Introduction

Resection rates for patients with Crohn's disease (CD) have decreased over the past decades. Despite this trend, studies indicate that the rates of re-resections remain close to 30% over a 20-year period (1). There are still several unresolved questions related to risk factors, disease progression, treatment response and monitoring.

Aims & Methods

We aimed to investigate the association of clinical risk factors, disease course related to intestinal resection and risk of re-resection. Using surgical procedure and diagnosis codes within the electronic health record system and the Danish National Patient Register, we established a population-based cohort with all CD patients who underwent a primary intestinal resection between 2010 and 2020 in a region of Denmark with a background population of 2.730.000 (46% of the Danish population). Individual patient data with clinical characteristics, disease course, medical treatments, type of surgical procedures and complications as well as imaging and endoscopies were collected in a REDcap database. To characterize the cohort, we used nonparametric statistics including median, interquartile range (IQR), and percentages.

Results

A total of 939 patients had a resection performed within the study period of which 633 received a primary resection with a follow-up of 118 months (IQR: 69-170). Of those, 617 (97,5%) had a full dataset available for analysis (Table 1). Median age at diagnosis was 28 years (IQR: 21-44), and 222 (36%) were smokers. Distribution of disease location at diagnosis were L1 ileal 271 (44%), L2 colonic 70 (11%), L3 ileocolonic 264 (43%), L4 upper GI 10 (2%), with disease phenotype B1 non-stricturing/penetrating 172 (28%), B2 stricturing 317 (51%), B3 penetrating 79 (13%), and perianal 23 (4%). A total of 317 (51%) received corticosteroids within the first year of diagnosis. Prior to the first resection 329 (53%) patients received immunomodulators and 300 (49%) biologics. Postoperative readmission-rate within 30 days was 19% across the cohort. A total of 2019 colonoscopies (SES-CD and Rutgeerts score) and 3217 imaging examinations were registered. Median number of months from first to second, second to third, and third to fourth resection were 12 (IQR: 6-41), 22 (IQR: 7-49), and 28 (IQR 7.5-53.5) respectively.

Table 1. Basic characteristics for primary and re-resections including medical and surgical specifications.

Conclusion

The initial analysis of this population-based cohort demonstrates that despite high biological therapy exposure before first resection and onwards, one fourth of patients will need additional resections within ten years. Despite their young age, patients undergoing intestinal resections have a high risk of complications, with one in five needing readmissions within 30 days. We are currently analyzing the role of prophylactic vs. on-demand biologics, post-surgery imaging results, and other factors for risk of flare/resection and risk-factors of post-surgery morbidity in this cohort.

References

1.Tsai L, Ma C, Dulai PS, Prokop LJ, Eisenstein S, Ramamoorthy SL, et al. Contemporary Risk of Surgery in Patients With Ulcerative Colitis and Crohn's Disease: A Meta-Analysis of Population-Based Cohorts. Clin Gastroenterol Hepatol. 2020.

Disclosure

AP: reports research grants and personal fees from Janssen, Takeda, and MSD, personal fees from Bristol Myers Squibb. National coordinator of studies from AbbVie, Boehringer Ingelheim and Bristol Myers Squibb. None of these pertain to the research submitted here.
JR: None
EHH: None
RN: None
HSRJ: None
DC: None
VAL: None
ES: None
NA: None
KAV: None
FRP: None
PDO: None
KAF: None
CFB: None
LTS: None
IG: reports research grants from Pharmacosmos, Intuitive Surgical, and personal fees for congress attendance and presentations from Pharmacosmos, Intuitive Surgical, Johnson and Johnson. None of these pertain to the research submitted here.
PMK: None
JB: reports grants and personal fees from AbbVie, grants and personal fees from Janssen-Cilag, personal fees from Celgene, grants and personal fees from MSD, personal fees from Pfizer, grants and personal fees from Takeda, grants and personal fees from Tillots Pharma, personal fees from Samsung Bioepis, grants, and personal fees from Bristol Myers Squibb, grants from Novo Nordisk, personal fees from Pharmacosmos, personal fees from Ferring, personal fees from Galapagos, outside the submitted work.
JS: has received research grants from Takeda, Janssen, the Danish Research Council, and the Capital Region Denmark, and is national coordinator of studies from AbbVie, Arena Pharmaceuticals, Ely Lilly, and Boehringer Ingelheim. None of these pertain to the research submitted here.

