Ustekinumab concentrations shortly after escalation to monthly dosing may identify endoscopic remission in refractory Crohn’s disease

2021 ◽  
Vol Publish Ahead of Print ◽  
Author(s):  
Jurij Hanžel ◽  
Matic Koželj ◽  
Ana Špes Hlastec ◽  
Tina Kurent ◽  
Nejc Sever ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Endoscopic Remission ◽  
Monthly Dosing

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.

The Correlation between Vitamin D Levels and the Risk of Postoperative Recurrence in Crohn’s Disease

Digestion ◽  
2021 ◽  
pp. 1-9
Author(s):  
Akihiro Yamada ◽  
Yuga Komaki ◽  
Fukiko Komaki ◽  
Haider Haider ◽  
Dejan Micic ◽  
...  
Keyword(s):  
Vitamin D ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Postoperative Recurrence ◽  
Recurrence Rates ◽  
Reactive Protein ◽  
Endoscopic Recurrence ◽  
Vitamin D Levels ◽  
Endoscopic Remission ◽  
The University

<b><i>Background and Aims:</i></b> Vitamin D deficiency has been associated with disease activity in Crohn’s disease (CD). We assessed whether there is a correlation between vitamin D levels and the risk of postoperative recurrence in CD. <b><i>Methods:</i></b> CD patients who underwent surgery were identified from a prospectively maintained database at the University of Chicago. The primary endpoint was the correlation of serum 25-hydroxy vitamin D levels measured at 6–12 months after surgery and the proportion of patients in endoscopic remission, defined as a simple endoscopic score for CD of 0. Clinical, biological (C-reactive protein), and histologic recurrences were also studied. <b><i>Results:</i></b> Among a total of 89 patients, 17, 46, and 26 patients had vitamin D levels of &#x3c;15, 15–30, and &#x3e;30 ng/mL, respectively. Patients with higher vitamin D levels were significantly more likely to be in endoscopic remission compared to those with lower levels (23, 42, and 67% in ascending tertile order; <i>p</i> = 0.028). On multivariate analysis, vitamin D &#x3e;30 ng/mL (odds ratio [OR] 0.22, 95% confidence interval [CI] 0.07–0.66, <i>p</i> = 0.006) and anti-tumor necrosis factor agent treatment (OR 0.25, 95% CI 0.08–0.83, <i>p</i> = 0.01) were associated with reduced risk of endoscopic recurrence. Rates of clinical, biological, and histologic remission trended to be higher in patients with higher vitamin D levels (<i>p</i> = 0.17, 0.55, 0.062, respectively). <b><i>Conclusion:</i></b> In the present study, higher vitamin D level was associated with lower risk of postoperative endoscopic CD recurrence. Further, studies are warranted to assess the role of vitamin D in postoperative CD recurrence.

P089 REAL-WORLD EXPERIENCE: CLINICAL AND ENDOSCOPIC EFFECTIVENESS OF STANDARD VEDOLIZUMAB DOSING AND MODIFIED MAINTENANCE DOSING IN PATIENTS WITH MODERATE-SEVERE CROHN’S DISEASE

2020 ◽  
Vol 26 (Supplement_1) ◽  
pp. S75-S75
Author(s):  
Scott D Lee ◽  
Anand Singla ◽  
Caitlin Kerwin ◽  
Kindra Clark-Snustad
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Adverse Events ◽  
Real World ◽  
Clinical Remission ◽  
Mucosal Healing ◽  
Clinical Disease ◽  
Endoscopic Remission ◽  
Starting Dose

