炎症性肠病的维持缓解治疗

溃疡性结肠炎的维持缓解治疗 溃疡性结肠炎(UC)主要累及结、直肠黏膜或黏膜下层.虽然UC严重患者在行全结肠切除术后,可得到彻底治愈,但目前尚无彻底治愈UC的药物疗法.因此,初发活动性UC患者在第一阶段诱导缓解有效后,应继续进行第二阶段维持缓解治疗,即治疗应顺序进行,先治疗急性与活动性病变,后进行维持治疗.     

解读非住院溃疡性结肠炎患者内科治疗临床实践指南——多伦多共识

2015年非住院溃疡性结肠炎患者内科治疗临床实践指南―多伦多共识主要包括5个方面要点:(1)5-氨基水杨酸类药物仍然是治疗轻中度溃疡性结肠炎的一线药物;(2)糖皮质激素只用于活动性溃疡性结肠炎的诱导缓解,不用于维持治疗;(3)免疫制剂不能用于诱导缓解,可以用于维持缓解,其作用和地位有所下降;(4)生物制剂已经成为中重度或者顽固性溃疡性结肠炎一线或者二线治疗药物;(5)粪微生物移植等探索性临床研究仍缺乏大规模多中心临床验证。本文对有关内容进行介绍并加以解读。     

白细胞分离法在溃疡性结肠炎中的应用

白细胞分离法(LCAP)是一种新型血液净化技术,其在溃疡性结肠炎的治疗中显示出较好的临床效果.LCAP可获得较高的临床缓解率,并在促进黏膜修复及维持长期缓解中起到一定作用,同时其具有较好的安全性.LCAP的临床价值有待于进一步的研究.     

溃疡性结肠炎中西医结合诊疗进展

[视频简介] 溃疡性结肠炎治疗缺乏特异性,容易反复发作、并发症多.本视频讲座讲解溃疡性结肠炎中西医结合诊疗进展,对轻中度溃疡性结肠炎通过美沙拉嗪优化治疗和中西医结合治疗,快速诱导缓解并长期维持患者,对顽固性溃疡性结肠炎可以采用英夫利昔单抗、阿达木单抗、乌司奴单抗、维得利珠单抗等生物治疗或者选择性白细胞吸附治疗、粪菌移植...     

类固醇激素依赖型溃疡性结肠炎缓解期IL-23表达的研究

目的 探讨IL-23在缓解期类固醇激素依赖型溃疡性结肠炎患者结肠组织中表达的病理意义.方法 采用Western blot分析及免疫组化SABC法检测15例缓解期激素依赖型溃疡性结肠炎患者炎症修复区结肠组织IL-23的蛋白表达情况,予统计学软件统计分析,并以30例缓解期的一般溃疡性结肠炎患者（15例SASP维持治疗,15例强的松维持治疗）炎症修复区结肠组织及10例正常结肠黏膜组织为对照组.结果 与正常对照组比较,SASP维持治疗及强的松维持治疗缓解期一般溃疡性结肠炎患者炎症修复区结肠组织IL-23的蛋白表达均轻度升高（P〉0.05）,而缓解期激素依赖型溃疡性结肠炎患者炎症修复区结肠组织IL-23的蛋白表达显著高于一般溃疡性结肠炎组（P〈0.01）.结论 IL-23的过度表达可能在溃疡性结肠炎类固醇激素依赖发病机制中起关键作用.     

类固醇激素依赖型溃疡性结肠炎缓解期IL-23表达的研究

目的 探讨IL-23在缓解期类固醇激素依赖型溃疡性结肠炎患者结肠组织中表达的病理意义.方法 采用Western blot分析及免疫组化SABC法检测15例缓解期激素依赖型溃疡性结肠炎患者炎症修复区结肠组织IL-23的蛋白表达情况,予统计学软件统计分析,并以30例缓解期的一般溃疡性结肠炎患者(15例SASP维持治疗,15例强的松维持治疗)炎症修复区结肠组织及10例正常结肠黏膜组织为对照组.结果 与正常对照组比较,SASP维持治疗及强的松维持治疗缓解期一般溃疡性结肠炎患者炎症修复区结肠组织IL-23的蛋白表达均轻度升高(P>0.05),而缓解期激素依赖型溃疡性结肠炎患者炎症修复区结肠组织IL-23的蛋白表达显著高于一般溃疡性结肠炎组(P<0.01).结论 IL-23的过度表达可能在溃疡性结肠炎类固醇激素依赖发病机制中起关键作用.     

