Background: Patients suffering from inflammatory bowel diseases (IBD) and treated with originator infliximab are increasingly being switched to biosimilars. Some patients, however, are "reverse... Show moreBackground: Patients suffering from inflammatory bowel diseases (IBD) and treated with originator infliximab are increasingly being switched to biosimilars. Some patients, however, are "reverse switched" to treatment with the originator. Here we assess the prevalence of reverse switching, including its indication and outcomes.Methods: In this retrospective multicenter cohort study, data on patients with IBD from 9 hospitals in the Netherlands were collected. All adult patients with IBD were included if they previously had been switched from originator infliximab to the biosimilar CT-P13 and had a follow-up time of at least 52 weeks after the initial switch. The reasons for reverse switching were categorized into worsening gastrointestinal symptoms, adverse effects, or loss of response to CT-P13. Drug persistence was analyzed through survival analyses.Results: A total of 758 patients with IBD were identified. Reverse switching was observed in 75 patients (9.9%). Patients with reverse switching were predominantly female (70.7%). Gastrointestinal symptoms (25.5%) and dermatological symptoms (21.8%) were the most commonly reported reasons for reverse switching. In 9 patients (12.0%), loss of response to CT-P13 was the reason for reverse switching. Improvement of reported symptoms was seen in 73.3% of patients after reverse switching and 7 out of 9 patients (77.8%) with loss of response regained response. Infliximab persistence was equal between patients who were reverse-switched and those who were maintained on CT-P13.Conclusions: Reverse switching occurred in 9.9% of patients, predominantly for biosimilar-attributed adverse effects. Switching back to originator infliximab seems effective in patients who experience adverse effects, worsening gastrointestinal symptoms, or loss of response after switching from originator infliximab to CT-P13. Show less
Background: Fistulas represent a frequent and severe complication in patients with Crohn disease (CD). Tumor necrosis factor-alpha (TNF-alpha), transforming growth factor-beta, and interleukin (IL)... Show moreBackground: Fistulas represent a frequent and severe complication in patients with Crohn disease (CD). Tumor necrosis factor-alpha (TNF-alpha), transforming growth factor-beta, and interleukin (IL)-13 are known to trigger epithelial-mesenchymal transition (EMT), promoting fistula formation. Here, we investigated the role of T-lymphocytes (T cells) in fistula pathogenesis.Methods: CD3(+)CD8(-), CD3(+)CD8(+), or CD45(+)CD3(-) cells from healthy volunteers, patients with CD, and patients with CD with perianal fistula were co-cultured with HT-29 cells. The EMT, cytokine production, and mRNA expression were analyzed. Perianal CD fistula specimens were immunohistochemically stained for cytokines and their receptors. The effect of cytokines on EMT induction was investigated using an EMT spheroid model.Results: Patients with CD with fistula revealed more CD3(+)CD8(-) and less CD3(+)CD8(+) T cells in blood than healthy control patients and patients with CD without fistula. In perianal fistula specimens, CD4(+) cells-and to a lesser extent CD8(+) cells-were highly present around fistula tracts. When co-cultured with HT-29 cells, both cell subsets promoted EMT-related gene expression and TNF-alpha production in a time-dependent manner. The CD3(+)CD8(-) T cells from patients with CD with fistula also produced higher amounts of IL-13 than cells from healthy control patients or patients with CD without a fistula. We found that IL-22 and IL-22R(alpha 1) were highly expressed in perianal CD fistula specimens and that IL-22 cotreatment potentiated TNF-alpha-induced EMT in HT-29 spheroids.Conclusions: Our data indicate that both CD3(+)CD8(-) and CD3(+)CD8(+) T cells play an important role in the pathogenesis of perianal CD fistulas by the secretion of TNF-alpha. Our data support clinical evidence indicating that anti-TNF-alpha therapy is effective in fistula treatment and identify IL-13 and IL-22 as possible novel therapeutic targets for fistula therapy. Show less
Background Fistulas represent a frequent and severe complication in patients with Crohn disease (CD). Tumor necrosis factor-alpha (TNF-alpha), transforming growth factor-beta, and interleukin (IL)... Show moreBackground Fistulas represent a frequent and severe complication in patients with Crohn disease (CD). Tumor necrosis factor-alpha (TNF-alpha), transforming growth factor-beta, and interleukin (IL)-13 are known to trigger epithelial-mesenchymal transition (EMT), promoting fistula formation. Here, we investigated the role of T-lymphocytes (T cells) in fistula pathogenesis. Methods CD3(+)CD8(-), CD3(+)CD8(+), or CD45(+)CD3(-) cells from healthy volunteers, patients with CD, and patients with CD with perianal fistula were co-cultured with HT-29 cells. The EMT, cytokine production, and mRNA expression were analyzed. Perianal CD fistula specimens were immunohistochemically stained for cytokines and their receptors. The effect of cytokines on EMT induction was investigated using an EMT spheroid model. Results Patients with CD with fistula revealed more CD3(+)CD8(-) and less CD3(+)CD8(+) T cells in blood than healthy control patients and patients with CD without fistula. In perianal fistula specimens, CD4(+) cells-and to a lesser extent CD8(+) cells-were highly present around fistula tracts. When co-cultured with HT-29 cells, both cell subsets promoted EMT-related gene expression and TNF-alpha production in a time-dependent manner. The CD3(+)CD8(-) T cells from patients with CD with fistula also produced higher amounts of IL-13 than cells from healthy control patients or patients with CD without a fistula. We found that IL-22 and IL-22R(alpha 1) were highly expressed in perianal CD fistula specimens and that IL-22 cotreatment potentiated TNF-alpha-induced EMT in HT-29 spheroids. Conclusions Our data indicate that both CD3(+)CD8(-) and CD3(+)CD8(+) T cells play an important role in the pathogenesis of perianal CD fistulas by the secretion of TNF-alpha. Our data support clinical evidence indicating that anti-TNF-alpha therapy is effective in fistula treatment and identify IL-13 and IL-22 as possible novel therapeutic targets for fistula therapy. Show less
Inflammatory Bowel Diseases (IBD) such as Crohn’s disease (CD) and ulcerative colitis (UC) are chronic immunological digestive diseases with a progressive character and associated with significant... Show moreInflammatory Bowel Diseases (IBD) such as Crohn’s disease (CD) and ulcerative colitis (UC) are chronic immunological digestive diseases with a progressive character and associated with significant healthcare costs. Different solutions have been proposed such as innovation in care monitoring or implementation of electronic health (eHealth). IBD is one of many chronic diseases that could benefit from eHealth, adding smartphone applications to the toolbox for care management has the potential improve disease understanding, enhance medication adherence, improve patient-physician communications, and for earlier interventions by medical professionals when problems arise. Furthermore, the accessibility to Big Data and increased computational resources have paved the way for Artificial Intelligence (AI) to provide potential solutions for the management of prototypical complex diseases with advanced heterogeneity and alternating disease states, like IBD. In this thesis we assessed the current economic and psychosocial impact of IBD by assessing its effect on indirect costs, productivity and caregiving. Furthermore, we observed if we can proactively identify IBD patients’ needs using eHealth and Artificial Intelligence. Lastly, we analyze the impact of monitoring IBD patients using eHealth interventions in order to facilitate the delivery of high-value care. Show less
