奥马珠单抗治疗慢性自发性荨麻疹的进展

【摘要】 慢性自发性荨麻疹指不明原因反复发作风团超过6周,伴或不伴血管神经性水肿。其发病的中心环节是肥大细胞和嗜碱性粒细胞激活、脱颗粒。奥马珠单抗是一种人源化、重组单克隆IgG抗体,能选择性结合游离IgE抗体Fc段,阻断IgE?FCεRⅠ轴所引起的肥大细胞、嗜碱性粒细胞激活。已发布评价奥马珠单抗治疗慢性自发性荨麻疹的Ⅲ期临床试验有3项,证实了奥马珠单抗在治疗难治型慢性自发性荨麻疹的有效性和安全性。     

奥马珠单抗在慢性荨麻疹治疗中的应用

慢性荨麻疹目前发病机制尚不明确,反复发作,严重影响患者的生活质量。目前指南推荐使用的抗组胺药物在部分患者中治疗效果并不理想。奥马珠单抗是一种新型的生物制剂,其治疗慢性荨麻疹的疗效已经在临床试验中得到证实,并已应用到难治性慢性荨麻疹的治疗中,但关于其具体机制、用法用量以及不良反应等问题仍没有达成共识。本文对奥马珠单抗在慢性荨麻疹治疗中的作用机制、用法用量、治疗效果以及不良反应进行综述。     

奥马珠单抗治疗慢性自发性荨麻疹的疗效及安全性分析

【摘要】 目的 回顾分析奥马珠单抗治疗慢性自发性荨麻疹（CSU）的疗效、安全性及停药复发情况。方法 回顾北京大学第一医院皮肤科门诊2018年2月至2021年1月使用奥马珠单抗治疗的CSU病例,分析其临床特征,采用门诊随访形式,通过荨麻疹控制评分（UCT）、皮肤病生活质量指数（DLQI）评估疾病严重程度,监测不良事件及停药后复发情况。正态分布的计量资料组间比较采用独立样本t检验或方差分析,非正态分布的计量资料组间比较采用Mann-Whitney U检验、Wilcoxon符号秩和检验或Kruskal-Wallis H检验,计数资料组间比较采用卡方检验或Fisher 精确检验。结果 纳入59例CSU患者,奥马珠单抗治疗至少3个月,其中45例治疗达6个月,15例达12个月。经奥马珠单抗治疗,UCT从基线期3.0（1.0,6.0）分上升至第1个月11.0 （3.0,14.0）分和第3个月15.0 （12.0,16.0）分（均P < 0.05）。DLQI从基线期16.0（12.0,20.0）分下降至第1个月7.0 （1.0,13.0）分和第3个月1.0 （0.0,4.0）分（均P < 0.05）。疾病部分或完全控制的比例在基线期为0,第1个月上升至44.1%,第3个月达78.0%,第6个月达88.9%。疾病对生活质量存在重度或极重度影响的比例在基线期为84.7%,第1个月降至30.5%,第3个月降至15.3%,第6个月降至4.4%。对奥马珠单抗治疗完全反应组和部分反应组比无反应组病程更短（t = -2.894,P = 0.011;t = -2.511,P = 0.036）;完全反应组比部分反应组和无反应组治疗时间更长（t = 2.479,P = 0.039;t = 2.677,P = 0.022）。慢反应组与快反应组相比,基线DLQI更高（Z = -2.622,P = 0.009）,基线UCT更低（Z = -2.746,P = 0.006）。19例患者病情完全控制后停药,其中13例（68.4%）在停药7（5,8）周后复发,复发后UCT评分高于治疗前（Z = 3.172,P = 0.001）,复发组比未复发组病程更长（Z = -2.635,P = 0.007）。复发后5例重新开始奥马珠单抗治疗,均再次得到部分或完全控制。治疗期间报告不良反应事件均为轻中度。结论 奥马珠单抗能够有效控制CSU症状,提高患者生活质量,且安全性较好,但停药后复发率高,复发后重新开始奥马珠单抗治疗仍有效。     

