克罗恩病英夫利昔单抗治疗失应答的影响因素分析

目的 分析克罗恩病(CD)英夫利昔单抗(IFX)治疗失应答的影响因素.方法 回顾性分析使用IFX治疗的63例CD患者的临床资料,包括年龄、性别、发病至治疗时间(病程)、蒙特利尔分型(包括诊断时年龄A、病变部位L和疾病行为B)、联用免疫制剂、联合肠内营养、合并瘘管、合并肛周病变、合并肠外表现、治疗前克罗恩病活动指数(CDAI))评分、BMI、CRP、CRP降低率[(第四次治疗前CRP-基线CRP)/基线CRP]、基线红细胞沉降率(ESR)、基线血红蛋白(Hb)、基线白蛋白(ALB)等.根据IFX诱导治疗3次后的CDAI评分分为原发失应答组和应答组,应答组的患者根据应答情况分为继发失应答组和持续应答组.比较原发失应答组和应答组以及继发失应答组和持续应答组的上述临床资料,采用Logistic回归分析CD患者IFX治疗失应答的影响因素.结果 63例CD患者中,22例(34.9％)患者发生IFX治疗失应答,发生原发失应答的患者8例(12.7％),继发失应答的患者14例(22.2％),原发失应答组和应答组患者BMI、疾病行为和联合肠内营养比较,P均<0.05.未发现原发失应答的独立预测因素;继发失应答组和持续应答组患者性别、CDAI评分和Hb比较,P均<0.05,治疗前CDAI评分>220分是继发失应答的独立预测因素(P<0.05).结论 IFX治疗CD患者失应答不可避免.患者的疾病行为、BMI和联合肠内营养是IFX治疗原发失应答的可能影响因素.CDAI评分>220分为IFX治疗继发失应答的独立预测因素,性别、CDAI评分和Hb与IFX治疗继发失应答有关.     

胶囊内镜在小肠克罗恩病英夫利西单抗治疗第14周疗效评估中的应用价值

目的 评价小肠受累的克罗恩病（CD）患者使用英夫利西（IFX）单抗治疗第14周临床缓解情况,以及采用胶囊内镜联合回结肠镜评估肠道黏膜愈合情况的临床价值。方法回顾性分析23例接受IFX治疗的小肠受累的CD患者的临床资料。观察治疗前和治疗后第14周时患者实验室指标（血常规、C反应蛋白、白蛋白）、克罗恩病活动度指数（CDAI）、胶囊内镜Lewis评分、克罗恩病简化内镜评分（SES-CD）、不良反应及并发症的情况。结果与治疗前相比,治疗后第14周23例CD患者的CDAI评分和炎症指标、C反应蛋白均显著下降（P＜0.01）,体重指数（BMI）和白蛋白均明显升高（P＜0.05）,临床缓解率为91.3％（21／23）。在IFX治疗第14周,8／23（34.8％）的患者达到小肠黏膜愈合,12／21（57.1％）达到回末及结肠黏膜愈合,而仅7／21（33.3％）达到小肠和结肠均黏膜愈合。治疗第14周时,达到临床缓解期、炎症指标正常且回末及结肠达到黏膜愈合（SES-CD评分≤2）的12例患者中,仍有5例（41.7％）患者处于小肠炎症活动期（LS评分＞135）。结论IFX可以有效诱导小肠受累的CD患者实现临床缓解和黏膜愈合。CD患者中回末同小肠其他部位愈合情况并不同步,因而对于小肠和结肠均受累的CD患者评估疗效和黏膜愈合情况时,在排除肠梗阻和严重肠腔狭窄后,仍有必要联合胶囊内镜和回结肠镜进行全消化道评估。     

