Multiparametric Evaluation Predicts Different Mid-Term Outcomes in Crohn’s Disease

Aim: To evaluate if a single and/or combined (clinical, endoscopic and radiological) assessment could predict clinical outcomes in Crohn’s disease (CD). Methods: We prospectively evaluated 57 CD cases who underwent both a colonoscopy and a CT-enterography (CTE). Harvey-Bradshaw Index (HBi), SES-CD (and/or Rutgeerts score) and the radiological disease activity were defined to stratify patients according to clinical, endoscopic and radiological disease activity respectively. Hospitalizations, surgery, therapeutic changes and deaths were evaluated up to 36 months (time 1) for 53 patients. Results: CTE and endoscopy agreed in stratifying disease activity in 47% of cases (k = –0.05; p = 0.694), CTE and HBi in 35% (k = 0.09; p = 0.08), endoscopy and HBi in 39% (k = 0.13; p = 0.03). Taken together, CTE, endoscopy and HBi agreed only in 18% of cases (k = 0.01; p = 0.41). Among the 11 cases with mucosal healing, only 3 (27%) showed transmural healing. Patients with endoscopic activity needed significantly more changes of therapy compared to patients with endoscopic remission (p = 0.02). Patients with higher transmural or clinical activity at baseline required significantly more hospitalizations (p < 0.01). Hospitalization rate decreases with an increase in the number of parameters indicating remissions at baseline (p = 0.04). Conclusions: Clinical, endoscopic and radiological assessments offer complementary information and could predict different mid-term outcomes in CD.

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

Therapeutic Advances in Gastroenterology ◽

10.1177/17562848211006672 ◽

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

Inflammatory Bowel Diseases ◽

10.1093/ibd/zaa010.187 ◽

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 >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.

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

Inflammatory Bowel Diseases ◽

10.1093/ibd/izab259 ◽

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.

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Ileal Crohn's disease activity predicted by ruler: CT enterography histopathology correlation

The Egyptian Journal of Radiology and Nuclear Medicine ◽

10.1016/j.ejrnm.2017.01.001 ◽

2017 ◽

Vol 48 (1) ◽

pp. 7-13

Author(s):

Tamer W. Kassem

Keyword(s):

Crohn’S Disease ◽

Crohn's Disease ◽

Disease Activity ◽

Ct Enterography ◽

Crohn’S Disease Activity

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Randomised trial of mycophenolate mofetil versus azathioprine for treatment of chronic active Crohn’s disease

Gut ◽

10.1136/gut.44.5.625 ◽

1999 ◽

Vol 44 (5) ◽

pp. 625-628 ◽

Cited By ~ 147

Author(s):

M F Neurath ◽

R Wanitschke ◽

M Peters ◽

F Krummenauer ◽

K-H Meyer zum Büschenfelde ◽

...

Keyword(s):

Crohn’S Disease ◽

Mycophenolate Mofetil ◽

Side Effects ◽

Crohn's Disease ◽

Disease Activity ◽

Activity Index ◽

Randomised Trial ◽

Chronic Inflammatory Disease ◽

Clinical Activity ◽

Small Subset

BACKGROUNDCrohn’s disease is a chronic inflammatory disease of the alimentary tract. Azathioprine is an effective agent in the management of chronic active Crohn’s disease leading to long term remission of disease activity. Such treatment leads to limited efficacy or side effects in a small subset of patients.AIMSTo compare efficacy and side effects of treatment with azathioprine plus corticosteroids versus mycophenolate mofetil (MMF) plus corticosteroids in patients with chronic active Crohn’s disease.METHODSSeventy patients with chronic active Crohn’s disease (Crohn’s disease activity index (CDAI) greater than 150) were randomised for treatment with azathioprine/cortisone or MMF/cortisone. Corticosteroid dosage was tapered according to a standard protocol. Disease activity was monitored by clinical scores after one, two, three, and six months.RESULTSTreatment of patients with moderately active (CDAI 150–300) Crohn’s disease with MMF/cortisone led to a significant reduction in clinical activity scores comparable to treatment with azathioprine/cortisone. Treatment of patients with highly active Crohn’s disease (CDAI greater than 300) with MMF/cortisone caused significant suppression of clinical activity earlier than azathioprine/cortisone treatment. Treatment with MMF/cortisone was associated with few adverse effects.CONCLUSIONTreatment of chronic active Crohn’s disease with MMF plus cortisone appears to be effective and well tolerated and should be considered in patients allergic to azathioprine or in whom azathioprine has failed.

