硫唑嘌呤维持克罗恩病临床缓解的疗效与安全性

目的了解硫唑嘌呤维持克罗恩病患者临床缓解的疗效及安全性。方法收集1998—2005年13例经口服泼尼松或病变肠段切除术后获得临床缓解的克罗恩病患者，分析经硫唑嘌呤治疗前及平均治疗（每天2mg／kg）达18个月后的克罗恩病活动指数（CDAI）、Harvey-Bradshaw指数、泼尼松剂量减少情况、生物学指标变化及有无不良反应，并进行统计学分析。结果硫唑嘌呤治疗后，患者的CDAI评分下降，平均为96．1分，10例患者保持完全缓解（76．9％）。Harvey-Bradshaw指数平均下降1．8分，11例缓解（84．6％）。两种评估方法结果密切相关（r=0．8）。9例患者在开始服用硫唑嘌呤同时，缓慢递减泼尼松剂量（每天或隔天5～10mg）或停服。绝大多数患者血小板计数、红细胞沉降率及D反应蛋白能保持在诱导缓解后的正常值范围内。血清总蛋白及白蛋白值在诱导缓解后进一步升高达正常（或接近正常）值水平。除个别患者肝酶发生轻度（〈正常2倍）升高外，大多数患者在应用硫唑嘌呤前后无明显变化。少数患者发生短暂的白细胞减少或轻度肝转氨酶升高，在密切观察及保肝治疗后继续治疗。1例患者在同时服用5-氨基水杨酸制剂（6个月）时，发生白细胞减少与肝转氨酶轻度升高而停药。结论除少数患者发生不良反应外，硫唑嘌呤在泼尼松或手术治疗诱导缓解后，能使大多数克罗恩病患者继续保持临床缓解。     

克罗恩病长期免疫抑制治疗的疗效

目的 研究中国汉族人群克罗恩病的临床表现特征和中长期免疫抑制剂治疗的疗效.方法 分析2003年至2010年178例克罗恩病患者的相关临床特征数据及诊断方法.所有患者均采用泼尼松和免疫抑制剂(硫唑嘌呤)治疗.每2周进行临床随访,每4周复查红细胞沉降率和C反应蛋白,每3～6个月行克罗恩病活动指数(CDAI)评分.结果 克罗恩病的发病高峰在18～30岁,从出现症状到确诊的平均时间为(8.3±3.7)个月,确诊时有34.8％(62/178例)的患者已因病情进展而出现相应的并发症.硫唑嘌呤平均剂量为(1.24±0.16)mg/kg,不良反应的总停药率为15％(25/167).长期随访中的手术干预率为15.1％(22/146).治疗后3个月,患者红细胞沉降率、C反应蛋白明显下降并趋于正常,6个月后CDAI评分也明显降低.结论 大部分中国克罗恩病患者对免疫抑制剂有良好的耐受性,且在低于欧美推荐剂量的情况下,仍能获得较好的中长期临床疗效.     

英夫利昔单用和联合硫唑嘌呤治疗克罗恩病的疗效分析

目的比较英夫利昔(Infliximab,IFX)单药治疗和英夫利昔联合硫唑嘌呤(Azathioprine,AZA)治疗中重度克罗恩病(Crohn′s disease,CD)患者的疗效。方法选取2010年6月至2014年5月在南方医科大学南方医院消化科进行治疗的47例中重度CD患者为研究对象,按照治疗方式的不同,将患者分为IFX组29例和IFX+AZA组18例。观察两组患者治疗前、治疗后第14周和第30周的实验室指标(WBC、ESR、CRP、ALB)、克罗恩病活动度指数(CDAI)、临床缓解率、克罗恩病简化内镜评分(SESCD)、黏膜愈合率以及不良反应的情况。结果第14周时,IFX组和IFX+AZA组的临床缓解率分别为:58.6%(17/29)vs 72.2%(13/18),(P0.05);黏膜愈合率分别为:51.7%(15/29)vs 55.6%(10/18),(P0.05)。两组患者的WBC水平均较治疗前显著下降,BMI和ALB水平显著升高。第30周时,IFX组和IFX+AZA组的临床缓解率分别为:75.9%(22/29)vs 88.9%(15/18),(P0.05);部分患者在第30周复查内镜,两组的黏膜愈合率分别为:47.1%(8/17)vs 83.3%(5/6),(P0.05)。两组患者的WBC水平均较治疗前显著下降,BMI和ALB水平升高。结论 IFX和IFX+AZA两种方法均可有效诱导和维持中度CD患者临床缓解和黏膜愈合,但后者疗效有更优趋势。     