Abstract Background Vedolizumab (VDZ) is an effective treatment for Crohn’s disease (CD); however, inadequate and loss of response is common. Pivotal VDZ trials evaluated alternative dosing intervals, demonstrating numeric but not statistical superiority in efficacy as compared to FDA-approved dosing. The safety and effectiveness of FDA-approved and modified-dosing schedules in a real-world population are unknown. We aimed to evaluate clinical and endoscopic effectiveness & safety of standard and modified maintenance VDZ dosing in a real world cohort. Methods We retrospectively reviewed CD patients (pts) treated with &gt;3 months VDZ, assessing Harvey Bradshaw Index (HBI), Simple Endoscopic Score for Crohn’s disease (SESCD), Short Inflammatory Bowel Disease Questionnaire (SIBDQ), C-reactive protein (CRP), albumin and hematocrit prior to and following standard VDZ dosing, and prior to and following modified VDZ maintenance dosing. We measured duration on therapy and adverse events. Results We identified 226 eligible pts, mean age 41.5 years, 55.3% female, median disease duration 10 years, 88.9% with prior biologic exposure. Mean duration on VDZ was 28.3 months. Standard VDZ dosing: 61.5% of pts with active clinical disease and adequate follow up data achieved clinical response after 3–12 months; 41.0% had clinical remission. 51.9% of pts with active endoscopic disease and adequate follow up data achieved mucosal improvement; 42.3% had endoscopic remission; 26.0% had mucosal healing after 3–24 months. 50.0% of pts with elevated CRP and adequate follow up data normalized CRP after 3–12 months. Modified maintenance dosing: 72 non-remitters to standard VDZ dosing received modified VDZ maintenance dosing. 51.5% of pts with active clinical disease prior to starting dose modification and adequate follow up data achieved clinical response after 3–12 months of modified maintenance dosing; 42.4% had clinical remission. 22.2% of pts with SESCD ≥3 prior to starting dose modification achieved mucosal improvement after 3–24 months; 22.2% had mucosal healing. 26.7% of pts with SESCD ≥4 prior to starting modified dosing had endoscopic remission after 3–24 months. 50.0% of pts with elevated CRP and adequate follow up data normalized their CRP after 3–12 months. Safety: 82.7% of pts reported ≥1 adverse events, most commonly infection and worsening CD symptoms. Discussion Standard VDZ dosing resulted in clinical and endoscopic improvement in pts with moderate-severe CD, with prior exposure to multiple advanced therapies. For non-remitters to standard dosing, modified VDZ maintenance dosing improved clinical disease activity in ∼50% of pts and improved endoscopic disease activity in ∼20% of pts, suggesting that for pts who did not achieve remission with standard VDZ dosing, modified VDZ dosing may result in clinical and endoscopic improvement.

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.

Recommendations for Standardizing Clinical Trial Design and Endoscopic Assessment in Postoperative Crohn’s Disease

2021 ◽  
Author(s):  
Jurij Hanzel ◽  
Vipul Jairath ◽  
Peter De Cruz ◽  
Leonardo Guizzetti ◽  
Lisa M Shackelton ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Disease Activity ◽  
Trial Design ◽  
Clinical Trial Design ◽  
End Point ◽  
Endoscopic Remission ◽  
Medical Therapies ◽  
Endoscopic Assessment

Abstract Background The lack of standardized methods for clinical trial design and disease activity assessment has contributed to an absence of approved medical therapies for the prevention of postoperative Crohn’s disease (CD). We developed recommendations for regulatory trial design for this indication and for endoscopic assessment of postoperative CD activity. Methods An international panel of 19 gastroenterologists was assembled. Modified Research and Development/University of California Los Angeles methodology was used to rate the appropriateness of 196 statements using a 9-point Likert scale in 2 rounds of voting. Results were reviewed and discussed between rounds. Results Inclusion of patients with a history of completely resected ileocolonic CD in regulatory clinical trials for the prevention of postoperative recurrence was appropriate. Given the absence of approved medical therapies, a placebo-controlled design with a primary end point of endoscopic remission at 52 weeks was appropriate for drug development for this indication; however, there was uncertainty regarding the appropriateness of a coprimary end point of symptomatic and endoscopic remission and the use of currently available patient-reported outcome measures. The modified Rutgeerts Score, endoscopic assessment of the anastomosis, and a minimum of 5cm of neoterminal ileum were also appropriate; although the appropriateness of other indices including the Simple Endoscopic Score for CD for endoscopic assessment of postoperative CD activity was uncertain. Conclusions A framework for regulatory trial design for the prevention of postoperative CD recurrence and endoscopic assessment of disease activity has been developed. Research to empirically validate end points for these trials is needed.

scholarly journals P343 Efficacy of adalimumab in mild-to-moderate inflammatory bowel disease: Real-life data from single-centre experience in the long-term period

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S329-S330
Author(s):  
F Akyüz ◽  
A Ormeci ◽  
N Namazova ◽  
M Guzel ◽  
A Abbasgoulizadeh ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Response Rate ◽  
Real Life ◽  
Loss Of Response ◽  
Endoscopic Remission ◽  
Inflammatory Bowel

