Search

Background: This study investigated the safety and effectiveness of ustekinumab (UST) in Korean patients with Crohn's disease (CD)., Methods: Adult patients with CD treated with UST were prospectively enrolled in the K-STAR (Post-MarKeting Surveillance for Crohn's Disease patients treated with STelARa) study between April 2018 and April 2022. Both the clinical effectiveness and adverse effects of UST therapy were analyzed. Missing data were handled using nonresponder imputation (ClinicalTrials.gov Identifier: NCT03942120)., Results: Of the 464 patients enrolled from 44 hospitals across Korea, 457 and 428 patients (Crohn's disease activity index ≥150) were included in the safety analysis and effectiveness analysis sets, respectively. At weeks 16 to 20 after initiating UST, clinical response, clinical remission, and corticosteroid-free remission rates were 75.0% (321 of 428), 64.0% (274 of 428), and 61.9% (265 of 428), respectively. At week 52 to 66, clinical response, clinical remission, and corticosteroid-free remission rates were 62.4% (267 of 428), 52.6% (225 of 428), and 50.0% (214 of 428), respectively. Combined effectiveness (clinical response + biochemical response) was achieved in 40.0% (171 of 428) and 41.6% (178 of 428) at week 16 to 20 and week 52 to 66, respectively. Biologic-naïve patients exhibited significantly higher rates of combined effectiveness than biologic-experienced patients (50.3% vs 30.7% at week 16-20, P < .001; 47.7% vs 36.0% at week 52-66, P = .014). No additional benefits were observed with the concomitant use of immunomodulators. Ileal location was independently associated with a higher probability of clinical remission compared with colonic or ileocolonic location at week 52 to 66. Adverse and serious adverse events were observed in 28.2% (129 of 457) and 12.7% (58 of 457), respectively, with no new safety signal associated with UST treatment., Conclusions: Ustekinumab was well-tolerated, effective, and safe as induction and maintenance therapy for CD in Korea., (© 2024 Crohn’s & Colitis Foundation. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation.)

