Infliximab for Induction and Maintenance Therapy for Ulcerative Colitis

Rutgeerts, Paul; Sandborn, William J.; Feagan, Brian G.; Reinisch, Walter; Olson, Allan; Johanns, Jewel; Travers, Suzanne; Rachmilewitz, Daniel; Hanauer, Stephen B.; Lichtenstein, Gary R.; Villiers, Willem J.S. de; Present, Daniel H.; Sands, Bruce E.; Colombel, Jean Fréd́eric

doi:10.1056/nejmoa050516

Cited by 3,437 publications

(2,855 citation statements)

References 39 publications

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“…The central role identified for TNF led to the approval of infliximab (Remicade®), a monoclonal antibody to TNF, as the first biologic therapy for the treatment of patients with active CD. Two large, phase III, randomized placebo-controlled trials have also demonstrated efficacy of infliximab in UC (30). The data in the present study demonstrate similar mucosal TNF production in biopsies from patients with active UC and CD, providing indirect evidence supporting the use of anti-TNF therapies for both these forms of IBD.…”

Section: Discussionsupporting

confidence: 70%

“…The chemokine MCP-1 (also known as CCL2 or MCAF/JE) has previously been shown to increase when colon cells are exposed to inflammatory stimuli (32) and to be elevated in UC (30,32). Previous work has shown that MCP-1 is produced by fibroblasts and smooth muscle, endothelial, epithelial, and activated peripheral blood mononuclear cells (27,34).…”

Section: Discussionmentioning

confidence: 99%

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Bromelain treatment decreases secretion of pro-inflammatory cytokines and chemokines by colon biopsies in vitro

Onken

Greer

Calingaert

et al. 2008

Clinical Immunology

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Oral bromelain has been anecdotally reported to decrease inflammation in ulcerative colitis (UC). Proteolytically active bromelain is known to decrease expression of mRNAs encoding proinflammatory cytokines by human leukocytes in vitro. To assess the effect of bromelain on mucosal secretion of cytokines in inflammatory bowel disease (IBD), endoscopic colon biopsies from patients with UC, Crohn's disease (CD), and non-IBD controls were treated in vitro with bromelain or media, then cultured. Secretion of pro-inflammatory cytokines and chemokines was measured. Significant increases in granulocyte colony stimulating factor (G-CSF), interferon (IFN)-γ, interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF) were detected in the media from actively inflamed areas in UC and CD as compared with non-inflamed IBD tissue and non-IBD controls. In vitro bromelain treatment decreased secretion of G-CSF, granulocyte-macrophage colony stimulating factor (GM-CSF), IFN-γ, CCL4/macrophage inhibitory protein (MIP)-1β, and TNF by inflamed tissue in IBD. Bromelain may be a novel therapy for IBD.

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Section: Discussionsupporting

confidence: 70%

Section: Discussionmentioning

confidence: 99%

Bromelain treatment decreases secretion of pro-inflammatory cytokines and chemokines by colon biopsies in vitro

Onken

Greer

Calingaert

et al. 2008

Clinical Immunology

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“…Clinical data included: age, gender, family history of IBD, co-morbidities, (e.g. diabetes and/or hypertension), traditional risk factors for the onset of atherosclerosis (Blood Pressure, Body Mass Index, smoking, TotalCholesterol, Triglycerides, LDL-Cholesterol, HDL-Cholesterol), disease features (IBD type, extent, extra-intestinal manifestations, previous surgery), disease activity assessed by Mayo Score [32] for UC and the Harvey Bradshaw Index for CD [33], C-reactive protein (CRP) values, concomitant drug therapies. A blood sample was drawn for the evaluation of lipid profile and other laboratory parameters.…”

Section: Patient's Selectionmentioning

confidence: 99%

“…In addition, no significant differences have been found between values of IMT, PWV and Aortic Aix among IBD patients in relation to disease duration and activity. In fact, although the Mayo Score [32] and the Harvey Bradshaw Index [33] are indices widely used in clinical trials, they do not really reflect the control of mucosal inflammation and need to be integrated by biomarkers and endoscopic scores. In addition, the absence of correlation between disease duration and hemodynamic measurements was also confirmed by linear regression analysis.…”

