Cyclosporine in Severe Ulcerative Colitis Refractory to Steroid Therapy

Lichtiger, Simon; Present, Daniel H.; Kornbluth, Asher; Gelernt, Irwin M.; Bauer, Joel J.; Galler, Greg; Michelassi, Fabrizio; Hanauer, Stephen B.

doi:10.1056/nejm199406303302601

Cited by 1,559 publications

(1,084 citation statements)

References 15 publications

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“…18 The fact that calcineurin inhibitors, which mainly suppress the expression of IL2, are effective in treatment-resistant UC, but not in CD, might also point to a key role for this interleukin in UC. 28 Further support for the importance of IL2 in UC comes from the fact that a pilot trial with antibodies against the IL2 receptor in treatment-resistant UC was successful. 29 The fact that both a lack of IL2 and an excess of IL2 predispose to colitis is however puzzling.…”

Section: Discussionmentioning

confidence: 99%

“…Allelic association testing and a pooled analysis using a Cochran-Mantel-Haenszel test were performed. Results: All four SNPs were strongly associated with UC in all three cohorts and reached genome-wide significance in the pooled analysis (rs13151961 p = 1.35610 210 , rs13119723 p = 8.60610 28 , rs6840978 p = 3.07610 28 , rs6822844 p = 2.77610 29 ). A moderate association with CD was also found in the pooled analysis (p value range 0.0016-9.86610 25 ).…”

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confidence: 94%

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203 Genetic Variants in the Region Harbouring IL2/IL21 Associated to Ulcerative Colitis

Festen¹,

Goyette²,

Scott³

et al. 2009

Gastroenterology

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 94%

203 Genetic Variants in the Region Harbouring IL2/IL21 Associated to Ulcerative Colitis

Festen¹,

Goyette²,

Scott³

et al. 2009

Gastroenterology

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“…Clinical disease activity was determined by the Colitis Activity Index (CAI) [24] (from 0 to 21; severe disease defined as > 12, inactive disease < 4) on week 0 or just before treatment, and after 1, 2, 4, 6 and 8 weeks of treatment. Quality of life was assessed at week 1, 4 and 8 by means of the Inflammatory Bowel Disease Questionnaire (IBDQ) [25].…”

Section: Methodsmentioning

confidence: 99%

“…Treatment was discontinued if there was no improvement after 4 weeks according to the CAI [24], or in any patient with progression of disease activity at any control visit. Other predefined reasons for discontinuation were heparin-induced thrombocytopenia (HIT) type 2 [27,28] and/or severe bleeding (defined as Hb < 5.0 mmol/l, Hb > 2.0 mmol/l below baseline value, blood loss with blood pressure <80/50 mmHg and/or need for blood transfusion).…”

Section: Methodsmentioning

confidence: 99%

Thrombin generation in mesalazine refractory ulcerative colitis and the influence of low molecular weight heparin

Vrij

Oberndorff-Klein-Woolthuis

Dijkstra

et al. 2007

J Thromb Thrombolysis

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Background In ulcerative colitis (UC), a state of hypercoagulation has frequently been observed. Low molecular weight heparin (LMWH) has shown beneficial effects as an adjuvant treatment of steroid refractory UC in open trials. We assessed potential therapeutic effects of the LMWH reviparin in hospitalised patients with mesalazine refractory UC, as well as its influence on haemostasis factors. Methods Twentynine patients with mild-to-moderately active UC were included in a double-blind placebo controlled trial. All patients had a flare-up of disease under mesalazine treatment. Reviparin (Clivarin Ò ) 3,436 IU anti-Xa/0.6 ml or placebo s.c. was added, and self-administered twice daily for 8 weeks. Patients were monitored for possible adverse events and changes in clinical symptoms. Endoscopical, histological, biochemical and haemostasis parameters were analysed. Results Tolerability and compliance were excellent and no serious adverse events occurred. No significant differences were observed on the clinical, endoscopical and histological outcome, as compared to placebo. A high intrinsic and extrinsic thrombin potential was found before LMWH therapy. However, the significant reduction in the thrombin generation by LMWH was not related to the reduction in disease activity. Conclusion The LMWH reviparine reduces thrombin generation in patients with mild-to-moderately active, mesalazine refractory UC, but is not associated with a reduction in disease activity.

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“…20,21 A multicentre double-blind, randomized, controlled trial in North America demonstrated the bene®t of intravenous cyclosporin for severe ulcerative colitis refractory to intensive steroid therapy compared to placebo. 22 Twenty patients were randomized to receive either cyclosporin or placebo after 7±10 days of unsuccessful steroid therapy. Nine of 11 patients who received cyclosporin (i.e.…”

Section: Response To Treatmentmentioning

confidence: 99%

The management of severe ulcerative colitis

Hyde

Jewell²

1997

Aliment Pharmacol Ther

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Severe ulcerative colitis is a potentially life‐threatening condition but the mortality has fallen dramatically over the past 30–40 years. It is now less than 2%, including surgical mortality, and should only be seen in patients with significant co‐existing disease. Early recognition of the severity of the colitis, intensive medical therapy, close liaison between physician and surgeon, and prompt surgery when necessary have all contributed to this improved outcome. Despite the use of high‐dose intravenous corticosteroids, 20–30% of patients will make a poor response and will require urgent surgery. The use of intravenous cyclosporin has proved effective at reducing the immediate surgical rate in this group of unresponsive patients and appears safe. Whether cyclosporin reduces the need for surgery in the longer term is much less certain. Clinical, radiological, endoscopic and laboratory parameters can now be used to predict the course of a severe attack. These help in the timing of urgent surgery and are potentially helpful in determining when to begin other therapies such as cyclosporin.

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Cyclosporine in Severe Ulcerative Colitis Refractory to Steroid Therapy

Abstract: Intravenous cyclosporine therapy is rapidly effective for patients with severe corticosteroid-resistant ulcerative colitis.

Cited by 1,559 publications

References 15 publications

203 Genetic Variants in the Region Harbouring IL2/IL21 Associated to Ulcerative Colitis

203 Genetic Variants in the Region Harbouring IL2/IL21 Associated to Ulcerative Colitis

Thrombin generation in mesalazine refractory ulcerative colitis and the influence of low molecular weight heparin

The management of severe ulcerative colitis

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