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Introduction: Comparative effectiveness research provides data on the relative benefits and risks between treatments. In Crohn's disease (CD), however, there are few head-to-head studies comparing advanced therapies and none with long-term follow-up. Real-world effectiveness, defined by treatment persistence, obtained from prospective population-based patient cohorts, may help determine the best sequencing and positioning of biological agents., Methods: We analyzed the prospectively collected population-based Australian national Pharmaceutical Benefits Scheme dispensing data registry (2005-2019) for CD. There is no mandated biological agent prescribing order, and all citizens and permanent residents are eligible for treatment irrespective of insurance status. Propensity score matching was performed to reduce selection bias., Results: There were 2,029 lines of therapy in 1,446 patients (median age 43 years, interquartile range 34-58, 44% male patients) over the 15-year period with 5,618 patient-years of follow-up. Per line of therapy, 915/2,029 (45.1%) patients used adalimumab, 722/2,029 (35.6%) used infliximab, 155/2,029 (7.6%) used vedolizumab, and 237/2,029 (11.7%) used ustekinumab. When used in biological agent-naive patients, there was no difference in persistence between any agent ( P > 0.05). Used after first line in biological agent-experienced CD, ustekinumab had significantly better persistence than non-ustekinumab biological agents ( P = 0.0018), vs anti-tumor necrosis factor (TNF) alpha therapy ( P = 0.006) or vedolizumab ( P < 0.001). Ustekinumab persistence was unaffected by prior biological agent exposure ( P = 0.51). After anti-TNF use, ustekinumab had superior persistence to an alternative anti-TNF agent ( P = 0.033) and to vedolizumab ( P = 0.026). Using a propensity score-matched analysis adjusted for age, immunomodulator use, and bio-exposed status, ustekinumab had superior persistence to anti-TNF ( P = 0.01). Multivariate predictors of worse persistence were the use of a non-ustekinumab biological agent (adjusted hazard ratio 2.10, P < 0.001), and bio-experienced status (adjusted hazard ratio 1.23, P < 0.001)., Discussion: This large national prospective database with nonhierarchical prescribing of biological agents did not identify superior persistence of any agent in bio-naive CD. However, for patients with bio-experienced CD, persistence was greater with ustekinumab., (Copyright © 2024 by The American College of Gastroenterology.)

Introduction: Ulcerative colitis (UC) is a chronic condition that may require long-term treatment. We report the final efficacy and safety results of the UNIFI long-term extension study of ustekinumab in patients with UC through 4 years., Methods: Ustekinumab induction responders who completed 44 weeks of maintenance treatment and agreed to enter the long-term extension continued their subcutaneous maintenance therapy (90 mg ustekinumab every 8 or 12 weeks [q8w or q12w] or placebo). Starting at week 56, randomized patients could receive dose adjustment to 90 mg q8w. Symptoms and adverse events were assessed through the study; endoscopic assessment was conducted at week 200., Results: Of the 348 patients randomized to subcutaneous ustekinumab at maintenance baseline (q8w and q12w combined), 55.2% were in symptomatic remission at week 200. A greater proportion of biologic-naive patients (67.2% [117/174]) were in symptomatic remission than those with a history of biologic failure (41.6% [67/161]). Among patients in symptomatic remission at week 200, 96.4% were corticosteroid-free. Of the 171 patients with endoscopic evaluation at week 200, 81.6% (71/87) in the q12w group and 79.8% (67/84) in the q8w group had endoscopic improvement. From weeks 156 to the final safety visit (up to week 220), no deaths, major adverse cardiovascular events, or tuberculosis occurred in patients receiving ustekinumab. Nasopharyngitis, UC worsening, and upper respiratory tract infections were the most frequently reported adverse events., Discussion: The long-term efficacy of ustekinumab maintenance in patients with UC was confirmed through 4 years. No new safety signals were observed. ClinicalTrials.gov number NCT02407236., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.)

Introduction: Infertility may occur in women with Crohn's disease (CD) and ulcerative colitis (UC), especially after surgery such as ileal pouch-anal anastomosis (IPAA). Assisted reproductive technology (ART) may be an option, but the safety and efficacy in this setting has been based on small cohorts to date. We performed a systematic review and meta-analysis to address this data gap., Methods: A systematic review and random-effects meta-analysis was performed until May 2020. The primary outcomes were pregnancy and live birth rates per cycle of ART., Results: Eleven studies met inclusion criteria for the systematic review and 4 for the meta-analysis. Compared with the general population, women with CD (with and without previous surgery) had no difference in pregnancy rates (odds ratio [OR] = 0.69, 95% confidence interval [CI]: 0.45-1.05) but had reduced live births (OR = 0.67, 95% CI: 0.53-0.85) per cycle of ART. ART live birth rates are not reduced in women with medically managed CD; however, they are 49%-71% lower after CD-related surgery. Women with UC had no difference in both pregnancy rates (OR = 0.99, 95% CI: 0.63-1.55) and live birth rates (OR = 0.88, 95% CI: 0.67-1.17); however, live birth rates were reduced after IPAA failure (hazard ratio = 0.36, 95% CI: 0.14-0.92). Two studies did not identify any significant safety signals., Discussion: ART is safe and effective in patients with UC and medically managed CD, with pregnancy and live birth rates similar to that of the general population. However, within the limitations of the available literature, current data suggest that efficacy is reduced in women with CD-related surgery and IPAA failure. Greater gastroenterologist awareness of ART is needed to facilitate timely fertility therapy referral when indicated, particularly in CD., (Copyright © 2021 by The American College of Gastroenterology.)

