Intestinal resection rates in Crohn’s disease decline across two different epidemiological areas: a consistent observation not merely due to introduction of anti-TNFα

Beelen, Evelien M J; Woude, C. Janneke van der; Vries, Annemarie C. de

doi:10.1136/gutjnl-2019-319321

Cited by 4 publications

(4 citation statements)

References 3 publications

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“…Actually, the risk of intestinal resection could be influenced by several factors other than medication, such as improved access to diagnostic procedures, improved awareness of the disease, early CD diagnosis before development of bowel damage, and strict monitoring strategies. 50 , 51 Additionally, the clinical decision-making on intestinal resection for patients with CD can be influenced by multiple factors, including the preferences of patients and physicians, medical costs, and cultural differences. Hence, subsequent well-designed studies controlling multiple potential confounders and applying a consistent treatment algorithm for CD patients are required to prove the causal relationship between various drugs and intestinal resection.…”

Section: Discussionmentioning

confidence: 99%

Clinical Features and Long-term Prognosis of Crohn’s Disease in Korea: Results from the Prospective CONNECT Study

Hong

Cheon

et al. 2022

Gut and Liver

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Background/Aims: The prospective Crohn's Disease Clinical Network and Cohort Study is a nationwide multicenter cohort study of patients with Crohn's disease (CD) in Korea, aiming to prospectively investigate the clinical features and long-term prognosis associated with CD.Methods: Patients diagnosed with CD between January 2009 and September 2019 were prospectively enrolled. They were divided into two cohorts according to the year of diagnosis: cohort 1 (diagnosed between 2009 and 2011) versus cohort 2 (between 2012 and 2019). Results: A total of 1,175 patients were included, and the median follow-up duration was 68 months (interquartile range, 39.0 to 91.0 months). The treatment-free durations for thiopurines (p<0.001) and anti-tumor necrosis factor agents (p=0.018) of cohort 2 were shorter than those of cohort 1. Among 887 patients with B1 behavior at diagnosis, 149 patients (16.8%) progressed to either B2 or B3 behavior during follow-up. Early use of thiopurine was associated with a reduced risk of behavioral progression (adjusted hazard ratio [aHR], 0.69; 95% confidence interval [CI], 0.50 to 0.90), and family history of inflammatory bowel disease was associated with an increased risk of behavioral progression (aHR, 2.29; 95% CI, 1.16 to 4.50). One hundred forty-one patients (12.0%) underwent intestinal resection, and the intestinal resection-free survival time was significantly longer in cohort 2 than in cohort 1 (p=0.003). The early use of thiopurines (aHR, 0.35; 95% CI, 0.23 to 0.51) was independently associated with a reduced risk of intestinal resection. Conclusions:The prognosis of CD in Korea appears to have improved over time, as evidenced by the decreasing intestinal resection rate. Early use of thiopurines was associated with an improved prognosis represented by a reduced risk of intestinal resection.

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Section: Discussionmentioning

confidence: 99%

Clinical Features and Long-term Prognosis of Crohn’s Disease in Korea: Results from the Prospective CONNECT Study

Hong

Cheon

et al. 2022

Gut and Liver

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“…Inflammatory bowel disease (IBD), comprising Crohn's disease and ulcerative colitis, a chronic immunologically mediated disease with various risk factors, has traditionally been found in North America and Western Europe but, in recent years, is increasing globally 1 . Clinical outcomes for IBD have improved, as evidenced by decreased intestinal resection rates in Crohn's disease 2 . However, IBD is still regarded as an incurable chronic and debilitating intestinal disease with limited available therapies, which causes an increased risk for colon cancer, depression, and morbidity 3 .…”

Section: Introductionmentioning

confidence: 99%

“…1 Clinical outcomes for IBD have improved, as evidenced by decreased intestinal resection rates in Crohn's disease. 2 However, IBD is still regarded as an incurable chronic and debilitating intestinal disease with limited available therapies, which causes an increased risk for colon cancer, depression, and morbidity. 3 Developing novel anti-IBD therapies is needed to improve the life quality of IBD patients.…”

