抗IgE抗体在支气管哮喘中的应用

IgE在支气管哮喘发病中起着关键作用。奥马珠单抗（omalizumab）足重组人源化抗IgE单克隆抗体,其与游离IgE结合可显著降低游离IgE水平。通过卜调嗜碱性粒细胞、肥大细胞和树突状细胞上的IgE高亲和力受体,可有效防止炎症介质的释放,进而阻止哮喘的发生和进展。多项临床研究证实,奥马珠单抗可明显改善哮喘症状,减少哮喘急性发作,减少口服或吸入型糖皮质激素用量,改善哮喘患者的生活质量。其耐受性良好,使用安全、不良反应发生率低,是临床哮喘治疗的新策略。本文综述相关领域的研究近况。     

抗IgE单克隆抗体奥马珠单抗治疗哮喘的研究进展

哮喘是由免疫球蛋白E（immunoglobulin E, IgE）抗体介导的超敏反应性疾病,其症状发生和气道高反应性与IgE密切相关。奥马珠单抗是重组人源化抗IgE单克隆抗体,能与血清中的游离IgE特异性结合,剂量依赖性地降低游离IgE水平。通过阻断IgE与其受体的结合、降低IgE与其受体的亲和力、阻止嗜碱性粒细胞和肥大细胞脱颗粒、抑制炎症细胞的激活和炎症介质的释放,奥马珠单抗可明显改善哮喘症状评分、减少哮喘急性发作、减少口服或吸入糖皮质激素的用量、改善哮喘患者的生活质量。奥马珠单抗的疗效已得到临床试验的证实,且其耐受性良好。     

奥马珠单抗治疗2例高水平IgE过敏性哮喘患儿的用药监护

目的 探讨奥马珠单抗对高水平IgE过敏性哮喘患儿的临床疗效和安全性。方法 回顾性分析2020年8月至2021年5月期间,上海市儿童医院呼吸科收治的应用奥马珠单抗治疗的2例过敏性哮喘患儿的临床资料,并在结束治疗后进行定期药学随访,分析奥马珠单抗治疗剂量和疗程、治疗效果及药物不良反应情况。结果 2例患儿在接受奥马珠单抗治疗后哮喘症状控制满意,减少哮喘治疗过程中吸入激素使用剂量,鼻部症状减轻。2例患儿共接受奥马珠单抗皮下注射20次,未见不良反应,在结束治疗后定期药学随访,结果显示,患儿身体状况良好。结论 奥马珠单抗用于高水平IgE过敏性哮喘患儿的治疗,可以改善哮喘控制症状,长期安全性良好,但其合适的用药剂量和疗程尚需进一步经验积累。     

奥马珠单抗治疗过敏性疾病及其相关进展

目的:归纳IgE单克隆抗体——奥马珠单抗在过敏性疾病治疗中的应用进展,同时介绍阻断IgE信号转导以治疗过敏性疾病的研究新进展。方法:查阅美国国立生物技术信息中心(NCBI)和相关专业学术期刊全文数据库1993-2013年有关奥马珠单抗以及阻断IgE信号转导以治疗过敏性疾病的研究文献,对相关研究进展作一整理归纳。结果与结论:奥马珠单抗抑制IgE和相关变应原介导的免疫反应,在哮喘、变应性鼻炎、过敏性皮肤疾病等过敏性疾病治疗中发挥了良好作用,具有良好的应用前景。通过阻断IgE信号转导以治疗过敏性疾病的策略也值得期待。     

医药互动模式下注射用奥马珠单抗的合理用药分析

目的 分析注射用奥马珠单抗的使用情况,并提出改进和防范举措,促进合理用药。方法 通过医院信息系统收集2020年12月至2022年3月首都医科大学附属北京朝阳医院门诊使用注射用奥马珠单抗的处方记录,依据医药互动模式制订奥马珠单抗合理用药点评路径,从用药指征、用法用量和其他不适宜3个维度开展处方点评。结果 共收集2818条使用注射用奥马珠单抗的处方记录,涉及355例患者的就诊信息,主要诊断均为支气管哮喘。通过处方点评发现,注射用奥马珠单抗存在不合理用药17例（4.79%）,均为无适应证用药,即不符合将奥马珠单抗用于大剂量吸入性糖皮质激素,并联合长效β2受体激动剂等其他控制药物治疗后症状仍未得到控制,且血清总IgE水平升高的重度过敏性哮喘患者;注射用奥马珠单抗起始用药剂量和使用频次均按药品说明书要求,且给药途径及其他均未见不合理。结论 医药互动模式下的合理用药点评可以更好地促进注射用奥马珠单抗在哮喘患者中的合理使用。     