Introduction

CD is a chronic progressive disease associated with bowel damage and disability and with a globally increasing prevalence. Contemporary reports on the clinical presentation, disease outcomes, and treatment choices in newly diagnosed patients across Europe are important to inform physicians.

Aims & Methods

To describe the clinical characteristics in a contemporary European cohort of recently diagnosed CD patients. The Crohn´s Disease Cohort (CROCO) is an ongoing multicentre, European, prospective cohort study of recently diagnosed CD patients (within 12 months following diagnosis) intended to characterize bowel damage progression and disability. Herin, we report on the characteristics of CD-patients at inclusion in the study.

Results

Between Aug/21-April/24, 316 patients (58% male, 47% smoker or ex-smokers) with a median age at diagnosis of 34.4 (IQR 24.8; 49.6), were recruited from 17 centres. The median delay between symptoms onset and diagnosis was 6.5 months (IQR 2; 17.5); median disease duration at the time of inclusion was 3.9 months (IQR 1.6; 7.6); Ileal involvement (L1/L3) was reported in 86%. Overall, 15% had perianal disease and 28% had extra-intestinal manifestations, the most frequent being arthritis/arthralgia. One-third (32%) had evidence of either stricturing (B2) (17%) or penetrating (B3) (15%) phenotype; 7% had an intestinal-related surgery, and 2% perianal surgery. Fifty-nine (21%%) patients had at least one CD-related hospitalization. Median faecal calprotectin was was 236µg/g (IQR 75; 731) and median C-reactive protein was 4mg/L (IQR 1.2; 11). Regarding the therapies receiveid from diagnosis to inclusion, 54% of the patients had received systemic steroids, 18% 5ASA, 10% IM monotherapy, and 43% started biological therapy (126 anti-TNF, 6 anti-IL 12/23 and 3 anti-integrin).

Conclusion

In this prospective cohort of newly diagnosed CD-patients, more than one-third of the patients presented with a complicated phenotype despite a short delay between onset of symptoms and diagnosis. Steroids remain frequently used, however early and effective therapy was started in approximately in 40% of patients, highlighting the changing paradigm in CD treatment.

