Progressive Bowel Damage Research Articles

Prevention of Postoperative Recurrence in CD: Tailoring Treatment to Patient Profile.

Crohn's disease (CD) is an immune-mediated condition characterized by the transmural inflammation of the gut tissue, associated with progressive bowel damage often leading to surgical intervention. As operative resection of the damaged segment is not curative, a majority of patients undergoing intestinal resections for complicated CD present disease recurrence within 3 years after the intervention. Postoperative recurrence can be defined as endoscopic, clinical, radiological or surgical. Endoscopic recurrence rates within 1 year exceed 60% and the severity, according to the Rutgeerts' score, is associated with worse prognosis and can predict clinical recurrence (in up to 1/3 of the patients). Most importantly, about 50% of patients will undergo a reoperation after 10 years of their first intestinal resection. Therefore, the prevention of postoperative recurrence in CD remains a challenge in clinical practice and should be properly managed. We aim to summarize the most recent data on the definition, risk factors, assessment and treatment of postoperative CD recurrence.

P117 Can we identify risk factors for the progression of bowel damage in Crohn’s disease using the Lémann index?

P117 Can we identify risk factors for the progression of bowel damage in Crohn’s disease using the Lémann index?

Earlier Anti-Tumor Necrosis Factor Therapy of Crohn’s Disease Correlates with Slower Progression of Bowel Damage

Crohn's disease (CD) follows a relapsing and remitting course incurring cumulative bowel damage over time. The question of whether or not the timing of the initiating biologic therapy affects long-term disease progression remains unanswered. Herein, we calculated rates of change in the Lémann index-which quantifies accumulated bowel damage-as a function of the time between the disease onset and initiation of biologic therapy. We aimed to explore the impact of the earlier introduction of biologics on the rate of progression of long-term cumulative bowel damage. Medical records of CD patients treated during 2009-2014 at The Mount Sinai Hospital were queried. Inclusion criteria were two comprehensive assessments allowing calculation of the index at t1 and t2: two time-points ≥ 1year apart. Patients with biologics introduced before or within 3months at inclusion (t1) were defined as Bio-pre-t1 and those who did not as Bio-post-t1. The rate of disease progression was calculated as the change in the index per year during t1-t2. A total of 88 patients were studied: 58 Bio-pre-t1 and 30 Bio-post-t1. Among the 58 Bio-pre-t1 cases, damage progressed in 29 (50%), regressed in 20 (34.5%), and stabilized in 9 (15.5%). Median time to initiation of biologics among patients whose index improved was nominally shorter compared to that in patients whose index progressed (8 vs. 15years). Earlier introduction of biologics tended to correlate with the slower rate of progression (ρ = 0.241; p = 0.069). Earlier introduction of biologics tended to correlate with the slower progression of bowel damage in CD, reflected by the reduced rate of Lémann index progression.

Su1892 - Factors Associated with Intestinal Resection in Crohn's Disease Patients with Bowel Damage Progression as Assessed by Lemann Index

Su1892 - Factors Associated with Intestinal Resection in Crohn's Disease Patients with Bowel Damage Progression as Assessed by Lemann Index

Su1893 - Patients with Persistently Clinically Silent Crohn's Disease can have Insidious, but Uneventful, Progression of Bowel Damage Due to small Bowel Stricturing as Assessed by Lemann Index

Su1893 - Patients with Persistently Clinically Silent Crohn's Disease can have Insidious, but Uneventful, Progression of Bowel Damage Due to small Bowel Stricturing as Assessed by Lemann Index

Identification of Endpoints for Development of Antifibrosis Drugs for Treatment of Crohn’s Disease