类固醇激素依赖型溃疡性结肠炎缓解期IL-23表达的研究

目的 探讨IL-23在缓解期类固醇激素依赖型溃疡性结肠炎患者结肠组织中表达的病理意义.方法 采用Western blot分析及免疫组化SABC法检测15例缓解期激素依赖型溃疡性结肠炎患者炎症修复区结肠组织IL-23的蛋白表达情况,予统计学软件统计分析,并以30例缓解期的一般溃疡性结肠炎患者(15例SASP维持治疗,15例强的松维持治疗)炎症修复区结肠组织及10例正常结肠黏膜组织为对照组.结果 与正常对照组比较,SASP维持治疗及强的松维持治疗缓解期一般溃疡性结肠炎患者炎症修复区结肠组织IL-23的蛋白表达均轻度升高(P>0.05),而缓解期激素依赖型溃疡性结肠炎患者炎症修复区结肠组织IL-23的蛋白表达显著高于一般溃疡性结肠炎组(P<0.01).结论 IL-23的过度表达可能在溃疡性结肠炎类固醇激素依赖发病机制中起关键作用.     

Infliximab在溃疡性结肠炎中的研究进展

肿瘤坏死因子α（TNF-α）是炎症性肠病黏膜炎症中的一种关键介质,其嵌合型单克隆抗体Infliximab可拮抗其生物活性,起全面抗炎作用。Infliximab已用于克罗恩病的诱导和维持缓解,但在溃疡性结肠炎中研究较少。本文就Infliximab在溃疡性结肠炎中的治疗做一综述。     

口服5氨基水杨酸治疗溃疡性结肠炎——包括服柳氨磺胺吡啶有副作用的患者

柳氮磺胺吡啶(SASP)是治疗轻中度活动性溃疡性结肠炎或维持缓解的有效药物,但因其副作用发生率高达21%以上而限制其应用。5-氨基水杨酸(5-ASA)是该药的活性成分,对局部肠粘膜炎症有治疗作用。本文研究在于确定对 SASP 有副作用的溃疡性结肠炎患者服用5-ASA 的缓解率和副作用发生率,对用5-ASA 有效的患者并进一步评价其在维持缓解方面的作用。方法 85例活动性溃疡性结肠炎,其中51例对小量(2g/d)SASP 有副作用而需停药。本研究分两     

重症溃疡性结肠炎的内科治疗

参照1973年全国慢性非感染肠道疾病学术研讨会制定的溃疡性结肠炎的诊断标准,对北京协和医院1974年1月至1995年1月的溃疡性结肠炎住院病人共148例进行了分析,着重探讨了我院对重症溃疡性结肠炎的药物治疗经验。结果显示:21年间溃疡性结肠炎在内科消化病的年住院率呈上升趋势,重症患者占 72.3 ％。其临床治疗仍以激素,水杨酸偶氮磺胺吡啶和免疫抑制剂为主要治疗药物。本病在我院内科治疗的临床缓解率达95.9 ％,其中重症的临床缓解率达95,3 ％,死亡率为6.08 ％。我们提出对溃疡性结肠炎的内科治疗应遵循尽早控制症状、维持缓解、预防复发、防治并发症和掌握手术时机的原则;并根据病变的范围、疾病的活动性和严重程度、病程、病人的全身情况、以前用药情况和有无并发症等进行综合治疗。     

Refractory Distal Ulcerative Colitis Responsive to 5-Aminosalicylate Enemas

Patients with distal ulcerative colitis may be refractory to standard drug therapy. 5-Aminosalicylate, the active moiety of sulfasalazine, is effective topically in new onset distal colitis. Six patients with distal colitis unresponsive to sulfasalazine and corticosteroids had a prompt and dramatic response to the administration of 5-aminosalicylate enemas with clinical, sigmoidoscopic, and histological improvement. Topical 5-aminosalicylate should be a useful addition to the current available therapies for some patients with refractory distal ulcerative colitis.     

Effect of infliximab in the treatment of refractory inflammatory bowel disease with complication]

BACKGROUND/AIMS: Many studies on infliximab have confirmed its efficacy in the remission induction and even maintenance in refractory and fistulizing Crohn's disease. We report the treatment efficacy of infliximab in Crohn's disease and ulcerative colitis refractory to steroid treatment and the complications of infliximab treatment. METHODS: We performed infliximab administration in 5 cases (3 Crohn's disease, 2 ulcerative colitis) refractory to systemic steroid treatment and 5 cases of Crohn's disease with fistula. Patients received an intravenous infusion of infliximab at 3-5 mg/kg body weight. RESULTS: In 3 cases of refractory Crohn's patients, clinical response and remission induction were obtained in 2 (67%) and 1 cases (33%). After infusion of infliximab, the occlusion of internal fistula could be found in all 2 cases. Two out of 3 cases of anal fistula were completely healed. In two cases of refractory ulcerative colitis, one case who showed clinical manifestation of toxic megacolon had improved and avoided the colectomy, but the other case did not respond to the infusion of infliximab and underwent colon resection. CONCLUSIONS: We found that administration of infliximab is an effective alternative for refractory and fistulizing Crohn's disease but further studies are necessary for refractory ulcerative colitis.     

