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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. [ABSTRACT FROM AUTHOR]

LINKED CONTENT: This article is linked to Yiu et al papers. To view these articles, visit https://doi.org/10.1111/apt.18006 and https://doi.org/10.1111/apt.18114 [ABSTRACT FROM AUTHOR]

The article compares the influence of environmental risk factors and genetic factors in causing inflammatory bowel diseases (IBDs) based on epidemiological studies of migrants. Topics discussed include incidence of IBD in migrants, hygiene factors and the role of genetic risk factors and epigenetic changes. It also outlines the limitations of migrant studies on IBD.

Background/aims: To examine the association between use of oral contraceptive pills (OCPs) and the risk of developing inflammatory bowel diseases (IBD), in a modern cohort., Methods: A prospective nested case-control study across sites in the Asia-Pacific region was conducted; involving female IBD cases and asymptomatic controls. Subjects completed a questionnaire addressing questions related to OCP use. Primary outcome was the risk of development of IBD of those exposed to OCP versus non-exposure. Secondary outcomes were development of Crohn's disease (CD) versus ulcerative colitis (UC), and whether age of first use of OCP use may be associated with risk of IBD., Results: Three hundred and forty-eight female IBD cases (41% CD, median age: 43 years) and 590 female age-matched controls were recruited. No significant association was found between OCP use and the risk of IBD (odds ratio [OR], 1.65; 95% confidence interval, 0.77-3.13; P =0.22), CD (OR, 1.55) or UC (OR, 1.01). The lack of association persisted when results were adjusted for age and smoking. IBD cases commenced OCP use at a younger age than controls (18 years vs. 20 years, P =0.049)., Conclusions: In this large cohort of subjects from the Asia-Pacific region, we found a modest but not significantly increased risk of developing IBD amongst OCP users., Competing Interests: CONFLICT OF INTEREST: No potential conflict of interest relevant to this article was reported.

Introduction: Despite being an overall safe drug, several long-term adverse effects are associated with proton pump inhibitors (PPIs). The link between PPI use and gastric neuroendocrine tumors (NETs), gastric adenocarcinomas and Barrett's esophagus progression gastric cancers has been investigated due to PPI-induced hypergastrinemia., Areas Covered: The pathophysiological mechanisms underlying PPI exposure and gastric NETs, gastric adenocarcinomas and Barrett's esophagus progression are discussed. The quality of randomized control studies, cohort studies and case reports investigating the link between gastric cancers and PPIs are examined. Recommendations for clinicians are provided., Expert Opinion: PPIs cause a hypergastrinemic state, increasing enterochromaffin-like cell dysplasia and risk of gastric NET development, increasing gastritis severity in the context of Helicobacter pylori infection, and progression of carcinogenesis in a certain predisposed subset of Barrett's esophagus patients. There are case reports of PPI-induced gastric NETs and adenocarcinomas as consequences of these effects. In pernicious anemia and chronic gastritis, clinicians should be aware of potential increased risk of gastric NET development with chronic PPI use in these patients. Eradication status of H. pylori prior to commencing long-term PPI therapy should be established to reduce the risk of severe atrophic gastritis and development of gastric dysplasia.