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Using CT Enterography to Monitor Crohn's Disease Activity: A Preliminary Study

American Journal of Roentgenology ◽

10.2214/ajr.07.2877 ◽

2008 ◽

Vol 190 (6) ◽

pp. 1512-1516 ◽

Cited By ~ 54

Author(s):

Amy K. Hara ◽

Shayan Alam ◽

Russell I. Heigh ◽

Suryakanth R. Gurudu ◽

Joseph G. Hentz ◽

...

Keyword(s):

Crohn’S Disease ◽

Crohn's Disease ◽

Disease Activity ◽

Ct Enterography ◽

Crohn’S Disease Activity ◽

Preliminary Study

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P417 Long-term deep remission after adalimumab discontinuation in Crohn’s disease patients

Journal of Crohn s and Colitis ◽

10.1093/ecco-jcc/jjab076.541 ◽

2021 ◽

Vol 15 (Supplement_1) ◽

pp. S423-S423

Author(s):

L Melotti ◽

F Rizzello ◽

C Calabrese ◽

N Dussias ◽

P Gionchetti

Keyword(s):

Crohn’S Disease ◽

Crohn's Disease ◽

Mucosal Healing ◽

Treatment Withdrawal ◽

Biologic Agent ◽

Drug Discontinuation ◽

Endoscopic Remission ◽

Observational Cohort

Abstract Background Adalimumab is a safe and effective drug in treatment of Crohn’s Disease (CD). Current literature is not definitive regarding an exact timing for treatment withdrawal and disease relapses after drug discontinuation. Methods We conducted a single-centre, retrospective, observational cohort study involving patients affected by Crohn’s Disease (CD) treated with adalimumab. Of 575 patients treated with adalimumab for CD, 149 patients suspended treatment for stable deep remission (clinical steroid-free, biochemical, endoscopic remission defined as mucosal healing). Of these, 126 have a minimum follow up of 4 years, the other 23 where lost or finished the follow-up. Patients were assessed clinically, laboratoristically and endoscopically for 4 years. Relapse was defined as clinical (HBI > 4) and biochemical (PCR > 0.5 mg/dL). Results Of the 126 patients with 4 years follow-up, 64 (51%) maintained deep remission during the 4 year follow-up period. Of these, 38 (59%) were on exit-therapy with thiopurines. Twenty-seven patients (18%) had relapsed by year 1, 24 (18%) by year 2, 8 (6%) by year 3, and 1 (0.8%) by year 4. Relapses needed surgical therapy in 9 (15%) cases, whereas 36 (60%) were retreated with adalimumab and 4 (7%) with another biologic agent. The remaining 11 patients (18%) were treated only with a course of steroids. Conclusion Patients who suspend treatment with adalimumab for stable deep remission maintain remission in the long term in approximately half of cases. The majority of relapses occur in the first 24 months after discontinuation.

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Diagnosis and Outcome of Oesophageal Crohn’s Disease

Journal of Crohn s and Colitis ◽

10.1093/ecco-jcc/jjz201 ◽

2019 ◽

Vol 14 (5) ◽

pp. 624-629

Author(s):

Rita Vale Rodrigues ◽

Margaret Sladek ◽

Konstantinos Katsanos ◽

C Janneke van der Woude ◽

Juan Wei ◽

...