CESI、简化CDAI和CRP在评估小肠克罗恩病病变范围和活动程度中的应用价值

背景：小肠克罗恩病（CD）是一种慢性、反复发作性疾病。目前胶囊内镜评分指数（CESI）、简化CDAI和CRP在评估小肠CD病变范围和活动程度中的应用价值的研究甚少。目的：探讨CESI、简化CDAI和CRP在评估小肠CD病变范围和活动程度中的应用价值。方法：纳入行胶囊内镜检查并最终确诊为小肠CD的患者58例。分析简化CDAI和CRP与小肠病变范围的关系：评估小肠CD患者临床特征与CESI的相关性：计算简化CDAI和CRP判断胶囊内镜下炎症活动期的敏感性、特异性、阳性预测值、阴性预测值和准确性。对治疗后11例小肠CD患者行胶囊内镜复查．分析CESI改变与简化CDAI和CRP改变的相关性。结果：不同小肠病变范围的简化CDAI和CRP相比差异无统计学意义（P〉0．05）;小肠CD患者临床特征与CESI无关;简化CDAI和CRP判断胶囊内镜下炎症活动期的敏感性、特异性、阳性预测值、阴性预测值和准确性均较低。治疗后,CESI改变与简化CDAI和CRP改变无相关性（P〉0．05）。结论：简化CDAI和CRP并不能反映胶囊内镜下小肠CD患者病变范围和活动程度：小肠CD的胶囊内镜下黏膜修复情况与临床症状和生化指标的改善不一致．胶囊内镜下病变好转迟滞于简化CDAI和CRP的改善。     

英夫利西治疗克罗恩病的疗效评价及对黏膜愈合影响的初步研究

目的 评价克罗恩病(CD)患者使用英夫利西(IFX)的疗效及对黏膜愈合和促进瘘管闭合的影响.方法 收集2007年9月至2011年2月上海交通大学医学院附属瑞金医院消化科使用IFX治疗的CD患者的临床资料,回顾性分析IFX的疗效和安全性.IFX治疗后疗效评价内容包括实验室指标、临床疗效、瘘管治疗疗效和黏膜修复.统计学处理采用t检验和Wilcoxon符号秩和检验.结果 共22例患者纳入本次研究,男11例,女11例,平均29.3岁.予IFX 5～I0 mg/kg剂量在第0、2、6周诱导缓解治疗,随后每隔8周维持治疗.22例患者中,有16例活动性CD,1例中途退出,其余15例在治疗第14周时,11例缓解、2例临床有效、2例无效.14周时克罗恩病活动指数(CDAI)评分(112±80)和ESR[( 13±11)mm/1 h]与0周时的(186±88)、(21±15)mm/1 h相比均下降(Z值分别为-2.712和-2.378,P值分别=0.04和0.007).10例有瘘管的患者中2例无效退出,8例患者的瘘管对IFX部分反应;6例在维持治疗期间持续有反应,但未见瘘管完全闭合消失.7例患者在使用IFX治疗5次(24周)后内镜复查,治疗后简化克罗恩病内镜评分(SES-CD)评分(3.21±2.89)较治疗前(5.86±3.02)下降(Z=-2.38,P＝0.018).9例患者共发生11次不良事件,以输注反应、呼吸道感染多见,无严重不良反应发生.结论 IFX可快速改善患者临床症状,安全性高.而且IFX在黏膜愈合和瘘管治疗方面的作用可在用药早期显现.     

英夫利西单抗治疗克罗恩病的临床疗效及影响因素

目的 分析英夫利西单抗（IFX）治疗克罗恩病（CD）的有效性及其影响因素。方法 回顾性纳入2018年1月1日至2022年7月1日于同济大学附属上海市第十人民医院的IFX治疗的CD住院患者375例,收集患者IFX治疗前基线资料及用药第54周随访资料,包括年龄、性别、病程、蒙特利尔分型、手术史、既往用药史、身高、体重、克罗恩病疾病活动度评分（CDAI）、简化克罗恩病内镜评分（SES-CD）,评估IFX治疗1年CD患者的临床和内镜应答率、缓解率。利用卡方检验、单因素及多因素分析发现影响IFX治疗CD有效性的关键因素。结果 375例CD有352例为IFX药物治疗,23例为回肠造口术后启用IFX治疗。352例CD患者中,72.7%患者治疗1年后达临床应答（ΔCDAI≥70）,61.4%达临床缓解（第54周CDAI<150）,56.3%达内镜应答（ΔSES-CD≥50%）,37.6%达内镜缓解（SES-CD≤2）。23例回肠造口术后CD患者中,4.3%达内镜缓解（Rutgeert评分相似文献   

