scholarly journals OP17 Impact of phenotypic and genetic factors on Crohn’s Disease evolution in a cohort of 13,926 patients

2021 ◽  
Vol 15 (Supplement_1) ◽  
pp. S016-S017
Author(s):  
Q Zhang ◽  
L Fachal ◽  
R Shawky ◽  
M Parkes ◽  
C Anderson ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Disease Progression ◽  
Management Strategies ◽  
Standards Of Care ◽  
Disease Evolution ◽  
The Impact ◽  
Disease Location ◽  
Over Time

Abstract Background Patients with Crohn’s disease (CD) can develop complications including stricturing and penetrating disease [1, 2]. Although reliable baseline predictors of disease progression are urgently needed to inform management strategies, few studies have comprehensively explored the phenotypic and genetic determinants of disease progression in a sufficiently powered cohort. Methods We used data from 13,926 patients with CD in the UK IBD BioResource to investigate the effects of clinical phenotypes and genetics on CD progression. Median follow-up was 10.6 years and total follow-up was 193,033 patient-years. We applied the Montreal classification system to define disease as B1 (inflammatory), B2 (stricturing) and B3 (penetrating). Patients with B2 or B3 disease (N = 5,185) were compared to patients with B1 disease (N = 8,471) in a multivariate model fitted with both phenotype data and a polygenic score that we developed. Associations with q-values (false discovery rate adjusted p-values) less than 0.05 were defined as statistically significant. Results CD progression occurred over time from diagnosis (Figure 1). Consistent with previous findings, we confirmed factors including smoking, disease location and perianal disease were associated with disease progression [3] (Table 1). The impact of a genetic influence on disease progression was confirmed and shown to be independent of genetic effects on disease location [4]. Early prescription of medications showed a protective effect on disease progression: Infliximab, adalimumab and thiopurines significantly reduced the chance of B2/B3 progression when prescribed within two years of diagnosis. Additionally, we observed a decreased progression to B2/B3 disease in patients diagnosed recently (between 2012–2020) compared to those diagnosed before 2012. This finding persisted after conditioning on exposure to biologics and correcting for follow-up time and interval to first thiopurine prescription, and thus may be indicative of other improvements in standards of care in recent years. Conclusion Using a large, well-characterised cohort we confirm the importance of disease location, smoking status and genetics on disease progression. We highlight the positive impact of early medication prescription on disease progression and discover an independent signal relating to potential improvements in the standard of care in CD over time. These results create the framework for reliable predictors of CD progression that may better guide future CD management strategies. References

scholarly journals P240 CDEIS score of 2 is optimal cut-off associated with lower risk of disease progression in early Crohn’s disease: Data from the CALM study

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S264-S266
Author(s):  
R Ungaro ◽  
R Jordan ◽  
C Yzet ◽  
P Bossuyt ◽  
F Baert ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Disease Progression ◽  
Lower Risk ◽  
Perianal Fistula ◽  
Youden Index ◽  
History Of ◽  
Risk Of Disease ◽  
Over Time

Abstract Background The optimal endoscopic target in early Crohn’s disease (CD) that limits long-term disease complications is unknown. Methods We analysed medical records from patients who had follow-up data since the end of CALM. Patients with Crohn’s disease endoscopic index of severity (CDEIS) scores at the end of CALM were included. The primary outcome was a composite of major adverse outcomes reflecting CD progression: new internal fistula/abscess, stricture, perianal fistula/abscess, CD hospitalisation, or CD surgery since the end of CALM. We compared median CDEIS and per cent improvement from baseline CDEIS. Youden index analysis was used to identify optimal CDEIS cut-off score associated with CD progression. Kaplan–Meier and Cox regression methods were used to compare rates of progression by different CDEIS targets. Multivariable models were adjusted for age, prior surgery, and stricturing behaviour. Results 110 patients with median age 28 (IQR 22–38) years, disease duration 0.2 (0.1–0.5) years, and median follow up of 3.1 (1.9–4.4) years were included. Eleven per cent had a history of stricture, 5.5% history of surgery, and 52% were originally in the tight control arm of the CALM study. Median CDEIS score at end of CALM was 3 (0–5.4) and 32 (29%) patients had disease progression. Baseline median CDEIS score was similar between those with and without progression [10.9 (7.5–15.5) vs. 11.9 (8–17.5)]. Median CDEIS score at the end of CALM was higher among those with progression [1.3 (0–5.1) vs. 4.9 (3–9.1), p < 0.001)]. Patients within higher quartiles of CDEIS score had higher rates of progression over time (Figure 1). Patients without disease progression had a greater median decrease in CDEIS score from baseline to end of CALM [90% (60–100%) vs. 50% (30–80%), p < 0.001]. The optimal CDEIS score cut-off was 2 with sensitivity 84%, specificity 60% and NPV 90% for progression. Patients with CDEIS ≤ 2 had less progression over time compared with patients with > 50% improvement from baseline CDEIS (not reaching CDEIS ≤ 2) and those not meeting either endpoint (Figure 2). On adjusted analysis, CDEIS score ≤ 2 was associated with a decreased risk of progression (aHR 0.23, 95% CI 0.09–0.56). Conclusion In early CD, a CDEIS score ≤ 2 is optimal cut-off associated with a lower risk of disease progression.

