A Nomogram Combining Fecal Calprotectin Levels and Plasma Cytokine Profiles for Individual Prediction of Postoperative Crohn’s Disease Recurrence

Abstract Background The aims of this study were to characterize the immune response profile in patients with Crohn’s disease (CD) and early postoperative recurrence (POR), to identify predictive biomarkers, and to develop a noninvasive predictive tool for individual estimation of POR risk. Methods Sixty-one patients who had undergone ileocolonic resection for CD were prospectively included and followed up for 24 months. Fecal calprotectin (FC), analytical parameters, and plasma cytokines were obtained before surgery and at various time points during postoperative follow-up. Morphological recurrence was assessed by ileocolonoscopy or magnetic resonance enterography within 6–12 months after surgery. Clinical activity was scored using the Harvey-Bradshaw Index. Results Twenty-seven patients (44.3%) had morphological recurrence during follow-up. Fecal calprotectin values were significantly associated with POR risk over time. The receiver operating characteristic curve for FC provided an area under the curve (AUC) of 0.88 (95% confidence interval, 0.75–0.96), and morphological recurrence was best predicted by FC ≥160 μg/g at 6 months after surgery (85% sensitivity, 70% specificity, 26% predictive positive value, 98% negative predictive value [NPV]). The plasma cytokine profile showed higher presurgery interleukin (IL)-13 plasma levels and higher IL-6 and interferon (IFN)-γ levels at 6 months after surgery in patients with POR compared with patients without recurrence. The combination of FC, IL-6, and IFN-γ values at 6 months gave an AUC of 0.90 for predicting an early recurrence. Conclusions FC values <160 μg/g at 6 months have a high NPV to rule out early lesions. Combined values of FC, IL-6, and IFN-γ levels at 6 months postsurgery constitute a prognostic index with a high predictive capacity to assess the risk of early POR.

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P286 Ustekinumab for Crohn’s Disease: Two-Year Results of the Initiative on Crohn and Colitis (ICC) Registry, a Nationwide Prospective Observational Cohort Study

Journal of Crohn s and Colitis ◽

10.1093/ecco-jcc/jjab076.411 ◽

2021 ◽

Vol 15 (Supplement_1) ◽

pp. S319-S320

Author(s):

T Straatmijer ◽

V B C Biemans ◽

F Hoentjen ◽

N K H de Boer ◽

A G Bodelier ◽

...

Keyword(s):

Crohn’S Disease ◽

Crohn's Disease ◽

Real World ◽

Clinical Remission ◽

Prospective Cohort ◽

Upper Airway ◽

Fecal Calprotectin ◽

Regular Care ◽

Observational Cohort

Abstract Background Ustekinumab is a monoclonal antibody that selectively targets p40, a shared subunit of the cytokines interleukin (IL)-12 and IL-23. It is registered for the treatment of Crohn’s disease (CD) and ulcerative colitis. We assessed the two-year efficacy and safety of ustekinumab in a real world, prospective cohort of CD patients. Methods CD patients who started ustekinumab in regular care were prospectively enrolled in the nationwide Initiative on Crohn and Colitis Registry. At week 0, 12, 24, 52 and 104, clinical remission (HBI ≤ 4 points), biochemical remission (fecal calprotectin (FC) ≤200 μg/g and/or CRP ≤5 mg/L), peri-anal fistula remission, extra-intestinal manifestations, ustekinumab dosage and safety outcomes were determined. Patients starting therapy less than two years ago were excluded for the current evaluation. The primary outcome was corticosteroid-free clinical remission at week 104. Results In total, 252 CD patient with at least two years of follow up were included. Of all included patients, the proportion of patients in corticosteroid-free clinical remission at week 12, 24, 52 and 104 was 32.3% (81/251), 41.4% (104/251), 39% (97/249) and 34.0% (84/247), respectively. Of the 97 patients in corticosteroid free clinical remission at week 52, 58 (59.8%) were still in corticosteroid-free clinical remission at week 104. In patients with combined clinical and biochemical disease activity at baseline (n=122), the corticosteroid-free clinical remission rates were 23.8% (29/122), 35.2% (43/122), 40.0% (48/120) and 32.8% (39/119) at week 12, 24, 52 and 104, respectively. The probability of remaining on ustekinumab treatment after 52 and 104 weeks was 64.3% and 54.8%, respectively. There were no predictive factors associated with corticosteroid-free clinical remission at week 104 on univariate and multivariate analysis. Most common adverse events were headache, skin reaction and musculoskeletal complaints. Two patients stopped ustekinumab due to an infection after 8 and 30 weeks of treatment (mild fever syndrome and moderate upper airway infection, respectively). The main reason for discontinuing treatment after 52 weeks was loss of response (66.7%). Conclusion Ustekinumab was effective and relatively safe in our real world, prospective cohort of CD patients. After 104 weeks of ustekinumab treatment, one third of patients were in corticosteroid-free clinical remission.

