Long-term outcome of maintenance infliximab therapy in children with Crohnʼs disease

Hyams, Jeffrey S.; Lerer, Trudy; Griffiths, Anne M.; Pfefferkorn, Marian; Kugathasan, Subra; Evans, Jonathan; Otley, Anthony; Carvalho, Ryan; Mack, David; Bousvaros, Athos; Rosh, Joel R.; Mamula, Petar; Kay, Marsha; Crandall, Wallace; Oliva-Hemker, Maria; Keljo, David J.; LeLeiko, Neal S.; Markowitz, James

doi:10.1002/ibd.20845

Cited by 165 publications

(136 citation statements)

References 24 publications

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“…TNF-a, which is a pleiotropic cytokine, plays a fundamental role in inflammatory conditions such as colitis by triggering the accumulation and activation of leukocytes (76). Therefore, TNF-a is an important therapeutic target and several engineered Abs against TNF-a are beneficial in the treatment of IBD (77). IL-6 is produced by various cell types and exerts pleiotropic effects on different organ systems.…”

Section: Discussionmentioning

confidence: 99%

Porcine β-Defensin 2 Attenuates Inflammation and Mucosal Lesions in Dextran Sodium Sulfate–Induced Colitis

Han¹,

Zhang

Xia

et al. 2015

The Journal of Immunology

133

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Intestinal permeability plays a critical role in the etiopathogenesis of ulcerative colitis. Defensins, including porcine β-defensin (pBD)2, are crucial antimicrobial peptides for gut protection owing to their antibacterial and immunomodulatory activities. The purpose of this study was to investigate the protective effects of pBD2 on mucosal injury and the disruption of the epithelial barrier during the pathological process of dextran sodium sulfate (DSS)–induced colitis. The effects and mechanism of pBD2 were evaluated both using a DSS-induced C57BL/6 mouse model and, in vitro, using Caco-2 and RAW264.7 cells. DSS-induced colitis was characterized by higher disease activity index, shortened colon length, elevated activities of myeloperoxidase and eosinophil peroxidase, histologic evidence of inflammation, and increased expression levels of TNF-α, IL-6, and IL-8. pBD2 increased the expression of zonula occludens-1, zonula occludens-2, claudin-1, mucin-1, and mucin-2 mRNA and proteins, and it decreased permeability to FITC-D, as well as apoptosis, in DSS-treated mice. pBD2 also decreased inflammatory infiltrates of the colon epithelium. In Caco-2 cells, pBD2 increased transepithelial electrical resistance and mucin mRNA expression, and it decreased the permeability of FITC-D while preserving the structural integrity of the tight junctions. The effects of pBD2 appeared to be through upregulation of the expression of genes associated with tight junctions and mucins, and by suppressing DSS-induced increases in inflammation, inducible NO synthase, cyclooxygenase-2, and apoptosis. These results show that pBD2 improves DSS-induced changes in mucosal lesions and paracellular permeability, possibly by affecting the activation of NF-κB signaling. The present study demonstrates that intrarectal administration of pBD2 may be a novel preventive option for ulcerative colitis.

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Section: Discussionmentioning

confidence: 99%

Porcine β-Defensin 2 Attenuates Inflammation and Mucosal Lesions in Dextran Sodium Sulfate–Induced Colitis

Han¹,

Zhang

Xia

et al. 2015

The Journal of Immunology

133

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“…One, a 9-yr-old female from the UK developed TB septic arthritis [166], the other a 9-yr-old female from the Netherlands initially received etanercept, then infliximab after which she developed extrapulmonary TB [167]. There are even fewer published data regarding the use of infliximab in juvenile idiopathic arthritis and in inflammatory bowel disease [168,169] with, however, only one documented case of a child developing TB whilst on infliximab for juvenile idiopathic arthritis [170]. Adaluzimab and abatacept have so far only included trials with ,200 children with juvenile idiopathic arthritis, but they had relatively short follow-up.…”

Section: Special Considerations In Childrenmentioning

confidence: 99%

The risk of tuberculosis related to tumour necrosis factor antagonist therapies: a TBNET consensus statement