Keyword(s):

Crohn’S Disease ◽

Crohn's Disease ◽

Case Reports ◽

Case Series ◽

Disease Diagnosis ◽

Mucosal Healing ◽

Case Report Form ◽

Endoscopic Remission ◽

Mean Time

Abstract Background and Aims Crohn’s disease [CD] can involve any part of the gastrointestinal tract. We aimed to characterize the clinical, endoscopic and histological features and treatment outcomes of CD patients with oesophageal involvement. Methods We collected cases through a retrospective multicentre European Crohn’s and Colitis Organisation CONFER [COllaborative Network For Exceptionally Rare case reports] project. Clinical data were recorded in a standardized case report form. Results A total of 40 patients were reported (22 males, mean [±SD, range] age at oesophageal CD diagnosis: 25 [±13.3, 10–71] years and mean time of follow-up: 67 [±68.1, 3–240] months). Oesophageal involvement was established at CD diagnosis in 26 patients [65%] and during follow-up in 14. CD was exclusively located in the oesophagus in two patients. Thirteen patients [32.2%] were asymptomatic at oesophageal disease diagnosis. Oesophageal strictures were present in five patients and fistulizing oesophageal disease in one. Eight patients exhibited granulomas on biopsies. Proton-pump inhibitors [PPIs] were administered in 37 patients [92.5%]. Three patients underwent endoscopic dilatation for symptomatic strictures but none underwent oesophageal-related surgery. Diagnosis in pre-established CD resulted in treatment modifications in 9/14 patients. Clinical remission of oesophageal disease was seen in 33/40 patients [82.5%] after a mean time of 7 [±5.6, 1–18] months. Follow-up endoscopy was performed in 29/40 patients and 26/29 [89.7%] achieved mucosal healing. Conclusion In this case series the endoscopic and histological characteristics of isolated oesophageal CD were similar to those reported in other sites of involvement. Treatment was primarily conservative, with PPIs administered in the majority of patients and modifications in pre-existing inflammatory bowel disease-related therapy occurring in two-thirds of them. Clinical and endoscopic remission was achieved in more than 80% of the patients.

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Role of MR Enterography in Evaluation of Disease Activity in Pediatric Crohn’s Disease: Correlation between MR Enterography and Pediatric Crohn’s Disease Activity Index Scores

Journal of Gastrointestinal and Abdominal Radiology ◽

10.1055/s-0040-1701328 ◽

2020 ◽

Vol 03 (02) ◽

pp. 118-125

Author(s):

Shilpa Radhakrishnan ◽

Amarnath Chellathurai ◽

Srinivas Sankaranrayanan ◽

Dharani Sankar ◽

Suja Rajan

Keyword(s):

Crohn’S Disease ◽

Crohn's Disease ◽

Disease Activity ◽

Activity Index ◽

Disease Activity Index ◽

Mr Enterography ◽

Clinical Activity ◽

Positive Correlation

Abstract Objectives The aim of the study was to assess the role of MR Enterography (MRE) in the diagnosis and follow-up of children with Crohn’s disease (CD) and to correlate disease activity indices with known MRE features of active disease. Methods This was a retrospective study including 24 patients (median age 11 years, 17 males) with clinically and histologically proven CD who underwent MRE. Two previously validated MRE scores—Magnetic Resonance Enterography Global Score (MEGS) and CD MRI index (CDMI)—were calculated. A correlative analysis was made between the Pediatric Crohn’s Disease Activity Index (PCDAI) score and MRE scores as well as individually with each MR variable. Comparison of both the MR scores was made between patients with different disease activity. Results MEGS and PCDAI scores showed strong positive correlation (r = 0.724, p = < 0.001); CDMI and PCDAI scores showed moderate positive correlation (r = 0.661, p = 0.0004). There was statistically significant difference in the MR scores between patients grouped by clinical activity. Among individual MR variables, mural thickness and enhancement best predicted the disease activity. Conclusions MRE-based scores and findings correlate with clinical activity in pediatric CD. Thereby, MRE can be considered a valuable tool in the management of CD, predicting disease activity and offering a potential alternative to endoscopy in monitoring patients during follow-up.

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