早期应用英夫利昔单抗联合硫唑嘌呤治疗合并2个以上预后不良高危因素克罗恩病疗效及安全性研究

目的探讨英夫利昔单抗(IFX)联合硫唑嘌呤(AZA)治疗合并2个以上预后不良高危因素克罗恩病(CD)患者的疗效及安全性。方法回顾性分析2013年3月至2015年6月中国医科大学附属盛京医院接受早期IFX联合AZA治疗的18例合并≥2个预后不良高危因素CD患者的临床资料。比较治疗前、治疗后14、30周患者实验室指标、克罗恩病活动指数(Best CDAI)评分、克罗恩病简化内镜评分(SES-CD)、瘘管愈合率及不良反应的情况。结果 18例患者均完成14周的治疗,其中9例完成30周的治疗。与治疗前相比,治疗后第14周患者Best CDAI、SES-CD评分、红细胞沉降率(ESR)及C反应蛋白(CRP)明显下降(P0.05);红细胞比容(HCT)、白蛋白(ALB)及体重指数(BMI)明显升高(P0.05)。与治疗后第14周相比,治疗后第30周患者Best CDAI、SES-CD评分进一步显著下降(P0.05);BMI进一步上升(P0.05)。第14、30周临床缓解率分别为83.3%(15/18)、88.9%(8/9);内镜下黏膜愈合率分别为11.1%(2/18)、55.6%(5/9)。6例合并有肛瘘的CD患者中2例完成第30周的治疗。治疗后第14周,6例瘘管部分愈合;2例患者完成了30周的治疗,瘘管均完全愈合。2例在第2周出现一过性肝功能异常,3例患者在第6周时出现WBC计数下降,经相应治疗短期内恢复正常,均未影响继续治疗。所有患者随访至2016年10月11日未观察到药物相关感染及恶性肿瘤等不良事件发生。结论 IFX早期联合AZA治疗合并≥2个预后不良高危因素的CD患者,可有效改善临床症状,控制全身炎症状态;持续治疗能够有效诱导并维持疾病缓解,促进内镜下肠黏膜愈合,促进瘘管愈合;且并未明显增加不良反应的发生。     

血清英夫利西单抗谷浓度、抗英夫利西单抗抗体水平监测在英夫利西单抗维持治疗克罗恩病患者中的临床应用

背景:随着英夫利西单抗(IFX)广泛用于克罗恩病(CD)的治疗,部分患者对IFX治疗失应答,具体机制尚未明确,可能与抗英夫利西单抗抗体(ATI)的形成密切相关。目前国内尚无ATI阳性率的相关报道。目的:评估血清英夫利西单抗谷浓度(IFX-TLs)、ATI水平监测在IFX维持治疗CD患者中的临床作用。方法:连续纳入2016年1月—2017年3月上海仁济医院接受IFX治疗的CD患者76例。检测血清IFX-TLs和ATI水平。根据CDAI评分将患者分为活动期组和缓解期组,比较血清IFX-TLs、ATI、C反应蛋白(CRP)和红细胞沉降率(ESR)水平。结果:76例CD患者中,2例(2.6%)ATI阳性,45例(59.2%)患者处于缓解期,31例(40.8%)为活动期。缓解期组IFX-TLs[2.84(1.30,4.96)μg/mL对4.08(1.29,6.72)μg/mL]、ATI[8.00(5.27,14.89)ng/mL对7.00(4.40,25.00)ng/mL]与活动期组相比无明显差异(P=0.484,P=0.454),而活动期组CRP、ESR水平均显著高于缓解期组(P=0.038,P=0.009)。Logistic回归分析显示CD活动性与CRP相关(OR=6.082,95%CI:1.348~27.436,P=0.019),与IFXTLs、ATI和ESR均无关(P0.05)。结论:CD活动性可能与CRP相关,而与IFX-TLs、ATI和ESR均无关。     

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。     

英夫利昔在克罗恩病诱导缓解中的作用及随访研究

目的 探讨英夫利昔(IFX)在克罗恩病诱导缓解中的作用并随访其诱导缓解的效果.方法 10例克罗恩病患者接受IFX(5 mg/kg)、5-氨基水杨酸(5-ASA)、硫唑嘌呤(AZA)诱导缓解和维持缓解治疗.在0、10、22和50周时进行克罗恩病活动指数(CDAI)、C-反应蛋白(CRP)、红细胞沉降率(ESR)、丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)、总胆红素(TBil)、结合胆红素(CB)、肌酐(Scr)检测.在0、10和50周时进行克罗恩病简化内镜评分(SES-CD).记录不良反应.结果 10周时所有患者均获缓解,CDAI、CRP、ESR和SES-CD均较0周时显著降低(P值均＜0.01).1例患者在30周时因复发终止随访.50周时,有6例患者CDAI、CRP、ESR、SES-CD与10周时比较略增高,但差异无统计学意义(P值分别=0.2001、0.0600、0.1328、0.4230),与0周时比较则均显著降低(P值分别=0.0005、0.0087、0.0054、0.0163).所有患者均未出现严重不良反应.结论 IFX诱导CD缓解效果确切,部分CD患者在IFX诱导缓解后使用5-ASA和AZA维持缓解有效.     

