Korean Crohn's Disease Patients Research Articles

P1221 Analysis Of Oral And Intestinal Microbiome Of Korean Patients With Crohn's Disease

Abstract Background We aimed to conduct a study comparing the fecal and oral microbiomes of Korean Crohn's disease patients with those of healthy individuals. Since most of microbial study of inflammatory bowel disease patients are conducted overseas, this study would reveal if the microbiome of Korean patients and patients of other countries are the same or not. Also, since the process of fecal sample collection is inconvenient, saliva sample analysis was performed to find a relevance of disease activity. Methods This single center study recruited patients with CD between September 2022 and January 2023. At first visitation, stool collecting tube and saliva collecting tube were given to CD patient. Collected stools samples and saliva samples were sent to the environmental bioengineering laboratory in Korea University and assessed by 16S rRNA sequencing. Results 26 CD patients and 6 healthy individuals were enrolled to this study. In the comparison of helathy individual’s fecal microbiome, the flora of fecal sample of CD patients were slightly different. The diversity of microbiome was decreased in CD patients compared to healthy individuals. There were 17 species existed only in CD patient’s feces. The most frequently detected one was Ruminococcus gnavus, and the the highest abundance was Unclassified Fusobacterium. In the phylum level of bacteria, Bacteroidota, Firmicutes, and Proteobacteria were predominant. Saliva samples showed no significant difference between CD patient and control. Conclusion Fecal sampling can be usefully used as a diagnostic test technique that can reflect CD patients’ microbiota. Similar to patient in overseas, dysbiosis of fecal microbiome and abundant species were detected.

P712 Real-World Efficacy And Safety Of Ustekinumab And Adalimumab In Patients With Crohn’s Disease: Propensity Matched Analysis

Abstract Background Ustekinumab (UST), an anti-IL-12/23 p40 monoclonal antibody, was shown to be as effective and safe as the anti-TNF-alpha monoclonal antibody adalimumab (ADL) in the treatment of Crohn's disease (CD). Most studies on UST in patients with CD have been conducted in the Western patients and lack in Asian patients with CD. This study aimed to compare real-world clinical efficacy and safety of UST with ADL in Korean CD patients with anti-TNF naïve and failure group. Methods The retrospective single-center cohort study was conducted on the adult patients with moderated to severe active Crohn’s disease, from 2010 to July 2022. Medical records was extracted from the Clinical Data Werehouse of Samsung Medical Center, Seoul, Korea. Propensity-matched analysis was performed to evaluate patient-reported outcome (PRO)-based clinical remission (PRO3<13) at week 52 and 96 in patient treated with UST and ADL. Subgroup analysis was performed on the biologics-naïve and anti-TNF-failure patients. Results A total of 188 CD patients treated with UST and and 299 received with ADL were enrolled. In a propensity -matched cohort adjusted with age, sex, initial CDAI score, and Montreal classification, the clinical remission rate was higher in UST group than ADL at week 52 (Odds ratio [OR] 2.7, 95% confidence interval [CI] 1.31-5.58, P = 0.007) and at week 96 (OR 12.0, 95% CI 1.56-92.29, p = 0.017). In subgroup analysis, there was no significant difference in both group in biologics-naïve group, whereas UST group showed higher clinical remission compared with ADL group in anti-TNF failure group (OR 4.67, 95% CI 1.34-16.23, p = 0.016). Biochemical remission (CRP < 0.05) showed no significant difference between both groups at week 52 and 96. Severe adverse effects leading to biologics discontinuation was numerically high in UST group and ADL group (1, 0.53% vs. 7, 2.34%, p = 0.160). Conclusion Compared with ADL, UST showed comparable efficacy in biologic-naïve patients and superior efficacy in anti-TNF failure patients with CD in Korean patients with CD.

Changes in the Long-term Prognosis of Crohn's Disease between 1986 and 2015: The Population-Based Songpa-Kangdong Inflammatory Bowel Disease Cohort Study.