Section: Introductionmentioning

confidence: 99%

St. John’s Wort alleviates dextran sodium sulfate‐induced colitis through pregnane X receptor‐dependent NFκB antagonism

et al. 2021

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St. John's wort (SJW), from traditional herbs, activates the pregnane X receptor (PXR), a potential drug target for treating inflammatory bowel disease (IBD).However, how SJW alleviates dextran sodium sulfate (DSS)-induced experimental IBD by activating PXR is unknown. To test this, PXR-humanized, wild-type (WT) and Pxr-null mice, primary intestinal organoids cultures, and the luciferase reporter gene assays were employed. In vivo, a diet supplemented with SJW was found to activate intestinal PXR both in WT and PXR-humanized mice, but not in Pxr-null mice. SJW prevented DSS-induced IBD in PXR-humanized and WT mice, but not in Pxr-null mice. In vitro, hyperforin, a major component of SJW, activated PXR and suppressed tumor necrosis factor (TNF)α-induced nuclear factor (NF) κB translocation in primary intestinal organoids from PXR-humanized mice, but not Pxr-null mice. Luciferase reporter gene assays showed that hyperforin dose-dependently alleviated TNFα-induced NFκB transactivation by activating human PXR in Caco2 cells. Furthermore, SJW therapeutically attenuated DSS-induced IBD in PXR-humanized mice. These data indicate the therapeutic potential of SJW in alleviating DSS-induced IBD in vivo, and TNFα-induced NFκB activation in vitro, dependent on PXR activation, which may have clinical implications for using SJW as a herbal drug anti-IBD treatment.

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“… 2 Anti‐tumor necrosis factor (TNF) α therapy has resulted in a paradigm shift in the management of CD, improving outcomes and reducing intestinal resection rates. 3 , 4 On the other hand, loss of responsiveness after anti‐TNFα agent treatment has been reported. 5 Moreover, a risk of increased susceptibility to infections and a possible propensity for malignancy have limited the long‐term use of these drugs.…”

Section: Introductionmentioning

confidence: 99%

Phase 1 study on the safety and efficacy of E6011, antifractalkine antibody, in patients with Crohn's disease

Matsuoka

Hibi

Tsubouchi

et al. 2021

J of Gastro and Hepatol

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Background and Aim: E6011 is a humanized monoclonal antibody targeting fractalkine (FKN), a CX3C chemokine, which regulates leukocyte trafficking during inflammation. We evaluated the safety and pharmacokinetic profile of E6011 in patients with Crohn's disease (CD) and also performed preliminary pharmacodynamic (PD) and efficacy assessments. Methods: This study included a 12-week multiple ascending dose (MAD) phase (2, 5, 10, and 15 mg/kg intravenously every 2 weeks, n = 6, 8, 7, and 7, respectively) and a 40-week Extension phase (n = 12) at the same dose as the MAD phase. Serum E6011, serum total FKN (free soluble FKN and E6011-FKN complex) as a PD marker and CD activity index were evaluated. The primary outcome was safety assessment in the MAD phase. Results: Twenty-seven (96%) of 28 patients had previously been treated with anti-tumor necrosis factor α agents. During the MAD phase, adverse events (AEs) occurred in 18 (64%). The most common AE was nasopharyngitis (five patients, 18%). No severe AEs occurred. Serious AEs occurred in three patients, progression of CD in two, and anemia in one. Serum E6011 concentrations increased dose-dependently after infusion and reached a plateau around 4-6 weeks. Serum total FKN rose simultaneously. Five (18%) patients developed anti-E6011 antibodies during the study. Overall, clinical response and clinical remission were observed at Week 12 in 40% (10/25) and 16% (4/25) of active CD patients, respectively. Conclusion: E6011 was well-tolerated and might be effective in CD patients. These findings need to be clarified in a randomized controlled study.

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Intestinal resection rates in Crohn’s disease decline across two different epidemiological areas: a consistent observation not merely due to introduction of anti-TNFα

Cited by 4 publications

References 3 publications

Clinical Features and Long-term Prognosis of Crohn’s Disease in Korea: Results from the Prospective CONNECT Study

Clinical Features and Long-term Prognosis of Crohn’s Disease in Korea: Results from the Prospective CONNECT Study

St. John’s Wort alleviates dextran sodium sulfate‐induced colitis through pregnane X receptor‐dependent NFκB antagonism

Phase 1 study on the safety and efficacy of E6011, antifractalkine antibody, in patients with Crohn's disease

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