Intestinal fibrosis is a challenge to management of patients with Crohn's disease (CD); there is an urgent need to expedite development of antifibrosis drugs for this disease. The International Organization for the Study of Inflammatory Bowel Disease (IOIBD) aimed to identify a set of endpoints that can be used to determine efficacy of antifibrosis agents tested in clinical trials of patients with CD. We conducted a systematic review to identify clinical, radiologic, biochemical, endoscopic, and composite endpoints used in assessing activity of fibrostenosing CD and response to treatment, and determined their operational properties. A panel of IOIBD experts performed a consensus process to identify the best endpoints for inclusion in clinical trials, through a 2-round, Delphi-style online survey. A total of 36 potentially relevant endpoints for intestinal fibrosis were selected and assessed. Forty-eight physicians with expertise in inflammatory bowel disease, from 5 regions (North America, Europe, Middle East, Asia/Pacific, and Latin America), participated in the Delphi consensus process. A core set of 13 endpoints (complete clinical response, long-term efficacy, sustained clinical benefit, treatment failure, radiological remission, normal quality of life, clinical remission without steroids, therapeutic failure, deep remission, complete absence of occlusive symptoms, symptom-free survival, bowel damage progression, and no disability) were rated as critical. Agreement was high among the experts. Members of the IOIBD reached expert consensus on a set of endpoints that can be used to assess antifibrosis agents in trials of patients with CD. Studies are needed to clarify methods for measuring these outcomes and validate measurement instruments.

P187 Correlation between the Lemann Index and the Inflammatory Bowel Disease-Disability Index in Crohn’s disease

Crohn’s disease (CD) is a chronic progressive destructive disease resulting in cumulative structural bowel damage, which may predict long-term disability. The Lemann Index (LI) has been developed to measure CD-related bowel damage, including surgical resection and The presence of stricturing and penetrating lesions; it could range from 0 to 140. The Inflammatory Bowel Disease-Disability Index (IBD-DI) has recently been validated to assess disability in a patient with IBD; it could range from 0 to 100. The aim of the study was to measure bowel damage by using the LI and disability by using the IBD-DI in a cohort of CD patients and to evaluate the correlation between the two indices. We performed a prospective study in the tertiary referral centre in Lille, from September 2016 to November 2016, including all consecutive CD outpatients. Bowel damage was assessed by the LI calculated according to the published protocol and disability by the IBD-DI questionnaire. Factors associated with LI and IBD-DI levels were identified by a median comparison test or means of bivariate analyses of variance. The correlation between the two indices was determined by a Spearman correlation test. 130 CD patients were consecutively included. The mean of LI was 11.9 ± 14.1 and ranged from 0 to 72.5. The LI significantly increased with disease duration: median value of 0.9 (IQR, 0.3–2.2) for disease duration < 2 years, 1.6 (IQR, 0.3–10.8) for disease duration ≥2 and <10 years and 16.5 (IQR, 9.1–23.4) for disease duration ≥10 years. Anal location and exposition to anti TNF were associated with higher LI levels (p < 0.005). Among patients exposed to anti TNF, the LI was lower in patients who were exposed in the first two years of the disease (p = 0.015). The others factors associated with bowel damage were: previous intestinal resection, clinical and biological disease activity and exposition to immunosuppressants (p < 0.005). The mean of IBD-DI was 28.8 ± 6.3 and ranged from 0 to 71. The factors associated with disability were: female gender, anal location, extradigestive manifestations, clinical and biological disease activity and exposition to anti TNF (p < 0.005). No significant correlation was found between LI and IBD-DI (ρ = 0.12; CI 95% −0.05–0.29; p = 0.15). Only a correlation between the anus LI and the IBD-DI was observed: ρ = 0.20 (CI 95% 0.003 −0.36), (p = 0.02). Bowel damage but not disability increased with disease duration. Importantly, early introduction of anti TNF treatment prevented bowel damage progression. CD anal location was associated with high levels of LI and IBD-DI underlying the necessity to introduce early and intensive treatments in this CD population. No correlation was observed between the LI and the IBD-DI.

Towards new therapeutic paradigms beyond symptom control in the management of inflammatory bowel diseases.

Inflammatory bowel diseases, Crohn's disease and ulcerative colitis are chronic relapsing conditions that may result in progressive bowel damage, high risk of complications, surgery and permanent disability. The conventional therapeutic approach for inflammatory bowel diseases is based mainly on symptom control. Unfortunately, a symptom-based therapeutic approach has little impact on major long-term disease outcomes. In other chronic disabling conditions such as diabetes, hypertension and rheumatoid arthritis, the development of new therapeutic approaches has led to better outcomes. In this context a "treat to target" strategy has been developed. This strategy is based on identification of high-risk patients, regular assessment of disease activity by means of objective measures, adjustment of treatment to reach the pre-defined target. A treat to target approach has recently been proposed for inflammatory bowel disease with the aim at modifying the natural history of the disease. In this review, the evidence and the limitations of the treat to target paradigm in inflammatory bowel disease are analyzed and discussed.