重度哮喘使用奥马珠单抗治疗无效的患者特征

目的了解重度哮喘使用奥马珠单抗治疗无效的患者特征。方法选择2018年3月至2021年2月接受奥马珠单抗治疗的118例重度哮喘患者作为研究对象,比较奥马珠单抗治疗有效组和无效组的临床特征,评估与奥马珠单抗治疗失败相关的因素,并分析奥马珠单抗治疗失败后接受替代治疗患者的临床结局。结果奥马珠单抗治疗有效组和无效组的治疗时间、使用糖皮质激素、合并嗜酸性粒细胞性慢性鼻-鼻窦炎(ECRS)以及合并嗜酸粒细胞性中耳炎(EOM)情况比较,差异有统计学意义(P<0.05);Logistic回归分析发现,合并ECRS、合并EOM为奥马珠单抗治疗失败的独立影响因素(P<0.05)。结论合并ECRS、EOM可能会导致重度哮喘患者使用奥马珠单抗治疗无效,建议此类患者考虑采用抗白介素(IL)-5抗体或抗IL-5Rα抗体治疗。     

奥马珠单抗治疗变应性鼻炎疗效与安全性的Meta分析

目的系统分析奥马珠单抗治疗难治型变应性鼻炎的疗效及安全性。方法通过搜索PubMed,Cochrane Library,CNKI及万方数据库,收集奥马珠单抗治疗难治型变应性鼻炎的随机对照试验(RCT),使用Revman 5.3软件对数据进行Meta分析,评价奥马珠单抗的疗效及安全性。结果 Meta分析结果显示,奥马珠单抗在降低鼻部症状方面差异有统计学意义,药物引起的不良反应差异无统计学意义。结论奥马珠单抗在缓解鼻部症状等方面具有显著的效果,是一种相对安全的药物。     

咳嗽变异性哮喘病人行支气管激发试验前后血清IgE变化

目的 探讨咳嗽变异性哮喘病人行支气管激发试验前后IgE变化。方法 分别对16例咳嗽变异性哮喘病人行支气管激发试验(BPT),并在试验前后监测血清IgE水平。结果 BPT阳性16例。气道高反应性者血清总IgE BPT后较BPT前明显增高(P<0.01)。屋尘激发后,特异性IgE较激发前增高(P<0.05)。尘螨激发后,特异性IgE亦较激发前增高(P<0.05)。结论 咳嗽变异性哮喘患者的血清IgE水平明显升高,与支气管激发试验阳性率显著相关,对咳嗽变异性哮喘患者行支气管激发试验,同时测定血清IgE水平,可早期发现哮喘,指导临床治疗。     

瑞利珠单抗治疗严重哮喘的研究现状北大核心CSCD

支气管哮喘是一种常见的气道慢性炎症性疾病,严重影响患者的生活质量。部分患者在根据指南进行用药后症状仍得不到良好改善,特别是吸入糖皮质激素治疗后症状仍不能得到充分控制的嗜酸性粒细胞升高的哮喘患者。瑞利珠单抗是一种人源化白细胞介素-5(IL-5)抗体,2017年全球哮喘防治创议(GINA)推荐将瑞利珠单抗作为≥18岁成人重症哮喘患者抗IL-5治疗选项。本文就瑞利珠单抗的制备、作用机制、临床评价、安全性及展望等方面进行综述。     