奥马珠单抗治疗儿童日光性荨麻疹一例并文献复习

日光性荨麻疹传统治疗方案主要有抗组胺药物、光硬化、白三烯受体拮抗剂,然而有很多患者对传统治疗方案反应不佳。既往报道奥马珠单抗治疗儿童日光性荨麻疹有效,本文报道奥马珠单抗治疗儿童日光性荨麻疹一例,并进行文献复习。患者为一例3岁男性患儿,日晒后全身红斑、风团伴瘙痒1年。给予患者奥马珠单抗150 mg皮下注射,患者好转出院。随访22个月,患者目前维持奥马珠单抗治疗中,皮疹无复发。     

真实世界下奥马珠单抗治疗难治性正常补体性荨麻疹性血管炎疗效分析

目的:评估真实世界下奥马珠单抗对于治疗难治性正常补体性荨麻疹性血管炎(NUV)的有效性及安全性。方法:收集2016年1月至2022年3月就诊于山东省第一医科大学附属皮肤病医院的6例使用奥马珠单抗治疗难治性NUV患者的数据,通过荨麻疹性血管炎活动度评分(UVAS)和皮肤科生活质量指数(DLQI)评价治疗情况,每4周记录相应评分。并回顾文献,进行临床总结。结果:我院共治疗6例NUV患者,治疗时间12～32周。2例基线IgE高的患者,在第8周达到完全缓解;4例IgE正常的患者,均在第8周达到了部分缓解：缓解率100%。回顾既往报道的14例患者,发现300 mg/4周的剂量治疗NUV更普遍且有效。尚未发现患者发生不良反应。结论:奥马珠单抗治疗难治性正常荨麻疹性血管炎安全有效。     

奥马珠单抗治疗27例人工荨麻疹回顾分析

【摘要】 目的 通过分析真实世界奥马珠单抗治疗人工荨麻疹的数据,评估奥马珠单抗治疗人工荨麻疹的临床疗效和安全性。方法 回顾分析北京大学第一医院皮肤科门诊2018年2月到2021年5月完成16周奥马珠单抗治疗的人工荨麻疹病例资料,比较治疗前后关键摩擦阈值（CFT）和激发试验瘙痒评分、荨麻疹控制评分（UCT）、皮肤病生活质量指数（DLQI）、慢性荨麻疹生活质量问卷（CU-Q2oL）,记录治疗期间患者报告的不良事件。治疗前后组内数据比较采用Wilcoxon符号秩和检验。结果 纳入27例完成16周奥马珠单抗治疗的人工荨麻疹患者。27例患者基线期CFT均为4,UCT为7.0（5.0,8.0）分,DLQI为9.0（6.0,10.0）分,CU-Q2oL为63.0（50.0,72.0）分。在治疗第4周,9例（33.3%）患者CFT由4降为0,27例患者UCT评分上升至14.0（12.0,16.0）分（Z = 4.548,P＜0.05）,DLQI下降至2.0（0.0,2.0）分（Z = 4.513,P＜0.05）,CU-Q2oL下降至32.0（25.0,41.0）分（Z = 4.433,P＜0.05）。治疗第16周,UCT升至15.0（14.0,16.0）分,DLQI降至0.0（0.0,1.0）分,CU-Q2oL降至25.0（23.0,30.0）分。治疗期间无药物相关严重不良事件报告。结论 奥马珠单抗可有效改善人工荨麻疹的症状,提高患者生活质量,且具有良好的安全性。     