Background: We investigated the real-life effectiveness and safety of vedolizumab (VDZ) induction therapy among Korean patients with Crohn disease (CD) or ulcerative colitis (UC) for whom anti-tumor necrosis factor therapy previously failed., Methods: Adult patients who started VDZ induction therapy at 16 centers were prospectively enrolled in the Korean VDZ nationwide registry. The coprimary outcomes were clinical remission, defined as a Crohn's Disease Activity Index score <150 points and a partial Mayo score ≤2 points with a combined rectal bleeding and stool frequency subscore ≤1 point at week 14 and endoscopic remission defined as a Mayo endoscopic subscore ≤1 point. We also analyzed predictors of clinical remission., Results: Between August 2017 and November 2019, a total of 158 patients (80 with CD and 78 with UC) received VDZ induction therapy. Clinical remission rates among patients with CD and patients with UC were 44.1% and 44.0%, respectively. Among patients with UC, the endoscopic remission rate was 32.4%. Clinical response and remission rates showed increasing trends during induction therapy. Multivariable analysis revealed that clinical response at week 6 was the only predictor of clinical remission at week 14 for both patients with CD and patients with UC. Among patients who experienced 1 or more adverse events (n = 71; 44.9%), disease exacerbation (n = 28; 17.7%) was the most common adverse event., Conclusions: Among Korean patients with CD or UC for whom anti-tumor necrosis factor therapy failed, VDZ induction therapy was effective and safe. The early clinical response was associated with clinical remission after VDZ induction therapy., (© 2021 Crohn’s & Colitis Foundation. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Up to 60% of patients with ulcerative colitis (UC) ultimately fail anti-tumor necrosis factor (TNF) treatment. We aimed to investigate early predictive markers of clinical and endoscopic outcomes in patients with UC who were anti-TNF-naïve commencing anti-TNF treatment, with particular focus on changes in albumin and C-reactive protein levels in the first 2 weeks of treatment., Methods: We retrospectively investigated 210 patients with UC who started infliximab or adalimumab between 2009 and 2016 (male, 62.4%; median age at diagnosis, 37.9 years [interquartile range, 25.5-48.9 years]; median follow-up duration, 3.3 years [1.9-5.0 years]). Logistic and Cox proportional-hazards regressions were performed to identify variables associated with primary nonresponse (PNR), endoscopic outcomes, time-to-colectomy, and anti-TNF failure., Results: Forty-one patients (19.5%) experienced PNR; week 0/week 2 ratio serum albumin was associated with PNR (adjusted odds ratio [aOR], 1.8; 95% confidence interval [CI], 1.1-2.9, per interquartile range increase). Week 0/week 2 ratio albumin was also associated with endoscopic response (aOR, 0.28; 95% CI, 0.31-0.82) and endoscopic remission (aOR, 0.61; 95% CI, 0.39-0.96) at weeks 8 to 14, time-to-colectomy (adjusted hazard ratio, 2.12; 95% CI, 1.29-3.49) and time-to-anti-TNF failure (adjusted hazard ratio, 1.54; 95% CI, 1.22-1.96), regardless of age, disease severity, or in-patient status. Association with time-to-colectomy and anti-TNF failure was externally validated in an independent cohort of inpatients with UC starting infliximab., Conclusions: Change in serum albumin within the first 2 weeks of anti-TNF treatment is predictive of PNR, endoscopic outcomes, time-to-colectomy, and anti-TNF failure in patients with UC. Timely access to this biomarker enables early identification of patients with UC at risk of anti-TNF failure and may guide early optimization of anti-TNF treatment to improve disease outcomes., (© 2020 Crohn’s & Colitis Foundation. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Many patients with Crohn's disease (CD) are treated with medications, including steroids, immunomodulators, and anti-tumor necrosis factor alpha (anti-TNF-α) agents, at the time of surgery. This study evaluated the effects of these medications on postoperative complications in CD patients., Methods: This retrospective study analyzed patients who underwent bowel resection for CD between January 2006 and December 2015. Postoperative complications were defined as a Clavien-Dindo classification of grade 2A or higher within the first 30 days after surgery., Results: Of the 817 patients enrolled, 687 patients received bowel resection and anastomosis without stoma formation. Of 687 patients, 381 (55.5%) were being treated with preoperative medications at the time of surgery (medication group) and 306 (44.5%) were not (nonmedication group). The overall rate of postoperative complications was not different between the medication and nonmedication groups (23.4% vs 21.9%, P = 0.36). Preoperative treatments with immunomodulators plus anti-TNF-α agents (relative risk [RR], 2.314; 95% confidence interval [CI], 1.126-4.753; P = 0.022) and treatment with immunomodulators plus steroids (RR, 2.536; 95% CI, 1.124-5.725; P = 0.025) were risk factors for infectious complications. Preoperative treatments with immunomodulators plus anti-TNF-α agents (RR, 2.731; 95% CI, 1.102-6.769; P = 0.03) and treatment with immunomodulators plus steroids (RR, 3.118; 95% CI, 1.169-8.320; P = 0.023) were significantly associated with increased risk of intra-abdominal sepsis., Conclusions: Preoperative treatments with immunomodulators plus anti-TNF-α agents or steroids were risk factors for infectious complications, especially intra-abdominal sepsis in patients who underwent bowel resection and anastomosis., (© 2019 Crohn’s & Colitis Foundation. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Although colonoscopy is useful for differentiating between Crohn's disease (CD) and intestinal tuberculosis (ITB), the technique has limitations. We developed a practical prediction model for differentiating between CD and ITB using laboratory and radiologic parameters and colonoscopic characteristics., Methods: We prospectively enrolled 80 patients newly diagnosed with CD (n = 40) and ITB (n = 40). We developed a new prediction score by integrating colonoscopic, laboratory, and radiologic parameters. The score's predictive ability was validated on an additional 37 patients., Results: The accuracy of colonoscopic scoring for differentiation was 81.2% (65/80), with 65.0% sensitivity for CD and 97.5% for ITB. In multivariate analysis, positive IgA and/or IgG anti-Saccharomyces cerevisiae antibody and involvement of the proximal intestine were the independent laboratory and radiologic parameters for CD, and positive QuantiFERON-TB Gold In-Tube Test and typical pulmonary TB findings were the parameters for ITB. A new prediction scoring combining colonoscopic, laboratory, and radiologic factors increased the accuracy of diagnosis from 81.2% to 96.3% (77/80). The CD prediction score (from -2 to 2) estimated the likelihood of CD, from 0.3% for patients scoring -2 to 100% for patients scoring 2. The area under the receiver operating characteristic curve of the score was 0.990 in the development group and 0.981 in the validation group., Conclusions: The new prediction model using a CD prediction score can be useful for calculating the probability of either CD or ITB at initial evaluation (NCT01392365).

