炎症性肠病患者英夫利西单抗个体化治疗的研究进展

英夫利西单抗(IFX)是首个被批准用于治疗炎症性肠病(IBD)的单克隆抗体,对IBD患者的诱导和维持治疗均有较好疗效,但临床仍有部分患者疗效欠佳甚至失应答.IFX体内药动学受抗IFX抗体(ATI)、疾病炎症反应程度、遗传等多方面因素的影响,可使其血药谷浓度(IFX-TLs)降低.IBD患者体内IFX-TLs和ATI与临...     

英夫利西单抗联合硫唑嘌呤片对炎症性肠病患者T淋巴细胞的影响

目的观察英夫利西单抗联合硫唑嘌呤片对炎症性肠病(Inflammatory bowel disease,IBD)患者外周血T淋巴细胞的影响。方法将98例活动期IBD患者按照疾病种类分为UC组(溃疡性结肠炎,50例),CD组(克罗恩病,48例)。每个疾病种类下设研究组和对照组,对照组在常规治疗基础上行静脉滴注英夫利西治疗,研究组在对照组基础上行口服硫唑嘌呤治疗。另将同期健康体检人员25例列为健康组作为参照。对比治疗后研究组和对照组临床疗效及外周血T淋巴细胞水平。结果治疗后研究组总有效率均显著高于各自对照组:UC组(96.00%vs.72.00%),CD组(91.66%vs.66.66%),差异有统计学意义(P<0.05);治疗后,两组外周血总T淋巴细胞(CD3^+)及亚群CD4^+T淋巴细胞、CD8^+T淋巴细胞的比例水平均较治疗前显著升高,CD4^+/CD8^+比例较治疗前显著降低,差异有统计学意义(P<0.05)。研究组对T淋巴细胞水平改善情况显著优于各自对照组,差异有统计学意义(P<0.05)。UC组联合治疗后,CD3^+、CD4^+、CD8^+、CD4^+/CD8^+水平恢复至同期健康组水平,CD组联合治疗后CD3^+、CD4^+、CD8^+水平恢复至同期健康组水平。结论英夫利西单抗联合硫唑嘌呤片能显著提高IBD患者T淋巴细胞水平,缓解患者淋巴细胞分布异常,恢复受损免疫功能,提高治疗有效率。     

英夫利西单抗对溃疡性结肠炎患者外周血淋巴细胞亚群的影响

目的观察英夫利西单抗（IFX）对溃疡性结肠炎（UC）患者外周血淋巴细胞亚群分布的影响。方法将医院收治并接受IFX治疗的23例溃疡性结肠炎患者作为观察组,以同时期23名健康体检者作为对照组。观察组患者于入组第0,2,6周分别接受IFX静脉滴注治疗,剂量为5 mg/kg,第14周维持治疗1次。治疗前后采用Mayo评分、简化CD活动指数（CDAI）评分及内镜下CD严重度指数（CDEIS）评分对观察组治疗疗效进行评估。采集观察组治疗前1 d、治疗14周后及对照组患者空腹静脉血样本,检测总T淋巴细胞、总B淋巴细胞、CD4＋T淋巴细胞、CD8＋T淋巴细胞及NK细胞的比例。结果观察组治疗后Mayo评分、CDAI评分及CDEIS评分均较治疗前显著改善（P〈0.05）;IFX治疗前,观察组中16例临床治疗有效患者外周血总T淋巴细胞、CD8＋T淋巴细胞及NK细胞比例明显高于其余7例治疗无效组患者（P〈0.05）;观察组治疗后总T淋巴细胞、CD4＋T淋巴细胞、CD8＋T淋巴细胞及NK细胞比例均明显增高（P〈0.05）,总B淋巴细胞比例未见明显改变（P〉0.05）。治疗后观察组总T淋巴细胞、总B淋巴细胞、CD4＋T淋巴细胞及CD8＋T淋巴细胞与对照组相比均未见明显差异（P〉0.05）,NK细胞比例显著低于对照组（P〈0.05）。结论外周血淋巴细胞亚群的改变与UC的发病明显相关,IFX治疗UC具有良好的临床疗效。     