内镜指数评估克罗恩病患者疾病活动度的临床研究

背景:小肠克罗恩病(CD)是一种发病原因不明的慢性非特异性炎症,目前缺乏可明确评估CD病情进展的标准,各内镜指数评估CD患者疾病活动度仅限于单一指标。目的:探讨内镜指数评估CD患者疾病活动度的临床价值以及各参数之间的相关性。方法:选择2008年1月—2012年12月延安大学附属医院CD患者60例,以60名健康体检者作为对照。分别以CECDAI评分、CDAI评分、Lewis评分评估CD患者疾病活动度,并分析其与CRP、ESR的相关性。结果:CD组CRP、ESR水平显著高于对照组(P0.05)。不同CECDAI评分组间CDAI评分和Lewis评分差异有统计学意义(F=5.53,P0.05;F=22.64,P0.05)。不同CDAI评分组之间CECDAI评分差异有统计学意义(F=3.55,P0.05)。不同Lewis评分组之间CECDAI评分差异有统计学意义(F=4.26,P0.05)。CD患者CECDAI评分与CDAI评分、Lewis评分、CRP、ESR呈正相关(P0.05);CDAI评分与CRP、ESR呈正相关(P0.05);与Lewis评分无关(P0.05);Lewis评分与CRP、ESR无关(P0.05)。结论:CECDAI评分、CDAI评分、Lewis评分、CRP、ESR在一定程度上能反映CD患者的疾病活动度,可联合用于评估CD疾病活动度。     

Effect of leukocytapheresis therapy using a leukocyte removal filter in Crohn's disease

Eighteen patients with active Crohn's disease were treated with one leukocytapheresis session per week for a five-week intensive therapy, decreasing to one leukocytapheresis session per month for five sessions of initial maintenance therapy. Nutritional indices, inflammatory reactions, flow cytometry profiles, and cytokine production were also assessed before and after the intensive and initial maintenance therapy. Nine of the patients (50%) attained remission at the end of the intensive therapy. The nine non-remission patients had exhibited longer periods of suffering and more severely affected sites prior to the therapy. In 14 of 18 patients (77.8%), the nutritional indices, Internal Organization of Inflammatory Bowel Disease (IOIBD) score and Crohn's Disease Activity Index (CDAI) improved from the pretherapy levels, but only the remission group (50%) showed improvement in C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR). The remission group showed significantly higher pretherapy CD4+ CD45+ cell ratios and interleukin-2 (IL-2) production than the non-remission group, and significantly lower activated cells.     

Optimized timing of using infliximab in perianal fistulizing Crohn's disease

Infliximab(IFX), as a drug of first-line therapy, can alter the natural progression of Crohn's disease(CD), promote mucosal healing and reduce complications,hospitalizations, and the incidence of surgery. Perianal fistulas are responsible for the refractoriness of CD and represent a more aggressive disease. IFX has been demonstrated as the most effective drug for the treatment of perianal fistulizing CD. Unfortunately, a significant proportion of patients only partially respond to IFX, and optimization of the therapeutic strategy may increase clinical remission.There is a significant association between serum drug concentrations and the rates of fistula healing. Higher IFX levels during induction are associated with a complete fistula response in these patients. Given the apparent relapse of perianal fistulizing CD, maintenance therapy with IFX over a longer period seems to be more beneficial. It appears that patients without deep remission are at an increased risk of relapse after stopping anti-tumor necrosis factor agents.Thus, only patients in prolonged clinical remission should be considered for withdrawal of IFX treatment when biomarker and endoscopic remission is demonstrated, especially when the hyperintense signals of fistulas on T2-weighed images have disappeared on magnetic resonance imaging.Fundamentally, the optimal timing of IFX use is highly individualized and should be determined by a multidisciplinary team.     

Effectiveness of Concomitant Enteral Nutrition Therapy and Infliximab for Maintenance Treatment of Crohn’s Disease in Adults

Background

One of the problems associated with infliximab (IFX) treatment for Crohn’s disease (CD) is loss of response during maintenance therapy.

Aims

The aim of this multicenter, retrospective, cohort study was to determine whether enteral nutrition (EN) added to the IFX therapy regimen is effective for maintaining remission in adult CD patients.