Introduction: Esophagogastric junction outflow obstruction (EGJOO) defined on high-resolution esophageal manometry (HRM) poses a management dilemma given marked variability in clinical manifestations. We hypothesized that findings from provocative testing (rapid drink challenge and solid swallows) could determine the clinical relevance of EGJOO., Methods: In a retrospective cohort study, we included consecutive subjects between May 2016 and January 2020 with EGJOO. Standard HRM with 5-mL water swallows was followed by provocative testing. Barium esophagography findings were obtained. Cases with structural obstruction were separated from functional EGJOO, with the latter categorized as symptom-positive or symptom-negative. Only symptom-positive subjects were considered for achalasia-type therapies. Sensitivity and specificity for clinically relevant EGJOO during 5-mL water swallows, provocative testing, and barium were calculated., Results: Of the 121 EGJOO cases, 76% had dysphagia and 25% had holdup on barium. Ninety-seven cases (84%) were defined as functional EGJOO. Symptom-positive EGJOO subjects were more likely to demonstrate abnormal motility and pressurization patterns and to reproduce symptoms during provocative testing, but not with 5-mL water swallows. Twenty-nine (30%) functional EGJOO subjects underwent achalasia-type therapy, with symptomatic response in 26 (90%). Forty-eight (49%) functional EGJOO cases were managed conservatively, with symptom remission in 78%. Although specificity was similar, provocative testing demonstrated superior sensitivity in identifying treatment responders from spontaneously remitting EGJOO (85%) compared with both 5-mL water swallows (54%; P < 0.01) and barium esophagography (54%; P = 0.02)., Discussion: Provocative testing during HRM is highly accurate in identifying clinically relevant EGJOO that benefits from therapy and should be routinely performed as part of the manometric protocol., (Copyright © 2020 by The American College of Gastroenterology.)

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.

Background: Studies have reported the effect of gender in the context of assessing predictors of survival from colorectal cancer (CRC); however, few have specifically addressed the impact of gender on the clinical and pathological outcomes of CRC. Appreciation of gender disparities may assist in the implementation of measures to address these differences, and improve the overall outcomes of patients with CRC., Methods: The South Western Sydney Colorectal Tumour Group registry, which encompasses a population in excess of 800,000, prospectively collects data on new patients with CRC. Data from 1997 to 2004 were collected, including demography, site, grade, histopathology, stage, treatment, and survival., Results: In total, 2,050 consecutive patients (44% women) with CRC were analyzed. Compared to men, women were older (median 69 yr, range 27-95 yr vs 67, range 22-92 yr, P= 0.001), had more emergency surgery for CRC-related complications (18.8%vs 15.1%, P= 0.03), had more proximal cancers (42.2%vs 31.5%, P < 0.001), had more poorly differentiated cancers (16.9%vs 12.9%, P= 0.01), and had fewer radiotherapy treatments for Dukes B and C rectal cancers (36.4%vs 48.1%, P= 0.02). Young women (aged 50 yr and below) had significantly better overall survival compared to young men; in this group, female gender predicted improved overall survival independent of age, emergency surgery, site, grade, and stage (hazard ratio [HR] 0.46, 95% confidence interval [CI] 0.25-0.86, P= 0.01). Similarly, young women had significantly better cancer-specific survival (HR 0.46, 95% CI 0.25-0.85, P= 0.01). However, older women (aged over 50 yr) had worse survival independent of age, emergency surgery, site, grade, and stage (HR 1.38, 95% CI 1.14-1.68, P= 0.001). There were no gender differences in screening, histopathology, stage, or utilization of chemotherapy., Conclusions: This study demonstrated an opposing effect of gender on overall and cancer-specific survival at either side of the age of 50 yr. The protective effect of estrogen on CRC may be an important factor. Women had a greater proportion of emergency surgery, which was related to the predominance of proximal cancers in this gender. Women also had more proximal cancers, thereby limiting flexible sigmoidoscopy as a screening test.

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.