Mo1800 - Persistent Symptoms, CRP Elevation and Treatment Changes Over Time in Crohn's Disease Patients are Associated with Bowel Damage Progression as Expressed by Deterioration of Lemann Index Score

Mo1800 - Persistent Symptoms, CRP Elevation and Treatment Changes Over Time in Crohn's Disease Patients are Associated with Bowel Damage Progression as Expressed by Deterioration of Lemann Index Score

Structural bowel damage in quiescent Crohn’s disease

BackgroundCrohn’s disease is associated with accumulation of progressive structural bowel damage (SBD) leading to the development of stenotic and penetrating complications. The data pertaining to the course of progression of SBD is scarce. The Lemann index (LI) is a novel tool for evaluation of SBD that incorporates pan-enteric clinical, endoscopic and imaging data. AimsTo evaluate the progression of SBD in quiescent CD patients. MethodsPatients with known quiescent small bowel Crohn’s disease (CD) for at least 3 months (CDAI<220) were prospectively recruited and underwent repeated magnetic resonance enterographies (MRE) and video capsule endoscopies (VCE). Patients were assessed for SBD on initial and follow-up evaluation using relevant clinicopathological data, MRE and VCE results. Significant structural bowel damage (SBD) was identified as LI>4.8, and progression of SBD as LI>0.3. ResultsSixty one patients were enrolled in the study. Significant SBD was detected 13 (21.4%) on enrollment. Duration of disease (p=0.036) and history of CD-related surgery (p=0.0001) were associated with significant BD. Forty one patients underwent a follow-up MRE (14.8±2.5 months apart). LI was similar at baseline and follow-up. There was a negligible change in LI between the evaluations. ConclusionsIn patients with quiescent Crohn’s disease, structural bowel damage was stable over a median of 14 months follow-up.

P296 Persistent symptoms, CRP elevation and treatment changes over time in Crohn's disease patients are associated with bowel damage progression as expressed by deterioration of Lemann Index score

P296 Persistent symptoms, CRP elevation and treatment changes over time in Crohn's disease patients are associated with bowel damage progression as expressed by deterioration of Lemann Index score

The impact of co-existing immune-mediated diseases on phenotype and outcomes in inflammatory bowel diseases.

Inflammatory bowel diseases lead to progressive bowel damage and need for surgery. While the increase in prevalence of other immune-mediated diseases in IBD is well recognised, the impact of this on the natural history of IBD is unknown. To determine the impact of concomitant immune-mediated diseases on phenotypes and outcomes in IBD. Patients with IBD enrolled in a prospective registry were queried about the presence of other immune-mediated diseases, defined as those where immune dysregulation plays a role in pathogenesis. Demographics and disease-related information were obtained. Subjects also completed measures of quality of life. Multivariable regression models compared disease phenotype and outcomes of IBD patients with and without other immune-mediated diseases. The cohort included 2145 IBD patients among whom 458 (21%) had another immune-mediated disease. There was no difference in CD phenotype between the two groups. UC patients were more likely to have pancolitis in the presence of another immune-mediated disease (62%) compared to those without (52%, P=0.02). IBD patients with another immune-mediated disease had higher rates of needing anti-TNF biologics [Odds ratio (OR) 1.31, 95% CI 1.05-1.63] and surgery (OR 1.26, 95% CI 0.99-1.61). The presence of another immune-mediated disease was also associated with lower disease-specific and general physical quality of life. The presence of another immune-mediated disease in IBD patients was associated with higher likelihood of pancolonic involvement in UC, and a modest increase in need for IBD-related surgery and anti-TNF biological therapy. Such patients also experienced worse quality of life.