Mortality in adult-onset and elderly-onset IBD: a nationwide register-based cohort study 1964–2014

Gut ◽  
2019 ◽  
Vol 69 (3) ◽  
pp. 453-461 ◽  
Author(s):  
Ola Olén ◽  
Johan Askling ◽  
Michael C Sachs ◽  
Martin Neovius ◽  
Karin E Smedby ◽  
...  
Keyword(s):  
Cohort Study ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Adult Onset ◽  
Risk Of Death ◽  
Increased Risk ◽  
Elderly Onset ◽  
Incident Cases ◽  
Over Time

ObjectivesTo examine all-cause and cause-specific mortality in adult-onset and elderly-onset IBD and to describe time trends in mortality over the past 50 years.DesignSwedish nationwide register-based cohort study 1964–2014, comparing mortality in 82 718 incident IBD cases (inpatient and non-primary outpatient care) with 10 times as many matched general population reference individuals (n=801 180) using multivariable Cox regression to estimate HRs. Among patients with IBD, the number of participants with elderly-onset (≥60 years) IBD was 17 873.ResultsDuring 984 330 person-years of follow-up, 15 698/82 718 (19%) of all patients with IBD died (15.9/1000 person-years) compared with 121 095/801 180 (15.1%) of reference individuals, corresponding to an HR of 1.5 for IBD (95% CI=1.5 to 1.5 (HR=1.5; 95% CI=1.5 to 1.5 in elderly-onset IBD)) or one extra death each year per 263 patients. Mortality was increased specifically for UC (HR=1.4; 95% CI=1.4 to 1.5), Crohn’s disease (HR=1.6; 95% CI=1.6 to 1.7) and IBD-unclasssified (HR=1.6; 95% CI=1.5 to 1.8). IBD was linked to increased rates of multiple causes of death, including cardiovascular disease (HR=1.3; 1.3 to 1.3), malignancy (HR=1.4; 1.4 to 1.5) and digestive disease (HR=5.2; 95% CI=4.9 to 5.5). Relative mortality during the first 5 years of follow-up decreased significantly over time. Incident cases of 2002–2014 had 2.3 years shorter mean estimated life span than matched comparators.ConclusionsAdult-onset and elderly-onset patients with UC, Crohn’s disease and IBD-unclassified were all at increased risk of death. The increased mortality remained also after the introduction of biological therapies but has decreased over time.

scholarly journals DOP11 Normalisation of faecal calprotectin within 12 months of diagnosis is associated with a reduced risk of disease progression in Crohn’s disease

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S048-S049
Author(s):  
N Plevris ◽  
J Fulforth ◽  
P Jenkinson ◽  
M Lyons ◽  
C Chuah ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Disease Progression ◽  
Perianal Disease ◽  
Faecal Calprotectin ◽  
Decision Algorithm ◽  
Risk Of Disease ◽  
Incident Cases ◽  
Reduced Risk