Solovič

Sester

Gómez-Reino

et al. 2010

European Respiratory Journal

447

341

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Anti-tumour necrosis factor (TNF) monoclonal antibodies or soluble TNF receptors have become an invaluable treatment against chronic inflammatory diseases, such as rheumatoid arthritis, inflammatory bowel disease and psoriasis. Individuals who are treated with TNF antagonists are at an increased risk of reactivating latent infections, especially tuberculosis (TB).Following TNF antagonist therapy, the relative risk for TB is increased up to 25 times, depending on the clinical setting and the TNF antagonist used. Interferon-c release assays or, as an alternative in individuals without a history of bacille Calmette-Guérin vaccination, tuberculin skin testing is recommended to screen all adult candidates for TNF antagonist treatment for the presence of latent infection with Mycobacterium tuberculosis.Moreover, paediatric practice suggests concomitant use of both the tuberculin skin test and an interferon-c release assay, as there are insufficient data in children to recommend one test over the other. Consequently, targeted preventive chemotherapy is highly recommended for all individuals with persistent M. tuberculosis-specific immune responses undergoing TNF antagonist therapy as it significantly reduces the risk of progression to TB. This TBNET consensus statement summarises current knowledge and expert opinions and provides evidence-based recommendations to reduce the TB risk among candidates for TNF antagonist therapy.KEYWORDS: Interferon-c release assay, tuberculin skin test, tuberculosis, tumour necrosis factor T umour necrosis factor (TNF) and TNF receptors play a key role in mediating immune responses in acute and chronic inflammation [1][2][3]. Over the past decade, TNF antagonists in the form of anti-TNF monoclonal antibodies or TNF fusion protein have become an invaluable treatment against chronic inflammatory diseases, such as rheumatoid arthritis, psoriasis and psoriatic arthritis, ankylosing spondylitis, juvenile idiopathic arthritis and inflammatory bowel disease [4][5][6][7]. Tuberculosis (TB) is a granulomatous disease caused by infection with Mycobacterium tuberculosis.Most of the individuals who are thought to have become infected with M. tuberculosis will never develop TB due to the control exercised by the host immune system [8,9]. One of the key cytokines in the immune response against infection with M. tuberculosis is TNF, which is also critical for the integrity of the granuloma [10]. Individuals who are being treated with anti-TNF therapies are at increased risk of developing TB. Following TNF antagonist therapy, the relative risk for TB is increased 1.6-25.1 times, depending on the clinical setting and the TNF antagonist used [4,7,11,12]. The majority of cases of TB related to TNF antagonist therapies occur in close temporal proximity to

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“…along the past ten years, more than 50 publications addressed to the treatment of iBD, including CD in its different forms, prove the positive results of the long and medium term therapy with the chimeric monoclonal antibody, including for infants [70][71][72][73][74][75][76][77][78] . The first promising responses for 61% of the treated patients versus 17% on placebo come from double prospective study (placebo-medicine) conducted with more than 100 patients with CD refractory to the conventional treatment, with high levels of disease activity, using different doses of infliximab (5, 10 and 20 mg/kg).…”

Section: Vol 31 Nºmentioning

confidence: 99%

Crohn's Disease: current state of biological therapy

Júnior¹

2011

J. Coloproctol. (Rio J.)

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The inflammatory bowel diseases (IBD) are defined as nonspecific chronic intestinal inflammations with possible systemic involvement. IBD have unknown etiology. The inflammatory process is complex and heterogeneous, both as to the characterization of the disease that affects the digestive tract, without an intelligible pattern of revelation and balance, and in its different systemic damages when including the extensive and severe extraintestinal symptoms. Aparently, the natural history of the disease is irregular in relation to the offending agent system and the attacked system, both in the intestinal and extraintestinal teguments. Isolated aspects showing irregularity in this balance gives us the notion that IBD, especially Crohn's disease, can be caused by the stimulation of an immune response caused by damaging agents (intestinal bacteria), but mediated by inadequate genetic factors, whose expressions determine different individual susceptibilities. These observations have been shown in genetic studies that emphasize the importance of pathological interaction between host and bacteria subsidized by a genomic region that contains genes producing proteins (NOD2 -nucleotide-binding oligomerization domain containing 2) participating in an enhanced defense response by the tissue. Increased numbers and the activation of these cells in the intestinal mucosa elevate local levels of tumor necrosis factor α (TNF-α), interleukin-1β, interferon-γ, and cytokines of the interleukin-23-Th17 pathway. So, it can be assumed that the susceptibility, which is a result of genetic alterations, is connected to an exaggerated response in the pro-inflammatory phase because of a dysfunction in the intestinal immune system. The identification of tumor necrosis factor (TNF-α) as the active element in the pro-inflammatory inadequate response gave rise to the heightened production of biological substances that could block TNF-α, at different levels, opening a large field of view to new treatment of IBD.

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Long-term outcome of maintenance infliximab therapy in children with Crohnʼs disease

Abstract: Infliximab maintenance therapy was a durable and effective treatment that was associated with prolonged corticosteroid withdrawal over a 3-year period in children with CD.

Cited by 165 publications

References 24 publications

Porcine β-Defensin 2 Attenuates Inflammation and Mucosal Lesions in Dextran Sodium Sulfate–Induced Colitis

Porcine β-Defensin 2 Attenuates Inflammation and Mucosal Lesions in Dextran Sodium Sulfate–Induced Colitis

The risk of tuberculosis related to tumour necrosis factor antagonist therapies: a TBNET consensus statement

Crohn's Disease: current state of biological therapy

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