奥马珠单抗治疗儿童和老年慢性自发性荨麻疹患者的短期疗效及安全性

目的 探讨奥马珠单抗治疗儿童和老年慢性自发性荨麻疹患者的短期疗效及安全性。方法 对2020年6月—2022年10月于天津医科大学总医院门诊就诊并使用奥马珠单抗治疗的儿童(<18岁)及老年(>65岁)慢性自发性荨麻疹患者的相关临床资料进行分析。结果 33例儿童组患者注射1次后51.52%完全缓解，42.42%部分缓解；24例老年组患者注射1次后45.83%完全缓解，29.17%部分缓解；治疗期间随注射次数增加，两组缓解率持续提高并保持较高水平，且相关评分持续好转，无严重不良反应出现。与老年患者相比，儿童患者出现其他过敏性共病的几率更高，疾病严重程度更轻，总IgE水平更高，对奥马珠单抗治疗的应答比例更高(P<0.05)。8例患者停药后复发，重新启动奥马珠单抗治疗仍然有效。结论 儿童及老年慢性自发性荨麻疹患者使用奥马珠单抗治疗的疗效显著，安全性良好，且儿童患者疗效优于老年患者。     

抗IgE疗法——奥马珠单抗治疗慢性荨麻疹专家共识

【摘要】 慢性荨麻疹是一种常见的免疫相关性皮肤病,具有反复发作、迁延不愈等特点,部分患者对常规抗组胺药物治疗效果不佳,生活质量受到严重影响。目前,国内外多项研究证实,一类以新型生物制剂为主的抗IgE疗法能够较为有效和安全地应用于慢性荨麻疹等疾病的治疗。为规范并促进临床医生对抗IgE疗法的应用和认识,基于国外指南及近年相关研究报道,中华医学会皮肤性病学分会荨麻疹研究中心组织有关专家制订本共识,以奥马珠单抗为代表,详细介绍抗IgE疗法治疗慢性荨麻疹的具体机制、应用方案和注意事项,为皮肤科医务工作者提供相关的理论依据和用药指导。     

慢性特发性荨麻疹治疗策略

慢性特发性荨麻疹也称慢性原发性荨麻疹,是指无明显诱因突然,持续性或者间歇性出现的伴有瘙痒的风团或者血管性水肿,每周发病超过2次且病程超过6周.目前慢性特发性荨麻疹的病因及发病机制仍不十分明确,部分患者未能得到有效治疗而影响生活质量.根据EAACI/GA2LEN/EDF/WAO国际指南,常规剂量的第二代抗组胺药为一线治疗...     

奥马珠单抗对慢性自发性荨麻疹患者的临床疗效和安全性分析

目的:观察奥马珠单抗治疗慢性自发性荨麻疹（CSU）的临床疗效和安全性。方法:回顾性分析2020年3-9月在中国医学科学院皮肤病医院诊断为CSU并接受奥马珠单抗（300 mg/4周,皮下注射）治疗3次的60例患者的临床资料。分别在第0、2、4、6、8、10、12周使用7 d荨麻疹活动评分（UAS7）和慢性荨麻疹生活质量评...     

生物制剂治疗慢性荨麻疹的进展

慢性荨麻疹是皮肤科常见的一种反复发作的过敏性疾病,抗组胺药是一线治疗药物,但近一半患者疗效欠佳.慢性荨麻疹病因复杂,包括Th1/Th2细胞亚群失衡、炎症介质异常、IgE及抗IgE高亲和力受体的抗体异常等,可能是慢性荨麻疹难以治愈的重要原因之一.生物制剂对免疫异常具有选择性调节或阻滞作用,成为慢性荨麻疹及其他荨麻疹疾病的治疗新手段或方法.这些生物制剂主要有:卡介苗多糖核酸、丙种球蛋白、肿瘤坏死因子α抑制剂、白细胞介素1阻滞剂、利妥昔单抗、奥马珠单抗等,在慢性荨麻疹治疗中具有重要地位,其中奥马珠单抗是抗lgE单克隆抗体,具有良好的疗效/风险比,耐受性好,是治疗慢性荨麻疹较理想的生物制剂之一.     

