重度溃疡性结肠炎的治疗

Cheifetz AS，Stern J．Garud S．el a1．Cyclosporine is safe and effective in patients with severe ulcera tive colitis．J Clin Gastroenter01．20ll，45．107 -11 2．
Infliximab
Jarnerot G, Hertervig E, Friis-Liby I et al. Infliximab as rescue therapy in severe t o moderately severe ulcerative colitis: a randomized, placebo-controlled study. Gastroenterology 2005; 128 (7): 1805–11. Maser EA, Deconda D, Lichtiger S, Ullman T, Present DH, Kornbluth A. Cyclospor
Rescue Therapy
Approximately 15% of patients with ulcerative colitis will have a severe attack requiri
ng hospitalisation for intravenous steroids at some stage in their illness.
ine and infliximab as rescue therapy for each other in patients with steroid-refrac
tory ulcerative colitis. Clin Gastroenterol Hepatol. 2008; 6: 1112–16. Ljchtenstein GR，Abreu MT，Cohen R．et al. American Gastroenterological Ass ociation Institute technical review on corticosteroids，immunomodulators．and i nfliximab in inflammatory bowel disease．Gastroenterology. 2006. 130：940-987 ．
Toxicity may be reduced at a dose of 2 mg/kg/day intravenous cyclosporin.
Loftus CG，Loftus EV Jr，Sandborn WJ．Cyclosporin for refractory ulcerative colitis．GUt．2003，52; 1 72—173．
Sixty per cent of patients treated with corticosteroids will be symptom free by the e nd of five days, 15% will have significant improvement, and 25% will not improve. Steroid resistance was defined as unresponsiveness to oral or intravenous corticost eroid therapy (equivalent to a daily dose of more than 30 mg of prednisolone) over at least two weeks. Those who fail to improve may be treated with intravenous cyclosporin, infliximab, o ral tacrolimus or undergo colectomy. Caprilli R，Viscido A，Latella G．Current management of severe ulcerative colitis． Nat CIin Pract Gastroenterol Hepatol，2007，4：92-101．
Long term response rates following short term treatment with intravenous cyclosporin in controlled trials ranged from 45% (without azathioprine maintenance) to 78% (with azathioprine).
Infliximab
BACKGROUND: Infliximab is used for treatment of Crohn's disease and, following the Active Ulcerative Coliti
s Trials (ACT) 1 and 2, it has been used as rescue and maintenance therapy in moderate and severe ulcerati ve colitis (UC). AIM: To report on English experience with maintenance infliximab in terms of response and colectomy rates and side-effect profile in UC. METHODS: A retrospective audit conducted by using a web-based questionnaire filled in by 12 gastroentero logists from six English centres. RESULTS: Of the 38 patients receiving induction with infliximab, 28 (73.6%) maintained an ongoing respons e (8-weekly infusions 5 mg/kg) for a mean duration of 16.8 months (range 4-59), with 21 (55.3%) being in r emission. Three of 38 patients (7.9%) who also responded had a secondary loss of response after an avera ge of 10 months (range 8-13); seven of 38 patients (18.4%) showed no response. The colectomy rate was seven of 38 (18.4%, five non-responders and two with secondary loss of response). Adverse effects occurr ed in five patients (13.2%). Two discontinued infliximab (alopecia, invasive breast cancer). The three less-s evere adverse effects were acute and delayed-type hypersensitivity reactions and one persistent otitis media CONCLUSION: Our experience suggests acceptable response rates, colectomy rates and side-effect profile of maintenance therapy with infliximab in moderate and severe UC. Russo EA, Harris AW, Campbell S et al. Experience of maintenance infliximab therapy for refractory ulcerativ e colitis from six centers in England. Aliment Pharmacol Ther. 2009; 29: 308–314.
重症溃疡性结肠炎的治疗
Introduction
IBD是一种病因尚不十分清楚的慢性非特异性肠道炎症，包括UC和CD 。
其发病率呈逐年上升趋势，且多为青壮年发病，临床表现复杂，并发症严重
，肠外表现多样，严重影响个人生活质量和社会生产力。 此外，因其有癌变的风险，备受广大医生的重视。 近年来在国内外IBD基础与临床研究高潮迭起，基础研究的成果直接指向临 床治疗，取得了划时代的进展。 探讨和摸索适合国人的治疗方案以降低重症UC的并发症和死亡率显得十分 重要。
There is a small risk of opportunistic infection and death (1–2%) during combined cyclosporin, corticost
eroid, and azathioprine therapy, but lower doses of cyclosporin may improve the safety profile.
An initial dose of 2 mg/kg/day intravenous cyclosporin appears to be as effective as 4 mg/kg/day and i
s thus preferred from the standpoint of safety.
Tacrolimus (FK506)
Tacrolimus (FK506) is an immunosuppressive macrolide isolated from fermentation broth of Streptomyces tsukubaensis. It potently inhibits helper T lymphocyte activation. In fact, tacrolimus has been shown to inhibit transcription of the early activation genes for cy tokines such as interleukin 2 (IL-2), tumour necrosis factor a (TNF-a), and interferon c (IFNc) in T cells. Its immunosuppressive effect appears to be mediated, in part, through inhibition of IL-2 synt hesis and release, as well as a decrease in the number of IL-2 receptors on activated lymph
CsA
There have been four controlled studies of intravenous cyclosporin in pa col
itis.
Intravenous cyclosporin (with or without continued intravenous corticosteroids) is effective in 50–80% o f patients with severe ulcerative colitis.