Background: Although anti-tumor necrosis factor (TNF) agents are effective in patients with inflammatory bowel disease (IBD), many patients either do not respond to anti-TNF treatment or lose response over time. The aim of this study was to determine factors associated with response to anti-TNF therapy in IBD., Methods: Patients with Crohn's disease (CD) or ulcerative colitis who had consented to participate in a genetics registry and been treated with anti-TNF agents were evaluated retrospectively and categorized as primary nonresponders or secondary nonresponders. We evaluated clinical, serological, and genetic characteristics associated with primary nonresponse or time to loss of response to anti-TNF agents., Results: We included 314 CD (51 [16.2%] primary nonresponders and 179 [57.0%] secondary nonresponders) and 145 subjects with ulcerative colitis (43 [29.7%] primary nonresponders and 74 [51.0%] secondary nonresponders). Colonic involvement (P = 0.017; odds ratio = 8.0) and anti-TNF monotherapy (P = 0.017; odds ratio = 4.9) were associated in a multivariate analysis with primary nonresponse to anti-TNF agents in CD. In addition, higher anti-nuclear cytoplasmic antibody levels (P = 0.019; hazard ratio = 1.01) in CD, anti-nuclear cytoplasmic antibody positivity (P = 0.038; hazard ratio = 1.6) in ulcerative colitis, and a positive family history of IBD (P = 0.044; hazard ratio = 1.3) in all patients with IBD were associated with time to loss of response to anti-TNF agents. Furthermore, various known IBD susceptibility single-nucleotide polymorphisms and additional variants in immune-mediated genes were shown to be associated with primary nonresponse or time to loss of response., Conclusions: Our results may help to optimize the use of anti-TNF agents in clinical practice and position these therapies appropriately as clinicians strive for a more personalized approach to managing IBD.

Background: A considerable number of patients with Crohn's disease (CD) develop irreversible intestinal damage, although the early administration of immunomodulatory or biological therapies might prevent this. The aims of our study were to develop and validate a novel predictive model that can be used to predict the risk of surgical intervention in Korean patients with CD., Methods: The prognostic model was derived from the multicenter longitudinal CONNECT (CrOhn's disease cliNical NEtwork and CohorT) study cohort consisting of 1338 patients with CD, who were split into training and validation sets. The Korean Crohn's Disease Prediction (KCDP) model was developed with the training set data using the Cox proportional hazards model and multivariate analysis, and was then validated using the validation set., Results: A total of 1271 patients with CD were analyzed. During the follow-up period of 10,188 patient-years (median 7.1 yrs), 361 patients (28.4%) underwent CD-related surgery. Age at diagnosis, jejunal involvement, initial disease behavior, and perianal disease at diagnosis were associated with a poor prognosis and included in the KCDP model, which showed a modest discrimination ability with a Harrel's c-index of 0.731 at 5 years, and was well calibrated (Hosmer-Lemeshow χ = 8.230, P = 0.511)., Conclusions: This is the first validated surgery risk prediction model for Korean patients with CD; it provides accurate individualized estimates of the probability of surgery using clinical parameters collected at diagnosis. This model might guide appropriate patient selection for the early intensive treatment of CD.

Background: Cytomegalovirus (CMV) colitis can contribute to an unfavorable outcome of acute severe ulcerative colitis (ASUC). The purpose of this study was to evaluate the clinical outcomes of ASUC according to the CMV status and identify risk factors for CMV colitis in patients with ASUC., Methods: We retrospectively analyzed patients with ASUC from 2011 to 2014 according to the criteria of Truelove and Witts. CMV colitis was diagnosed by histopathological and/or immunohistochemical analysis of tissue samples. The risk factors for CMV colitis were investigated and clinical outcomes were assessed using the rate of rescue therapy and colectomy., Results: Of 149 patients with ASUC, 50 (33.6%) were diagnosed with CMV colitis. During admission, 16 of 149 patients (10.7%) underwent colectomy: 7 of 50 (14.0%) in the ASUC-CMV group versus 9 of 99 (9.1%) in the ASUC-only group (P = 0.364). The need for rescue therapy was 2.28-fold higher in the ASUC-CMV group than in the ASUC-only group in multivariate analysis (95% confidence interval, 1.10-4.72). Multivariate analysis also revealed that recent use of high-dose steroids (odds ratio, 3.30; 95% confidence interval, 1.33-8.19) and a higher Mayo score (odds ratio, 1.58; 95% confidence interval, 1.05-2.38) were risk factors for CMV colitis., Conclusions: CMV colitis often occurs in ASUC, particularly in patients who have recently been treated with high-dose steroids and have a higher Mayo score on admission. Patients with ASUC and CMV colitis seem to have a poorer prognosis, as indicated by the greater need for rescue therapy.

