assessed at weeks 4,8,16, and 24. Further serial analyses included patient-reported outcomes [PRO2], faecal calprotectin [fCal], and ustekinumab serum levels. Results SES-CD decreased from 11.5 [8.0–18.0] at baseline to 9.0 [6.0–16.0] at week [w]24 [p = 0.0009], but proportions of patients achieving endoscopic response [20.5%] or endoscopic remission [7.1%] were low. Clinical remission rates were 39.5% at w24. After IV induction, fCal dropped from baseline [1242.9 μg/g] to w4 [529.0 μg/g] and w8 [372.2 μg/g], but increased again by w16 [537.4 μg/g] and w24 [749.0 μg/g]. A clear exposure-response relationship was observed, both during induction and during maintenance therapy, with different thresholds depending on the targeted outcome. Conclusions In this cohort of refractory CD patients, ustekinumab showed good clinical remission rates but limited endoscopic remission after 24 weeks. Our data suggest that higher doses may be required to achieve better endoscopic outcomes.

Highly Bioavailable Curcumin Derivative Ameliorates Crohn’s Disease Symptoms: A Randomized, Double-Blind, Multicenter Study

2020 ◽  
Vol 14 (12) ◽  
pp. 1693-1701 ◽  
Author(s):  
Ken Sugimoto ◽  
Kentaro Ikeya ◽  
Shigeki Bamba ◽  
Akira Andoh ◽  
Hiroshi Yamasaki ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Nuclear Factor Κb ◽  
Blood Levels ◽  
Serious Adverse Events ◽  
Double Blind ◽  
Endoscopic Remission ◽  
Remission Rates ◽  
Anal Lesions ◽  
Curcumin Derivative

Abstract Background & Aims The new curcumin derivative Theracurmin® has a 27–fold higher absorption rate than natural curcumin powder. Theracurmin® is an inhibitor of nuclear factor-κB, which mediates the expression of inflammatory cytokines. The effect of Theracurmin® on inflammatory bowel disease in humans has not been explored; therefore, we investigated the efficacy and safety of Theracurmin® in patients with Crohn’s disease. Methods In this randomized, double-blinded study performed at 5 independent medical centers in Japan, Theracurmin® (360 mg/day, n = 20) or placebo (n = 10) was administered to patients with active mild-to-moderate Crohn’s disease for 12 weeks. The agent’s efficacy was assessed by evaluating clinical and endoscopic remission, healing of anal lesions, and blood levels of inflammatory markers. Results In the Theracurmin® group, a significant reduction in clinical disease activity was observed in week 12 relative to that in week 0 (p = 0.005). On intention-to-treat analysis, clinical remission rates were 35%, 40%, and 40% at weeks 4, 8, and 12, respectively, which were significantly higher than those in the placebo group (all 0%; p = 0.033, p = 0.020, and p = 0.020, respectively). Furthermore, reduction in endoscopic Crohn’s disease severity (p = 0.032) was observed at week 12 in the Theracurmin® group. The endoscopic remission rates were 15% and 0% in the Theracurmin® and placebo groups, respectively. Significant healing of anal lesions (p = 0.017) was observed at week 8 in the Theracurmin® group. No serious adverse events were observed in either group throughout the study. Conclusions Theracurmin® shows significant clinical and endoscopic efficacy together with a favorable safety profile in patients with active mild-to-moderate Crohn’s disease. Clinical trial UMIN registration ID UMIN000015770.