Background/AimsThe long-term course of Crohn’s disease (CD) has never been evaluated in non-Caucasian population-based cohorts. The aim of the present study was to evaluate the long-term prognosis of Korean CD patients in the well-defined population-based Songpa-Kangdong inflammatory bowel disease cohort.MethodsOutcomes of disease and their predictors were evaluated for 418 patients diagnosed with CD between 1986 and 2015.ResultsDuring a median of 123 months, systemic corticosteroids, thiopurines, and anti-tumor necrosis factor (TNF) agents were administered to 58.6%, 81.3%, and 37.1% of patients, respectively. Over time, the cumulative probability of starting corticosteroids significantly decreased (p=0.001), whereas that of starting thiopurines and anti-TNFs significantly increased (both p<0.001). The cumulative probability of behavioral progression was 54.5% at 20 years, and it significantly decreased during the anti-TNF era. Intestinal resection was required for 113 patients (27.0%). The cumulative probabilities of intestinal resection at 1, 5, 10, 20, and 25 years after CD diagnosis were 12.7%, 16.5%, 23.8%, 45.1%, and 51.2%, respectively. Multivariable Cox regression analysis identified stricturing behavior at diagnosis (adjusted hazard ratio [aHR], 2.70; 95% confidence interval [CI], 1.55 to 4.71), penetrating behavior at diagnosis (aHR, 11.15; 95% CI, 6.91 to 17.97), and diagnosis of CD during the anti-TNF era (aHR, 0.51; 95% CI, 0.35 to 0.76) as independently associated with intestinal resection. The standardized mortality ratio among CD patients was 1.36 (95% CI, 0.59 to 2.68).ConclusionsThe long-term prognosis of Korean patients with CD is at least as good as that of Western CD patients, as indicated by the low intestinal resection rate. Moreover, behavioral progression and intestinal resection rates have decreased over the past 3 decades.

Predictors of reoperation for perianal fistula in Crohn's disease

Treating perianal fistula in cases of Crohn's disease (CD) remains challenging and the postoperative recurrence rate of perianal fistula is 22%-28%. This study aimed to identify the predictive risk factors for reoperation in Korean CD patients with perianal fistula. Medical records of the patients with clinically and pathologically confirmed CD who underwent surgical treatment for perianal fistulas at four referral centers in Korea between March 2010 and February 2020 were retrospectively reviewed. The rate of reoperation due to perianal fistula recurrence, which was defined as any subsequent surgery for perianal fistula or abscess, and the potential risk factors for reoperation were analyzed. Fifty-one patients at a mean age of 22 years were included in the study. During a median follow-up period of 26 months (range 2-89 mo), 21 (41.2%) patients underwent reoperation because of recurrent perianal fistula or abscess. The median interval from the first surgery to reoperation was 13 months. A multivariate Cox regression analysis revealed that drug escalation (from 5-aminosalicylic acid [5-ASA] to thiopurine or from 5-ASA or thiopurine to anti-tumor necrosis factor agents) after the first surgery was associated with a reduced likelihood of reoperation (hazard ratio 0.316, 95% confidence interval 0.117-0.858, P=0.024). The postoperative recurrence rate was relatively high (41.2%) after the first surgery for perianal fistula in Korean patients with CD. Drug escalation therapy after the first surgery may help reduce the need for reoperation for perianal fistula.

Clinical outcomes and long-term prognosis of perianal Crohn's disease in an Asian population.

The clinical impact of perianal Crohn's disease (CD) (pCD), a well-known poor prognostic factor of CD, has not been fully evaluated in Asian patients. We investigated the outcomes of CD in Korean patients according to the presence of pCD at CD diagnosis. Using 2010-2014 data from the national health insurance claims database, we evaluated the disease course of CD according to the presence of pCD at CD diagnosis. The results were verified in a hospital-based cohort of 2923 patients. The cumulative risk of intestinal resection was lower in patients with pCD at diagnosis than in those without, in the population-based cohort (9.1% vs 14.7% at 5years after diagnosis, P<0.001), but it was similar between the two groups in the hospital-based cohort (36.8% vs 36.8% at 10years after diagnosis, P=0.950). Moreover, the cumulative risk of behavioral progression was not significantly different between the two groups in the hospital-based cohort (43.4% vs 41.6% at 10years after diagnosis, P=0.366). On multivariable analysis, pCD at CD diagnosis was not a predictor of intestinal resection, behavioral progression, CD-related hospital admission, or diverting surgery; however, it was an independent predictor of proctectomy (hazard ratio [HR] 3.210, P<0.001) and anorectal cancer (HR 3.104, P=0.047). Although the presence of pCD increased the risk of proctectomy and anorectal cancer in Asian patients, the clinical impact of pCD on the overall outcomes of patients with CD may be less significant in Asian patients compared with Western patients.