Methods

Patients with CD who had started IFX therapy between April 2003 and March 2008 at any one of the seven participating medical centers and who met the following inclusion criteria were enrolled in the study: remission after triple infusions of IFX followed by IFX maintenance therapy every 8 weeks, and follow-up data available for ≥1 year. Remission was defined as a C-reactive protein (CRP) level of <0.3 mg/dL, and recurrence was defined as an increase in CRP to ≥1.5 mg/dL or shortening of the IFX interval. Patients were classified by EN dosage into two groups (EN group and non-EN group). The cumulative remission period and related factors were analyzed.

Results

Of the 102 adult CD patients who met the inclusion criteria, 45 were in the EN group and 57 were in the non-EN group. The cumulative remission rate was significantly higher in the EN group than in the non-EN group (P = 0.009). Multivariate analysis revealed that EN was the only suppressive factor for disease recurrence (P = 0.01).

Conclusions

The results demonstrate that among this CD patient cohort, EN combined with IFX maintenance treatment was clinically useful for maintaining remission.     

Impact of enteral nutrition on energy metabolism in patients with Crohn’s disease

AIM: To investigate the impact of enteral nutrition(EN) on the body composition and metabolism in patientswith Crohn's disease(CD). METHODS: Sixty-one patients diagnosed with CD were enrolled in this study. They were given only EN(enteral nutritional suspension, TPF, non-elemental diet) support for 4 wk, without any treatment with corticosteroids, immunosuppressive drugs, infliximab or by surgical operation. Body composition statistics such as weight, body mass index, skeletal muscle mass(SMM), fat mass, protein mass and inflammation indexes such as C-reactive protein(CRP), erythrocyte sedimentation rate(ESR) and CD activity index(CDAI) were recorded before and after EN support. RESULTS: The 61 patients were divided into three groups according to CDAI before and after EN support: A(active phase into remission via EN, n = 21), B(remained in active phase before and after EN, n = 19) and C(in remission before and after EN, n = 21). Patients in group A had a significant increase in SMM(22.11 ± 4.77 kg vs 23.23 ± 4.49 kg, P = 0.044), protein mass(8.01 ± 1.57 kg vs 8.44 ± 1.45 kg, P = 0.019) and decrease in resting energy expenditure(REE) per kilogram(27.42 ± 5.01 kcal/kg per day vs 22.62 ± 5.45 kcal/kg per day, P 0.05). There was no significant difference between predicted and measured REE in active CD patients according to the HarrisBenedict equation. There was no linear correlation between the measured REE and CRP, ESR or CDAI in active CD patients. CONCLUSION: EN could decrease the hypermetabolism in active CD patients by reducing the inflammatory response.     

英夫利西单抗治疗克罗恩病的疗效分析

目的 探讨TNFα单克隆抗体英夫利西(infliximab,IFX)单抗治疗活动性克罗恩病(CD)的疗效与安全性.方法 对传统药物治疗后未能完全缓解、手术治疗后复发或对药物不耐受的CD患者,于0、2、6周时静脉输注IFX(5 mg/kg)诱导缓解治疗,并对第一次输注后14周内的临床疗效,包括疾病活动度、血生化指标及结肠镜表现作出评估.结果 10例患者接受了IFX治疗,其中男8例,女2例,中位年龄31.4岁.5例患者IFX治疗1周后即感症状得到改善,主观症状评分从2.2±0.6降为1.2±0.4(P<0.05);简化CD活动性指数(H-B指数)从6.6±1.6降为2.1±1.0(P<0.05);ESR、C反应蛋白、血清总蛋白及白蛋白也有明显改善;内镜下CD严重度指数也得到明显改善.治疗过程中未观察到输注反应;1例患者在第3次IFX输注后,血ALT及AST暂时性升高;1例患者输注后35周出现严重贫血(三系列均减少).结论 经3次IFX静脉输注方案治疗,本组患者的临床症状及结肠镜下表现可获得较快、较好的改善.IFX长期应用的安全性尚需进一步扩大样本的研究.     