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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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Induction of Remission in Pediatric Crohn’s Disease Patients Assessed by the Mucosal Inflammation Noninvasive Index

Journal of Clinical Medicine ◽

10.3390/jcm10235613 ◽

2021 ◽

Vol 10 (23) ◽

pp. 5613

Author(s):

Roma Herman ◽

Paulina Dumnicka ◽

Stanisław Pieczarkowski ◽

Krzysztof Fyderek

Keyword(s):

Crohn’S Disease ◽

Crohn's Disease ◽

Induction Therapy ◽

Activity Index ◽

Disease Activity Index ◽

Fecal Calprotectin ◽

Mucosal Healing ◽

Mucosal Inflammation ◽

Exclusive Enteral Nutrition

Mucosal healing (MH) is the main therapeutic goal of Crohn’s disease (CD). The Mucosal Inflammation Noninvasive Index (MINI) appears to be a promising tool for distinguishing MH from its inflammation. This study aims to evaluate MINI in monitoring remissions induced by exclusive enteral nutrition (EEN) in pediatric CD patients. Out of 55 newly diagnosed CD children, 31 who completed 6–8 weeks of EEN were analyzed. Clinical and biochemical data, activity of CD assessed with the Pediatric Crohn’s Disease Activity Index (PCDAI) and MINI were compared within seven days pre- and post-EEN. Response to induction therapy was defined as a decrease of PCDAI by >12.5 points. The follow-up was performed up to 12 months after EEN termination. Out of 31 children who completed 6–8 weeks of EEN, eight required corticosteroids in addition to EEN. Twenty-four patients (77%) responded to induction therapy. In responders, MINI decreased from 19 (Q1:17; Q3:22) to 12 (Q1:6; Q3:14), p < 0.001. The diagnostic accuracy of post-EEN MINI and post-EEN fecal calprotectin (FC) for treatment failure were AUC: 0.899 (95%CI: 0.737–1.000) and 0.762 (95%CI: 0.570–0.954), respectively. In the follow-up of 25 patients (80.6%), the post-EEN MINI of ≥13 points predicted CD relapse (87.5% sensitivity; 64.7% specificity), while FC had no prognostic value. MINI allows for monitoring of EEN and is superior in predicting disease relapse to FC.

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P583 Real-life efficacy and safety of Ustekinumab as second- or third-line therapy in Crohn’s disease: results from a large Italian cohort study

Journal of Crohn s and Colitis ◽

10.1093/ecco-jcc/jjab076.704 ◽

2021 ◽

Vol 15 (Supplement_1) ◽

pp. S536-S537

Author(s):

G Mocci ◽

A Cuomo ◽

L Allegretta ◽

G Aragona ◽

R Colucci ◽

...