Background: Recent genetic association studies identified more than 160 susceptibility loci for inflammatory bowel disease in Caucasian populations, but studies in Asian populations are limited. We have previously reported 3 loci associated with Korean ulcerative colitis (UC)., Methods: Using the Immunochip custom single nucleotide polymorphisms (SNP) array designed for dense genotyping of 186 known disease loci from 12 immune-mediated diseases, we analyzed 705 patients with UC and 1178 controls for 536,821 SNPs (89,057 genotyped and 447,764 imputed) in the discovery stage followed by replication in additional 980 affected individuals and 2694 controls in a Korean population., Results: We confirmed the associations of 10 known UC risk loci in Koreans: rs76418789 in IL23R (combined P = 1.25 × 10), rs4728142 in IRF5 (combined P = 3.17 × 10), rs1830610 near JAK2 (combined P = 2.28 × 10), rs1555791 near TNFRSF14 (combined P = 1.62 × 10), rs880790 between IL10-IL19 (combined P = 3.73 × 10), rs10185424 between IL1R2-IL1R1 (combined P = 1.54 × 10), rs6478108 in TNFSF15 (combined P = 9.28 × 10), rs861857 between UBE2L3-YDJC (combined P = 3.05 × 10), rs1801274 in FCGR2A (discovery P = 1.54 × 10), and rs17085007 between GPR12-USP12 (discovery P = 3.64 × 10). The percentage of phenotype variance explained by the 13 risk loci (including 3 previously reported loci) was 5.61% in Koreans (on the liability scale, population prevalence = 0.0308%)., Conclusions: Our study increased the number of UC susceptibility loci in Koreans to 13 and highlighted the extensive sharing of genetic risk across populations of UC.

Background: No previous studies have evaluated the long-term outcomes of acute severe ulcerative colitis (ASUC) in non-Caucasian populations. The purposes of this study were to evaluate the short- and long-term outcomes of Korean patients with ASUC., Methods: We retrospectively analyzed 99 Korean patients with ASUC who satisfied the criteria given by Truelove and Witts between 1999 and 2005. The short-term outcome parameter was the colectomy rate during index hospitalization, and the long-term outcome parameters were the rates of colectomy and rehospitalization after discharge from index hospitalization., Results: During index hospitalization, 16 of 99 patients (16.2%) underwent colectomy: 6 of 71 responders (8.5%) to intravenous steroids on day 3 versus 10 of 28 nonresponders (35.7%), as assessed using the Oxford index (P = 0.002). Among 83 patients who avoided colectomy during index hospitalization, 13 patients (15.7%) underwent colectomy during the median follow-up period of 10.6 years. The cumulative probability of colectomy tended to be lower in complete responders on day 7 of intravenous steroid therapy (CR7) than in others: 3.7% versus 13.9% at 5 years and 7.6% versus 18.2% at 10 years (P = 0.100). The cumulative probability of rehospitalization was significantly lower in CR7 than in other patients: 20.5% versus 37.5% at 5 years and 31.4% versus 48.2% at 10 years (P = 0.043)., Conclusions: Assessing the degree of response to intravenous steroids helps predict the short- and long-term outcomes in patients with ASUC. Korean patients with ASUC may have better clinical courses than Caucasians, as indicated by the lower colectomy rate.

Background: Anti-tumor necrosis factor (anti-TNF) agents are widely used to treat patients with moderate-to-severe inflammatory bowel disease (IBD). We aimed to identify the risk factors for adverse skin lesions in patients with IBD receiving anti-TNF agents and assess the effect of concomitant use of azathioprine/6-mercaptopurine (AZA/6 MP)., Methods: A total of 500 patients (404 with Crohn's disease, 96 with ulcerative colitis) who received anti-TNF agents between June 2002 and July 2013 were identified and retrospectively investigated. We compared 47 patients with IBD with skin lesions with 443 patients with IBD without skin lesions to identify risk factors by univariate and multivariate analysis. The Kaplan-Meier method was used to estimate the cumulative incidence of adverse skin lesions in relation to the concomitant use of AZA/6 MP., Results: Eczematiform eruptions (n = 18, 38%) were the most common skin lesion type, followed by psoriasiform lesions (n = 13, 28%). A response to topical steroids was seen in 70% (33/47) of patients with skin lesions, and anti-TNF agents had to be discontinued in 9% (4/47). Concomitant use of AZA/6 MP decreased the risk of skin lesions in univariate (hazard ratio, 0.452; 95% CI, 0.251-0.814; P = 0.008) and multivariate (hazard ratio, 0.437; 95% CI, 0.242-0.790; P = 0.006) analysis. In addition, the cumulative incidence of adverse skin lesions was lower in patients on concomitant maintenance with AZA/6 MP (P = 0.009) than in those on anti-TNF monotherapy., Conclusions: Concomitant use of AZA/6 MP may decrease the occurrence of adverse skin lesions in patients receiving anti-TNF therapy.

