Methods: Efficacy outcomes of interest were clinical response, clinical remission and mucosal healing at week 6 (induction phase); and clinical remission, durable clinical response, durable clinical remission, mucosal healing and glucocorticoid-free remission at week 52 (maintenance phase). Differences in outcome rates between vedolizumab and placebo in Asian countries (Hong Kong, India, Malaysia, Singapore, South Korea, and Taiwan) were assessed using descriptive analyses, and efficacy and safety compared between Asian and non-Asian countries.

Results: During induction, in Asian countries (n = 58), clinical response rates at week 6 with vedolizumab and placebo were 55.2% and 24.1%, respectively (difference 31.0%; 95% confidence interval: 7.2%-54.9%). In non-Asian countries (n = 316), response rates at week 6 with vedolizumab and placebo were 45.9% and 25.8%, respectively. During maintenance, in Asian countries, clinical remission rates at 52 weeks with vedolizumab administered every 8 weeks, vedolizumab administered every 4 weeks and placebo were 9.1%, 36.8%, and 31.6%, respectively; corresponding rates for mucosal healing were 45.5%, 47.4%, and 47.4%, respectively. Vedolizumab was well-tolerated; adverse event frequency was comparable in Asian and non-Asian countries.

METHODS: We determined the frequency of opportunistic infections and tuberculosis in patients receiving vedolizumab in phase 3 clinical trials and post-marketing settings. We also evaluated adverse events reported in the post-marketing setting in patients with a history of or concurrent hepatitis B/C virus infection.

RESULTS: The incidence of opportunistic infections in patients receiving vedolizumab was 0.7 (GEMINI 1 and 2 clinical trials) and 1.0 (long-term safety study) per 100 patient-years, with 217 events reported in approximately 114,071 patient-years of exposure (post-marketing setting). Most opportunistic infections were nonserious and the majority of patients continued treatment with vedolizumab. Clostridium difficile was the most commonly reported infection, with an incidence rate of 0.5 per 100 patient-years (clinical trials). Tuberculosis was reported at 0.1 per 100 patient-years (clinical trials), with 7 events in the post-marketing setting. No tuberculosis-related deaths were reported in either setting. No cases of progressive multifocal leukoencephalopathy were reported. In 29 patients with a history of or concurrent hepatitis B/C infection in the post-marketing setting, no viral reactivation was observed.

METHODS: We collected data from 7954 asymptomatic subjects (age, 50-75 y) who received screening colonoscopy examinations at 14 sites in Asia. We randomly assigned 5303 subjects to the derivation cohort and the remaining 2651 to the validation cohort. We collected data from the derivation cohort on age, sex, family history of colorectal cancer, smoking, drinking, body mass index, medical conditions, and use of nonsteroidal anti-inflammatory drugs or aspirin. Associations between the colonoscopic findings of APN and each risk factor were examined using the Pearson χ2 test, and we assigned each participant a risk score (0-15), with scores of 0 to 3 as average risk and scores of 4 or higher as high risk. The scoring system was tested in the validation cohort. We used the Cochran-Armitage test of trend to compare the prevalence of APN among subjects in each group.

RESULTS: In the validation cohort, 79.5% of patients were classified as average risk and 20.5% were classified as high risk. The prevalence of APN in the average-risk group was 1.9% and in the high-risk group was 9.4% (adjusted relative risk, 5.08; 95% CI, 3.38-7.62; P < .001). The score included age (61-70 y, 3; ≥70 y, 4), smoking habits (current/past, 2), family history of colorectal cancer (present in a first-degree relative, 2), and the presence of neoplasia in the distal colorectum (nonadvanced adenoma 5-9 mm, 2; advanced neoplasia, 7). The c-statistic of the score was 0.74 (95% CI, 0.68-0.79), and for distal findings alone was 0.67 (95% CI, 0.60-0.74). The Hosmer-Lemeshow goodness-of-fit test statistic was greater than 0.05, indicating the reliability of the validation set. The number needed to refer was 11 (95% CI, 10-13), and the number needed to screen was 15 (95% CI, 12-17).

METHODS: A multi-center, prospective colonoscopy study involving 16 Asia-Pacific regions was performed from 2008 to 2015. Consecutive self-referred CRC screening participants aged 40-70 years were recruited, and each subject received one direct optical colonoscopy. The prevalence of CRC, ACN, and colorectal adenoma was compared among subjects with different FDRs affected using Pearson's χ2 tests. Binary logistic regression analyses were performed to evaluate the risk of these lesions, controlling for recognized risk factors including age, gender, smoking habits, alcohol drinking, body mass index, and the presence of diabetes mellitus.

RESULTS: Among 11,797 asymptomatic subjects, the prevalence of CRC was 0.6% (none: 0.6%; siblings: 1.1%; mother: 0.5%; father: 1.2%; ≥2 members: 3.1%, P<0.001), that of ACN was 6.5% (none: 6.1%; siblings: 8.3%; mother: 7.7%; father: 8.7%; ≥2 members: 9.3%, P<0.001), and that of colorectal adenoma was 29.3% (none: 28.6%; siblings: 33.5%; mother: 31.8%; father: 31.1%; ≥2 members: 38.1%, P<0.001). In multivariate regression analyses, subjects with at least one FDR affected were significantly more likely to have CRC (adjusted odds ratio (AOR)=2.02-7.89), ACN (AOR=1.55-2.06), and colorectal adenoma (AOR=1.31-1.92) than those without a family history. The risk of CRC (AOR=0.90, 95% confidence interval (CI) 0.34-2.35, P=0.830), ACN (AOR=1.07, 95% CI 0.75-1.52, P=0.714), and colorectal adenoma (AOR=0.96, 95% CI 0.78-1.19, P=0.718) in subjects with either parent affected was similar to that of subjects with their siblings affected.

METHODS: 28 experts from 11 countries reviewed the evidence and modified the statements using the Delphi method, with consensus level predefined as ≥80% of agreement on each statement. The Grading of Recommendation Assessment, Development and Evaluation (GRADE) approach was followed.

RESULTS: Consensus was reached in 26 statements. At an individual level, eradication of H. pylori reduces the risk of GC in asymptomatic subjects and is recommended unless there are competing considerations. In cohorts of vulnerable subjects (eg, first-degree relatives of patients with GC), a screen-and-treat strategy is also beneficial. H. pylori eradication in patients with early GC after curative endoscopic resection reduces the risk of metachronous cancer and calls for a re-examination on the hypothesis of 'the point of no return'. At the general population level, the strategy of screen-and-treat for H. pylori infection is most cost-effective in young adults in regions with a high incidence of GC and is recommended preferably before the development of atrophic gastritis and intestinal metaplasia. However, such a strategy may still be effective in people aged over 50, and may be integrated or included into national healthcare priorities, such as colorectal cancer screening programmes, to optimise the resources. Reliable locally effective regimens based on the principles of antibiotic stewardship are recommended. Subjects at higher risk of GC, such as those with advanced gastric atrophy or intestinal metaplasia, should receive surveillance endoscopy after eradication of H. pylori.