Disclosure

JB: Reports grants and personal fees from AbbVie, grants and personal fees from Janssen-Cilag, personal fees from Celgene, grants and personal fees from MSD, personal fees from Pfizer, grants and personal fees from Takeda, grants and personal fees from Tillots Pharma, personal fees from Samsung Bioepis, grants and personal fees from Bristol Myers Squibb, grants from Novo Nordisk, personal fees from Pharmacosmos, personal fees from Ferring, personal fees from Galapagos, outside the submitted work. NA: received speaker fees from Ferring and Janssen. PE: educational grants Jannsen; SV: Speaker fees from Abbvie, Ferring, Janssen Takeda. IR-L: has received financial support for travelling and educational activities from or has served as an advisory board member for Abbvie, Adacyte, Celltrion, Chiesi, Danone, Dr. Falk Pharma, Ferring, Faes Farma Janssen, Galapagos, MSD, Otsuka Pharmaceutical, Pfizer, Roche, Takeda, and Tillotts Pharma. IO: has served as speaker and/or consultant and has received educational funding from MSD, Abbvie, Pfizer, Takeda, Janssen, Faes Farma and Chiesi, and has received research funding from Abbvie and Faes Farma. DD: Lecture fee/consultancy from: Takeda, Pfizer, Janssen, Ferring, AbbVie, Eli-Lilly. SS: received consulting fees and advisory board fees from Takeda, AbbVie, Merck, Ferring, Pharmacocosmos, Warner Chilcott, Janssen, Falk Pharma, Biohit, TriGenix, Celgene, and Tillots Pharma; speaker honoraria from AbbVie, Takeda, Celltrion, Pfizer, Biogen, AbbVie, Janssen, Merck, Warner Chilcott, and Falk Pharma. VH: Has served as consultant, has served as speaker, has received travel support or research funding from MSD, AbbVie, Ferring, Dr. Falk Pharma, Tillotts Pharma, Pfizer, Takeda, Janssen, KernPharma Biologics, Adacyte, Sandoz, Biogen, Fresenius-Kabi, FAES Farma and Galapagos. MN: received board membership, consultancy, or lecture fees from Abbvie, Amgen, Biogen, Celltrion, Ferring, Fresenius-Kabi, Galapagos, Janssen, Lilly, Mayoli-Spindler, MSD, Nordic Pharma, Pfizer, Takeda, Viatris. MF: Lecture and consulting fees from Abbvie, Pfizer, Tillots, Takeda, Gilead, Arena, Sandoz, Celltrion, Galapagos, Celgene, Boehringer, Biogen, Viatris, Amgen, Fresenius, Celltrion, CTMA, Ferring and Janssen. MA: Speaker and consulting fees from Abbvie, Pfizer, Ferring and Janssen. BB: Speaker and consulting fees from Janssen, Takeda, Sofar, Alfasigma, Doxapharma. BB: Speaker and consulting fees from Janssen, Takeda, Sofar, Alfasigma, Doxapharma. RCU: has received consulting and/or advisory board fees from AbbVie, Bristol Myers Squibb, Celltrion, Janssen, Lilly, Pfizer, Roivant, Takeda. JC: receiving research grants from AbbVie, Janssen Pharmaceuticals and Takeda; receiving payment for lectures from AbbVie, Amgen, Anaptysbio, Allergan, Inc. Ferring Pharmaceuticals, Shire, and Takeda; receiving consulting fees from AbbVie, Amgen, Arena Pharmaceuticals, Boehringer Ingelheim, BMS, Celgene Corporation, Eli Lilly, Ferring Pharmaceuticals, Galmed Research, Genentech, Galxo Smith Kline, Japan Gastroenterological Endoscopy Society, Janssen Pharmaceuticals, Kaleido Biosciences, Imedex, Immunic, Iterative Scopes, Merck, Microba, Morgan, Lewis & Bockius LLP, Novartis, Otsuka Pharmaceutical Development PBM Capital, Pfizer, Protagonist Therapeutics Sanofi, Takeda, TiGenix, Vifor; and hold stock options in Intestinal Biotech Development. JT: Grant - AbbVie, Janssen Personal Fees - Pfizer, Janssen, Abbvie, sandoz.

Introduction

Crohn's disease (CD) location would influence the risk of complications and therapeutic strategies. The objective of this study was to compare the clinical presentation at diagnosis and the natural history of colonic CD in comparison to ileal CD and ulcerative colitis (UC) in pediatric-onset IBD.

Aims & Methods

All children (< 17 years) with a diagnosis of CD or UC made between 1988 and 2011 in a population-based registry were followed retrospectively until 2013. The presentation at diagnosis, the risks of complications, surgery, hospitalization and exposure to different treatments in ileal CD (L1), colonic CD (L2) and UC were compared. Disease location was defined at diagnosis. In case of extension of the disease (L1 or L2 to L3), follow-up was censored.