Background: Diffusion-weighted imaging (DWI) is a novel technique to evaluate bowel inflammation in Crohn's disease (CD). It is unknown whether and how DWI adds to the accuracy of conventional magnetic resonance enterography (MRE)., Methods: Fifty consecutive adults suspected of CD prospectively underwent clinical assessment, conventional MRE and DWI at b = 900 sec/mm without water enema, and ileocolonoscopy within 1 week. MRE images were interpreted with proper blinding. Forty-four patients finally diagnosed with CD (male:female, 34:10; 26.9 ± 6.1 yr) were analyzed. The per-segment accuracy of MRE for diagnosing active CD was assessed in the terminal ileum, right colon, and rectum using location-by-location matching with endoscopy as the reference standard., Results: The study evaluated 58 bowel segments with deep or superficial ulcers, 34 with aphthae, erythema, or edema only, and 35 without inflammation. Conventional MRE + DWI was more sensitive for bowel inflammation than conventional MRE alone (83% [76/92] versus 62% [57/92]; P = 0.001) largely because of additional detection of aphthae, erythema, or edema. The sensitivities for deep and overt ulcers were similar regardless of DWI, ranging from 88% to 97%. Conventional MRE + DWI was less specific than conventional MRE alone (60% [21/35] versus 94% [33/35]; P < 0.001), mostly because of many false positives in the colorectum. Positive DWI findings in the bowel showing active inflammation on conventional MRE were associated with higher Crohn's disease endoscopic index of severity score (P = 0.021) and deep ulcers (P = 0.01; diagnostic odds ratio, 12)., Conclusions: DWI performed without water enema is not useful for incremental detection of bowel inflammation. DWI may help identify more severe inflammation among bowel segments showing active inflammation on conventional MRE.

Background: Crohn's disease (CD) is an intractable inflammatory bowel disease of unknown cause. Recent genome-wide association studies of CD in Korean and Japanese populations suggested marginal sharing of susceptibility loci between Caucasian and Asian populations. As the 7 identified loci altogether explain 5.31% of the risk for CD, the objective of this study was to identify additional CD susceptibility loci in the Korean population., Methods: Using the ImmunoChip custom single-nucleotide polymorphism array designed for dense genotyping of 186 loci identified through GWAS, we analyzed 722 individuals with CD and 461 controls for 96,048 SNP markers in the discovery stage, followed by validation in an additional 948 affected individuals and 977 controls., Results: We confirmed 6 previously reported loci in Caucasian: GPR35 at 2q37 (rs3749172; P = 5.30 × 10, odds ratio [OR] = 1.45), ZNF365 at 10q21 (rs224143; P = 2.20 × 10, OR = 1.38), ZMIZ1 at 10q22 (rs1250569; P = 3.05 × 10, OR = 1.30), NKX2-3 at 10q24 (rs4409764; P = 7.93 × 10, OR = 1.32), PTPN2 at 18p11 (rs514000; P = 9.00 × 10, OR = 1.33), and USP25 at 21q11 (rs2823256; P = 2.49 × 10, OR = 1.35), bringing the number of known CD loci (including 3 in the HLA) in Koreans to 15. The 6 additional loci increased the total genetic variance for CD risk from 5.31% to 7.27% in Koreans., Conclusions: Although the different genetic backgrounds of CD between Asian and Western countries has been well established for the major susceptibility genes, our findings of overlapping associations offer new insights into the genetic architecture of CD.