Anti-TNF therapy is able to stabilize bowel damage progression in patients with Crohn’s disease. A study performed using the Lémann Index

AimsThe Lémann Index (LI) was developed to assess the cumulative structural damage of the intestinal tract in patients with Crohn’s Disease (CD) independently of clinical and biochemical activity. Recently, the goal of CD focused on obtaining mucosal healing and deep remission rather than simple symptom control. These new therapeutic aims emphasize the need to prevent progression of bowel damage. In this study we aimed to evaluate the influence of different treatments on structural damage progression, assessed by means of LI in a series of CD patients consistently treated with various drugs. MethodsThe LI was calculated at inclusion and at the end of follow-up in 104 CD patients subdivided according to treatments received: biological drugs (n=40, 38.4%), azathioprine (n=19, 18.3%), and mesalazine (n=45, 43.3%). ResultsThe median follow-up was 29 months, with no difference among groups. During follow-up, the median LI was stable in the biological group [from 6.3 (range, 0.6–37.3) to 6.4 (range, 0.6–37.6), P=0.543], whereas it significantly increased from 4.1 (range, 0.6–30) to 8.3 (range, 0.6–31.8) in the azathioprine group (P=0.0006), and from 2.4 (range, 0.6–25.8) to 4.1 (range, 0.6–28.8) in the mesalazine group (P<0.0001). Also during follow-up the LI increased significantly (P=0.004) in the azathioprine (68.4%) and mesalazine (60.0%) groups as compared with the biological therapy group (30.0%). ConclusionsIn CD patients the LI tends to increase over time, although the use of biological drugs rather than azathioprine or mesalazine seems to be able to reduce the progressive bowel damage.

Looking Beyond Mucosal Healing: Effect of Biologic Therapy on Transmural Healing in Pediatric Crohn's Disease.

Crohn's disease is a chronic inflammatory disease characterized by a progressive transmural bowel damage leading to complications. Anti-TNFα therapy is effective in achieving mucosal healing (MH), but its efficacy on transmural inflammation has been poorly investigated. The aim of this study is to evaluate, in pediatric Crohn's disease, the efficacy of anti-tumor necrosis factor α agents in inducing transmural healing (TH) as assessed by ultrasonography (US). Children with Crohn's disease requiring anti-tumor necrosis factor α therapy were prospectively enrolled. Clinical activity, laboratory tests, endoscopic activity, and transmural disease assessed by small intestine contrast US (SICUS) were evaluated at baseline (T0) and then after 9 to 12 months of therapy (T1). We evaluated US quantitative and qualitative parameters: disease extension (centimeters), bowel wall (BW) thickness >3 mm, BW vascularity and stratification strictures, and prestenotic dilatation. TH was defined as a BW thickness <3 mm and normalization of all US parameters at T1. Thirty-two patients were included. Patients with mucosal healing (MH) showed a significant decrease of BW thickness and disease extension at T1 (4.3 ± 1.4 mm and 8 ± 6.3 cm versus 6.1 ± 2.3 mm and 13 ± 5 cm at baseline, respectively) (P < 0.001). Increased vascularity of the BW was found in 80% of patients at T0 and in 18% at T1 (P < 0.001). These parameters did not change in patients without MH, despite clinical and laboratory remission. The presence of stenosis and prestenotic dilatation did not modify in any group. A complete TH was achieved in 14% of patients, all of them showing complete MH. Biologics induce clinical and laboratory remission and MH in pediatric CD. Although caution is needed due to the small sample size, our data suggest that transmural inflammation also improves during therapy, but a complete TH is achieved only in a small percentage of patients.

Peripheral Blood Eosinophilia as a Potential Marker of Bowel Damage Progression in Crohnʼs Disease a 5 Year Natural History Study

Peripheral Blood Eosinophilia as a Potential Marker of Bowel Damage Progression in Crohnʼs Disease a 5 Year Natural History Study

Sa1954 Sickest of the Sick: When Anti-TNF Agents Fail to Halt Progression of Bowel Damage in Crohn's Disease Over Time

Sa1954 Sickest of the Sick: When Anti-TNF Agents Fail to Halt Progression of Bowel Damage in Crohn's Disease Over Time

Risk of postoperative recurrence and postoperative management of Crohn's disease.

Crohn's disease (CD) is a chronic inflammatory disease of the digestive tract with systemic manifestations. Etiology is unknown, even if immunological, genetic and environmental factors are involved. The majority of CD patients require surgery during their lifetime due to progressive bowel damage, but, even when all macroscopic lesions have been removed by surgery, the disease recurs in most cases. Postoperative management represents therefore a crucial mean for preventing recurrence. Several drugs and approaches have been proposed to achieve this aim. Endoscopic inspection of the ileocolic anastomosis within 1 year from surgery is widely encouraged, given that endoscopic recurrence is one of the greatest predictors for clinical recurrence. A strategy should be planned only after stratifying patients according to their individual risk of recurrence, avoiding unnecessary therapies when possible benefits are reduced, and selecting high-risk patients for more aggressive intervention.