Keyword(s):

Crohn’S Disease ◽

Crohn's Disease ◽

Clinical Remission ◽

Large Population ◽

Real Life ◽

Previous Treatment ◽

Fecal Calprotectin ◽

Concomitant Treatment ◽

Efficacy And Safety

Abstract Background Ustekinumab (UST) is an anti-IL12/23 antibody for the treatment of Crohn’s Disease (CD). The aim of this study was to compare the efficacy and safety of UST in a large population-based cohort of CD patients who failed previous treatment with other biologics Methods 194 CD patients (108 males and 86 females, mean age 48 years (range 38–58 years) were retrospectively reviewed. 147 patients were already treated with anti-TNFα (75.8%), and 47 (24.2%) patients were already treated with anti-TNFα and vedolizumab. Concomitant treatment with steroids was present in 177 (91.2%) patients Results At week 12, clinical remission was achieved in 146 (75.2%) patients. After a mean follow-up of 6 months, clinical remission was maintained in 135 (69.6%) patients; at that time, mucosal healing was assessed in 62 (31.9%) patients, and it was achieved in 33 (53.2) patients. Three (1.5%) patients were submitted to surgery. Steroid-free remission was achieved in 115 (59.3%) patients. Both serum C-Reactive Protein and Fecal Calprotectin (FC) levels were significantly reduced with respect to baseline levels during follow-up. A logistic regression, UST therapy as thirdline therapy (after both anti-TNFα and vedolizumab), FC >200 μg/g, and HBI ≥8 were significantly associated with lack of remission. Adverse events occurred in 5 (2.6%) patients, and four of them required suspension of treatment Conclusion Ustekinumab seemed to be really effective and safe in CD patients unresponsive to other biologic treatments, especially when used as second-line treatment.

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Short and Long-Term Effectiveness of Ustekinumab in Patients with Crohn’s Disease: Real-World Data from a German IBD Cohort

Journal of Clinical Medicine ◽

10.3390/jcm8122140 ◽

2019 ◽

Vol 8 (12) ◽

pp. 2140 ◽

Cited By ~ 4

Author(s):

Alica Kubesch ◽

Laurenz Rueter ◽

Karima Farrag ◽

Thomas Krause ◽

Klaus Stienecker ◽

...

Keyword(s):

Crohn’S Disease ◽

Crohn's Disease ◽

Real World ◽

Treatment Options ◽

Fecal Calprotectin ◽

Real World Data ◽

Free Response ◽

Short And Long Term

Background and Aims: The IL-12/23 inhibitor ustekinumab (UST) opened up new treatment options for patients with Crohn’s disease (CD). Due to the recent approval, real-world German data on long-term efficacy and safety are lacking. This study aimed to assess the clinical course of CD patients under UST therapy and to identify potential predictive markers. Methods: Patients with CD receiving UST treatment in three hospitals and two outpatient centers were included and retrospectively analyzed. Rates for short- and long-term remission and response were analyzed with the help of clinical (Harvey–Bradshaw Index (HBI)) and biochemical (C-reactive protein (CRP), Fecal calprotectin (fCal)) parameters for disease activity. Results: Data from 180 patients were evaluated. One-hundred-and-six patients had a follow-up of at least eight weeks and were included. 96.2% of the patients were pre-exposed to anti- TNFα agents and 34.4% to both anti-TNFα and anti-integrin antibodies. The median follow-up was 49.1 weeks (95% CI 42.03-56.25). At week 8, 51 patients (54.8%) showed response to UST, and 24 (24.7%) were in remission. At week 48, 48 (51.6%) responded to UST, and 25 patients (26.9%) were in remission. Steroid-free response and remission at week eight was achieved by 30.1% and 19.3% of patients, respectively. At week 48, 37.6% showed steroid-free response to UST, and 20.4% of the initial patient population was in steroid-free remission. Conclusion: Our study confirms short- and long-term UST effectiveness and tolerability in a cohort of multi-treatment-exposed patients.

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P471 Predictors of bowel damage in long term progression of Crohn’s disease

Journal of Crohn s and Colitis ◽

10.1093/ecco-jcc/jjab076.594 ◽

2021 ◽

Vol 15 (Supplement_1) ◽

pp. S461-S461

Author(s):

A Fernandez Clotet ◽

J Panes ◽

E Ricart ◽

J Castro Poceiro ◽

M C Masamunt ◽

...