硫唑嘌呤治疗活动性克罗恩病的开放性前瞻性研究

目的 通过长程前瞻性研究观察硫唑嘌呤(AZA)治疗我国活动性克罗恩病(CD)患者的疗效及安全性.方法 收集活动性CD且需使用糖皮质激素治疗者60例,开始予AZA及糖皮质激素治疗,激素撤离后以AZA维持治疗.随访监测第12、24、48、72和96周的临床疗效、内镜下黏膜愈合程度及不良反应.结果 随访第12、24、48、72和96周患者的完全缓解率分别为55.0%、66.7%、61.7%、53.3%和53.3%.25例患者治疗前及治疗48周时行结肠镜检查,8例达到黏膜愈合者随访至第96周时均维持完全缓解(8/8),17例未达黏膜愈合者至第96周时维持完全缓解仅9例(9/17,P=0.026).比较第48周完全缓解组与未完全缓解组的特征,多因素Logistic回归分析显示治疗后超敏C反应蛋白恢复至正常值为AZA有效维持缓解的独立影响因素(OR=10.1,95%CI:1.8～57.9,P=0.09).16例(26.7%)患者发生不良反应,其中10例因不良反应而停药;WBC减少为最常见不良反应(18.3%),发生于用药全程.结论 AZA与糖皮质激素合用可有效诱导活动性CD缓解,AZA可有效维持撤离激素后的长程缓解,AZA最常见的不良反应是WBC减少.部分病例可获得病变肠黏膜愈合,达到黏膜愈合者可维持长程临床缓解.

Abstract：

Objective To evaluate the efficacy and safety of azathioprine (AZA) in long term treatment of patients with active Crohn's disease (CD) in China. Methods Sixty patients with active CD,who needed to be treated with systemic steroids, were recruited. All patients initially received AZA combined with steroids therapy and AZA was maintained for treatment after withdrawal of steroids. Clinical efficacy, endoscopic healing of mucosa and adverse events were assessed at the end of the 12th, 24th, 48th, 72th and 96th weeks. Results The complete remission (CR) of the patients at the 12th, 24th, 48th, 72th and 96th weeks was 55.0%, 66. 7%, 61. 7%, 53. 3% and 53. 3%,respectively. Endoscopic examination was performed in 25 patients before treatment and at the end of the 48th week. Eight of them achieved mucosal healing that was kept to the end of 96th week (8/8).Whereas only 9 out of 17 patients without mucosal healing achieved CR at the end of 96th week (9/17,P=0. 026). The clinical features were compared between CR group and non-CR group at the end of 48th week. Logistic regression analysis showed that regaining of hs-CRP was the only independent factor for maintaining remission by AZA treatment ( P= 0. 009,OR 10.1,95 % CI 1.8 ～ 57.9). Sixteen patients (26.7 % ) had adverse events. Ten (16.7 % ) of them had to halt treatment because of serious adverse events. Leucopenia was the most common adverse event and could be occurred at any time during the treatment. Conclusion AZA combined with steroid therapy can effectively induce remission of active CD. Long term steroid-free remission is also effectively maintained by AZA treatment. The most common adverse event is leucopenia and some patients can get mucosal healing. Those who get mucosal healing may have longer duration of remission.     