Delineation of Crohn's Disease Trajectories Using Change in Lémann Index: A Natural History Study.

Crohn's disease (CD) causes lifelong, progressive bowel damage, which may be quantified using the Lémann Index (LI). We aimed to analyze patterns of LI and its association with 5-year clinical course, in an independent cohort of CD patients. CD patients with 5-year follow-up from a registry maintained at a tertiary center were included. LI was calculated using a computerized metric from the first (LI1) and last (LI2) clinical encounters during the 5 years. Groups were created based on change in score (LI2-LI1) or the delta Lémann Index (DLI) as showing improvement, no change, or deterioration and used for association analysis with patterns of health care utilization, disease activity, and quality-of-life scores. A total of 363 CD patients with 5-year follow-up formed the study population [median age 43 y (interquartile range (IQR), 33.3 to 55 y); 57% female; median disease duration 12 y (IQR, 3 to 19 y), overall surgical exposure 69.7%]. Median (IQR) LI1, LI2, and DLI were 8 (0 to 54), 9 (0 to 75), and 0 (-22 to -47), respectively. Patients were stratified based on DLI into 3 groups: A: DLI<0; B: DLI=0; and C: DLI>0; which comprised 16.5%, 35.3%, and 48.2% of the cohort, respectively. Patients in group C had significantly higher CD-related surgical exposure, health care utilization, and annual use of steroids and biological agents. DLI showed independent significant positive correlation with perianal disease (P=0.044), steroid use (P=0.007), clinical visits (P<0.001), and new surgeries (P=0.001). Change in LI over time could function as a marker of disease trajectory for risk substratification and prognostication in CD.

1024 Faecal Calprotectin Measured by IBD Patients at Home - A New Clinical Tool

significantly younger, had shorter disease duration and underwent a greater number of CD related surgeries during the study period (Table 1). For the entire study cohort, LS1 ranged from 0-54 (mean 8.76±6), LS2 ranged from 0-46 (mean 9.98±8) and DLS ranged from -17 to 32 (mean 1.17±0). Based on DLS, five trajectories were created (A: DLS 5.36). Patients with silent CD had a significantly higher DLS compared to asymptomatic CD patients with no objective evidence of inflammation. A greater proportion of silent CD patients fell under trajectory D and E that signified progression of damage (Figure 1). CONCLUSION: CD patients, with silent disease (good quality of life but elevated CRP), demonstrate a higher likelihood of progression of bowel damage over 5y compared to asymptomatic CD patients with no objective evidence of inflammation. This may be attributed to the underestimation and more conservative treatment approach of this entity. Patients with silent CD may benefit from further evaluation, closer monitoring and possible aggressive management. Table 1: Baseline characteristics and Lemann scores for the study population

Evaluating Disability in Inflammatory Bowel Diseases: A Step Forward for Improved Care

Inflammatory bowel diseases (IBD), which include Crohn’s disease (CD) and ulcerative colitis (UC), are chronic lifelong diseases that evolve in a relapsing and remitting mode, causing progressive bowel damage over time. Most epidemiological studies show that there is a significant increase in IBD’s incidence in most regions of the world.1 Being a chronic life-long disease with a young age at onset, IBD’s prevalence will likely continue to increase in the following decades. The impact of IBD in patients and society is of extreme importance, considering that it is mainly diagnosed in young age, affecting people in their most productive years, interfering in their social, familial and personal interactions, capacity to acquire education, employment prospects and work ability.2 The clinical and therapeutic approach to IBD has been classically focused in clinical and endoscopic scores of gut inflammation, and the impact of disease in the interaction between the individual and his/her environment (disability) has been neglected as compared to other chronic diseases. Furthermore, the term disability in IBD has been used in a variable way, either to describe disease features associated with a worse prognosis (as in the seminal paper by Beaugerie et al.3), or to describe specific aspect of disability (such as work disability), creating therefore some confusion around what disability really refers to. Disability is an objective way of measuring the impairments, activity limitations, and participation restrictions that are experienced in