Background: To date, no large-scale studies have evaluated the prognosis of Crohn's disease (CD) over a period of 3 decades in non-Caucasian populations. The aims of this study were to update the current information on the long-term prognosis of CD using a large series of patients and to evaluate changes in treatment paradigms over time and their impact on the prognosis of CD in Korea., Methods: We retrospectively analyzed 2043 Korean patients with CD who visited the Asan Medical Center. The study subjects were divided into 3 groups according to the year of diagnosis (cohort 1: 1981-2000, cohort 2: 2001-2005, and cohort 3: 2006-2012)., Results: Azathioprine/6-mercaptopurine and anti-tumor necrosis factor agents have been used increasingly more frequently and earlier over the past 30 years, with a 5-year cumulative probability of prescription of 28.9% and 1.4%, respectively, in cohort 1 and 88.1% and 23.7%, respectively, in cohort 3 (P < 0.001). A total of 726 patients (35.5%) underwent intestinal resection, with a cumulative probability of intestinal resection 10, 20, and 30 years after diagnosis of 43.5%, 70.0%, and 76.1%, respectively. The cumulative probability of surgery was significantly lower in cohort 3 than in cohort 1 (P = 0.012). Early use of azathioprine/6-mercaptopurine was significantly associated with delayed need for intestinal resection by multivariate Cox analysis (hazard ratio: 0.63, 95% confidence interval: 0.46-0.85)., Conclusions: Korean patients with CD may have a similar clinical course to Westerners, as indicated by the intestinal resection rate. The surgery rate has decreased over time, and early use of azathioprine/6-mercaptopurine was related to its decrease.

Background: Little is known about the immune response to hepatitis A virus (HAV) vaccinations in patients with inflammatory bowel disease (IBD). We therefore assessed the immunogenicity of HAV vaccine in patients with IBD and evaluated the impact on vaccination efficacy of immunosuppressants, including corticosteroids, thiopurines, and anti-tumor necrosis factor (anti-TNF) agents., Methods: This open prospective study evaluated the efficacy of HAV vaccination in 419 anti-HAV-negative adult patients with IBD. Patients were vaccinated against HAV at 0 and 6 to 12 months, with seroconversion (anti-HAV immunoglobulin G) measured 1 to 3 months after the second dose., Results: Of the 419 vaccinated patients who finished the study protocol (mean age, 26.9 yr), 355 (84.7%) had Crohn's disease and 64 (15.3%) had ulcerative colitis. The overall seroconversion rate was 97.6% (409/419) but was significantly lower in patients treated with the anti-TNF monoclonal antibody infliximab or adalimumab than in those not treated (92.4% [85/92] versus 99.1% [324/327], P = 0.001). In addition, the seroconversion rate was significantly lower in patients treated with ≥2 than with <2 immunosuppressants (92.6% [50/54] versus 98.4% [359/365], P = 0.03). When comparing anti-TNF alone with anti-TNF and other immunosuppressants, there was no significant difference in seroconversion rates (odds ratio, 1.2; 95% confidence interval, 0.2-5.6; P = 0.83). The sample/cutoff ratio was significantly lower in patients who did receive anti-TNF therapy than in those who did not (5.5 versus 9.6; P < 0.001)., Conclusions: Although HAV vaccination is generally effective in patients with IBD, the seroconversion rate is lower in patients receiving anti-TNF agents (ClinicalTrials.gov registration number NCT01341808).

Background: Although infliximab is widely accepted as a therapeutic option for inflammatory bowel disease, its therapeutic efficacy for the treatment of intestinal Behçet's disease (BD) is unknown. We investigated the short-term and long-term response rates to infliximab in intestinal BD and predictive factors of sustained treatment response following infliximab treatment., Methods: This study was conducted using a retrospective noncontrolled review of medical records from 8 tertiary hospitals in Korea. We collected clinical, demographic, and laboratory data for patients with 28 patients with intestinal BD who received at least 1 dose of infliximab. Response rates of infliximab at 2, 4, 30, and 54 weeks for each patient and factors predictive of sustained response were investigated. Adverse events were also identified., Results: The median duration of follow-up after initial infliximab infusion was of 29.5 months. The clinical response rates at 2, 4, 30, and 54 weeks were 75%, 64.3%, 50%, and 39.1%, respectively, with clinical remission rates of 32.1%, 28.6%, 46.2%, and 39.1%, respectively. After multivariate analysis, older age at diagnosis (≥40 yr), female sex, a longer disease duration (≥5 yr), concomitant immunomodulator use, and achievement of remission at week 4 were found to be predictive factors of sustained response. There was 1 serious infection but no malignancies or deaths in this study., Conclusions: Infliximab was a well-tolerated and effective therapy for patients with moderate-to-severe intestinal BD. Moreover, we found 5 predictive factors associated with sustained response, which might assist in optimal patient selection for infliximab treatment.