奥马珠单抗治疗难治性慢性自发性荨麻疹的疗效预判分析

目的探索预测奥马珠单抗治疗难治性慢性自发性荨麻疹(CSU)疗效的因子。方法收集2019—2021年苏州大学附属第二医院皮肤科门诊和病房收治的经奥马珠单抗治疗的难治性CSU患者40例, 收集患者的临床资料、治疗前7天荨麻疹活动度评分(UAS7)、皮肤病生活质量指数(DLQI)。治疗前测定基线免疫球蛋白E(IgE)、嗜酸性粒细胞及嗜碱性粒细胞数、IgG型抗甲状腺过氧化物酶(TPO)抗体、平均血小板体积、C反应蛋白、D-二聚体、补体C3、C4、白细胞介素(IL)-2、IL-4、IL-6、IL-10、IL-17A、肿瘤坏死因子(TNF)-α、γ干扰素(IFN-γ)水平、CD4+ T细胞及CD8+ T细胞百分比, 并进行自体血清皮肤试验(ASST)。奥马珠单抗治疗12周后, 根据UAS7评分将40例CSU患者分为应答良好组和应答不佳组, 比较两组患者上述指标的差异。采用受试者工作曲线(ROC)分析两组间差异有统计学意义的连续型变量指标, 测定预测因子的准确度并确定连续型变量指标的最佳临界值;对组间差异有统计学意义的分类变量, 计算其预测应答不佳的灵敏度和特异度;采用Pearson相关分析法分析各...     

Impact of COVID-19 pandemic on the course of refractory chronic spontaneous urticaria under omalizumab treatment

BackgroundThe course of chronic spontaneous urticaria (CSU) can be influenced by infections, depression, and stress.ObjectiveOur aim was to investigate the impact of the COVID-19 pandemic on the course of refractory CSU together with patient adherence to omalizumab and treatment adjustments.MethodsUrticaria Activity Score (UAS7) was used to assess disease activity. Fear of COVID-19 Scale (FC-19s), and Depression Anxiety Stress Scale (DASS-21s) were performed to assess mental health status. All scales were performed during the Quarantine Period (QP) and Return to the Normal Period (RTNP). UAS7 Before Pandemic (BP) was recorded from the patients medical records.ResultsThe authors evaluated 104 omalizumab-receiving CSU patients. UAS7 scores during QP were significantly higher than those in RTNP and BP (p < 0.01). DASS-21 and FC-19 scores were significantly higher during QP compared to RTNP (p < 0.01). Nineteen (18.2%) patients ceased omalizumab, 9 patients prolonged the intervals between subsequent doses during the pandemic. UAS7 scores in QP were significantly higher in patients who ceased omalizumab than in those who continued (p < 0.001). Among patients who continued omalizumab, 22.4% had an increase in urticaria activity and higher FC-19 scores in comparison with those with stable disease activity (p = 0.008).Study limitationsThe small sample size of patients with prolonged intervals of omalizumab and the lack of mental health evaluation with the same tools prior to the study.ConclusionFear induced by COVID-19 can determine an increase in disease activity. Therefore, patients on omalizumab should continue their treatment and prolonged interval without omalizumab can be considered in patients with good urticaria control.     

Omalizumab is an effective and rapidly acting therapy in difficult-to-treat chronic urticaria: A retrospective clinical analysis

