Use of biologics for inflammatory bowel disease in Hong Kong: consensus statement.

UNLABELLED: OBJECTIVE; With the increasing use of biologics in patients with inflammatory bowel disease, the Hong Kong IBD Society developed a set of consensus statements intended to serve as local recommendations for clinicians about the appropriate use of biologics for treating inflammatory bowel disease. PARTICIPANTS: The consensus meeting was held on 9 July 2011 in Hong Kong. Draft consensus statements were developed by core members of the Hong Kong IBD Society, including local gastroenterologists and colorectal surgeons experienced in managing patients with inflammatory bowel disease. EVIDENCE: Published literature and conference proceedings on the use of biologics in management of inflammatory bowel disease, and guidelines and consensus issued by different international and regional societies on recommendations for biologics in inflammatory bowel disease patients were reviewed. CONSENSUS PROCESS: Four core members of the consensus group drafted 19 consensus statements through the modified Delphi process. The statements were first circulated among a clinical expert panel of 15 members for review and comments, and were finalised at the consensus meeting through a voting session. A consensus statement was accepted if at least 80% of the participants voted "accepted completely or "accepted with some reservation". CONCLUSIONS: Nineteen consensus statements about inflammatory bowel disease were generated by the clinical expert panel meeting. The statements were divided into four parts which covered: (1) epidemiology of the disease in Hong Kong; (2) treatment of the disease with biologics; (3) screening and contra-indications pertaining to biologics; and (4) patient monitoring after use of biologics. The current statements are the first to describe the appropriate use of biologics in the management of inflammatory bowel disease in Hong Kong, with an aim to provide guidance for local clinical practice.

Comparison of clinical characteristics and management of inflammatory bowel disease in Hong Kong versus Melbourne.

BACKGROUND AND AIM: Inflammatory bowel disease (IBD), common in Melbourne, was rare but is now increasing in incidence in Hong Kong (HK). To investigate whether these are the same diseases in the West and East, potential causes of changing incidence, and to plan resource needs, an appreciation of clinical characteristics in contrasting populations is essential. METHODS: Disease characteristics were collected from prospectively populated IBD databases in two specialist centers in Melbourne, Australia and HK. RESULTS: Of 795 patients (Crohn's disease [CD] : ulcerative colitis [UC] Melbourne 272:159 and HK 161:203), the age of diagnosis was higher, there were proportionally more male patients with CD but no UC sex difference, fewer patients were current or ex-smokers (CD 8% vs 50%; UC 17% vs 35%) and a family history of IBD was less common (2% vs 11%; P < 0.001) in HK compared to Melbourne. Stricturing and perianal CD were more common in HK (12% vs 6%; P < 0.001; and 29% vs 16%; P = 0.001, respectively). In HK for UC, more patients had extensive disease at diagnosis (42% vs 22%) but colectomy was less common (7% vs 20%; P < 0.001). In Melbourne there was greater steroid use at diagnosis and patients were more likely to receive an immunomodulator or anti-tumor necrosis factor agent. CONCLUSIONS: IBD in HK was diagnosed at an older age, and had more complicated disease behavior than in Melbourne. Medical therapy, however, was less intense in HK. These differences may relate to real differences in disease or delayed diagnosis due to late presentation and less disease recognition in HK.

Long-term follow-up of ulcerative colitis in the Chinese population.

OBJECTIVES: The incidence of ulcerative colitis (UC) in Asia is increasing but reports on its long-term course are few. We set out determine the incidence, prevalence, and survival rate of UC in the Chinese population and phenotypic stability by longitudinal follow-up. METHODS: A cohort of Chinese UC patients were followed up in a tertiary referral center in Hong Kong between 1985 and 2006. Clinical data were prospectively collected since 2001. Population statistics were obtained from the Census and Statistics Department of Hong Kong for the calculation of age-specific incidence, prevalence, and survival. The disease phenotypes at diagnosis and upon follow-up were documented. RESULTS: A total of 172 patients (51.7% men) with a median age at diagnosis of 37.0 years (range: 12.0-85.0) were included. The cohort was observed for a total of 1,393 person-years with a median follow-up duration of 7.0 years (range: 0.5-22.0). The age-standardized incidence and prevalence rates of UC per 100,000 were 2.1 (95% confidence interval, CI: 1.1-3.7) and 26.5 (95% CI: 22.6-30.9), respectively, in 2006. The 10-year cumulative rate of proximal extension was 23.8%. Only one patient developed colorectal cancer during the observation period. The cumulative colectomy rates were 2.4% and 7.6% at 1 and 10 years of follow-up. Overall survival was similar to that expected (P=0.07). CONCLUSIONS: The incidence of UC has increased sixfold in the past two decades in Hong Kong. The complication, colorectal cancer, and colectomy rates are low in Chinese patients but increase with duration of illness.

Non-NSAID non-H. pylori ulcer disease.