Abstract Background Faecal calprotectin (FC) demonstrates an excellent correlation with endoscopic inflammation. In addition, a treatment-decision algorithm for Crohn’s disease (CD) incorporating FC outperforms and improves 12-month mucosal healing compared with a strategy based on symptoms alone. The aim of this study was to determine whether normalisation of FC (<250 μg/g) within 12-months of diagnosis is associated with a reduction in disease progression in CD. Methods This was a retrospective cohort study performed at a tertiary IBD centre. All incident cases of CD diagnosed between 2005 and 2017 were identified. Patients with an FC measurement of >250 μg/g at diagnosis who also had at least 1 follow-up FC measured within the first 12-months of diagnosis and >12 months of follow-up were included. The primary endpoint was a composite of progression in Montreal disease behaviour (B1 to B2/3 or B2 to B3 or new perianal disease), surgery or hospitalisation. Results A total of 375 patients were included with a median follow-up of 5.3 years (IQR 3.1–7.4). Normalisation of FC (<250 μg/g) within 12 months of diagnosis was confirmed in 43.5% (n = 163/375) of the cohort. On multivariable Cox-proportional hazards regression analysis, individuals who normalised their FC within 12 months of diagnosis had a significantly lower risk of composite disease progression (HR 0.351, 95% CI 0.235–0.523, p < 0.001) (Figure 1). Cumulative rates of composite disease progression were 7.8%, 21.4% and 29.9% in those that normalised their FC vs. 22.8%, 50.7% and 60.5% in those that did not at 2, 5 and 7 years after diagnosis, respectively. In addition, normalisation of FC was the only predictor that remained significant for all the separate progression end-points (progression in Montreal behaviour / new perianal disease: HR 0.250, 95% CI 0.122–0.512, p < 0.001; hospitalisation: HR 0.346, 95% CI 0.217–0.553, p < 0.001; surgery: HR 0.370. 95% CI 0.181–0.755, p = 0.006). The strongest predictor of whether an individual normalised their FC within 12 months was the commencement of a biologic within 3 months of diagnosis (OR 4.288, 95% CI 1.585–11.0601, p = 0.004). Conclusion Normalisation of FC by 12-months of diagnosis is associated with a reduced risk of disease progression in CD. Our data provide strong support for implementation of treat-to-target strategies earlier than previously tested in Crohn’s disease. The immediate implication for healthcare providers and patients is that by ensuring resolution of mucosal inflammation - measured by proxy with faecal calprotectin, and regardless of other variables - within 1 year of diagnosis has a dramatic effect on disease course.

scholarly journals P115 Real-world experience of peri-operative treatments on surgical complications after Ileo-caecal resection in Crohn’s disease

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S193-S194
Author(s):  
S Di Stefano ◽  
C Liefferinckx ◽  
A Cremer ◽  
L Amininejad ◽  
A Van Gossum ◽  
...  
Keyword(s):  
Risk Factors ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Anastomotic Leakage ◽  
Surgical Complications ◽  
Protective Role ◽  
Infectious Complications ◽  
Surgical Recurrence ◽  
The Impact

Abstract Background The current recommendations remain vague as to whether biologics are safe or deleterious when surgery is contemplated in patients with Crohn’s disease (CD). Conflicting data do not enable to adopt a definitive position on the time to surgery. The aims of this study were to evaluate the impact of perioperative treatments on the rate of surgical complications and to report surgical recurrence rate of CD after ileo-caecal (IC) resection. Methods This was a retrospective monocentric cohort study of consecutive CD patients who underwent IC resection between 1996 and 2018. An ethical committee has been approved (P2019/376). The overall rate of surgical complications was evaluated within 30 days after surgery. The effect of pre- and postoperative treatments was assessed on overall morbidity, general and infectious complications, anastomotic leakage and risk factors. Statistical analyses were performed using SPSS. Results Demographic data of the 165 CD patients who underwent a primary IC resection are presented in Table 1. The median age at time of the first IC resection was 35 years (IQR 24–44) while the median follow-up was 6.1 years (IQR 1–11). The overall rate of complications was 18% including 8.7% and 3.3% patients with infectious complications and anastomotic leakage, respectively. No risk factors have been found to be associated with surgical complications. In particular, immunosuppressants and biologics did not increase the risk of surgical complications. Twenty-four per cent of patients (n = 39/160) needed a second IC resection due to stenosis at the anastomosis site in 69.2% of cases (n = 27/39). Surgical recurrence was found to increase linearly over time with a second surgery after a median follow-up of 8 years (IQR 2–12). Anti-TNF used as post-operative treatment had a protective role on surgical recurrence in multivariable regression with odd ration (OR) of 0.15, p = 0.001 (Table 2). Conclusion Prevalence of complications after an IC resection in CD patients was of 18% in this retrospective monocentric cohort. No risk factors were found to be associated with surgical complications. Anti-TNF seems to have a protective role on surgical recurrence.

scholarly journals P618 Treatment outcomes of patients with Crohn’s disease and complex perianal fistula in five European countries: the PREFACE retrospective study