Refractory Inflammatory Bowel Disease

Opinion statement Therapeutic options for refractory colonic inflammation in patients with ulcerative colitis or Crohn’s disease have recently been augmented by the introduction of biologic therapies. Intravenous corticosteroids and cyclosporin A remain the standard therapies for severe ulcerative colitis. Monoclonal antibodies directed at tumor necrosis factor alfa (TNF-α) have proven to be most efficacious in patients with severe or refractory Crohn’s disease. Immunomodulatory therapy with azathioprine, 6-mercaptopurine, or methotrexate has demonstrated efficacy for maintenance of remission in patients with refractory ulcerative colitis or Crohn’s disease. The use of experimental biologic agents may be considered for those patients who fail to respond to or remain dependent on corticosteroids. Surgical intervention is indicated for patients with severe colitis who fail to respond to medical therapy or develop life-threatening complications such as perforation or toxic megacolon.     

Refractory inflammatory bowel disease

Opinion statement Therapeutic options for refractory colonic inflammation in patients with ulcerative colitis or Crohn’s disease have recently been expanded with the introduction of biologic therapies. Intravenous corticosteroids and cyclosporine A remain the standard therapies for severe ulcerative colitis. Monoclonal antibodies directed at tumor necrosis factor-α have proven to be exceptionally efficacious in patients with severe or refractory Crohn’s disease. Immunomodulatory therapy with azathioprine, 6-mercaptopurine, or methotrexate has demonstrated efficacy for maintenance of remission in patients with refractory ulcerative colitis or Crohn’s disease. The use of experimental biologic agents may be considered for those patients who fail to respond to or remain dependent on corticosteroids. Surgical intervention still remains for patients with severe colitis who fail to respond to medical therapy or develop life-threatening complications such as perforation or toxic megacolon.     

Anti-tumour necrosis factor alpha (Infliximab) in the treatment of severe ulcerative colitis: result of an open study on 13 patients

BACKGROUND: Conventional treatment options for patients with severe steroid-refractory ulcerative colitis include intravenous cyclosporine, which is frequently burdened by toxicity, or colectomy. Preliminary data suggest a benefit from anti-tumour necrosis factor alpha (Infliximab) therapy in patients with steroid refractory ulcerative colitis. AIM: To evaluate the efficacy of Infliximab in the treatment of severe ulcerative colitis refractory to conventional therapy PATIENTS AND METHODS: A series of 13 patients with severe ulcerative colitis, refractory to therapy with methyl-prednisolone, 60 mg daily for seven or more days, were treated with a single intravenous infusion of Infliximab 5 mg/kg. RESULTS AND CONCLUSIONS: Of these 13 patients, 10 (77%) had a clinical response to therapy defined by a clinical activity index 10 on two consecutive days. In 2 patients (15%) total colectomy was necessary on account of clinical worsening whilst one patient refused surgery and was lost to follow-up. All patients who responded showed very rapid clinical improvement, within 2 to 3 days of infusion. Infusion with Infliximab produced no significant adverse events. The mean time of follow-up was 10.1 months (range 5-12; during this time, 9 out of 10 patients (90%) maintained clinical remission and were able to discontinue corticosteroid therapy. Infliximab appears to be an effective agent for inducing long-standing remission in refractory patients with severe ulcerative colitis.     

Low molecular weight heparin treatment in steroid refractory ulcerative colitis: clinical outcome and influence on mucosal capillary thrombi.

BACKGROUND: In ulcerative colitis, a state of hypercoagulation has frequently been observed. Unfractionated heparin has shown beneficial effects as an adjuvant treatment of steroid refractory ulcerative colitis in open trials and in one placebo-controlled trial. Low molecular weight heparin (LMWH) offers advantages in the method of administration, but it has not been evaluated in severe ulcerative colitis. We therefore assessed the tolerability, safety and potential therapeutical effects of LMWH in hospitalized patients with steroid refractory ulcerative colitis. METHODS: Twenty-five patients with severely active ulcerative colitis were included in an open-labelled trial. All patients had a flare-up of disease under glucocorticosteroid treatment. Nadroparine calcium 5.700 IE anti-Xa/0.6 mL s.c. was self-administered twice daily for 8 weeks. Patients were monitored for possible adverse events, and changes in clinical symptoms and in laboratory, endoscopical and histological results were analysed. RESULTS: Tolerability and compliance were excellent and no serious adverse events occurred. In 20 of 25 patients, a good clinical and laboratory response was observed. Also, the endoscopic and histological signs of inflammation were found to be significantly improved. However, this was not accompanied by a significant reduction in the number of mucosal microvascular thrombi after 8 weeks of LMWH treatment. CONCLUSION: LMWH may be a safe adjuvant therapy for patients with active, glucocorticosteroid refractory ulcerative colitis.     

