Impact of the increasing use of immunosuppressants in Crohn's disease on the need for intestinal surgery

Cosnes, Jacques; Nion–Larmurier, Isabelle; Beaugerie, Laurent; Afchain, Pauline; Tiret, Emmanuel; Jp, Gendre

doi:10.1136/gut.2004.045294

Cited by 619 publications

(399 citation statements)

References 21 publications

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“…Our study echoed the observed trends that more IM but less 5-ASA products are currently used in CD management [18][19][20][21][22] . Immunomodulators are effective maintenance medications and azathioprine has been shown to modestly lower the risk of surgery [23][24][25] .…”

Section: Discussionsupporting

confidence: 74%

Impact of medical therapy on patients with Crohn’s disease requiring surgical resection

Hong

Round

et al. 2014

WJG

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AIM:To evaluate the impact of medical therapy on Crohn's disease patients undergoing their first surgical resection. METHODS:We retrospectively evaluated all patients with Crohn's disease undergoing their first surgical resection between years 1995 to 2000 and 2005 to 2010 at a tertiary academic hospital (St. Paul's Hospital, Vancouver, Canada). Patients were identified from hospital administrative database using the International Classification of Diseases 9 codes. Patients' hospital and available outpatient clinic records were independently reviewed and pertinent data were extracted. We explored relationships among time from disease diagnosis to surgery, patient phenotypes, medication usage, length of small bowel resected, surgical complications, and duration of hospital stay. surgery. Within cohort B, 38 patients (33.3%) received anti-tumor necrosis factor (TNF) agent. No patient in cohort A was exposed to anti-TNF agent. Compared to patients not on anti-TNF agent, ones exposed were younger at diagnosis (anti-TNF vs without anti-TNF: A1/A2/A3 39.5% vs 11.8%, 50% vs 73.7%, 10.5% vs 14.5%, P = 0.003) and had longer median time to surgery (90 mo vs 48 mo, P = 0.02). Combination therapy further extended median time to surgery. Using timedependent multivariate Cox proportional hazard model, patients who were treated with anti-TNF agents had a significantly higher risk to surgery (adjusted hazard ratio 3.57, 95%CI: 1.98-6.44, P < 0.0001) compared to those without while controlling for gender, disease phenotype, smoking status, and immunomodulator use. RESULTS: CONCLUSION:Significant changes in patient phenotypes and medication exposures were observed between the two surgical cohorts separated by a decade.

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Section: Discussionsupporting

confidence: 74%

Impact of medical therapy on patients with Crohn’s disease requiring surgical resection

Hong

Round

et al. 2014

WJG

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“…The introduction of corticosteroid therapy in the 1950s transformed the outcome for patients with UC but not all patients respond, the overall lifetime colectomy rate still runs at about one-third, 20 and steroid-related side effects are common, even with short-term use. This study shows that a modified-release formulation of a poorly absorbed corticosteroid, prednisolone metasulfobenzoate (Predocol), has similar efficacy at 40 mg ⁄ day to a conventional tapering regimen of standard prednisolone, when assessed at 2 months.…”

Section: Discussionmentioning

confidence: 99%

Clinical trial: oral prednisolone metasulfobenzoate (Predocol) vs. oral prednisolone for active ulcerative colitis

Rhodes

Robinson

Beales

et al. 2007

Aliment Pharmacol Ther

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“…17,24 Indeed, despite therapeutic developments, the numbers of patients ultimately requiring surgical intervention remains high. 25 With this in mind, there is a significant need for new approaches to the treatment of IBD, which may be used in addition to or in combination with existing approaches to alleviate symptoms in patients.…”

Section: Inflammatory Bowel Disease (Ibd)mentioning

confidence: 99%

Hydroxylases as therapeutic targets in inflammatory bowel disease

Cummins

Doherty

Taylor

2013

Laboratory Investigation

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Inflammatory bowel disease (IBD) is a common and debilitating clinical disorder comprising ulcerative colitis and Crohn's disease. IBD occurs when inappropriate immunological activity in the intestinal mucosa results in epithelial barrier dysfunction leading to exposure of the mucosal immune system to luminal antigenic material. This in turn results in the cycles of inflammation and further barrier dysfunction which underlie disease progression. Although significant therapeutic advances have been made over the last decade, current immunosuppressive and anti-inflammatory treatments for IBD have significant limitations due to lack of treatment response in some patients and adverse effects, including increased risk of infection and malignancy. Recent studies using experimental models of IBD have identified that intracellular hydroxylases, a group of enzymes responsible for oxygen sensing and activation of adaptive transcriptional responses to hypoxia may represent a new class of therapeutic targets in IBD. Hydroxylase inhibitors are effective in ameliorating symptoms of colitis at least in part through the promotion of intestinal epithelial barrier function. The mechanism of this protection is due to activation of hypoxia-sensitive transcription factors, including the hypoxiainducible factor (HIF) and nuclear factor kappa-B (NF-kB), which activate specific epithelial barrier-protective transcriptional programs. In this review, the mechanism(s) of action and the therapeutic potential of small molecule hydroxylase inhibitors for the treatment of IBD will be discussed.

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Impact of the increasing use of immunosuppressants in Crohn's disease on the need for intestinal surgery

Cited by 619 publications

References 21 publications

Impact of medical therapy on patients with Crohn’s disease requiring surgical resection

Impact of medical therapy on patients with Crohn’s disease requiring surgical resection

Clinical trial: oral prednisolone metasulfobenzoate (Predocol) vs. oral prednisolone for active ulcerative colitis

Hydroxylases as therapeutic targets in inflammatory bowel disease

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