Non-NSAID non-Helicobacter pylori ulcer disease, which was believed to account for a minority of bleeding gastroduodenal ulcers, has been increasingly recognized for the past decade. Current data suggest that both relative proportion and actual numbers of patients with non-NSAID non-H. pylori ulcers have increased, whereas the prevalence of H. pylori-positive ulcers has declined. There is evidence to support that non-NSAID non-H. pylori ulcers associate with a higher risk of recurrent ulcer bleeding and a higher overall mortality as compared to H. pylori-positive ulcer disease. Patients with non-NSAID non-H. pylori ulcers are often older, sicker and more frequently experience bleeding episodes while in hospital. The pathogenesis of non-NSAID non-H. pylori ulcer is largely unknown and the efficacy of acid suppressants in the management and prevention of the disease remains to be defined. Well-designed, large-scale studies are awaited to shed light on this emerging condition.

Upper gastrointestinal tract phenotype of Crohn's disease is associated with early surgery and further hospitalization.

BACKGROUND: According to the Montreal Classification, upper gastrointestinal tract phenotype L4 is uncommon in Caucasian patients with Crohn's disease (CD) but carries excess risk of recurrence. We studied the clinical course of CD in Chinese patients presenting with the L4 phenotype and factors predicting its occurrence upon longitudinal follow-up. METHODS: This prospective cohort study included 132 Chinese CD patients (median age at diagnosis, 30.0 years, range: 14.0-77.0 years) who were followed for 770 person-years. Demographic data including disease behavior and location, details of surgery, and hospitalization were collected. The Kaplan-Meier method was used to estimate the probabilities of further hospitalization and major surgery followed by Cox proportional hazards regression to determine if clinical variables independently predicted the endpoints. RESULTS: The L4 phenotype was found in 30 (22.7%) patients at presentation. There were significantly more stricturing (46.7% versus 18.6%) and penetrating (30.0% versus 3.9%) phenotypes in the L4 group than in the non-L4 group (P < 0.0001). The 3-year cumulative probability of further hospitalization was 86.9% (95% confidence interval [CI]: 73.8%-100.0%) in the L4 group as compared with 49.3% (95% CI: 39.3%-59.3%) in the non-L4 group (log-rank test, P < 0.0001). The L4 phenotype independently predicted further hospitalization (adjusted hazards ratio [HR]: 2.1; 95% CI: 1.3-3.5). The cumulative probability of major surgery was significantly higher in the L4 than in the non-L4 group (P < 0.0001). Eighteen (17.6%) patients developed the L4 phenotype on follow-up and the stricturing phenotype predicted its occurrence (adjusted HR: 5.5; 95% CI: 2.2-14.0). CONCLUSIONS: Chinese CD patients more often had the L4 phenotype, which predicted the need of subsequent hospitalization.

Changes in Crohn's disease phenotype over time in the Chinese population: validation of the Montreal classification system.

BACKGROUND: Phenotypic evolution of Crohn's disease occurs in whites but has never been described in other populations. The Montreal classification may describe phenotypes more precisely. The aim of this study was to validate the Montreal classification through a longitudinal sensitivity analysis in detecting phenotypic variation compared to the Vienna classification. METHODS: This was a retrospective longitudinal study of consecutive Chinese Crohn's disease patients. All cases were classified by the Montreal classification and the Vienna classification for behavior and location. The evolution of these characteristics and the need for surgery were evaluated. RESULTS: A total of 109 patients were recruited (median follow-up: 4 years, range: 6 months-18 years). Crohn's disease behavior changed 3 years after diagnosis (P = 0.025), with an increase in stricturing and penetrating phenotypes, as determined by the Montreal classification, but was only detected by the Vienna classification after 5 years (P = 0.015). Disease location remained stable on follow-up in both classifications. Thirty-four patients (31%) underwent major surgery during the follow-up period with the stricturing [P = 0.002; hazard ratio (HR): 3.3; 95% CI: 1.5-7.0] and penetrating (P = 0.03; HR: 5.8; 95% CI: 1.2-28.2) phenotypes according to the Montreal classification associated with the need for major surgery. In contrast, colonic disease was protective against a major operation (P = 0.02; HR: 0.3; 95% CI: 0.08-0.8). CONCLUSIONS: This is the first study demonstrating phenotypic evolution of Crohn's disease in a nonwhite population. The Montreal classification is more sensitive to behavior phenotypic changes than is the Vienna classification after excluding perianal disease from the penetrating disease category and was useful in predicting course and the need for surgery.

The use of tacrolimus in the treatment of inflammatory bowel disease.