2021 ◽  
Vol 15 (Supplement_1) ◽  
pp. S560-S560
Author(s):  
M Ferrante ◽  
L Siproudhis ◽  
G Poggioli ◽  
M Reinshagen ◽  
S Milicevic ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Treatment Outcomes ◽  
Index Date ◽  
Perianal Fistula ◽  
European Countries ◽  
Standards Of Care ◽  
Patient Level ◽  
Remission Rates

Abstract Background Presence of fistulas in Crohn’s disease (CD) is an indicator of poor prognosis; 20% of CD patients suffer from perianal fistula. There are few studies specifically designed to assess treatment outcomes in complex perianal fistula (CPF) in CD. This retrospective chart review study describes the outcomes of patients with CPF in CD in five European countries after medical and/or surgical treatment. Methods Adult patients with CD receiving treatment for a new episode of CPF during the eligibility period (September 2011 to September 2014), in Belgium, France, Germany, Italy and Spain, were included. Index date was defined as date of any medical or surgical CPF treatment initiation. Data was collected from CD diagnosis to at least 3 years after index date (except for deceased or lost to follow-up patients) to describe patient characteristics and treatments used for all CPF episodes since CD diagnosis. Effectiveness outcomes were measured as remission rates based on Fistula Drainage Assessment (FDA) recorded in medical charts for fistula reported at index date (index fistula). Remission rates are expressed as percentage rates on patient level after 6- and 12-months follow-up period. For calculation of treatment outcomes, the most recent FDA prior to the respective timepoint was used. Results A total of 372 patients (51% male) with a mean (SD) age of 38 (13) were included by 31 sites. Median time since CD diagnosis was 7 years, and median length of follow-up was 6 years. A total of 498 CPFs were presented at index date and during FU period. Out of the 498 CPFs, 94% were treated with at least one surgical intervention (most frequent: 61% long-term seton placement, 51% surgical drainage) and 82% with at least one medical treatment (most frequent: 40% anti-TNFs, 33% antibiotics, 16% immunosuppressants). After 6 months the remission rate at patient level for index fistula was 28% and after 12 months 35%. Conclusion Current standards of care achieved remission in one third of patients with CPF in CD over a period of one year. Improved therapeutic strategies and new treatment options are required to improve outcomes in this manifestation of CD.

Predicting and explaining inflammation in Crohn’s disease patients using predictive analytics methods and electronic medical record data

2018 ◽  
Vol 25 (4) ◽  
pp. 1201-1218 ◽  
Author(s):  
Bhargava K Reddy ◽  
Dursun Delen ◽  
Rupesh K Agrawal
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Prediction Models ◽  
Predictive Analytics ◽  
Area Under The Curve ◽  
Gradient Boosting ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
The Impact ◽  
Disease Location

Crohn’s disease is among the chronic inflammatory bowel diseases that impact the gastrointestinal tract. Understanding and predicting the severity of inflammation in real-time settings is critical to disease management. Extant literature has primarily focused on studies that are conducted in clinical trial settings to investigate the impact of a drug treatment on the remission status of the disease. This research proposes an analytics methodology where three different types of prediction models are developed to predict and to explain the severity of inflammation in patients diagnosed with Crohn’s disease. The results show that machine-learning-based analytic methods such as gradient boosting machines can predict the inflammation severity with a very high accuracy (area under the curve = 92.82%), followed by regularized regression and logistic regression. According to the findings, a combination of baseline laboratory parameters, patient demographic characteristics, and disease location are among the strongest predictors of inflammation severity in Crohn’s disease patients.

scholarly journals Efficacy of early intervention on the bowel damage and intestinal surgery of Crohn’s disease, based on the Lémann index

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Mingming Zhu ◽  
Qi Feng ◽  
Xitao Xu ◽  
Yuqi Qiao ◽  
Zhe Cui ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Early Intervention ◽  
Crohn's Disease ◽  
Bowel Resection ◽  
Intestinal Resection ◽  
Intestinal Surgery ◽  
History Of ◽  
Disease Behavior ◽  
The Impact

