Infliximab for Crohnʼs disease in the Swiss IBD Cohort Study

Juillerat, Pascal; Pittet, Valérie; Vader, John‐Paul; Burnand, Bernard; Gonvers, Jean‐Jacques; Saussure, Philippe de; Mottet, Christian; Seibold, Frank; Rogler, Gerhard; Sagmeister, Markus; Felley, Christian; Michetti, Pierre; Froehlich, Florian

doi:10.1097/meg.0b013e32833eaa8a

Cited by 10 publications

(3 citation statements)

References 22 publications

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“…Inflammatory conditions, which are accompanied by intestinal tight junction function changes, are common in IBD and NEC [ 5 , 6 ]. Pro-inflammatory cytokines, especially TNF-α, act an important role in those tight junction function changes, and several studies have been proved that TNF-α antagonists provide benefit to patients or rat models [ 19 , 20 ]. However, the precise mechanism in this process is largely unknown.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of Autophagic Degradation Process Contributes to Claudin-2 Expression Increase and Epithelial Tight Junction Dysfunction in TNF-α Treated Cell Monolayers

Zhang

Yan²,

Xiao³

et al. 2017

IJMS

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Tight junction dysfunction plays a vital role in some chronic inflammatory diseases. Pro-inflammatory cytokines, especially tumor necrosis factor alpha (TNF-α), act as important factors in intestinal epithelial tight junction dysfunction during inflammatory conditions. Autophagy has also been shown to be crucial in tight junction function and claudin-2 expression, but whether autophagy has an effect on the change of claudin-2 expression and tight junction function induced by TNF-α is still unknown. To answer this question, we examined the expression of claudin-2 protein, transepithelial electrical resistance (TER), and permeability of cell monolayers, autophagy flux change, and lysosomal pH after TNF-α with or without PP242 treatment. Our study showed that claudin-2 expression, intestinal permeability, microtubule-associated protein 1 light chain 3B II (LC3B-II) and sequestosome 1 (P62) expression largely increased while TER values decreased in TNF-α treated cell monolayers. Further research using 3-methyladenine (3-MA), bafilomycin A1, and ad-mCherry-GFP-LC3B adenovirus demonstrated that LC3B-II increase induced by TNF-α was attributed to the inhibition of autophagic degradation. Moreover, both qualitative and quantitative method confirmed the increase of lysosomal pH, and mammalian target of rapamycin (mTOR) inhibitor PP242 treatment relieved this elevation. Moreover, PP242 treatment also alleviated the change of autophagy flux, TER, and claudin-2 expression induced by TNF-α. Therefore, we conclude that increase of claudin-2 levels and intestinal epithelial tight junction dysfunction are partly caused by the inhibition of autophagic degradation in TNF-α treated cell monolayers.

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Section: Discussionmentioning

confidence: 99%

Inhibition of Autophagic Degradation Process Contributes to Claudin-2 Expression Increase and Epithelial Tight Junction Dysfunction in TNF-α Treated Cell Monolayers

Zhang

Yan²,

Xiao³

et al. 2017

IJMS

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“…However, the treatment of CD appeared to be appropriate in most patients according to cohort studies from Switzerland and Europe 32,33 .…”

Section: Introductionmentioning

confidence: 99%

Addressing current treatment challenges in Crohn's disease in real life: A physician's survey

Vavricka

Radivojevic²,

Manser³

et al. 2014

Digestive and Liver Disease

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BACKGROUND: In recent years several trials have addressed treatment challenges in Crohn's disease. Clinical trials however, represent a very special situation. AIMS: To perform a cross-sectional survey among gastroenterologists on the current clinical real life therapeutic approach focussing on the use of biologics. METHODS: A survey including six main questions on clinical management of loss of response, diagnostic evaluation prior to major treatment changes, preference for anti-tumour necrosis factor (TNF) agent, (de-)escalation strategies as well as a basic section regarding personal information was sent by mail to all gastroenterologists in Switzerland (n=318). RESULTS: In total, 120 questionnaires were analysed (response rate 37.7%). 90% of gastroenterologists in Switzerland use a thiopurine as the first step-up strategy (anti-TNF alone 7.5%, combination 2.5%). To address loss of response, most physicians prefer shortening the interval of anti-TNF administration followed by dose increase, switching the biologic and adding a thiopurine. In case of prolonged remission on combination therapy, the thiopurine is stopped first (52.6%) after a mean treatment duration of 15.7 months (biologic first in 41.4%). CONCLUSIONS: Everyday clinical practice in Crohn's disease patients appears to be incongruent with clinical data derived from major trials. Studies investigating reasons underlying these discrepancies are of need to optimize and harmonize treatment.

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“…In a Swiss cohort of 146 patients with CD treated with infliximab, the mean age at diagnosis was 27 years and the mean disease duration was 9 years, also making the Swiss cohort older than the Polish one. 20 Immunosuppressive therapy was administered in 44% of the Swiss patients. This cohort again had a higher prevalence of women (55%).…”

mentioning

confidence: 99%

Possible under-treatment of women in Poland with Crohn’s disease: a subgroup analysis from a prospective multicenter study of the use of anti-TNFs

Eder¹,

Kłopocka²,

Wiśniewska-Jarosińska³

et al. 2017

Polish Archives of Internal Medicine

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Infliximab for Crohnʼs disease in the Swiss IBD Cohort Study

Cited by 10 publications

References 22 publications

Inhibition of Autophagic Degradation Process Contributes to Claudin-2 Expression Increase and Epithelial Tight Junction Dysfunction in TNF-α Treated Cell Monolayers

Inhibition of Autophagic Degradation Process Contributes to Claudin-2 Expression Increase and Epithelial Tight Junction Dysfunction in TNF-α Treated Cell Monolayers

Addressing current treatment challenges in Crohn's disease in real life: A physician's survey

Possible under-treatment of women in Poland with Crohn’s disease: a subgroup analysis from a prospective multicenter study of the use of anti-TNFs

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