Tacrolimus is a calcineurin inhibitor that suppresses pro-inflammatory cytokine production and T-cell activation. These immunosuppressant effects have been used to treat inflammatory bowel disease, especially fistulising Crohn's disease and refractory ulcerative colitis. The more predictable oral bioavailability and better side-effect profile makes tacrolimus a more favourable choice as compared with ciclosporin. Dose-dependent side effects, such as nephrotoxicity, are reported but are mostly reversible with dose reduction or cessation of therapy. Topical tacrolimus has also been used to treat pyoderma gangrenosum, an extra-intestinal manifestation of inflammatory bowel disease. Tacrolimus is well-tolerated and should be considered as an alternative agent in the treatment of inflammatory bowel disease, especially those intolerant or refractory to the more conventional immunomodulators.

Long-term follow-up of patients with obscure gastrointestinal bleeding after negative capsule endoscopy.

BACKGROUND AND AIMS: Capsule endoscopy (CE) is one of the widely accepted investigations for obscure gastrointestinal bleeding (OGIB), but little is known about the impact of CE on the long-term outcome of patients with OGIB. We studied the long-term outcome of patients with OGIB after CE examination. PATIENTS AND METHODS: Forty-nine consecutive patients (45% men, mean age 58.3 yr) who underwent CE for OGIB were studied. The most clinically relevant finding that was related to bleeding was identified by CE. All patients were followed up for at least 12 months for clinical overt and occult bleeding. RESULTS: The median follow-up was 19 months (range 12 to 31). Possible bleeding lesions were detected by CE in 31 (63.3%) patients, and 15 (30.6%) patients, underwent further interventions including laparotomy and push enteroscopy. The overall long-term rebleeding rate in this cohort was 32.7%. The cumulative rebleeding rate was significantly lower in patients with a negative CE (5.6%) than in patients with a positive CE (48.4%, p=0.03 log-rank test). The sensitivity and negative predictive value of CE in predicting rebleeding were 93.8% and 94.4%, respectively. CONCLUSIONS: Patients with OGIB and negative CE had a very low rebleeding rate, and further invasive investigations can be deferred.

Association of intestinal granulomas with smoking, phenotype, and serology in Chinese patients with Crohn's disease.

INTRODUCTION: Crohn's disease (CD) is a heterogenous disease characterized by variable manifestations and outcomes, and increasing in incidence in China. Phenotypic classification has been proposed to assist in subtyping of disease. Non-caseating intestinal granulomas are a hallmark of CD, but whether intestinal granulomas help predict Chinese CD phenotypes or determine severity, is not known. AIMS: To determine the association between intestinal granulomas with CD phenotype, severity, risk factors, and serological markers. METHODS: This was a single-centre study of consecutive definite Chinese CD cases. Granulomas were diagnosed by an experienced GI pathologist. Correlation with the Vienna Classification and other parameters was performed. RESULTS: Eighty Chinese CD patients were recruited, 40 (50%) of whom had intestinal granulomas. Intestinal granulomas were independently associated with the stricturing behavior (OR: 4.71; 95% CI: 1.41-15.72), colonic location of disease (OR: 26.96; 95% CI: 2.68-271.14), but not with age of CD diagnosis. Current or previous smoking protected against the development of granulomas (OR: 0.16; 95% CI: 0.04-0.59). Granulomas were not associated with peri-anal involvement, extra-intestinal manifestations, anti-neutrophil cytoplasmic antibody or anti-Saccharomyces cerevisiae antibody serology, or severity of CD gauged by the requirement of major intestinal surgery or immunomodulating therapy. CONCLUSIONS: Intestinal granulomas in the setting of CD may be helpful in determining phenotypic subtypes of CD, but is unhelpful in predicting disease severity. Smoking impairs the formation of granulomas in CD.

Inter-observer variations on interpretation of capsule endoscopies.

OBJECTIVE: Capsule endoscopy is a novel investigation for diagnosing small bowel diseases. However, its interpretation is highly subjective and the potential variability may compromise its accuracy and reliability. Here we studied the potential inter-observer variations on the interpretation of capsule endoscopy. METHOD: Two residents and one specialist in gastroenterology independently reviewed 58 capsule endoscopy studies in the same sequential order. The gastric transit time, small bowel transit time, and the most significant small bowel lesion were independently recorded. The consensus transit time was determined by the joint review of the three gastroenterologists. The 'gold standard' for small bowel diagnoses was based on final surgical, endoscopic findings or consensus diagnosis. RESULTS: Clinically significant and relevant small bowel lesions were found in 32 (55%) cases by consensus review. The overall mean accuracy in determining gastric emptying time, small bowel transit time and small bowel lesion was 89%, 76% and 80%, respectively. There was a significant difference in the accuracy between the residents and specialist on small bowel transit time (P<0.05) and small bowel diagnosis (P<0.05). The mean kappa values on small bowel diagnosis among the three viewers was 0.56 (range, 0.52-0.59). Among various small bowel diagnoses, small bowel bleeding was more accurately identified than other pathology. CONCLUSIONS: Our results show that there is moderate degree of inter-observer discrepancies on the interpretation of capsule endoscopy. A second reading by an experienced viewer might improve the diagnostic accuracy of this investigation.