炎症性肠病患者英夫利西单抗相关肝损伤的Meta分析

目的 系统评价炎症性肠病(inflammatory bowel disease, IBD)患者使用英夫利西单抗(infliximab, IFX)后的肝损伤发生率。方法 计算机检索PubMed、Embase、Web of Science数据库(均从建库开始至2022年2月28日),检索使用IFX者致肝损伤的临床研究相关文献,并手工检索IFX致肝损相关文献补充纳入研究,采用R软件进行发生率的合并,并做亚组分析。对数据进行异质性检验,以确定采用固定模型或随机模型进行率的合并分析。采用敏感性分析评价研究文献质量对结果的影响,并进行发表偏倚检测。结果 共7篇文献入选,总肝损发生率为4%(95%CI:2%～7%)。IFX单用和联用致肝损伤发生率分别为4%(95%CI:1%～11%)和5%(95%CI:2%～13%),克罗恩病(Crohn’s disease, CD)患者和溃疡性结肠炎(Ulcerative Colitis, UC)患者用药后肝损伤发生率分别是3%(95%CI:1%～8%)和12%(95%CI:2%～30%)。结论 英夫利西单抗用药者肝损伤的发生率较高,应加强临床用药监测。     

应用英夫利西单抗治疗炎症性肠病的效果观察及护理

目的旨在对临床英夫利西单抗治疗炎症性肠病患者的效果观察及相关护理的总结与分析。方法 2011年3月至2013年2月间收治的12例英夫利西单抗治疗炎症性肠病患者的临床疗效进行观察与综合护理;并对治疗、护理情况进行分析与总结。结果 12例炎症性肠病患者在经英夫利西单抗治疗、综合护理之后,均未出现严重不良反应;且治疗前的主观症状评分、克罗恩病活动指数(CDAI)评分以及克罗恩病严重度指数(CDEIS)评分均较治疗前有明显改善(P<0.05);患者满意度高达100%。结论英夫利西单抗治疗炎症性肠病具有较理想的治疗效果;并在科学、有效的综合护理干预下,可以有效提高患者的治疗依从性、最大程度地减少药物不良反应,全面改善患者的生活质量,提高患者满意度。     

英夫利西单抗谷浓度、抗英夫利西单抗抗体及相关指标评估克罗恩病患者疾病活动的临床意义

目的 探讨英夫利西单抗(IFX)谷浓度、抗IFX抗体及相关指标评估克罗恩病(CD)疾病活动的临床意义。方法 根据CD活动指数评分将接受IFX治疗的45例CD患者分为缓解期组(<150分,32例)和活动期组(≥150分,13例)。比较两组IFX谷浓度、抗IFX抗体及相关指标水平。结果 缓解期组IFX谷浓度和抗IFX抗体均与活动期组相仿(P>0.05)。抗IFX抗体弱阳性和抗IFX抗体阳性患者IFX谷浓度均低于抗IFX抗体阴性患者[1.10(0.30,2.05)μg/mL和0.30(0.30,0.63)μg/mL vs.3.40(1.83,6.63)μg/mL](P<0.01)。缓解期组ESR和CRP低于活动期组,而白蛋白(Alb)高于活动期组(P<0.05)。CRP是CD疾病活动的独立影响因素(P<0.05),而尚未发现ESR、Alb、Hb、IFX谷浓度和抗IFX抗体是CD疾病活动的独立影响因素(P>0.05)。结论 抗IFX抗体阳性CD患者IFX谷浓度低于抗IFX抗体阴性患者。CRP是CD疾病活动的独立影响因素,而IFX谷浓度和抗IFX抗体对CD疾病...     

克罗恩病患者英夫利西单抗谷浓度分布及影响因素分析

目的:考察克罗恩病患者维持治疗期英夫利西单抗(IFX)稳态谷浓度的分布特点,分析影响IFX谷浓度的相关因素.方法:收集接受IFX常规给药方案治疗的克罗恩病患者相关临床资料,采用多重PCR技术结合高通量测序技术的靶向测序法获得患者相关基因多态性信息,借助酶联免疫吸附法检测IFX谷浓度,利用SPSS 20.0软件分析患者遗...     