奥马珠单抗对过敏性哮喘小鼠气道重塑的影响

目的研究奥马珠单抗对卵清蛋白诱导的过敏性哮喘小鼠模型气道重塑的影响,评估奥马珠单抗在哮喘气道重塑方面的疗效。方法采用野生型BALB/c雌性小鼠(6~8周龄),建立周期为44 d的卵清蛋白诱导的慢性哮喘小鼠模型。设立4组:正常组、模型组、治疗组和模型对照组。检测各组小鼠肺泡灌洗液细胞总计数及分类计数、肺组织病理学改变、肺匀浆细胞因子表达情况。结果治疗组小鼠与模型组相比,肺泡灌洗液细胞总数减少[(21.59±7.73)×10^(4)/mL比(109.83±16.54)×10^(4)/mL,P=0.011];其中,嗜酸性粒细胞计数显著降低[(9.27±5.41)×10^(4)/mL比(85.87±10.61)×10^(4)/mL,P=0.009)]。肺组织炎症细胞浸润明显减少,气道炎症减轻,苏木精-伊红染色(H&E)评分下降[(1.87±0.31)比(4.15±0.26),P<0.001];气道内黏液分泌、肺内胶原沉积均明显减轻,过碘酸-希夫(PAS)评分[(0.90±0.31)分比(2.10±0.32)分,P<0.001]和胶原阳性百分比[0.12%±0.03%比0.19%±0.05%,P=0.029]均降低。免疫组织化学染色显示治疗组小鼠气道平滑肌厚度[(4.79±0.30)μm比(6.31±0.44)μm,P<0.001]及肺组织CD31+血管计数[(7.99±9.96)/mm^(2)比(15.53±18.13)/mm^(2),P<0.001]与模型组相比减少。结论奥马珠单抗可以改善慢性过敏性哮喘小鼠的气道重塑。     

Omalizumab

* Omalizumab is a recombinant humanised monoclonal antibody which specifically binds to the C epsilon3 domain of immunoglobulin (Ig) E, the site of high-affinity IgE receptor binding. * Improvements in asthma symptoms and health-related quality-of-life, and a significant reduction in the frequency of asthma exacerbations were seen in allergic asthmatic patients treated with omalizumab. * Omalizumab was also effective in the treatment of children with allergic asthma demonstrating improvements in health-related quality-of-life and significant dosage reductions of inhaled corticosteroids. * Administration of omalizumab to patients with allergic rhinitis resulted in a rapid dose-dependent suppression of serum free IgE levels. * Omalizumab significantly improved health-related quality-of-life and nasal symptoms in patients with seasonal allergic rhinitis. Antihistamine requirements were also significantly reduced following treatment. * Adverse events were infrequent in clinical trials of omalizumab, and not significantly different from placebo. The most frequent drug-related event was mild to moderate urticaria.     

Omalizumab: the evidence for its place in the treatment of allergic asthma

Introduction:

Asthma is a chronic inflammatory airways disease associated with reversible airflow obstruction and bronchial hyperresponsiveness. Asthma is prevalent worldwide and results in significant morbidity, mortality, and healthcare costs, the majority of which arise from those with severe disease. Omalizumab is a monoclonal antibody to immunoglobulin E (IgE) that has been developed for the treatment of severe persistent allergic (IgE mediated) asthma.

Aims:

The aim of this review is to evaluate the available clinical evidence on omalizumab to determine the role it has to play in the treatment of persistent allergic asthma.

Evidence review:

There is clear evidence to show that omalizumab is effective in reducing the rate of asthma exacerbations, inhaled corticosteroid dose, and the need for rescue medication in patients with allergic asthma. Clinical data indicate beneficial effects on patient-reported symptoms and perceived quality of life, as well as a reduction in unscheduled healthcare visits. There is little evidence to suggest omalizumab may enhance lung function or reduce the requirement for oral corticosteroids. Omalizumab has a favorable safety profile, although anaphylaxis has occurred. A study in children showed similar results to those achieved in adults and adolescents, with fewer asthma exacerbations and school days missed. Omalizumab may be cost effective in patients when used as add-on therapy to inhaled corticosteroids and long-acting beta₂ agonists (LABA).

Place in therapy:

Omalizumab is an effective add-on therapy to inhaled corticosteroids and LABAs in adults and adolescents with severe persistent allergic asthma. Currently there is insufficient evidence to support the use of omalizumab in children.     