Incidence and Outcomes of Perianal Disease in an Asian Population with Crohn's Disease: A Nationwide Population-Based Study.

Little is known about the natural history of perianal fistulas in Asian populations with Crohn's disease (CD). We investigated the incidence and outcomes of perianal CD (pCD) in Korean CD patients. A nationwide population-based cohort of 6265 CD patients diagnosed in 2010-2014 was analyzed to investigate the incidence and outcomes of pCD. The results were validated in a hospital-based cohort of 2923 CD patients diagnosed in 1981-2015. Factors associated with pCD development were analyzed. The incidence and outcomes of pCD were compared between the prebiologic and biologic eras. pCD occurred in 39.2% of the population-based cohort and 56.1% of the hospital-based cohort during the median follow-up of 4.2 and 8.5years, respectively. The cumulative incidence of pCD was 40.0% at 5years after CD diagnosis in the population-based cohort and 62.5% at 20years in the hospital-based cohort. In multivariate analysis, pCD development was positively associated with male sex, younger age and colonic involvement at diagnosis, early diagnosis, and CD diagnosis in the prebiologic era. The cumulative probability of proctectomy at 10, 20, and 30years after pCD diagnosis was 2.9%, 12.2%, and 16.2%, respectively. The cumulative incidence of pCD occurring after CD diagnosis and the cumulative probability of proctectomy were significantly lower in the biologic era than in the prebiologic era (p < 0.001 and p = 0.03, respectively). Compared with Western patients with CD, Korean patients show a high incidence of pCD but have a low probability of proctectomy, suggesting the favorable course of pCD.

Therapeutic Efficacy of Exclusive Enteral Nutrition with Specific Polymeric Diet in Pediatric Crohn's Disease.

PurposeThe efficacy of exclusive enteral nutrition (EEN) with a polymeric diet has not been confirmed in Korean pediatric patients with Crohn's disease (CD). This study aimed to compare the effectiveness of EEN with a specific polymeric diet (Encover®) and corticosteroids (CSs) for the induction of remission in Korean pediatric CD patients.MethodsWe retrospectively compared data from 51 pediatric CD patients who underwent induction therapy with EEN (n=19) or CSs (n=32) at Severance Children's Hospital or Incheon St. Mary's Hospital in Korea. The primary endpoint of this study was the rate of clinical remission, defined as a Pediatric Crohn's Disease Activity Index (PCDAI) score <10, after 8 weeks of induction treatment. Clinical, laboratory, and growth data at post-induction as well as their changes from baseline were also compared between groups.ResultsAfter 8 weeks of induction therapy, clinical remission rates were 78.9% (15/19) and 65.6% (21/32) in the EEN and CS groups, respectively (p=0.313). No significant differences in PCDAI scores, laboratory variables, and growth parameters were noted between the two groups at post-induction. However, significant changes in albumin levels at post-induction were observed in the EEN group compared to the CS group (p=0.038).ConclusionOur results suggest that the effectiveness of EEN with a polymeric diet and CSs for induction therapy did not differ in Korean pediatric CD patients. EEN with a polymeric diet is a good first-line treatment option for the induction of remission in these patients.

Association of Perianal Fistulas with Clinical Features and Prognosis of Crohn's Disease in Korea: Results from the CONNECT Study.

Background/AimsThe disease course and factors associated with poor prognosis in Korean patients with Crohn’s disease (CD) have not been fully determined. The aim of this study was to explore potential associations between the clinical characteristics and long-term outcomes of CD and perianal fistulas in a Korean population.MethodsThe retrospective Crohn’s Disease Clinical Network and Cohort (CONNECT) study enrolled patients diagnosed with CD between July 1982 and December 2008 from 32 hospitals. Those followed for <12 months were excluded. Clinical outcomes were CD-related surgery and complications, including nonperianal fistulas, strictures, and intra-abdominal abscesses.ResultsThe mean follow-up period was 8.77 years (range, 1.0 to 25.8 years). A total of 1,193 CD patients were enrolled, of whom 465 (39.0%) experienced perianal fistulas. Perianal fistulizing CD was significantly associated with younger age, male gender, CD diagnosed at primary care clinics, and ileocolonic involvement. Both nonperianal fistulas (p=0.034) and intra-abdominal abscesses (p=0.020) were significantly more common in CD patients with perianal fistulas than in those without perianal fistulas. The rates of complicated strictures and CD-related surgery were similar between the groups. Independently associated factors of nonperianal fistulas were perianal fistulas (p=0.015), female gender (p=0.048), CD diagnosed at referral hospital (p=0.003), and upper gastrointestinal (UGI) involvement (p=0.001). Furthermore, perianal fistulas (p=0.048) and UGI involvement (p=0.012) were independently associated with the risk of intra-abdominal abscesses.ConclusionsPerianal fistulas predicted the development of nonperianal fistulas and intra-abdominal abscesses in Korean CD patients. Therefore, patients with perianal fistulizing CD should be carefully monitored for complicated fistulas or abscesses.