Abstract Background Clinicians aim to prevent progression of Crohn’s disease (CD); however, many patients require surgical resection because of cumulative bowel damage. The aim of this study was to evaluate the impact of early intervention on bowel damage in patients with CD using the Lémann Index and to identify bowel resection predictors. Methods We analyzed consecutive patients with CD retrospectively. The Lémann Index was determined at the point of inclusion and at follow-up termination. The Paris definition was used to subdivide patients into early and late CD groups. Results We included 154 patients, comprising 70 with early CD and 84 with late CD. After follow-up for 17.0 months, more patients experienced a decrease in the Lémann Index (61.4% vs. 42.9%), and fewer patients showed an increase in the Lémann Index (20% vs. 35.7%) in the early compared with the late CD group. Infliximab and other therapies reversed bowel damage to a greater extent in early CD patients than in late CD patients. Twenty-two patients underwent intestinal surgery, involving 5 patients in the early CD group and 17 patients in the late CD group. Three independent predictors of bowel resection were identified: baseline Lémann index ≥ 8.99, disease behavior B1, and history of intestinal surgery. Conclusions Early intervention within 18 months after CD diagnosis could reverse bowel damage and decrease short-term intestinal resection. Patients with CD with a history of intestinal surgery, and/or a Lémann index > 8.99 should be treated aggressively and monitored carefully to prevent progressive bowel damage.

scholarly journals P257 Prognostic value of bowel ultrasonography for the management of Crohn’s disease

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S278-S279
Author(s):  
C J Suarez Ferrer ◽  
J Poza Cordon ◽  
O Crivillen Anguita ◽  
E Martin Arranz ◽  
J L Rueda Garcia ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Statistical Significance ◽  
Disease Free Survival ◽  
Inflammatory Activity ◽  
Treat To Target ◽  
Clinical Relapse ◽  
Disease Evolution ◽  
Bowel Ultrasound

Abstract Background The ‘treat to target’ strategy for managing patients with Crohn’s disease (CD) requires simple, reliable and non-invasive monitoring tools. Bowel ultrasound is an emerging technology that could be useful in this field. The aim of our study is to determine whether bowel ultrasound is a useful tool to assess activity in CD and if its results correlate with long-term evolution of the disease. Methods Patients who had a bowel ultrasound for clinical practice between February 2013 and October 2018 in our centre were retrospectively included. Evolution of patients was assessed at follow-up based on the presence of echographic signs of activity and therapeutic changes solely based on echographic features. Results 277 CD patients were included, of which 51% (142 patients) are women with a mean age at diagnosis of CD 35.3 years old (18.7 SD). The median follow-up time was 24 months (range 5–73 months). Among patients included, echographic signs of inflammatory activity were identified in 166 patients (60%). Out of these, 116 patients (70%) received treatment step-up based on the results of ultrasound. It was observed that out of the 161 patients (58%) in which of the attending physician did not modify treatment after performing ultrasound, only 43 had activity on ultrasound (26.7%). Also among patients whose treatment was scaled, 100% had echographic activity. These differences reached statistical significance (p < 0.0001). Among patients with echographic activity, disease evolution was worse than in those without activity, presenting less time to the next disease flare. Thus median disease-free survival (without flares) after performing ultrasound was 18 months when ultrasonographic activity identified (although in most patients (70%) treatment was scaled) vs. 47 months in patients without ultrasound activity, with statistically significant differences (p < 0.0001). Conclusion Intestinal ultrasound is a technique capable of detecting inflammatory activity in patients with Crohn’s disease and the presence of ultrasound activity is a risk factor for a subsequent activity flare and/or clinical relapse.

scholarly journals Medical therapies for postoperative Crohn’s disease

2021 ◽  
Vol 14 ◽  
pp. 175628482199358
Author(s):  
Ravi S. Shah ◽  
Benjamin H. Click
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Management Strategies ◽  
Recurrence Risk ◽  
Postoperative Recurrence ◽  
Postoperative Management ◽  
Recurrence Rates ◽  
Endoscopic Recurrence ◽  
Surgical Recurrence

Postoperative recurrence of Crohn’s disease is common and requires a multidisciplinary approach between surgeons and gastroenterologists in the perioperative and postoperative period to improve outcomes in this patient population. Endoscopic recurrence precedes clinical and surgical recurrence and endoscopic monitoring is crucial to guide postoperative management. Risk stratification of patients is recommended to guide early prophylactic management, and follow-up endoscopic monitoring can guide intensification of therapy. This review summarizes evidence behind postoperative recurrence rates, disease monitoring techniques, nonbiologic and biologic therapies available to prevent and treat postoperative recurrence, risk factors associated with recurrence, and postoperative management strategies guided by endoscopic monitoring.

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