克罗恩病药物治疗进展

克罗恩病（CD）是一种难治性疾病,目前尚无疗效确切的治疗方法。近年来随着对该病发病机制研究的不断深入,其治疗策略正发生着巨大的变化。此文在回顾和重新评估传统药物（氨基水杨酸类、糖皮质激素、免疫抑制剂）的基础上,重点介绍针对肿瘤坏死因子、T细胞、黏附分子及其他细胞因子等新型生物学疗法。     

免疫抑制剂在克罗恩病中的应用与疗效分析

目的 探讨免疫抑制剂在克罗恩病(CD)中的应用与变迁、CD临床特点与免疫抑制剂疗效的关系.方法 回顾性分析1983年6月-2006年6月我院收治的105例CD患者.结果 (1)我院CD患者免疫抑制剂的使用,2000年后较2000年前显著增多(34.7%比3.0%,P=0.000).(2)免疫抑制剂的应用及临床特点:①中重度CD使用免疫抑制剂者明显多于轻度CD患者(28.9%比0);②免疫抑制剂的应用与CD病变部位无关,各部位应用免疫抑制剂的比例分别为小肠20.0%、结肠27.3%、回结肠27.1%(P=0.726);③应用免疫抑制剂者较未用者基础状态血清白蛋白偏低(31.9 g/L比35.1 g/L,P=0.047);④应用免疫抑制剂不能明显降低患者手术率(38.5%比50.0%,P=0.320).(3)在我国免疫抑制剂应用最多的是硫唑嘌呤,本组中应用硫唑嘌呤的19例CD患者的临床缓解率为68.4%,未缓解者的中性粒细胞较缓解者明显偏高(0.76比0.65,P=0.032).结论 免疫抑制剂在CD治疗中的应用呈逐年增多趋势.中重度CD、基础状态血清白蛋白水平低的CD患者需及早应用免疫抑制剂,而病变部位与是否需要应用免疫抑制剂无关.中性粒细胞高的CD患者应用硫唑嘌呤的疗效差.     

克罗恩病药物治疗进展

克罗恩病(CD)是一种难治性疾病,目前尚无疗效确切的治疗方法。近年来随着对该病发病机制研究的不断深入,其治疗策略正发生着巨大的变化。此文在回顾和重新评估传统药物(氨基水杨酸类、糖皮质激素、免疫抑制剂)的基础上,重点介绍针对肿瘤坏死因子、T细胞、黏附分子及其他细胞因子等新型生物学疗法。     

硫唑嘌呤治疗炎症性肠病疗效分析

迄今,关于硫唑嘌呤(免疫抑制药之一)治疗炎症性肠病药效及其预后预测指标均无相关研究,本文就此进行了分析。对象与方法 2 205例炎症性肠病患者,其中622例随机吸用了硫唑嘌呤,后者中克罗恩病272例,溃疡性结肠炎346例,未定性结肠炎4例。人均用药634d,人均随访达2 518d。尔后观察分析药物疗效及预后相关预测指标。     

英夫利西单抗联合硫唑嘌呤治疗中重度克罗恩病的疗效研究

背景:激素和免疫抑制剂是克罗恩病(CD)的传统治疗药物,然而部分CD患者对传统药物耐药或依赖。目的:评价英夫利西单抗联合硫唑嘌呤治疗中重度CD的有效性和安全性。方法:24例CD患者随机分为英夫利西单抗组、硫唑嘌呤组、英夫利西单抗联合硫唑嘌呤组(联合治疗组)。英夫利西单抗组于第0、2、6周给予英夫利西单抗5mg/kg,随后每隔8周给予英夫利西单抗5 mg/kg;硫唑嘌呤组给予硫唑嘌呤2.5 mg/kg qd;联合治疗组给予硫唑嘌呤2.5 mg/kg qd,并于第0、2、6周给予英夫利西单抗5 mg/kg,随后每隔8周给予英夫利西单抗5 mg/kg。治疗第26周末以CD疾病活动指数(CDAI)和内镜检查评价治疗疗效。治疗期间记录患者不良反应发生情况。结果:治疗第26周末,联合治疗组的临床总有效率和内镜下总有效率较英夫利西单抗组和硫唑嘌呤组均显著升高(P<0.05);治疗第26周末联合治疗组血红蛋白水平较治疗前显著升高(P<0.05),ESR和CRP水平治疗前均显著降低(P<0.05);治疗期间联合治疗组无严重不良反应发生。结论:对于激素抵抗或依赖的中重度CD患者,英夫利西单抗联合硫唑嘌呤的疗效优于单用英夫利西单抗或硫唑嘌呤。     