Postoperative course of Crohn disease according to timing of bowel resection: Results from the CONNECT Study.

Previous studies have demonstrated that early surgery in Crohn disease (CD) can result in a better clinical course than late surgery. The aim of this study was to compare the clinical course of CD following bowel resection performed at the time of diagnosis (early surgery) and during the course of the disease (late surgery).We reviewed medical records from a hospital-based cohort database that includes Korean CD patients diagnosed before 2009. Patients who underwent bowel resection were included. Age, sex, disease phenotype, time of surgery, medication history including use of corticosteroids, immunomodulators, and biologics, and further surgical history were assessed.In all, 243 CD patients who had undergone bowel resection were included, and 120 patients underwent surgery at the time of diagnosis, while 123 underwent surgery after diagnosis (median 105 months, range 2–277). The use of biologics was significantly higher in the late surgery group than in the early surgery group (P = .020). The use of immunomodulators and reoperation rates did not differ between the groups. Early surgery was associated with less use of biologics (Kaplan–Meier curve analysis P = .015). Multivariate analysis indicated that early surgery and old age at surgery were independent variables associated with less use of biologics.CD patients who underwent bowel resection at the time of diagnosis have a more favorable disease course, represented by less use of biologics. Early surgery might be a treatment option in a subset of CD patients.

Long-Term Outcomes of Adalimumab Treatment in 254 Patients with Crohn's Disease: A Hospital-Based Cohort Study from Korea.

Large-scale studies regarding the long-term outcomes of adalimumab (ADA) treatment in Asian patients with Crohn's disease (CD) are still scarce. We retrospectively analyzed the long-term outcomes of ADA treatment in Korean CD patients who commenced on scheduled ADA treatment at Asan Medical Center between November 2008 and July 2016. Clinical response was defined as maintaining ADA treatment without dose intensification (DI) and/or major abdominal surgery (MAS). Of the 254 patients who received at least two doses of ADA at 2-week intervals as induction therapy, 250 patients (98.4%) showed an initial favorable response by week 4. Among responders, 243 patients were followed up for longer than 4weeks and were included for further analysis. The median duration of ADA maintenance therapy was 19.4months. At the last follow-up, 45 patients (18.5%) required DI after a median of 16.8months and 31 (12.8%) required MAS after a median of 8.9months. Finally, 161 patients (66.3%) were still receiving ADA without DI and/or MAS. The cumulative probability of maintaining ADA without DI and/or MAS was 81.1% at 1year, and 36.5% at 5years. Secondary loss of response to previous infliximab (P=0.001) and elevated baseline C-reactive protein at starting ADA treatment (P=0.008) were identified as independent predictors of a poor response to ADA treatment using multivariate regression analysis. The long-term outcome of ADA treatment in a real-life cohort of Korean patients with CD appears to be comparable to that reported in previously published Western studies.

Incidence of and Risk Factors for Free Bowel Perforation in Patients with Crohn’s Disease

Incidence of and risk factors for intestinal free perforation (FP) in patients with Crohn's disease (CD) are not established. To establish rate of and risk factors for FP in a large cohort of CD patients. Medical records of CD patients who visited Asan Medical Center from June 1989 to December 2012 were reviewed. After matching the FP patients to controls (1:4) by gender, year, and age at CD diagnosis, and disease location, their clinical characteristics were compared using conditional logistic regression analysis. Among 2043 patients who were included in our study cohort, 44 patients (2.15%) developed FP over a median follow-up period of 79.8months (interquartile range 37.3-124.6), with an incidence of 3.18 per 1000 person-years [95% confidence interval (CI) 2.37-4.28]. All 44 patients underwent emergency surgery, and eight patients underwent reoperation within 12months (8/44, 18.2%). Multivariable-adjusted analysis revealed that anti-TNF therapy [odds ratio (OR), 3.73; 95% CI 1.19-11.69; p=0.024] was associated with an increased risk of FP. The incidence of FP in a large cohort of Korean CD patients was 2.15%, which was similar to that in Western reports. Anti-TNF therapy could be risk factors for FP.

