Infliximab Improves Quality of Life in Patients with Crohn's Disease

Lichtenstein, Gary R.; Bala, Mohan; Han, Chenglong; DeWoody, Kimberly; Schaible, T

doi:10.1097/00054725-200207000-00001

Cited by 133 publications

(94 citation statements)

References 19 publications

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“…Anti-TNF therapy is now an approved treatment for immune-inflammatory diseases, such as juvenile RA, ankylosing spondylitis, psoriatic arthritis, Crohn's disease, ulcerative colitis, and psoriasis. In all of these, the effect on patients has been dramatic (e.g., the healing of fistulas in Crohn's disease) and has greatly improved quality of life (38,39).…”

mentioning

confidence: 99%

Anti-TNF Therapy, from Rationale to Standard of Care: What Lessons Has It Taught Us?

Feldmann

Maini

2010

The Journal of Immunology

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In the mid-1980s, new molecular tools enabled the biology of cytokine expression and regulation to be studied. Our group uncovered a TNF-dependent cascade in active rheumatoid synovium, suggesting that TNF might be a therapeutic target; this concept was supported in an animal model of the disease. The proof of concept was a series of clinical trials, which have led to marked changes in the therapy of human rheumatoid arthritis and subsequently of other diseases. The work with TNF clearly demonstrated the importance of cytokines in medicine as well as the capacity of mAbs (or receptor fusion proteins) to be used long-term in large populations, thus changing the therapeutic landscape.

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mentioning

confidence: 99%

Anti-TNF Therapy, from Rationale to Standard of Care: What Lessons Has It Taught Us?

Feldmann

Maini

2010

The Journal of Immunology

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“…Moreover the quantitative relationship between the cytokines observed in vitro mimics that observed in the inflamed mucosa in vivo as IL-6, IL-1b, TNF-a and IFN-g are all strongly induced in in vitro by 'activated' PBLs, as well as in colonic biopsies obtained from patients with acute flares of UC. 19 The development of the anti-tumor necrosis factor (TNF) antibodies has revolutionized the management of many chronic-inflammatory diseases and is now an approved treatment for CD, UC, juvenile RA, ankylosing spondylitis, psoriatic arthritis and psoriasis 38,39 However, the mechanisms of their actions are unclear and B10% of patients with 'refractory' or newly diagnosed CD fail to respond to anti-TNF treatment. 40 In normal conditions TNF-a has important roles in the development of the immune system and host protection against infectious pathogens.…”

Section: Discussionmentioning

confidence: 99%

The anti-TNF-α antibody infliximab indirectly regulates PECAM-1 gene expression in two models of in vitro blood cell activation

Moriconi

Malik

Amanzada

et al. 2012

Laboratory Investigation

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Chronic inflammatory bowel diseases can be successfully treated with antibodies against the acute phase mediator TNF-a. The process of activation and of extravasation of inflammatory cells from the blood into the 'stressed' tissue site is controlled by cytokines and chemokines, which attract leukocytes and by adhesion molecules, which mediate their attachment and transmigration toward the affected cell(s). The changes in the gene expression of adhesion molecules taking place in those cells before attachment have been less investigated. Changes of PECAM-1, ICAM-1 and vascular cell adhesion molecule-1 (VCAM-1) gene expression were studied in phytohaemagglutinin (PHA)-and lipolysaccharide (LPS)-treated human peripheral blood leukocytes (PBLs), granulocytes and the human monocyte cell line U-937. Cells were treated either with PHA or with LPS in the presence or absence of infliximab and incubated with TNF-a, IFN-g and/or transforming growth factor beta (TGF-b) and treated as above. Activation of PBLs by PHA or LPS treatment triggered a sharp upregulation of ICAM-1, VCAM-1 gene expression and a time-dependent downregulation of PECAM-1 gene expression reaching a minimum 4 h from start of the experiment. The anti-TNF-a antibody infliximab, by neutralizing TNF-a and IFN-g production, completely reversed PECAM-1 mRNA downregulation and ICAM-1 and VCAM-1 upregulation. Immunostaining of PBLs cytospins with antibodies against PECAM-1 and ICAM-1 confirmed RT-PCR and western blot results. PBLs IFN-g or TNF-a treatment downregulated PECAM-1 in parallel with the upregulation of ICAM-1 and VCAM-1 gene expression, whereas TGF-b upregulated PECAM-1-and downregulated ICAM-1 and VCAM-1 gene expression counteracting the effect of TNF-a or IFN-g. Similar results were obtained in human U937 cells and in granulocyte cultures by TNF-a or IFN-g treatment. Taken together, these results suggest that infliximab, blocking TNF-a and IFN-g production, exerts its anti-inflammatory effect through inhibiting downregulation of PECAM-1 gene expression and upregulation of ICAM-1 and VCAM-1 expression in leukocytes of the peripheral blood. These results also suggest that TGF-b may thus be of therapeutic importance as an anti-inflammatory agent.

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“…I tre studier der man vurderte effekten av TNF-hemmere ved Crohns sykdom var fatigue sekundaert endepunkt (8,39,40).…”

Section: Behandling Av Fatigueunclassified

“…Lichtenstein og medarbeidere fant at signifikant flere som fikk infliksimab (n = 82) enn placebo (n = 23) fikk økt energi (39).…”

Section: Behandling Av Fatigueunclassified

Utmattelse ved inflammatorisk tarmsykdom

Grimstad

Norheim

2016

Tidsskriftet

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RESULTATER 28 av i alt 156 artikler ble inkludert. 13 ulike instrumenter for å måle fatigue og 11 mål på sykdomsaktivitet ble anvendt i de ulike studiene. Fatigue forekommer hyppigere hos dem som er rammet av inflammatorisk tarmsykdom (22 -77 %) enn i normalbefolkningen (2 -12 %). Aktiv sykdom og depresjon er assosiert med høyere grad av fatigue.FORTOLKNING Fatigue er et betydelig problem ved inflammatorisk tarmsykdom, og forekomsten og mulige risikofaktorer varierer fordi det er benyttet ulike mål for grad av utmattelse/fatigue og sykdomsaktivitet i heterogene studiepopulasjoner.

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Infliximab Improves Quality of Life in Patients with Crohn's Disease

Abstract: These results indicate that infliximab significantly improved quality of life in patients with active CD, increasing their ability to work and participate in leisure activities, and decreasing feelings of fatigue, depression, and anger.

Cited by 133 publications

References 19 publications

Anti-TNF Therapy, from Rationale to Standard of Care: What Lessons Has It Taught Us?

Anti-TNF Therapy, from Rationale to Standard of Care: What Lessons Has It Taught Us?

The anti-TNF-α antibody infliximab indirectly regulates PECAM-1 gene expression in two models of in vitro blood cell activation

Utmattelse ved inflammatorisk tarmsykdom

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