Location but Not Severity of Endoscopic Lesions Influences Endoscopic Remission Rates in Crohn's Disease: A Post Hoc Analysis of TAILORIX

2020 ◽  
Vol 116 (1) ◽  
pp. 134-141 ◽  
Author(s):  
Pauline Rivière ◽  
Geert D'Haens ◽  
Laurent Peyrin-Biroulet ◽  
Filip Baert ◽  
Guy Lambrecht ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Post Hoc Analysis ◽  
Endoscopic Remission ◽  
Remission Rates ◽  
Post Hoc

scholarly journals The Efficacy of Infliximab Monotherapy versus Infliximab-Azathioprine Sequential Treatment in Crohn’s Disease: Experience from a Tertiary Medical Center in China

2016 ◽  
Vol 2016 ◽  
pp. 1-6 ◽  
Author(s):  
Tianyu Zhang ◽  
Zhengting Wang ◽  
Rong Fan ◽  
Maochen Zhang ◽  
Yun Lin ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Clinical Remission ◽  
Remission Rate ◽  
Therapy Group ◽  
Sequential Therapy ◽  
Sequential Treatment ◽  
Monotherapy Group ◽  
Endoscopic Remission ◽  
Remission Rates

Objective.To evaluate the efficacy of infliximab (IFX) monotherapy versus infliximab-azathioprine sequential treatment in Crohn’s disease (CD) patients.Methods.Patients newly diagnosed with CD using IFX as induction therapy were enrolled. After 6 times of IFX infusions, they were divided into IFX monotherapy group and IFX-AZA sequential therapy group. Clinical remission rates were assessed at weeks 57, 84, 111, and 138 while endoscopic remission rates were assessed at weeks 84 and 138 to evaluate the efficacy of these two groups.Results.A total of seventy-nine patients had accomplished 138-week follow-up. At weeks 84 and 138, the deep remission rate (18/22 and 17/22) of IFX monotherapy group was significantly higher compared to IFX-AZA sequential therapy group (26/57 and 21/57) (P=0.004and 0.001, resp.). Similar findings were found in complete endoscopic remission rate. The clinical remission rates of IFX monotherapy group were similar to that of IFX-AZA sequential therapy group (P>0.05). At weeks 84 and 138, the endoscopic remission rate and the endoscopic improvement rate between these two groups displayed no significant difference (P>0.05).Conclusion.IFX monotherapy provides higher deep remission rate compared with IFX-AZA sequential therapy in two-year maintenance therapy. For patients who could not receive prolonged IFX therapy, IFX-AZA sequential therapy is acceptable, though long-term efficacy remains to be seen.

Outcomes of Passable and Non-passable Strictures in Clinical Trials of Crohn’s Disease: A Post-hoc Analysis

2021 ◽  
Author(s):  
Neeraj Narula ◽  
Emily C L Wong ◽  
Parambir S Dulai ◽  
John K Marshall ◽  
Jean-Frederic Colombel ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Activity Index ◽  
Disease Activity Index ◽  
Symptom Improvement ◽  
Logistic Regression Models ◽  
Post Hoc Analysis ◽  
Endoscopic Remission ◽  
Post Hoc ◽  
The Impact

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] <150, clinical response as a CDAI reduction of ≥100 points, and ER as SES-CD score <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.

scholarly journals Anastomotic Ulcers After Ileocolic Resection for Crohn’s Disease Are Common and Predict Recurrence

2019 ◽  
Vol 26 (7) ◽  
pp. 1050-1058 ◽  
Author(s):  
Robert P Hirten ◽  
Ryan C Ungaro ◽  
Daniel Castaneda ◽  
Sarah Lopatin ◽  
Bruce E Sands ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Multivariable Analysis ◽  
Disease Recurrence ◽  
Ileocolic Resection ◽  
Anastomotic Ulcer ◽  
Endoscopic Recurrence ◽  
Academic Center ◽  
Endoscopic Remission ◽  
The Impact

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 (>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.

scholarly journals Relevance of monitoring transmural disease activity in patients with Crohn’s disease: current status and future perspectives

2021 ◽  
Vol 14 ◽  
pp. 175628482110066
Author(s):  
Rune Wilkens ◽  
Kerri L. Novak ◽  
Christian Maaser ◽  
Remo Panaccione ◽  
Torsten Kucharzik
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Disease Activity ◽  
Symptom Control ◽  
Current Status ◽  
Clinical Relapse ◽  
Cross Sectional ◽  
Treatment Targets ◽  
Endoscopic Remission ◽  
Transmural Inflammation

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.

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