Anti-IgE therapy of asthma

There is a strong association between serum levels of immunoglobulin E (IgE) and asthma development. Allergen binds to IgE on basophils and mast cells, leading to cell degranulation and release of inflammatory mediators. A humanized antibody to IgE that reduces circulating free IgE, omalizumab (Genentech Inc/Novartis AG/Tanox Inc), inhibits the early- and late-phase response to allergen. In clinical trials of moderate-to-severe asthma, omalizumab allowed a reduction in oral and inhaled corticosteroids while improving peakflows and reducing exacerbations, particularly in patients at high risk of serious asthma-related morbidity. Omalizumab is a useful addition to the treatment armamentarium for patients with moderate-to-severe asthma.     

Anti-IgE therapy with omalizumab in asthma and allergic rhinitis

The pharmacology, efficacy, dosage, adverse effects, and economics of anti IgE (omalizumab) are discussed. Omalizumab is the generic name for the human/murine chimeric (recombinant humanized) monoclonal IgG antibody. Anti-IgE prevents IgE from attaching to effector cells, and thereby blunts IgE-mediated inflammatory responses. After subcutaneous administration its absorption is slow, reaching peak concentration in serum after an average of 7-8 days. At recommended doses, serum free IgE levels decrease within 1 hour following the first dose and are maintained between doses. Dose and dosing frequency are adjusted according to body mass and serum total IgE concentration before the start of treatment. Omalizumab administered subcutaneously is an effective treatment for add-on therapy in patients with poorly controlled, moderate-to-severe allergic asthma and allergic rhinitis (adults and adolescents > 12 years). It reduces the requirement for inhaled corticosteroids while protecting against disease exacerbation. Omalizumab is well tolerated, but the safety profile requires long-term assessment in adults as well as in children.     

Pharmacodynamics of omalizumab: implications for optimised dosing strategies and clinical efficacy in the treatment of allergic asthma

OBJECTIVE: Omalizumab (Xolair), is a recombinant humanised monoclonal anti-immunoglobulin E (IgE) antibody, for the treatment of allergic asthma. This review describes how the correlation between clinical outcomes and a suitable surrogate marker (free serum IgE) led to the development of an individualised dosing strategy for omalizumab. It also demonstrates how subsequent studies using this dosing strategy were able to achieve low levels of IgE and clinical benefit. DATA SOURCES: Published articles and data on file (Novartis Pharma AG, Genentech). RESULTS: Studies in patients with IgE-mediated diseases of the airways have shown that clinical benefit with omalizumab is observed when free IgE levels in serum are reduced to 50 ng/ml (20.8 IU/ml) or less (target 25 ng/ml (10.4 IU/ml)). The ability of omalizumab to reduce free IgE levels to such levels is dependent on dose, the patient's weight and baseline IgE level. To simplify dosing, and ensure that free IgE reduction is achieved, an individualised tiered dosing table was developed from which patients with asthma, depending on weight and starting IgE level, receive omalizumab 150-375 mg by subcutaneous injection every 2 or 4 weeks. This dosing strategy has proved clinically efficacious for improving disease control in patients with allergic asthma, as shown by significantly lower exacerbation rates and decreased dependence on treatment with inhaled corticosteroids, along with improvements in symptoms, lung function and usage of rescue bronchodilators. CONCLUSIONS: The clinical efficacy of omalizumab has been optimised through the development of an individualised dosing table that emerged from an understanding of the pharmacodynamics of this agent.     

Omalizumab: a recombinant humanized anti-IgE antibody for allergic asthma.