Keyword(s):

Crohn’S Disease ◽

Crohn's Disease ◽

Disease Duration ◽

Clinical Activity ◽

Inflammatory Bowel Disorder ◽

Damage Progression ◽

Inflammatory Bowel ◽

Main Determinants

Abstract Background Crohn’s disease is a chronic inflammatory bowel disorder that progresses to bowel damage over time. An image-based index, the Lémann Index, has been developed to measure the cumulative bowel damage. AIMS To characterize the long-term progression of bowel damage in Crohn’s disease based on changes in the Lémann Index and to determine risk factors for long term progression. Methods This was a single-center longitudinal cohort study. Patients who had participated in prospective studies on the accuracy of magnetic resonance imaging using endoscopy as gold standard and had a follow-up of at least 5 years were reevaluated after 5–12 years. Results Seventy-two patients were included. Lémann Index increased in 38 patients (52.8%), remained unchanged in 9 patients (12.5%) and decreased in 25 patients (34.7%). Small bowel score and surgery subscale significantly increased (p=0.002 and p=0.0001), whereas fistulizing subscale significantly decreased (p=0.001). Baseline parameters associated with bowel damage progression were ileum location (p=0.026), phenotype (stricturing, fistulizing or both with p=0.007, p=0.006 and p=0.035), disease duration >10 years (p=0.019) and baseline Lémann Index stricturing score (p=0.049). No correlation was observed between bowel damage progression and baseline clinical activity, biological markers or endoscopic lesions. Need of surgery during follow-up was a major determinant of bowel damage progression (p=0.0001). Baseline stricturing Lémann Index score was associated with the risk of future surgery (p=0.02). Conclusion Bowel damage, assessed by the Lémann Index, progresses in half of the patients with Crohn’s disease over a period of 5–12 years. The main determinants of bowel damage progression are ileum location, stricturing/fistulizing phenotype and disease duration.

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P501 Thiopurine withdrawal in patients with Crohn’s disease: the SURESTE study

Journal of Crohn s and Colitis ◽

10.1093/ecco-jcc/jjz203.630 ◽

2020 ◽

Vol 14 (Supplement_1) ◽

pp. S435-S436

Author(s):

E Sánchez Rodríguez ◽

R Sánchez Aldehuelo ◽

J Guardiola ◽

A Gutiérrez Casbas ◽

E Domènech ◽

...

Keyword(s):