Clinical correlations of infliximab trough levels and antibodies to infliximab in South Korean patients with Crohn's disease.

AIMTo investigate the clinical implications of infliximab trough levels (IFX-TLs) and antibodies to infliximab (ATI) levels in Crohn’s disease (CD) patients in Asian countries.METHODSIFX-TL and ATI level were measured using prospectively collected samples obtained with informed consent from CD patients being treated at Asan Medical Center, South Korea. We analyzed the correlations between IFX-TLs/ATI levels and the clinical activity of CD (quiescent vs active disease) based on the CD activity index, C-reactive protein level, and physician’s judgment of patients’ clinical status at enrollment. The impact of concomitant immunomodulators was also investigated.RESULTSThis study enrolled 138 patients with CD (84 with quiescent and 54 with active disease). In patients with quiescent and active diseases, the median IFX-TLs were 1.423 μg/mL and 0.163 μg/mL, respectively (P < 0.001) and the median ATI levels were 8.064 AU/mL and 11.209 AU/mL, respectively (P < 0.001). In the ATI-negative and -positive groups, the median IFX-TLs were 1.415 μg/mL and 0.141 μg/mL, respectively (P < 0.001). In patients with and without concomitant immunomodulator use, there were no differences in IFX-TLs (0.632 μg/mL and 1.150 μg/mL, respectively; P = 0.274) or ATI levels (8.655 AU/mL and 9.017 AU/mL, respectively; P = 0.083).CONCLUSIONIFX-TL/ATI levels were well correlated with the clinical activity in South Korean CD patients. Our findings support the usefulness of IFX-TLs/ATI levels in treating CD patients receiving IFX in clinical practice.

Underestimation of Smoking Rates in an East Asian Population with Crohn’s Disease

Background/AimsThe reported rates of current smoking at the time of Crohn’s disease (CD) diagnosis tend to be low in East Asian studies. However, we hypothesized that East Asian patients may be reluctant to disclose their smoking history, likely because of the influence of the Confucian culture.MethodsWe prospectively re-evaluated the smoking status at diagnosis in 1,437 Korean CD patients whose smoking status had been reported in our previous study.ResultsAfter re-evaluation, the current smokers at diagnosis increased from 388 patients (27.0%) to 445 patients (31.0%), indicating that 12.8% (57 of 445 patients) of the current smokers at diagnosis did not disclose their smoking status at their initial evaluation. The proportion of current smokers at diagnosis who had initially concealed their smoking status was significantly higher among the female patients (29.7%, 11/37) compared with the male patients (11.3%, 46/408) (p<0.005) and among the patients who were ≤18 years old at diagnosis (56.4%, 22/39) compared with the patients >18 years old at diagnosis (8.6%, 35/406) (p<0.001).ConclusionsSubgroups of Korean CD patients, particularly young patients and female patients, are reluctant to disclose their smoking history. Therefore, the suggestion that smoking is not a risk factor for the development of CD in East Asians should be made with caution.

Long-Term Outcomes of Infliximab Treatment in 582 Korean Patients with Crohn's Disease: A Hospital-Based Cohort Study.

To date, no large-scale studies have evaluated long-term outcomes of infliximab (IFX) treatment in Korean patients with Crohn's disease (CD). We analyzed long-term clinical responses to IFX in 582 Korean CD patients who received scheduled IFX treatments at Asan Medical Center. Clinical responses were defined as maintaining IFX without major abdominal surgery (MAS) or dose intensification. Between February 2002 and July 2015, a total of 11,990 IFX infusions were administered to 582 Korean patients with CD over a median period of 36months. At the end of follow-up, 316 (54.3%) were still receiving IFX without MAS (71 patients, 12.2%) or dose intensification (86 patients, 14.8%). IFX was stopped in 109 (18.7%) patients because of a loss of response (48 patients, 8.2%), adverse events (30 patients, 5.2%), or patient preferences or problems with reimbursement (31 patients, 5.3%). The cumulative survival for maintenance of IFX without MAS or dose intensification was 89.0, 75.9, 68.3, and 50.8% at 1, 2, 3, and 5years, respectively. Multivariate regression analysis identified older age at the initiation of IFX (≥40years, P=0.006) and a longer disease duration (≥3years, P=0.020) as independent positive predictors of a poorer response to IFX. The long-term efficacy of IFX in a large, real-life cohort of Korean patients with CD appears to be similar to that in previously published Western studies. Our findings support the early use of IFX to obtain better clinical outcomes.