Section: Impact Of Disease Features and Pharmacological Therapy On Hementioning

confidence: 99%

Increased expression of markers of early atherosclerosis in patients with inflammatory bowel disease

Cappello

Licata

Calvaruso

et al. 2017

European Journal of Internal Medicine

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Background & Aims:Recent studies documented an increased cardiovascular risk in patients with inflammatory bowel disease (IBD). Our study aimed at investigating the prevalence of intima-media thickness (IMT) of the carotid arteries and the arterial stiffness indices as markers of early atherosclerosis in young IBD patients. Methods: We recruited 68 consecutive IBD patients, and 38 matched healthy controls less than 45 years old (median age 31.6 ± 8.1 years). Clinical and demographic features, cardiovascular risk factors, history of cardiovascular events, concomitant therapies were registered on a dedicate database. Carotid IMT was evaluated by using high resolution B-mode ultrasonography. Arterial stiffness was assessed by measurement of carotidfemoral Pulse Wave Velocity (PWV) and Augmentation Index (AIx). Results: Total cholesterol (P b 0.013) and LDL-cholesterol (P b 0.019) levels were significantly lower in IBD patients compared to controls. Carotid IMT was higher in IBD than in controls (P b 0.047), but there was no statistically significant difference among Crohn's Disease (CD) and Ulcerative Colitis (UC) patients. Moreover, PWV and AIx were significantly higher in patients as compared to controls (P b 0.006 and P b 0.004 respectively). No medication seemed to affect vascular measurements, though stiffness parameters were significantly higher in patients treated with 5-ASA (11.9 (9.7) vs 18.2 (10.2), P b 0.021), suggesting a lack of efficacy of 5-ASA in protecting IBD patients from early atherogenesis. Conclusions: Young IBD patients show an increase in subclinical markers of atherosclerosis. Future studies need to address whether these markers result in an increased risk of cardiovascular events in these patient.

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“…Initial studies of infliximab for Crohn's disease revealed remarkable efficacy, with a majority of patients achieving normalization of Crohn's disease activity index scores and endoscopic healing of ulcerations [11]. Large, randomized controlled trials of infliximab in Crohn's disease and ulcerative colitis further supported these findings, demonstrating benefit for both induction and maintenance of response and remission [12][13][14][15][16][17]. Infliximab was granted orphan drug status and became the first FDAapproved medication for Crohn's disease in 1998 [18,19].…”

Section: Development Of Infliximabmentioning

confidence: 99%

The Impact of Therapeutic Antibodies on the Management of Digestive Diseases: History, Current Practice, and Future Directions

Sofia

Rubin

2017

Dig Dis Sci

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The development of therapeutic antibodies represents a revolutionary change in medical therapy for digestive diseases. Beginning with the initial studies that confirmed the pathogenicity of cytokines in inflammatory bowel disease, the development and application of therapeutic antibodies brought challenges and insights into their potential and optimal use. Infliximab was the first biological drug approved for use in Crohn's disease and ulcerative colitis. The lessons learned from infliximab include the importance of immunogenicity and the influence of pharmacokinetics on disease response and outcomes. Building on this foundation, other therapeutic antibodies achieved approval for inflammatory bowel disease and many more are in development for several digestive diseases. In this review, we reflect on the history of therapeutic antibodies and discuss current practice and future directions for the field.

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Infliximab for Induction and Maintenance Therapy for Ulcerative Colitis

Cited by 3,437 publications

References 39 publications

Bromelain treatment decreases secretion of pro-inflammatory cytokines and chemokines by colon biopsies in vitro

Bromelain treatment decreases secretion of pro-inflammatory cytokines and chemokines by colon biopsies in vitro

Increased expression of markers of early atherosclerosis in patients with inflammatory bowel disease

The Impact of Therapeutic Antibodies on the Management of Digestive Diseases: History, Current Practice, and Future Directions

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