Background: Recent genome-wide association studies and meta-analyses have identified 47 susceptibility loci for ulcerative colitis (UC) in Caucasian populations. A previous genome-wide association study of UC in a Japanese population suggested marginal sharing of susceptibility loci between Caucasian and Asian populations. We performed a genome-wide association studies to identify UC susceptibility loci in a Korean population and further comparative study., Methods: We analyzed 581,060 autosomal single-nucleotide polymorphisms (SNPs) in 388 individuals with UC and 739 control subjects in the discovery stage. For the validation, 64 suggestive SNPs were analyzed in an additional 417 affected individuals and 732 control subjects., Results: Three genetic loci were validated for significant association, and all were previously reported in Caucasians including the major histocompatibility complex region (top SNP, rs9271366; P = 1.03 × 10(-18), odds ratio [OR] = 2.10), 16q24.1 (rs16940186; P = 4.39 × 10(-10), OR = 1.56), and RNF186-OTUD3-PLA2G2E at chromosome arm 1p36.13 (top SNP, rs4654903 in OTUD3; P = 7.43 × 10(-9), OR = 0.64). Although failed to reach genome-wide statistical significance, 2 additional loci previously reported in Caucasians including rs17085007 at chromosome arm 13q12 and JAK2 at chromosome arm 9p24 were significant after Bonferroni correction (P(corrected) = 0.0016 and P(corrected) = 0.0056, respectively). FOS, UBE2L3, the JAK2 gene region, and rs1297265 at chromosome arm 21q21.1 likely play a role in both Crohn's disease and UC., Conclusions: Our data support the biologic significance of the overlapping loci for UC between Caucasian and Korean populations. Our data suggest that genetic associations for UC tend to overlap more extensively among different ethnic groups than those for Crohn's disease, which shows well-established dependence on ethnicity.

Background: Little is known about the clinical features of hepatitis B virus (HBV) infection in patients with inflammatory bowel disease (IBD). We therefore evaluated the influence of immunosuppressive treatment for IBD on the course of HBV infection and the effect of HBV infection on the therapeutic strategy and clinical course of IBD patients., Methods: We retrospectively evaluated the incidence of and risk factors for liver dysfunction in hepatitis B surface antigen (HBsAg)-positive IBD patients. Also, the clinical course of IBD patients with HBV infection was compared with matched IBD controls without HBV infection., Results: Of 4153 patients diagnosed with IBD between July 1989 and May 2011, 134 were HBsAg-positive, including 54 with Crohn's disease (CD) and 80 with ulcerative colitis (UC). Liver dysfunction was observed in 23 of the 134 (17.2%) HBsAg-positive patients. Prolonged immunosuppression (>3 months) was an independent predictor of liver dysfunction (odds ratio [OR] 3.06; 95% confidence interval [CI] 1.02-9.16). The rate of use of immunosuppressants, including corticosteroids (P = 0.005), azathioprine/6-mercaptopurine (P < 0.001), and infliximab (P = 0.026), was significantly lower in HBsAg-positive than HBsAg-negative IBD patients. Clinical outcomes, including admission rate, mean number of admissions, total proctocolectomy in UC patients, and mortality were worse in HBsAg-positive than HBsAg-negative IBD patients during the follow-up period., Conclusions: Liver dysfunction in HBsAg-positive IBD patients was more frequent in those with prolonged immunosuppression. IBD patients with chronic HBV infection used immunosuppressants less frequently and had a worse prognosis than those without it., (Copyright © 2012 Crohn's & Colitis Foundation of America, Inc.)

Background: Primary sclerosing cholangitis (PSC) is well known as one of the extraintestinal manifestations of ulcerative colitis (UC). However, the prevalence of PSC in UC patients together with the clinical characteristics and outcomes of UC associated with PSC (UC-PSC) are not clear in Asians., Methods: We retrospectively reviewed the medical records of UC patients who were registered and followed up at the Asan Medical Center. The prevalence of PSC in UC and the clinical features of UC-PSC compared with matched UC without PSC were investigated., Results: A total of 1849 patients diagnosed with UC between July 1977 and September 2009 were reviewed. Among these, 21 UC-PSC patients (1.1%) were identified. The cumulative probability of PSC after diagnosis of UC was 0.71% after 1-5 years, 1.42% after 10 years, 2.59% after 15 years, and 3.35% after 20-25 years. Compared with 63 matched UC alone patients, UC-PSC showed pancolitis (95.2%), rectal sparing (38.1%), and backwash ileitis (42.9%) more frequently (P < 0.001). During follow-up, three of 21 UC-PSC patients (14.3%) were diagnosed with colorectal neoplasia and three patients (14.3%) died of PSC-associated complications. UC-PSC patients were associated with increased probability of colorectal neoplasia development (P = 0.036) and a trend toward increased mortality compared with the UC alone group., Conclusions: The prevalence of PSC in Korean UC patients appears to be lower than that of Western patients. Similar to Caucasians, UC-PSC shows unique colonoscopic features and is associated with more frequent colorectal neoplasia development and poor prognosis in Korea., (Copyright © 2010 Crohn's & Colitis Foundation of America, Inc.)