Does the intestinal microbial community of Korean Crohn's disease patients differ from that of western patients?

BackgroundIntestinal microbiota play an important role in maintaining the homeostasis of the host immune system. To analyze the alteration of the intestinal microbial community structure in Korean Crohn’s disease (CD) patients, we performed a comparative metagenomic analysis between healthy people and CD patients using fecal samples and mucosal tissues of ileocecal valve.Methods16S rRNA genes from fecal samples or mucosal tissues of 35 CD patients and 15 healthy controls (HC) were amplified using a universal primer set and sequenced with GS FLX Titanium. The microbial composition and diversity of each sample were analyzed with the mothur pipeline, and the association between microbial community and clinical characteristics of the patients were investigated.ResultsThe contribution of bacterial groups to the intestinal microbial composition differed between CD and HC, especially in fecal samples. Global structure and individual bacterial abundance of intestinal microbial community were different between feces and ileocecal tissues in HC. In CD patients with active stage, relative abundances of Gammaproteobacteria and Fusobacteria were higher in both fecal and mucosal tissue samples. Moreover, the intestinal microbial community structure was altered by anti-tumor necrosis factor (anti-TNF) treatment.ConclusionsOur 16S rRNA sequence data demonstrate intestinal dysbiosis at the community level in Korean CD patients, which is similar to alterations of the intestinal microbial community seen in the western counterparts. Clinical disease activity and anti-TNF treatment might affect the intestinal microbial community structure in CD patients.Electronic supplementary materialThe online version of this article (doi:10.1186/s12876-016-0437-0) contains supplementary material, which is available to authorized users.

Clinical Features and Extraintestinal Manifestations of Crohn Disease in Children.

PurposeThe aim of this study was to investigate the clinical features and extraintestinal manifestations (EIMs) of Crohn disease (CD) in Korean pediatric patients.MethodsThe medical records of 73 children diagnosed with CD were retrospectively reviewed. Data regarding baseline demographic and clinical characteristics, including CD phenotype at diagnosis based on the Montreal classification, and clinical features and course of EIMs were investigated.ResultsFifty-two (71.2%) of the patients were males. The mean age of the patients was 12.5 years. The mean follow-up period was 3.4 years. The disease location was ileal in 3 (4.1%) of the patients, colonic in 13 (17.8%), ileocolonic in 56 (76.7%). The clinical behavior was inflammatory in 62 (84.9%) of the patients, stricturing in 8 (11.0%), and penetrating in 3 (4.1%). Perianal abscesses or fistulas were found in 37 (50.7%) of the patients. EIMs observed during the study period were anal skin tag in 25 patients (34.2%), hypertransaminasemia in 20 (27.4%), peripheral arthritis in 2 (2.7%), erythema nodosum in 2 (2.7%), vulvitis in 1 (1.4%), uveitis in 1 (1.4%), and pulmonary thromboembolism in 1 (1.4%).ConclusionPerianal diseases and manifestations were present in more than half of Korean pediatric CD patients at diagnosis. Inspection of the anus should be mandatory in Korean children with suspicious CD, as perianal fistulas, abscesses, and anal skin tags may be the first clue to the diagnosis of CD.

Clinical Factors and Disease Course Related to Diagnostic Delay in Korean Crohn's Disease Patients: Results from the CONNECT Study.