Pulse cyclophosphamide therapy for inflammatory bowel disease

AIM: To assess the efficacy of intravenous cyclophosphamide pulse therapy for refractory inflammatory bowel disease (IBD).METHODS: We included in our cohort eight patients with (moderate/severe) steroid refractory IBD (4 with ulcerative colitis and 4 with Crohn's disease). They all received 6 cycles of intravenous cyclophosphamide (800mg) per month.RESULTS: Patients entered into remission after the second/third cyclophosphamide pulse. Disease activity decreased. There were no side effects and toxicity. All the patients went into long lasting remission. All Crohn's disease patients and 3 of 4 ulcerative colitis patients achieved complete remission. One patient with ulcerative colitis showed an impressive clinical response but did not enter into remission. For the maintenance, patients with Crohn's disease were treated with methotrexate (15 mg/wk) and patients with ulcerative colitis were treated with azathioprine (2.5 mg/kg body weight/d).CONCLUSION: Remission was maintained in all patients for 6 mo on the average. The drug was well tolerated. These findings suggest that aggressive immunosuppressive therapy may be useful in some refractory patients and further controlled study should be considered in order to fully evaluate this type of treatment as a potential therapy for IBD.     

Pulse cyclophosphamide therapy for inflammatory bowel disease

AIM: To assess the efficacy of intravenous cyclophosphamide pulse therapy for refractory inflammatory bowel disease (IBD). METHODS: We included in our cohort eight patients with (moderate/severe) steroid refractory IBD (4 with ulcerative colitis and 4 with Crohn's disease). They all received 6 cycles of intravenous cyclophosphamide (800 mg) per month. RESULTS: Patients entered into remission after the second/third cyclophosphamide pulse. Disease activity decreased. There were no side effects and toxicity. All the patients went into long lasting remission. All Crohn's disease patients and 3 of 4 ulcerative colitis patients achieved complete remission. One patient with ulcerative colitis showed an impressive clinical response but did not enter into remission. For the maintenance, patients with Crohn's disease were treated with methotrexate (15 mg/wk) and patients with ulcerative colitis were treated with azathioprine (2.5 mg/kg body weight/d). CONCLUSION: Remission was maintained in all patients for 6 mo on the average. The drug was well tolerated. These findings suggest that aggressive immunosuppressive therapy may be useful in some refractory patients and further controlled study should be considered in order to fully evaluate this type of treatment as a potential therapy for IBD.     

Mucosal features and granulocyte–monocyte-apheresis in steroid-dependent/refractory ulcerative colitis

BACKGROUND: Mucosa-infiltrated granulocyte neutrophils are an early characteristic of inflammation and the main histological feature of active ulcerative colitis. Mucosal healing has recently been indicated as an important tool in the evaluation of response to treatment. While several studies have stressed the efficacy of granulocyte-monocyte-apheresis in inducing clinical remission in active ulcerative colitis, few data are available on mucosal features. AIM: Aim of this study was to assess the effects of granulocyte-monocyte-apheresis on clinical and mucosal features in patients with ulcerative colitis, dependent upon or refractory to steroids. MATERIAL AND METHODS: From April 2004 to April 2005, 12 patients (5 females, 7 males, mean age 49 years, range 33-71 years), with mild-moderate ulcerative colitis (six left colitis, six pancolitis) dependent/refractory upon steroids were enrolled. Each patient was treated for a 5-week period with five cycles of granulocyte-monocyte-apheresis. Patients were evaluated at baseline and 1 week after the last apheresis by means of Global Physician Assessment, quality of life features, laboratory tests (erythrocyte sedimentation rate, CRP, full blood count, faecal calprotectine), endoscopy and histology. RESULTS: At week 6 of follow-up, complete mucosal healing was observed in 3 out of 12 patients, partial mucosal healing in 8 patients and no change in 1 patient. Clinical response was complete in 8 out of 12 patients. CONCLUSIONS: These data suggest that granulocyte-monocyte-apheresis induces an improvement both in clinical and mucosal lesions in steroid-dependent/refractory ulcerative colitis. Of note, the reduction in granulocyte infiltration and the improvement in mucosal lesions are accompanied by a reduction in faecal calprotectine.     

Topical treatment of refractory distal ulcerative colitis with 5-ASA and sodium butyrate

Nine patients with distal ulcerative colitis refractory to standard therapy were treated with intrarectal instillation of a sodium butyrate solution and 5-ASA. A marked clinical, endoscopical and, to a smaller extent, histological improvement was observed in seven of nine patients. The clinical improvement usually occurred within the second week of therapy, and thus earlier than in previous cases treated with butyrate alone. This preliminary experience suggests that the combined butyrate-5-ASA treatment may prove a useful therapeutic tool in refractory distal ulcerative colitis and possibly increase the effectiveness of the individual therapeutic regimens.