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首页 » BIOON报道 » The Lancet:英夫利昔单抗或可有效治疗儿童川崎氏病

The Lancet:英夫利昔单抗或可有效治疗儿童川崎氏病

来源:生物谷 2014-03-04 11:51

2014年3月4日 讯 /生物谷BIOON/ --川崎氏病 ( Kawasaki disease,KD )是一种严重的儿童疾病,很多时候父母甚至是医生将这种疾病误认为是一种儿童病毒感染疾病,如果未能及时诊断和治疗,常常会引发患儿患上不可逆的心脏损伤疾病。

KD的征兆主要包括发烧并伴随有长时间的出疹、红眼以及皮肤脱屑等症状,这种疾病可以引发四分之一的患儿出现冠状动脉损伤,在患儿早期成年阶段往往会引发严重的心脏问题。通过单一进行静脉免疫球蛋白注射(IVIG)疗法后,仍有10%至20%的患儿会出现发烧的症状,而且IVIG抗性常常可以增加患儿的心脏损伤风险。

近日,来自加利福尼亚大学等处的研究人员通过研究针对KD患儿的起始阶段疗法,来阻断患儿出现IVIG抗性;与此同时研究人员也通过评估额外添加英夫利昔单抗后对患儿冠状动脉的异常影响情况,相关研究刊登于国际著名杂志The Lancet上。

肿瘤坏死因子α(TNFα)是机体产生的一种重要分子,其在KD患者炎性发病过程中扮演着重要角色,因此针对TNFα的疗法或许是治疗KD的有效手段;使用英夫利昔单抗来结合TNFα在早期阶段表现出较好的前景,在第一阶段并没有发现患者出现严重的副作用,随后的研究则发现,相比注射IVIG,英夫利昔单抗可以快速对患者进行退烧。

研究者Adriana H. Tremoulet表示,将英夫利昔单抗作为附加药物用于治疗急性KD患者并不能减少疗法的抗性,但是其相对来讲比较安全,可以明显缩短患者发号的天数以及降低炎性标志物的水平。

最后研究者认为,使用英夫利昔单抗对于婴儿和儿童来讲是比较安全的,其也可以帮助治疗KD患者早期症状的一个有效的疗法,对于患者的机体炎性水平以及冠状动脉损伤至关重要。(生物谷Bioon.com)

doi:10.1016/S0140-6736(13)62298-9
Infliximab for intensification of primary therapy for Kawasaki disease: a phase 3 randomised, double-blind, placebo-controlled trial

Dr Adriana H Tremoulet MD a c , Sonia Jain PhD b, Preeti Jaggi MD d, Susan Jimenez-Fernandez MD a c, Joan M Pancheri RN c, Xiaoying Sun MS b, John T Kanegaye MD a c, John P Kovalchin MD d, Beth F Printz MD a c, Prof Octavio Ramilo MD d, Prof Jane C Burns MD a c

Background Kawasaki disease, the most common cause of acquired heart disease in developed countries, is a self-limited vasculitis that is treated with high doses of intravenous immunoglobulin. Resistance to intravenous immunoglobulin in Kawasaki disease increases the risk of coronary artery aneurysms. We assessed whether the addition of infliximab to standard therapy (intravenous immunoglobulin and aspirin) in acute Kawasaki disease reduces the rate of treatment resistance. Methods We undertook a phase 3, randomised, double-blind, placebo-controlled trial in two children's hospitals in the USA to assess the addition of infliximab (5 mg per kg) to standard therapy. Eligible participants were children aged 4 weeks—17 years who had a fever (temperature ≥38·0°C) for 3—10 days and met American Heart Association criteria for Kawasaki disease. Participants were randomly allocated in 1:1 ratio to two treatment groups: infliximab 5 mg/kg at 1 mg/mL intravenously over 2 h or placebo (normal saline 5 mL/kg, administered intravenously). Randomisation was based on a randomly permuted block design (block sizes 2 and 4), stratified by age, sex, and centre. Patients, treating physicians and staff, study team members, and echocardiographers were all masked to treament assignment. The primary outcome was the difference between the groups in treatment resistance defined as a temperature of 38·0°C or higher at 36 h to 7 days after completion of the infusion of intravenous immunoglobulin. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, NCT00760435. Findings 196 patients were enrolled and randomised: 98 to the infliximab group and 98 to placebo. One patient in the placebo group was withdrawn from the study because of hypotension before receiving treatment. Treatment resistance rate did not differ significantly (11 [11·2%] for infliximab and 11 [11·3%] for placebo; p=0·81). Compared with the placebo group, participants given infliximab had fewer days of fever (median 1 day for infliximab vs 2 days for placebo; p<0·0001). At week 2, infliximab-treated patients had greater mean reductions in erythrocyte sedimentation rate (p=0·009) and a two-fold greater decrease in Z score of the left anterior descending artery (p=0·045) than did those in the placebo group, but this difference was not significant at week 5. Participants in the infliximab group had a greater mean reduction in C-reactive protein concentration (p=0·0003) and in absolute neutrophil count (p=0·024) at 24 h after treatment than did those given placebo, but by week 2 this difference was not significant. At week 5, none of the laboratory values differed significantly compared with baseline. No significant differences were recorded between the two groups at any timepoint in proximal right coronary artery Z scores, age-adjusted haemoglobin values, duration of hospital stay, or any other laboratory markers of inflammation measured. No reactions to intravenous immunoglobulin infusion occurred in patients treated with infliximab compared with 13 (13·4%) patients given placebo (p<0·0001). No serious adverse events were directly attributable to infliximab infusion. Interpretation The addition of infliximab to primary treatment in acute Kawasaki disease did not reduce treatment resistance. However, it was safe and well tolerated and reduced fever duration, some markers of inflammation, left anterior descending coronary artery Z score, and intravenous immunoglobulin reaction rates. Funding US Food and Drug Administration, Robert Wood Johnson Foundation, and Janssen Biotech.

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