英夫利昔治疗克罗恩病疗效与安全性的meta分析

[目的]通过运用meta分析,系统评价英夫利昔单抗治疗克罗恩病(CD)的疗效和安全性。[方法]通过检索中国期刊全文数据库、中国生物医学文献数据库、cochrane图书馆、Pubmed和西文生物医学数据库(EMCC)获取文献,纳入所有应用英夫利昔治疗CD的随机对照试验(randomized controlled trials,RCTs)。根据Jadad评分评价纳入文献的质量。2位作者独立提取资料并进行质量评价。对纳入文献采用固定效应模型进行meta分析,通过固定效应模型和随机效应模型分析比较的方法进行敏感性分析。[结果]共5个RCTs试验符合纳入标准,用于此次meta分析。Meta分析显示:①临床缓解:英夫利息单抗治疗CD的缓解率较安慰剂高;②临床应答:英夫利息单抗治疗CD的临床应答率高于安慰剂;③不良反应:英夫利西单抗治疗CD不良反应的发生率与安慰剂相比无明显差异;④复发率:英夫利息单抗治疗存在瘘管CD的复发率与安慰剂相比无明显差异。[结论]英夫利西单抗治疗CD具有一定疗效。     

Current status of thiopurine analogues in the treatment in Crohn's disease

In the last decades,with the development of biological therapy,the treatment paradigms in patients with Crohn's disease have continuously evolved.Several studies focusing on the optimal use of both traditional immunosupressants and biological therapy have been published,investigating conventional,accelerated step-up and topdown approaches.In addition,much emphasis has been placed in recent years on the determination of important predictive factors that could enable early patient stratification,which would l...     

The long-term outcome in Crohn's disease

The long-term outcome of Crohn's disease was reviewed in 139 patients who were treated at the Cleveland Clinic for a minimum of 15 years. At the time of diagnosis, 38 (27 percent), 39 (28 percent) and 62 (43 percent) patients had small-bowel, large-bowel, and ileocolic patterns of disease, respectively. The disease progressed with time and, eventually, 104 (75 percent) patients had ileocolic disease. One hundred twenty-two patients (88 percent) underwent at least one definitive operation for the disease. Forty-four (32 percent) patients had proctocolectomies and 65 (47 percent) have ileostomies. Associated manifestations of Crohn's disease occurred in a high proportion of patients; perianal disease in 78 (56 percent), intestinal fistulas in 45 (32 percent), extraintestinal disease in 49 (35 percent). Six patients died of causes directly related to the disease. Specific complications tend to occur at definite times in the course of the disease. Crohn's disease is not a benign condition. There is a relentless progression of the disease and a high incidence of complications when patients are followed over a long period. Read at the meeting of the American Society of Colon and Rectal Surgeons, Houston, Texas, May 11 to 15, 1986.     

Hepatocellular carcinoma occurring in a Crohn's disease patient

We report a case of hepatocellular carcinoma (HCC) occurring in a patient with Crohn's disease (CD) without chronic hepatitis or liver cirrhosis, and review the clinicopathological features of HCC in CD patients. A 37-year-old Japanese man with an 8-year history of CD and a medication history of azathioprine underwent resection of a liver tumor. The histopathology of the liver tumor was pseudoglandular type HCC. In the nonneoplastic liver, focal hepatocyte glycogenosis (FHG) was observed, however, there was no evidence of liver cirrhosis or primary sclerosing cholangitis. Only nine cases of HCC in CD patients have been reported previously in the English-language literature. Eight of 10 cases (including the present case) had received azathioprine treatment, and four of these cases also showed FHG, which is considered a preneoplastic liver lesion, within the non-neoplastic liver. Although the precise mechanism of the development of HCC in CD patients is controversial, these results suggest that azathioprine therapy and FHG in the non-neoplastic liver contribute to the development of HCC. These findings also indicate that it is important to survey CD patients treated with prolonged azathioprine therapy for potential liver tumors.     