注射用英夫利西单抗治疗难治型川崎病1例

川崎病的治疗一般使用丙种球蛋白及阿司匹林,难治型川崎病患儿的治疗可加用糖皮质激素. 该文报道的川崎病患儿对丙种球蛋白、糖皮质激素、乌司他汀、环磷酰胺均无反应,而通过注射用英夫利西单抗的治疗后患儿临床症状及炎症指标均好转.     

119例英夫利西单抗不良反应的文献分析

目的探讨英夫利西单抗不良反应的特点,为临床安全用药提供参考。方法在中国期刊全文数据库和万方数据库中,检索2008~2015年之间公开发表的关于英夫利西单抗不良反应的文献,对筛选出的119例病例进行回顾性分析。结果原患疾病主要包括类风湿性关节炎、强直性脊柱炎、溃疡性结肠炎、克罗恩病、银屑病/银屑病性关节炎、幼年特发性关节炎。不良反应最易发生于第3~4次输液期间。输液反应最常见,常累及的系统-器官主要包括皮肤黏膜(29.49%)、呼吸系统(30.77%)、消化系统(14.10%)、心血管系统(10.26%)等。多数药品不良反应预后良好。结论英夫利西单抗药品不良反应累及多个系统-器官,须提高警惕,注意监测,及时处理。     

克罗恩病治疗中英夫利西单抗药物监测的临床意义

目的：英夫利西单抗（infliximab,IFX）是首个用于克罗恩病的生物制剂,疗效显著,但30%~60%的患者会出现药物失应答。治疗药物监测（therapeutic drug monitoring,TDM）的应用,可为指导临床用药提供依据,达到安全、合理、有效、经济的用药目的。方法：通过查阅近年来在克罗恩病治疗中IFX药物监测的研究及应用情况,就IFX的药动学特点、影响因素、谷浓度及抗IFX抗体（antibodies to infliximab,ATI）与疗效相关性等作一综述。结果：研究显示,IFX免疫原性、患者病理生理状态、遗传因素、联合用药等与IFX药动学有关,监测IFX谷浓度及ATI水平能预测临床应答、内镜下表现及不良反应。结论：进行TDM可优化IFX药物治疗方案,更好地控制疾病活动度,具有重要的临床指导意义。     

Therapeutic drug monitoring of anti-TNF therapy in children with inflammatory bowel disease

Introduction: Although anti-TNF therapy has changed the scenery of pediatric inflammatory bowel diseases (IBD) immensely, there are still patients with an unfortunate outcome. Approximately one third of patients that initially respond to anti-TNF therapy will lose that response over time and need treatment optimization. Loss of response (LOR) is a big concern in IBD management and especially among pediatric patients where treatment options are more limited than in adults. In children it is even more important to sustain response with minimal toxicity. Therapeutic drug monitoring (TDM) is proposed as a tool to reach this goal.

Areas covered: This review focuses on the importance of TDM of anti-TNF and the role TDM has in clinical practice of pediatric IBD.

Expert opinion: Although TDM is not yet widely used in pediatric IBD, the available literature suggests it to be a promising tool, especially in patients with LOR to anti-TNF. There is increasing evidence that also in children, higher anti-TNF drug levels are associated with sustained response, and likewise low or undetectable trough levels increase the likelihood of LOR. TDM-based treat to target strategies are being designed in adult studies, but more prospective studies also in pediatric IBD populations looking at the role of proactive testing are needed.     

Treatment of inflammatory bowel disease (IBD)

Inflammatory bowel disease (IBD) is a chronic inflammatory disease of the gastrointestinal tract, which includes Crohn's disease (CD) and ulcerative colitis (UC). These diseases have become important health problems. Medical therapy for IBD has advanced dramatically in the last decade with the introduction of targeted biologic therapies, the optimization of older therapies, including rugs such as immunomodulators and 5-aminosalicylic acid (5-ASA), and a better understanding of the mucosal immune system and the genetics involved in the pathogenesis of IBD. The goal of IBD therapy is to induce and maintain remission. The current treatment paradigm involves a step-up approach, moving to aggressive, powerful therapies only when milder therapies with fewer potential side effects fail or when patients declare themselves to have an aggressive disease. This review focuses on the current treatments for inflammatory bowel disease.     