PURPOSE: The pharmacology, efficacy, dosage, adverse events, and economics of omalizumab are discussed. SUMMARY: Omalizumab, a recombinant DNA-derived humanized monoclonal antibody, binds to the C epsilon3 domain of immunoglobulin E (IgE) and forms complexes that inhibit the immune system's response to allergens by averting IgE-mediated inflammatory changes. Omalizumab exhibits a similar pharmacokinetic profile in adults, adolescents, and children. Omalizumab is indicated for adults and adolescents with moderate to severe persistent asthma who have a positive skin test or in vitro reactivity to a perennial aeroallergen and whose symptoms are inadequately controlled with inhaled corticosteroids. Because of the limited data regarding the safety and effectiveness of omalizumab in children, the drug is indicated for patients 12 years of age or older. The recommended starting dosage is 150-375 mg s.c. every two or four weeks. Dosages and frequency of dose administration are determined by total serum IgE level, measured before the start of treatment, and body weight. Omalizumab is generally well tolerated in adults and children with allergic asthma. Adverse events most commonly observed are injection-site reaction, viral infection, upper-respiratory-tract infection, sinusitis, headache, and pharyngitis. Three large phase III clinical trials demonstrated that omalizumab is more effective than placebo in controlling moderate to severe allergic asthma in patients who have poor disease control or exacerbations despite recommended therapy. Currently, there are no clinical comparisons of omalizumab with other standard treatments for asthma; therefore, it is difficult to determine its overall place in therapy. CONCLUSION: Omalizumab should be considered as a second-line therapy for patients with moderate to severe persistent allergic asthma.     

Omalizumab: an effective anti-IgE treatment for allergic asthma and rhinitis

IgE plays a crucial role in the pathophysiology of asthma and allergic rhinitis. Omalizumab is a humanized anti-IgE monoclonal antibody that binds to free IgE and prevents its binding to specific receptors on the surface of cells, thus preventing the release of immune mediators. Treatment with omalizumab in patients with asthma or allergic rhinitis results in a rapid and pronounced decrease in serum IgE levels that is correlated with an improvement in the severity of symptoms and in the quality of life of patients. Omalizumab has a good safety profile, with only mild to intermediate drug-related adverse events.     

Evaluation of IgE Antibodies to Omalizumab (Xolair®) and Their Potential Correlation to Anaphylaxis

Omalizumab (Xolair®) is a recombinant humanized monoclonal antibody that selectively binds to human immunoglobulin E (IgE). Omalizumab is used to treat IgE-mediated diseases such as chronic idiopathic urticaria (CIU) and moderate to severe allergic asthma. In pre-marketing clinical trials in patients with asthma, anaphylaxis was reported in 3 of 3,507 (0.1%) patients. In post-marketing spontaneous reports, the frequency of anaphylaxis attributed to omalizumab use was estimated to be at least 0.2% of patients based on an estimated exposure of about 57,300 patients from June 2003 through December 2006. To better understand the risk of anaphylaxis in patients with allergic asthma receiving omalizumab, a post-marketing pharmacosurveillance study was initiated in 2009. As part of this study, an assay was developed to detect antibodies of IgE isotype to omalizumab. Serum samples from patients in the study were evaluated using this assay. Our results indicated that there was no observable correlation between either anaphylaxis or skin test reactivity and the presence of antibodies of IgE isotype to omalizumab. Here, we discuss the development of this assay as well as the results of the immunogenicity assessment.Key Words: biotin-mutant omalizumab-AAA, DIG-FcεR1-IgG, IgE isotype, omalizumab (Xolair®), omalizumab/total IgE molar ratio     

Anti-IgE monoclonal antibody,omalizumab: a new treatment for allergic asthma

Omalizumab (Xolair^?; Genentech, USA/Tanox, Inc., USA/Novartis Pharma AG, Switzerland) – a humanised antibody to IgE that reduces circulating free IgE – has been developed for the treatment of allergic asthma. It inhibits the early- and late-phase response to allergens, suppresses eosinophilic and T cell inflammation in asthmatic airways and reduces the levels of high-affinity IgE receptors on basophils. In clinical trials of moderate-to-severe asthma, omalizumab allowed a reduction in inhaled corticosteroid dosage while improving peak flows and reducing exacerbations, particularly in patients at high-risk of serious asthma-related morbidity and improved quality of life scores. When added to existing therapies of patients with more severe asthma, omalizumab also improved asthma control. Additionally, in asthma patients with concomitant perennial allergic rhinitis, omalizumab provides improvement in these comorbid conditions. Omalizumab is well-tolerated by asthma patients and represents a new approach to the treatment of the moderate-to-severe asthmatic patient. It is likely that it will first be used at the more severe end of the asthmatic diathesis.