BackgroundOmalizumab (anti-IgE) therapy is effective and safe in chronic urticaria (CU) in placebo-controlled clinical trials but real life clinical data are scarce.ObjectiveTo better understand the effects of omalizumab in CU patients treated outside of clinical trials.MethodsIn this retrospective clinical analysis, we assessed responder rates, optimal dosage, response to up-/downdosing, time to relief of symptoms, rates of return and time of relapse after omalizumab administration, and safety in 51 CU patients, 20 with chronic spontaneous urticaria (CSU) alone, 21 with different forms of chronic inducible urticaria (CindU) and 10 with both.ResultsOmalizumab treatment led to complete remission in 83% of CSU and 70% of CindU patients. When starting with 150 mg omalizumab 4 weekly, only 2/15 CSU and 7/17 CindU patients required updosing to achieve complete remission. In CSU, 57% of complete responses occurred within week one, all on the first day. Relapses were 2–8 weeks in all but six patients, where they were <4 months. Omalizumab was safe. Efficacy was not correlated to baseline IgE levels.ConclusionClinical experience from more than 1250 injections in 51 patients over four years indicates that omalizumab is a rapidly acting, highly effective and safe drug in CSU and CindU patients. Our observations in a real life clinical setting support the recommendation of current EAACI/GA²LEN/EDF/WAO guideline for the management of urticaria to use omalizumab to treat urticaria patients.     

依匹斯汀和西替利嗪治疗慢性特发性荨麻疹对照观察

我们于2005年7月至2006年12月,分别用依匹斯汀、西替利嗪治疗慢性特发性荨麻疹(chronic idiopathic urticaria,CIU),进行随机、开放、对照的临床疗效观察,现报道如下.     

Clinical characteristics of pruritus in chronic idiopathic urticaria

BACKGROUND: Although pruritus is a predominant symptom of chronic idiopathic urticaria (CIU) its clinical characteristics have not been explored. OBJECTIVES: To characterize the clinical pattern and sensory and affective dimensions of the itch experience, utilizing a comprehensive itch questionnaire. METHODS: A structured questionnaire based on the McGill pain questionnaire was used in 100 patients suffering from CIU randomly recruited from a tertiary referral centre. RESULTS: All 100 patients recruited with CIU completed the questionnaire. In 68 patients pruritus appeared on a daily basis. Most patients experienced their pruritus at night and in the evening (n = 83), and 62 reported difficulty in falling asleep. Pruritus involved all body areas, but mostly the arms (n = 86), back (n = 78) and legs (n = 75). Accompanying symptoms were a sensation of heat in 45 patients and sweating in 15. Most patients (n = 98) were prescribed antihistamines (mainly sedating), of whom 34 experienced long-term relief. The sensation of itch was reported to be stinging (n = 27), tickling (n = 25) and burning (n = 23). Seventy-six patients found their pruritus bothersome, 66 annoying and 14 complained of depression. The itch intensity at its peak was more than double that felt after a mosquito bite. The worst itch scores of those who felt depressed were significantly higher than of those who did not (P = 0.018). There was a positive correlation between the sensory and affective scores during worst itch (P < 0.001). CONCLUSIONS: This study describes the itch experienced in CIU, highlighting sensory and affective dimensions. The itch questionnaire was found to be a valuable tool for evaluating pruritus in CIU and its unique features.     

窄谱中波紫外线联合抗组胺药治疗慢性自发性荨麻疹的疗效观察

目的观察窄谱中波紫外线(NB-UVB)联合抗组胺药治疗慢性自发性荨麻疹的疗效。方法 80例慢性荨麻疹患者,随机分为试验组和对照组,每组各40例。试验组采用NB-UVB光疗,每周2次,共24次,同时口服抗组胺药;对照组仅口服抗组胺药。比较两组治疗后的临床疗效以及随访12周内的复发情况。结果两组患者的症状和体征评分明显下降,且试验组下降更为明显(t=46.37,P0.05)。试验组的临床疗效明显优于对照组(χ~2=6.76,P0.05);且复发率明显低于对照组(χ~2=9.83,P0.01)。结论 NB-UVB安全有效,可作为慢性自发性荨麻疹的辅助治疗手段。     

Methotrexate-responsive chronic idiopathic urticaria: a report of two cases

Chronic idiopathic urticaria (CIU) may be severe and refractory to standard therapies. We describe two patients with CIU, neither of whom had detectable autoantibodies, in whom control of the disease was achieved with methotrexate.