Long-term treatment with infliximab in inflammatory bowel disease: safety and tolerability issues

Crohn's disease and ulcerative colitis represent the most common forms of inflammatory bowel disease (IBD), clinical conditions affecting the small and/or large bowel. It is well known that IBD is an immune-mediated condition and that TNF-α plays a pivotal role in the pathogenesis of the disease. TNF-α has been scrupulously studied as a target for therapeutic intervention in this setting. A number of biologic compounds have been developed, including the European Medicine Agency (EMEA)-approved agents, infliximab and adalimumab. Although their efficacy in induction and maintenance of remission has been established by several clinical trials, many issues regarding safety remain to be elucidated. In fact, anti-TNF treatment may be associated with a number of rare, but serious, adverse events, including infusion reactions, infections, lymphomas and other malignancies. A black-box warning has to be taken into consideration when looking at potential serious infections such as tuberculosis. Active infections, demyelinating disorders and severe heart failure are contraindications for anti-TNF treatment. This review focuses on drug toxicity and adverse events related to infliximab treatment in IBD.     

老年原发免疫性血小板减少症患者治疗前后T淋巴细胞亚群的临床研究

目的 检测老年原发免疫性血小板减少症(ITP)患者治疗前后T淋巴细胞亚群的动态变化, 探讨其在ITP发生发展中的作用。方法 采用流式细胞术测定ITP患者治疗前后及正常对照组外周血T淋巴细胞亚群的水平。结果 ITP患者治疗前后T淋巴细胞绝对值、CD3⁺、CD4⁺、CD8⁺、CD4⁺CD25⁺T淋巴细胞比例及CD4⁺/CD8⁺比值分别为(0.83±0.16)vs(1.74±0.36)、(71.71±1.07)% vs(72.69±1.35)%、(41.78±0.71)% vs(42.46±1.20)%、(29.67±0.97)% vs(28.56±1.75)%、(8.76±0.56)% vs(9.39±1.26)%、(1.42±0.07)vs(1.49±0.13), CD8⁺T淋巴细胞比例治疗后显著降低, 其余均显著升高, 差异有统计学意义(P<0.05)。结论 T淋巴细胞亚群的异常改变, 破坏自身免疫, 与病情相关, 可指导临床治疗, 并作为评估预后的参考指标。     

Management of patients with inflammatory bowel disease and spondyloarthritis

Introduction: More than half of the patients with inflammatory bowel disease (IBD) experience at least one extra-intestinal manifestation (EIM). The most common EIM in patients with IBD is spondyloarthritis (SpA). Microscopic intestinal inflammation is documented in almost 50% of the patients with SpA.

Areas covered: We give an overview of the classification, the epidemiology and the diagnosis of IBD and SpA. The treatment goals, the pharmacologic management options and the available treatment guidelines in IBD patients with SpA are discussed.

Expert commentary: The coexistence of IBD and SpA generates challenges and opportunities for both the gastroenterologist and the rheumatologist. The potential of drugs with a gut-specific mode of action in the treatment of IBD-related arthritis warrants further exploration.     

Desensitization of patients with allergic reactions to immunosuppressives in the treatment of inflammatory bowel disease

Crohn's disease and ulcerative colitis are chronic, immune-mediated inflammatory bowel diseases (IBDs) of unknown etiology with high morbidity in patients who are not receiving adequate medical treatment. A variety of medical therapies are currently available, and much progress has been made to alleviate symptoms and restore quality of life. The mainstay of treatment in those with moderate to severe disease consists of medications that alter or suppress the body's immunologic attack on its own gastrointestinal tract. The medications currently in use are highly effective when given in the appropriate clinical context, but side effects are not uncommon and must be treated expeditiously when they occur. One class of immunosuppressive medication, 6-mercaptopurine and its prodrug azathioprine, is effective at inducing remission and improving the lives of patients with IBD. The most common side effects of these drugs are allergic reactions and rarely can they be severe and life threatening. These reactions can sometimes be overcome by desensitizing the immune system to the drug. This review emphasizes allergy to 6-mercaptopurine and azathioprine and the process of desensitization when these allergic reactions occur in order to continue use of this important class of medication in the total treatment of IBD.     