Diagnostic delay frequently occurs in Crohn’s disease (CD) patients because of diagnostic limitations. However, diagnostic delay and its related factors remain poorly defined. Therefore, we aimed to identify the predictors associated with diagnostic delay and to evaluate the impact of diagnostic delay on clinical course in a Korean CD patient cohort. We performed a multicenter retrospective analysis of 1,047 CD patients registered in the Crohn’s Disease Clinical Network and Cohort study in Korea. The mean interval of diagnostic delay was 16.0 ± 33.1 months. Multivariate analysis showed that older age at diagnosis (≥40 years) (p = 0.014), concomitant upper gastrointestinal (UGI) disease (p = 0.012) and penetrating disease behavior at diagnosis (p = 0.001) were positively associated with long diagnostic delay (≥18 months). During the longitudinal follow-up, long diagnostic delay was independently predictive of further development of intestinal stenosis (hazard ratio [HR], 1.43; 95% confidence interval [CI], 1.07–1.93; p = 0.017), internal fistulas (HR, 1.62; 95% CI, 1.12–2.33; p = 0.011), and perianal fistulas (HR, 1.38; 95% CI, 1.06–1.80; p = 0.016). However, as for the risk of abscess formation, bowel perforation, and CD-related abdominal surgery, no significant association with diagnostic delay was observed. Older age at diagnosis, UGI involvement, and penetrating behavior are associated with long diagnostic delay in Korean CD patients. Moreover, diagnostic delay is associated with an increased risk of CD-related complications such as intestinal stenosis, internal fistulas, and perianal fistulas.

Association of TNFSF15 polymorphisms in Korean children with Crohn's disease.

Genome-wide association studies have identified tumor necrosis factor superfamily member 15 (TNFSF15) as a Crohn's disease (CD)-related gene. The aim of this study was to evaluate the association between five TNFSF15 polymorphisms and CD in Korean children and analyze their genotypes in relation to phenotype. Five single-nucleotide polymorphisms of TNFSF15 (rs3810936, rs6478108, rs6478109, rs7848647, rs7865494) were genotyped in 108 CD patients and in 599 healthy controls. Risk allele, genotype, and haplotype were analyzed in CD patients and controls, and genotype-phenotype relationships were studied. There were significant associations of rs3810936, rs6478108, rs6478109, rs7848647 with CD in Korean pediatric patients (P = 6.5×10(-8), P = 1.3×10(-8), P = 3.7×10(-8), P = 2.9×10(-8), respectively). The adjusted OR (aOR) for the homozygous risk allele genotype was significantly higher than that for the homozygous genotype for the opposite allele: rs3810936, aOR, 5.36 (95%CI: 2.61-10.98, P = 4.6×10(-6)); rs6478108, aOR, 6.62 (95%CI: 3.03-14.46, P = 2.2×10(-6)); rs6478109, aOR, 6.24 (95%CI: 2.85-13.66, P = 4.6×10(-6)); rs7848647, aOR, 6.32 (95%CI: 2.89-13.81, P = 3.8×10(-6)). The risk allele of rs3810936 was associated with later symptom onset, later diagnosis, and the presence of perianal lesion (P = 0.013, P = 0.016 and P = 0.029). There was a significant association of TNFSF15 with pediatric CD in Korean patients.

Factors Contributing to the Preference of Korean Patients with Crohn's Disease When Selecting an Anti-Tumor Necrosis Factor Agent (CHOICE Study).

Background/AimsTwo comparable anti-tumor necrosis factor (TNF) agents with different routes of administration (intravenous [iv] infliximab [IFX] vs subcutaneous [sc] adalimumab [ADA]) are available for patients with Crohn’s disease (CD) in Korea. This study aimed to identify the preferences of Korean CD patients for a specific anti-TNF agent and the factors contributing to the decision.MethodsA prospective survey was performed among anti-TNF-naive CD patients in 10 tertiary referral hospitals. A 16-item questionnaire addressed patient preferences and the factors contributing to the decision in favor of a particular anti-TNF agent. A logistic regression was conducted to assess predictive factors for ADA preference.ResultsOverall, 189 patients (139 males; mean age, 32.47±11.71 years) completed the questionnaire. IFX and ADA were preferred by 63.5% (120/189) and 36.5% (69/189) of patients, respectively. The most influential reason for choosing IFX was ‘doctor’s presence’ (68.3%, 82/120), and ADA was “easy to use” (34.8%, 24/69). Amid various clinicodemographic data, having a >60-minute travel time to the hospital was a significant independent predictive factor for ADA preference.ConclusionsA large number of anti-TNF-naive Korean patients with CD preferred anti-TNFs with an iv route of administration. The reassuring effect of a doctor’s presence might be the main contributing factor for this decision.

P589. Change in clinical features of Korean Crohn's Disease patients following the introduction of an anti-TNF-alpha agent: Results from the CONNECT study

P589. Change in clinical features of Korean Crohn's Disease patients following the introduction of an anti-TNF-alpha agent: Results from the CONNECT study