Crohn’S Disease ◽

Crohn's Disease ◽

Treatment Duration ◽

Disease Duration ◽

Specific Treatment ◽

Fecal Calprotectin ◽

Patient Choice ◽

Sustained Remission ◽

Upper Gastrointestinal

Abstract Background Thiopurine (TP) withdrawal in patients with Crohn’s disease (CD) in clinical remission (CR) is controversial. Our aim was to describe the evolution of CD patients in CR who discontinued TP prescribed to maintain a remission previously achieved with medical treatment, and to detect predictors of reactivation after withdrawal. Methods Multicentric observational retrospective study including CD patients in RC under TP treatment, who electively discontinued TP. Relapse was defined as the need to start any specific treatment for CD, including surgery. Informed consent was obtained from the inclusion in the Eneida database. Results We included 78 patients (52.6% females, age 45(19–77) years) of whom 57 presented an inflammatory, 12 a stricturing and 9 a penetrating behaviour; 31 patients had terminal ileum involvement, 9 colonic, 36 ilecolonic, and 2 ileocolonic plus upper gastrointestinal involvement, whilst 17 also had perianal disease. Mean disease duration was 13.47 (3.02–35.02) years. 48.7% had never smoked whilst 24.4% were active smokers. TP was started to maintain remission previously achieved with medical therapies in 78 patients (100%). Median azathioprine dose was 2.11 (1.3–2.6) mg/kg/d, and of 6-mercaptopurine (6MP) 1.44 (1–2) mg/kg/day. The median duration of TP treatment was 52.79 (3–268) months and of steroid-free remission 49.41 (1–177) months. Reasons for TP withdrawal were: patient choice/request in 20 (25.6%), physician proposal in 28 (25.7%), drug-related adverse events in 19 (24.4%) and miscellaneous in 11 (14.1%). By the time of TP discontinuation, median CRP was 5.08 mg/l (0.1–157.9), fecal calprotectin(FC) 282.38 µg/g (2.4-4430) and a mean 0.45 (0–4) in Harvey–Bradshaw Index (HBI); those who relapsed presented median CRP of 15.31 mg/l (0.1–125.31), fecal calprotectin (FC) 462.22 µg/g (90–1240) and a mean 5.46 (0–15) in HBI. These differences were statistically significant. During a 5.08 (0.12–13.05) years follow-up, 38 (48.1%) patients relapsed, with treatment duration being the only factor associated to risk of relapse (Or = 0.659 IC95 0.43–0.98, p = 0.04) in the multivariant analysis (IMAGE1). Conclusion Thiopurine withdrawal in the context of sustained remission in CD is associated with relapse in almost half of the patients after a median follow-up of 5 years. Thiopurine treatment duration of shorter than 5 years was shown to carry greater risk for relapse.

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P717 Ustekinumab in Crohn’s disease: Real-world outcomes from the Sicilian Network for inflammatory bowel diseases (SN-IBD):–Preliminary results

Journal of Crohn s and Colitis ◽

10.1093/ecco-jcc/jjz203.845 ◽

2020 ◽

Vol 14 (Supplement_1) ◽

pp. S578-S578

Author(s):

A Viola ◽

G Fiocco ◽

A Alibrandi ◽

F S Macaluso ◽

M Cappello ◽

...

Keyword(s):

Crohn’S Disease ◽

Crohn's Disease ◽

Clinical Response ◽

Clinical Remission ◽

Demographic Data ◽

Real Life ◽

Primary Study ◽

Clinical Activity ◽

Secondary Failure

Abstract Background Ustekinumab is approved in Europe for the treatment of moderate-to-severe Crohn’s disease (CD) since 2016. Italian real-life data on efficacy and safety are scarce. The aim of this study was to assess effectiveness, safety and usage of Ustekinumab in an Italian cohort of patients. Methods Data of patients with moderate-to-severe CD who started Ustekinumab in Sicily were extracted from the database of the SN-IBD. Demographic data, disease-related data (disease duration, location, clinical activity) and previous therapies with biologics were collected. The primary study endpoints were steroid-free clinical remission and steroid-free clinical response at week 12, 24 and 52 on Ustekinumab therapy. Secondary study endpoints were: treatment persistence at 24 weeks, safety, and biochemical response (reduction of CRP). Results One hundred thirteen patients started Ustekinumab in Sicily. We performed a preliminary analysis only on patients who reached at least 24 weeks of follow-up. Ninety-three patients (M = 53%; mean age 45 ± 14.9 years) were included. At week 24, 38 patients (41%) achieved steroid-free clinical remission, 56 patients (60%) clinical response. From baseline to the end of follow-up there was a significant reduction of steroid use (41% vs. 21%, p = 0.038) and of mean HBI score (6.5 ± 4.4 vs. 4.8 ± 4.1; p < 0.001). No significant CRP changes were recorded during follow-up. Twelve patients (11%) discontinued therapy due to primary failure (3 patients), secondary failure (5 patients), adverse events (3 patients) and 1 patient was lost to follow-up. Kaplan–Meier survival analysis showed a persistence on therapy with Ustekinumab of 89% of patients after 24 weeks (Figure 1). Conclusion Preliminary data from our real-life cohort of treatment-refractory CD patients suggest a satisfactory effectiveness and a good safety profile of Ustekinumab.

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