N-乙酰基转移酶2基因型多态性与柳氮磺胺吡啶治疗炎症性肠病所产生不良反应的关系

目的探讨N-乙酰基转移酶2(NAT2)基因型多态性对柳氮磺胺吡啶(SASP)治疗炎症性肠病(IBD)时所产生不良反应的影响。方法在110例IBD患者及120例健康对照者中,采用聚合酶链反应-限制性片断长度多态性方法,检测NAT2野生型等位基因(NAT2*4)和3种突变型等位基因(NAT2*5B、*6A和*7B)频率,并对服用SASP的78例IBD患者进行NAT2基因型与SASP不良反应的相关性分析。结果慢型乙酰化基因型的IBD患者服用SASP后不良反应的发生率高于快型和中间型乙酰化基因型患者,差异有显著性(55%vs24.1%,OR=3.841,95%CI=1.322~11.161,P=0.011)。与磺胺吡啶(SP)剂量相关的不良反应在慢型乙酰化患者中的发生率也高于快型和中间型乙酰化患者(55%vs20%,OR=4.889,95%CI=1.625~14.704,P=0.003)。结论IBD患者SASP不良反应,特别是与SP剂量相关的不良反应,与NAT2慢型乙酰化基因型相关。     

肠道微生态与炎症性肠病

炎症性肠病(inflammatory bowel disease,IBD)是一组病因未明、发病机制亦不明确的慢性肠道炎症性疾病,主要包括克罗恩病(Crohn's disease,CD)和溃疡性结肠炎(ulcerative colitis,UC)。近几十年的研究结果认为,其发病是环境、易感基因和肠道微生态3个要素相互作用的结果,且这些要素使IBD成为一种适合研究宿主与肠道微生物相互作用的高优先平台。最近,肠道菌群的图谱分析将IBD的发病机制与菌群各组成部分特征的改变相联系,进一步支持"肠道微生物和宿主相互作用的改变能形成IBD"这一观点。该文回顾性分析有关IBD患者体内微生物的研究文献,综述肠道微生态失衡对IBD的多方面影响,以动物模型和临床验证资料阐述不同的治疗方法改善肠道微生态变化的最新进展。     

川崎病患儿血小板参数与T细胞亚群的变化

目的:观察川崎病患儿血小板参数和细胞免疫功能变化.方法:用自动血液分析仪测定48例川崎病患儿的血小板参数,其中30例用流式细胞仪同时检测T细胞亚群水平.结果:患病组在血小板数、血小板平均体积、血小板分布宽度及血小板压积方面均高于对照组,川崎病患儿血小板参数在病程第3周达到高峰.CD3 、CD4 T细胞和CD4 /CD8 比值较对照组降低,而CD8 和NK细胞与对照组无明显差异.结论:在川崎病的血管炎反应中,血小板起了重要作用,T细胞免疫有部分指标较正常低下,存在细胞免疫功能紊乱.     

Thiopurine drug adverse effects in a population of New Zealand patients with inflammatory bowel disease

PURPOSE: The thiopurine drugs, azathioprine and 6-mercaptopurine are effective in the treatment of inflammatory bowel disease (IBD). However, their use is limited by serious adverse effects that can lead to cessation of therapy. The incidence of these adverse effects has been reported to be approximately 9% but in Christchurch it was felt that the incidence was higher. METHODS: We searched our letter database to identify all patients with IBD who had received a thiopurine drug between 1996 and 2002. The case notes were then reviewed to identify those patients who had suffered an adverse effect that required cessation of the drug. RESULTS: From a total of 216 patients with IBD taking a thiopurine drug, 56 (25.9%) had an adverse reaction requiring cessation of the drug. Adverse effects included allergic-type (25%), liver test abnormalities (34%), nausea/vomiting (6%), bone marrow suppression (7%), pancreatitis (7%) and other (9%). Males were significantly more likely than females to have an allergic-type reaction (p = 0.003). All adverse effects resolved with cessation of the drug, with a median of 7 days to resolution. Of the patients with liver test abnormalities on azathioprine, most were able to tolerate 6-mercaptopurine, however challenge with 6-mercaptopurine was not successful for most other patients. CONCLUSIONS: In Canterbury, New Zealand, patients with IBD have a high rate of therapy-limiting adverse effects to thiopurine drugs. There is a significant gender bias for allergic-type adverse effects. Mechanisms for both these observations are not clear.