Results

A total of 215 L1 patients, 234 L2 patients and 337 UC patients were included. At diagnosis, the proportion of male (L1 53.5%; L2 53.4%; UC 42.7%; p=0.012), age at diagnosis (15.0; 13.7; 14.0 years; p=0.003), family history of IBD (12.6%; 12.7%; 5.0%; p=0.005), diagnostic delay (3.0; 3.0; 2.0 months; p=0.001) and smoking prevalence (11.6%; 8.1%; 5.6%; p=0.041) were different between the three groups. Over the study period, incidence of L1, L2 and UC were 0.65 [0.57-0.74], 0.71 [0.62-0.81] and 1.02 [0.92-1.14] per 100,000 person-years, respectively. Bloody stool and diarrhea at diagnosis was observed in 14.9% respectively; 44.4%; and 91.1% (p < 0.001) and 47.0%; 71.8%; and 65.0% (p < 0.001) of L1, L2 and UC. At diagnosis, granuloma was identified in 12.6% of L1 patients and 31.2% of L2 patients (p<0.001). The risk of extension to L3 was significantly higher in the L2 group than in the L1 group (at 5 years - 37% vs. 14%, p<0.001). L2 location was associated with a lower risk of luminal fistula (HR 0.41 [0.21-0.79], p=0.008) but a higher risk of anoperineal lesion (HR 2.11 [1.29-3.45], p=0.003). The prevalence of extra-intestinal manifestations, articular (p<0.001) and cutaneous (p<0.001) was higher in L2 CD. While the risk of surgery was significantly higher in case of L1 location (at 5 years - 37%, 13% and 13%; p<0.001), the risk of hospitalization (at 5 years - 22%, 39% and 33%; p=0.01), exposure to corticosteroids (at 5 years - 55%, 69% and 67%; p<0.001), immunosuppressants (at 5 years - 47%, 61% and 42% - p<0.001) and anti-TNF (at 5 years - 16%, 35% and 22%; p<0.001) were higher in case of L2 location.

Conclusion

The clinical presentation and evolution of ileal and colonic CD at diagnosis differ significantly. Colonic location is associated with a high risk of perianal CD, extra-intestinal manifestations, hospitalization and exposure to steroids, immunosuppressants and anti-TNFs. These differences could justify different therapeutic approaches in the future.

Introduction

Few population-based studies have investigated rates and management of perianal disease and long-term perianal surgery rates in Crohn’s disease (CD). The present study is a continuation of the Veszprem IBD population based cohort with a follow-up osince 1977.

Aims & Methods

Our aim was to analyze the long-term rates of perianal surgical procedures over different therapeutic eras in a prospective population-based database from Veszprem Province, including incident CD patients. Patient inclusion was between January 1, 1977 and December 31, 2018; follow-up ended December 31, 2020. Both in-hospital and outpatient records were collected. Perianal surgical procedure was defined as any perianal surgical procedure including fistulotomy, abscess drainage or seton placement. Surgery rates were examined in three different eras based on time of diagnosis: cohort-A, 1977-1995; cohort-B, 1996-2008; and cohort-C, 2009-2018.

Results

Data of 946 incident CD patients were analyzed (male/female: 496/450; median age at diagnosis: 28 years(y) [IQR: 22-40]). Median follow-up time for the entire cohort was 15 years (IQR: 9-21). Perianal disease at diagnosis was present in 17.4% (n=165) of the total cohort, and in 24.7%/ 18.5%/ 13.2% in cohorts A/B/C, respectively. By the end of follow-up, an additional 9.3% (n=88) of the total cohort developed perianal disease. Cumulative immunosuppressive and biologic therapy exposure increased by time. Cumulative probability of biological therapy after diagnosis in patients with perianal disease was 0.0±0% / 15.1±3.2% / 42.5±6.2% at 5 years after diagnosis between cohorts A/B/C. Biologic use was higher in patients with perianal disease compared to the overall population. [pLogRank<0.001]. The overall rate of perianal surgical procedures was 44.7% (113/253) in patients with perianal disease during the total follow-up. The cumulative probability of perianal surgical procedure in patients with perianal disease was 28.3±2.9% after 10 years, 41.0±3.5% after 20 years, and 64.1±5.1% after 30 years. No statistically significant differences have been observed in the cumulative probability of perianal intervention between cohorts A/B/C: 24.2±5.4%/ 19.9±3.5%/ 29.4±5.8% after 5 years; 33.9±6.0%/ 23.6±3.8%/ 31.7±6.1% after 10 years; [pLogRank=0.594]. Cox-regression multivariate analysis showed that stenosing or penetrating disease (B2/B3) behavior (HR 1.81; 95%CI 1.19-2.75; p=0.005) was independent predictor of perianal surgical procedure. Table 1.

Table 1. Predictive factors for first perianal surgical procedure in incident CD patients diagnosed between 1977 and 2018 – Cox-regression analysis

Conclusion

The burden of perianal disease and perianal surgical interventions was high in this cohort. Patients with perianal CD had higher exposure to biologicals. No difference was observed in perianal surgical intervention rates despite the increasing use of immunosuppressives and biologicals over time, however these procedures may partly represent a medical decision and the complex management of perianal disease.