Background: Distinguishing intestinal tuberculosis (ITB) from Crohn's disease (CD) is challenging. This study prospectively evaluated the clinical utility of the QuantiFERON-TB gold test (QFT) in the differential diagnosis of ITB and CD, and compared it with the clinical utility of the tuberculin skin test (TST)., Methods: Patients with suspected ITB or CD on colonoscopic findings were enrolled from 13 hospitals in Korea between June 2007 and November 2008. A QFT and TST were performed. When the initial diagnosis was not confirmed, 2-3 months of empiric antituberculous therapy was administered., Results: In all, 128 patients were analyzed; 64 patients had ITB and 64 patients had CD. The median age of patients with ITB was greater than the patients with CD (47 years versus 31 years, P < 0.001). The positive rate for the QFT and TST (≥10 mm) in patients with ITB was significantly higher than patients with CD (67% versus 9% and 69% versus 16%, respectively; P < 0.001). The QFT and TST had good agreement (κ = 0.724, P < 0.001). The diagnostic validity of QFT in ITB had a 67% sensitivity, 90% specificity, 87% positive predictive value, and 73% negative predictive value. There was no difference in these parameters between the QFT and TST. The likelihood ratio for a positive QFT was higher than a positive TST in the diagnosis of ITB (7.1 and 4.4, respectively)., Conclusions: The QFT is a limited but useful diagnostic aid in combination with the TST in the diagnosis of ITB., (Copyright © 2010 Crohn's & Colitis Foundation of America, Inc.)

Background: There is no disease activity index (DAI) currently available that can objectively assess the disease status of intestinal Behçet's disease (BD). The aim of this study was to develop a novel specific DAI for intestinal BD through a prospective study., Methods: Items included in the index were produced and graded by experts in intestinal BD. Two separate cohorts of patients (weighting and validation cohorts) with intestinal BD were prospectively enrolled, and their clinical and laboratory data were collected. Through weighting items by multiple regression modeling, the DAI for intestinal BD (DAIBD) was derived using the weighting cohort and validated using the validation cohort. The index's responsiveness was evaluated using a longitudinal cohort derived from the weighting cohort at a follow-up visit 2-3 months later., Results: A total of 110 patients with intestinal BD were enrolled in the weighting cohort. Eight of the 17 items selected by the experts accounted for 86.8% of the physician's global assessment (PGA) variance. The DAIBD calculated with gradations of weighted items correlated more strongly with PGA (r=0.850) than did the Crohn's disease activity index (CDAI) (r=0.649) in 50 patients of the validation cohort. Furthermore, quiescent, mild, moderate, and severe could be discriminated using the best cutoff scores. The DAIBD showed much higher responsiveness than did the CDAI (r=0.812 vs. 0.645, respectively) in 109 patients in the longitudinal cohort., Conclusions: This novel DAIBD is an easy, valid, and responsive index to assess disease activity and can be useful to physicians who treat intestinal BD.

Background: Recent genome-wide association studies in Caucasian populations identified IL23R and ATG16L1 as susceptibility genes to Crohn's disease (CD). We tested 5 IL23R single nucleotide polymorphisms (SNPs) and 12 ATG16L1 SNPs in Korean patients to determine whether these genes are associated with susceptibility to CD in a non-Caucasian population., Methods: We analyzed 5 IL23R SNPs and 12 ATG16L1 SNPs in 380 patients with CD and 380 healthy controls., Results: Two IL23R gene variants, an intronic SNP rs1004819 and intergenic SNP rs1495465, showed significant associations with CD; the adjusted odds ratio (aOR) for rs1004819 was 1.822 (95% confidence interval [CI] = 1.164-2.852, P = 0.009) and aOR for rs1495965 was 1.650 (95% CI = 1.102-2.471, P = 0.015). The genotype-phenotype analysis showed subphenotype specificity to stricturing and penetrating behaviors. On the other hand, none of the 12 ATG16L1 SNPs showed any positive association with CD in Koreans. The contribution of IL23R variants in Korean CD patients overall is low in comparison with studies of Caucasian., Conclusions: Our data in Koreans support the previous Caucasian reports of an association of the IL23R gene with CD.