外周血CD4~+CD25~+FOXP3~+调节性T细胞与炎症性肠病疾病活动度的关系

背景:炎症性肠病(IBD)的发病机制尚未完全阐明。调节性T细胞是一组具有免疫抑制作用的T细胞亚群,研究显示其改变与IBD的发病密切相关。目的:观察IBD患者外周血CD4~+CD25~+FOXP3~+调节性T细胞与疾病活动度的关系。方法:纳入克罗恩病(CD)和溃疡性结肠炎(UC)患者各31例,15例健康体检者作为正常对照。分别采用简化CD活动指数(CDAI)和临床活动度指数(CAI)评估CD和UC患者的疾病活动度,以流式细胞术检测外周血CD4~+CD25~+FOXP3~+调节性T细胞比例,同时检测ESR和血清CRP水平。结果:CD和UC患者外周血CD4~+CD25~+FOXP3~+调节性T细胞比例显著低于正常对照组(P0.05),并分别与简化CDAI评分和CAI评分呈负相关(P0.05),与ESR和血清CRP水平之间则无明显相关性。活动期CD和UC患者的ESR和血清CRP水平明显高于缓解期,但差异无统计学意义。ESR和CRP与疾病活动度评分之间亦无明显相关性。结论:CD4~+CD25~+FOXP3~+调节性T细胞在IBD的发生、发展中起重要作用,外周血调节性T细胞数量减少可能是IBD复发的重要因素。     

Efficacy and safety of adalimumab in Canadian patients with moderate to severe Crohn's disease: results of the Adalimumab in Canadian SubjeCts with ModErate to Severe Crohn's DiseaSe (ACCESS) trial

OBJECTIVE:

To evaluate open-label adalimumab therapy for clinical effectiveness, fistula healing, patient-reported outcomes and safety in Canadian patients with moderate to severe Crohn’s disease (CD) who were either naive to or previously exposed to antitumour necrosis factor (anti-TNF) therapy.

METHODS:

Patients with moderate to severe CD (CD activity index [CDAI] score of greater than 220, or Harvey-Bradshaw index [HBI] of 7 or greater) were eligible. Patients received open-label adalimumab as induction (160 mg and 80 mg subcutaneously [sc]) at weeks 0 and 2, respectively and maintenance (40 mg sc every other week) therapy. At or after eight weeks, patients with flare or nonresponse could have their dosage increased to 40 mg sc weekly. Patients were followed for a minimum of six months or until adalimumab was commercially available in Canada.

RESULTS:

Of the 304 patients enrolled, 160 were infliximab experienced, while 144 were anti-TNF naive. HBI remission (HBI score of 4 or lower) at week 24 was achieved by 53% of anti-TNF-naive and 36% of infliximab-experienced patients (P<0.01; P<0.001 for both groups for all visits versus baseline). Fistula healing rates at week 12 were 48% for anti-TNF-naive patients, and 26% for infliximab-experienced patients. At week 24, fistula healing rates were significantly greater for the anti-TNF-naive group (60% versus 28%; P<0.01). Improvements in quality of life and work productivity were sustained from week 4 to week 24 for all patients. Serious infections occurred in 2% of patients.

CONCLUSIONS:

Adalimumab therapy induced and sustained steroid-free remission in both infliximab-experienced and anti-TNF-naive patients with moderate to severe CD. Clinically meaningful rates of fistula healing were also observed. Improvements in patient-reported outcomes were sustained throughout the 24-week study period.     

The London Position Statement of the World Congress of Gastroenterology on Biological Therapy for IBD with the European Crohn's and Colitis Organization: when to start, when to stop, which drug to choose, and how to predict response?

The advent of biological therapy has revolutionized inflammatory bowel disease (IBD) care. Nonetheless, not all patients require biological therapy. Selection of patients depends on clinical characteristics, previous response to other medical therapy, and comorbid conditions. Availability, reimbursement guidelines, and patient preferences guide the choice of first-line biological therapy for luminal Crohn's disease (CD). Infliximab (IFX) has the most extensive clinical trial data, but other biological agents (adalimumab (ADA), certolizumab pegol (CZP), and natalizumab (NAT)) appear to have similar benefits in CD. Steroid-refractory, steroid-dependent, or complex fistulizing CD are indications for starting biological therapy, after surgical drainage of any sepsis. For fistulizing CD, the efficacy of IFX for inducing fistula closure is best documented. Unique risks of NAT account for its labeling as a second-line biological agent in some countries. Patients who respond to induction therapy benefit from systematic re-treatment. The combination of IFX with azathioprine is better than monotherapy for induction of remission and mucosal healing up to 1 year in patients who are na?ve to both agents. Whether this applies to other agents remains unknown. IFX is also effective for treatment-refractory, moderate, or severely active ulcerative colitis. Patients who have a diminished or loss of response to anti-tumor necrosis factor (TNF) therapy may respond to dose adjustment of the same agent or switching to another agent. Careful consideration should be given to the reasons for loss of response. There are insufficient data to make recommendations on when to stop anti-TNF therapy. Preliminary evidence suggests that a substantial proportion of patients in clinical remission for >1 year, without signs of active inflammation can remain in remission after stopping treatment.