Introduction

There is a scarcity of population-based studies investigating therapeutic strategies and the long-term disease outcomes in inflammatory bowel diseases (IBD) amongst the elderly. This is a population population-based cohort from Veszprem Province, Hungary, with a follow-up of the incidence and disease course for over 40 years.

Aims & Methods

Our aim was to analyze long-term disease course, surgery rates, medication exposures (especially biological therapy) in a prospective population-based cohort of incident, elderly onset Crohn’s disease and ulcerative colitis patients.
Patient inclusion was between January 1,1977 and December 31,2018. Patient follow-up ended December 31, 2020. Elderly-onset IBD was defined if diagnosis was established at more than 60 years of age. Disease outcomes and surgery rates were compared based on time of diagnosis: ‘pre-biological era’, 1977-2008; vs. ‘biological era’, 2009-2018. Both in-hospital and outpatient records were collected and comprehensively reviewed at diagnosis and during clinical follow-up.

Results

Data of 840 CD and 1,295 UC patients were analyzed, 58 and 183 of which were elderly-onset IBD patients, respectively. Proportion of patients with colonic (L2) disease location and stenosing behavior (B2) at diagnosis were higher in the elderly population compared to adult-onset CD (p=0.014 and p=0.017, respectively). In UC, the prevalence of extensive colitis was less amongst the elderly (p=0.001).
In time dependent analysis, the probability of biological therapy was 0.0±0% and 3.2±3.2% at 1 and 5 years from diagnosis in elderly CD patients, 7.8±3.3% and 16.6±4.8% among elderly UC patients, respectively. Biological therapy was significantly lower in elderly patients compared to adult-onset disease in CD [pLogRank=0.003], but similar exposure was seen amongst UC patients [pLogRank=0.770].
The cumulative probability of resective surgery in the elderly CD population was 31.1±6.1%, 32.9±6.2%, and 35.3±6.4% after 1, 5 and 10 years. There were no statistically significant differences in resective surgery rates between the elderly and adult-onset cohorts in CD [pLog Rank=0.838]. The cumulative probability of colectomy in elderly UC patients was 2.2±1.1%, 3.4±1.4%, and 3.4±1.4% after 1, 5 and 10 years, respectively. Colectomy rates in the elderly and adult-onset cohorts were similar [pLog Rank=0.435].
The probability of disease behavior progression in CD patients with luminal (B1) behavior into stenosing or penetrating phenotype (B2/B3) was lower among elderly patients, compared to adult-onset CD. [pLogRank=0.015]. Similarly, disease extent progression (E1/2>>E2/3) in elderly UC patients was also lower [pLogRank=0.022].
Logistic regression model showed that male gender (OR 0.22; 95%CI 0.07-0.72; p=0.013) stenosing or penetrating disease (B2/B3) behavior (OR 8.69; 95%CI 2.17-34.85; p=0.001) and ileal or ileo-colonic (L1/L3) location (OR 9.71; 95%CI 2.41-39.13; p=0.001) were predictors of resective surgery in elderly CD patients. Whereas, extensive colitis (E3) (OR 7.17; 95%CI 1.63-31.52; p=0.011), continuous disease activity (OR 11.07; 95%CI 2.28-53.77; p=0.010), and anaemia (OR 10.13; 95%CI 1.97-52.13; p=0.004) were predictors of colectomy in elderly UC.

Conclusion

Elderly patients represent an increasing proportion of the IBD population. Biological therapy use was lower in elderly CD, however no different in elderly UC compared to adult-onset populations. There were no significant differences in resective surgery and colectomy rates between the elderly and adult-onset cohorts, whereas disease phenotype progression was slower in the elderly.

References

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Disclosure

PLL has been a speaker and/or advisory board member: AbbVie, Amgen, Bristol Myers Squibb, Celltrion, Fresenius Kabi, Gilead, Janssen, Eli Lilly, Merck, Organon, Pendopharm, Pfizer, Roche, Sandoz and Takeda and has received unrestricted research grant: AbbVie, Gilead and Pfizer.