Current use of immunosuppressive agents in inflammatory bowel disease patients in East China

AIM： To investigate immunosuppressive agents used to treat inflammatory bowel disease （IBD） in East China.
METHODS： A retrospective review was conducted, involving 227 patients with IBD admitted to Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University from June 2000 to December 2007, Data regarding demographic, clinical characteristics and immunosuppressants usage were analyzed,
RESULTS： A total of 227 eligible patients were evaluated in this study, including 104 patients with Crohn＇s disease and 123 with ulcerative colitis. Among the patients, 61 had indications for immunosuppressive agents use. However, only 21 （34.4%） received immunosuppressive agents. Among the 21 patients, 6 （37.5%） received a subtherapeutic dose of azathioprine with no attempt to increase the dosage. Of the 20 patients that received immunosuppressive agent treatment longer than 6 mo, 15 patients went into remission, four patients were not affected and one relapsed. Among these 20 patients, four patients suffered from myelotoxicity and one suffered from hepatotoxicity.
CONCLUSION： Immunosuppressive agents are used less frequently to treat IBD patients from East China compared with Western countries. Monitoring immunosuppressive agent use is recommended to optimize dispensation of drugs for IBD in China.     

Perianal disease, small bowel disease, smoking, prior steroid or early azathioprine/biological therapy are predictors of disease behavior change in patients with Crohn＇s disease

AIM： To assess the combined effect of disease phenotype, smoking and medical therapy [steroid, azathioprine （AZA）, AZA/biological therapy] on the probability of disease behavior change in a Caucasian cohort of patients with Crohn＇s disease （CD）. METHODS： Three hundred and forty well-characterized, unrelated, consecutive CD patients were analyzed （M/F： 155/185, duration： 9.4 ± 7.5 years） with a complete clinical follow-up. Medical records including disease phenotype according to the Montreal classification, extraintestinal manifestations, use of medications and surgical events were analyzed retrospectively. Patients were interviewed on their smoking habits at the time of diagnosis and during the regular follow-up visits. RESULTS： A change in disease behavior was observed in 30.8% of patients with an initially non-stricturing, non-penetrating disease behavior after a mean disease duration of 9.0 ± 7.2 years. In a logistic regression analysis corrected for disease duration, perianal disease, smoking, steroid use, early AZA or AZA/ biological therapy use were independent predictors of disease behavior change. In a subsequent Kaplan-Meier survival analysis and a proportional Cox regression analysis, disease location （P = 0.001）, presence of perianal disease （P 〈 0.001）, prior steroid use （P = 0.006）, early AZA （P = 0.005） or AZA/biological therapy （P = 0.002）, or smoking （P = 0.032） were independent predictors of disease behavior change. CONCLUSION： Our data suggest that perianal disease, small bowel disease, smoking, prior steroid use, early AZA or AZA/biological therapy are all predictors of disease behavior change in CD patients.     

The resectional reoperation rate for Crohn's disease in a general community hospital

The severity of Crohn's disease has not been objectively estimated for patients treated at community hospitals. During an 11-year period, 105 patients underwent initial intestinal resection for Crohn's disease at a large community hospital. Follow-up data were actuarially analyzed. The overall resectional reoperation rate was 4.0 per cent per year the first seven years after initial resection and 1.9 per cent per year for the next ten years. Patients with small-bowel disease had a better prognosis than did patients with ileocolic disease. Patients who were less than 30 years of age at initial resection needed a second resection more often than did older patients. The 81 patients with initial resection after 1970 have had the lowest resectional reoperation rate yet reported: 2.8 per cent per year for ten years. The resectional reoperation rate for patients with Crohn's disease treated at this community hospital compares favorably with reoperation rates reported for patients at referral centers Read at the meeting of the American Society of Colon and Rectal Surgeons, San Francisco, California, May 2 to 6, 1982.