Abstract Background Adalimumab (ADA) is one of the most preferred anti-TNF agents because of its ease of use in real life. We aimed to evaluate the efficacy of ADA in the long-term period of inflammatory bowel disease (IBD) patients. Methods Patients treated with adalimumab (ADA) as the first- and second-line biological treatment for mild to moderate active IBD between January 2009 and March 2019 were included. The clinical and endoscopic response rate of ADA were evaluated, retrospectively. Remission was defined in ulcerative colitis patients (UC), if stool frequency ≤ 3/day with no bleeding and no mucosal lesions at the colonoscopy. Remission was defined in Crohn’s disease patients (CD) if CDAI &lt; 150 and mucosal healing at the colonoscopy. Results Fifty-eight patients (81% Crohn’s disease, 58.6% biologic naive) were included in this study. Mean age was 41.4 ± 12.3 years old (19–67 years) and 46.6% of them were female. Median follow-up time was 57 months in UC and 65 months in Crohn’s disease (CD). Infliximab experience rate before ADA in UC and CD was 36.4%, 42.6%, respectively. CD’s related surgery rate was 43.5%; surgery rate 87.5% before ADA therapy and 12.5% after ADA treatment. Clinical and endoscopic remission rates were 81.8% / 63.6% and 89.4%/ 63.4 in UC and CD, respectively at the end of follow-up period. Loss of response rate was 20% in UC and 28.3% in CD (table). Mean months for loss of response were 42 ± 25.4 months and 29.7 ± 12 months in UC and CD, respectively. Clinical remission was obtained by dose escalation in 66% of CD patients who had response loss. Loss of response rate was not significantly different between IFX naive and IFX experienced patients (p &gt; 0.05). There was no significant adverse event during the follow-up period. Conclusion In real life, the efficacy of ADA treatment is high in mild-to-moderate active IBD. Endoscopic remission was also acceptable for this group of patients.

scholarly journals P274 The clinical significance of anastomotic ulcers after ileocolic resection to predict postoperative recurrence of Crohn’s disease

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S288-S288
Author(s):  
J Y Kim ◽  
S H Park ◽  
Y J Kim ◽  
J C Park ◽  
S Noh ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Clinical Significance ◽  
Multivariable Analysis ◽  
Postoperative Recurrence ◽  
Ileocolic Resection ◽  
Single Centre ◽  
Endoscopic Recurrence ◽  
Endoscopic Remission

Abstract Background The Rutgeerts score (RS) is used to predict postoperative recurrence in Crohn’s disease (CD) patients after ileocolic resection primarily based on endoscopic finding at the neoterminal ileum. However, assessing anastomotic ulcers (AUs) is still a matter of debate. Our aim was to investigate the clinical significance of AUs on endoscopic recurrence in postoperative CD patients. Methods This was a single-centre retrospective study analysing postoperative CD patients with the RS of i0 to i1 at the first ileocolonoscopy within 1 year after ileocolic resection between 2000 and 2016 and those who underwent subsequent ileocolonoscopic follow-up. The study outcome was the clinical significance of AUs predicting endoscopic recurrence (RS ≥ i2b). Results Among 116 patients who were in endoscopic remission at the index postoperative ileocolonoscopy, 84.5% (98/116) underwent subsequent ileocolonoscopies. During the 30.0 months (interquartile ranges, 21.3–53.3) of median follow-up periods after the index ileocolonoscopy, 56.1% (55/98) showed endoscopic recurrence. Furthermore, 65.8% (48/73) with AUs and 75.5% (40/53) with major AUs defined as ulcer occupying ≥ 1/4 of the circumference or ≥ 3 ulcers confined to anastomotic ring, or any ulcers extended to ileocolic mucosa showed endoscopic recurrence. On multivariable analysis, the presence of AUs (adjusted hazard ratio [aHR], 4.33; 95% confidence interval [CI], 1.87–10.0; p &lt; 0.001) and major AUs (aHR, 3.64; 95% CI, 1.95–6.79; p &lt; 0.001) were associated with endoscopic recurrence, respectively. Conclusion AUs are associated with a significantly higher risk of endoscopic recurrence in postoperative CD patient who are in endoscopic remission.

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