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...     

中文版荨麻疹控制评分量表及信效度验证

【摘要】 目的 翻译荨麻疹控制评分（UCT）,并检验该量表的信效度、敏感性以及筛选准确性。方法 经过翻译、回译和文化调试,确定荨麻疹控制评分量表的条目。应用该量表调查51例慢性自发性荨麻疹（CSU）、41例慢性诱导性荨麻疹（CIndU）患者和11例CSU合并CIndU患者。入组后8周内,81例使用抗组胺药治疗,8例使用奥马珠单抗治疗,14例抗组胺药联合奥马珠单抗治疗。入组时和入组后第4、8周时,用皮肤病学生活质量指数（DLQI）、荨麻疹活动评分（UAS）评估生活质量损害和疾病活动情况。采用Cronbach′s α系数评估问卷内部一致性信度。通过与DLQI、UAS28评分比较,检验中文版UCT的聚合效度、已知族群效度、敏感性及筛选准确性。结果 中文版UCT包含4个条目,回顾性评价过去4周内疾病的临床症状和体征、对生活质量的影响、治疗效果和总体疾病控制情况。CSU组UCT量表各条目得分的Cronbach′s α系数为0.886 ~ 0.945,CIndU组为0.834 ~ 0.958。入组时,CSU组与CIndU组UCT与DLQI评分显著负相关（rs值分别为-0.672,-0.578,均P＜0.01）。第4周和8周时,CSU组UCT与UAS28、DLQI评分均呈显著负相关（4周：rs值分别为-0.654、-0.829,均P＜0.01;8周：rs值分别为-0.717、-0.765,均P＜0.01）,CIndU组UCT与DLQI评分亦显著负相关（rs值分别为-0.834、-0.778,均P＜0.01）。CSU组第4周与第8周之间UCT变化量与UAS变化量显著相关（rs = -0.569,P＜0.01）;与入组时比较,第4、8周时 UCT变化量与相应DLQI评分变化量显著相关（rs值分别为-0.693、-0.447,均P＜0.01）。对于CIndU组,与入组时比较,第4周与第8周时UCT变化量与DLQI变化量亦显著相关（rs值分别为-0.615、-0.408,均P＜0.01）。不同UAS、DLQI评分组间UCT评分差异均有统计学意义（均P＜0.05）。 结论 中文版UCT是有效、可靠的CSU和CIndU患者的临床管理工具,可用于评估疾病控制情况,在一定程度上反映疾病活动度及疾病相关生活质量。     

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。     

奥马珠单抗治疗老年中重度大疱性类天疱疮5例：前瞻性病例系列研究

目的 通过前瞻性病例系列研究设计,观察奥马珠单抗治疗老年中重度大疱性类天疱疮(BP)的长期临床疗效及安全性。方法 纳入5例老年中重度BP患者,在常规外用强效糖皮质激素、或联合系统治疗基础上予奥马珠单抗300 mg,每4周1次皮下注射,16周后根据病情予维持或调整剂量,疗程不低于24周,此后继续治疗并随访。主要结局为首次给药后4周内达到疾病控制的患者比例,同时于治疗前和首次治疗后第2、4、8、16、24周观察患者BP面积指数(BPDAI)、皮肤病生活质量指数(DLQI)、瘙痒数字评价量表(NRS)、嗜酸性粒细胞绝对数(EO)及抗BP180抗体值,同时评估疾病复发率与安全性。结果 5例患者在首次使用奥马珠单抗后4周内均达到了疾病控制,第24周时患者BPDAI评分、DLQI评分、瘙痒NRS评分、EO及抗BP180抗体值均较治疗前明显降低(P<0.05)。研究期间所有患者均未报告明显不良反应,其中2例患者在24周内复发。结论 奥马珠单抗可显著改善BP病情,提高患者生存质量,长期使用安全性良好。     

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...     

乌司奴单抗改善中、重度斑块状银屑病患者健康相关生活质量和临床疗效观察

目的:评估乌司奴单抗对中国3期、双盲、安慰剂对照临床(LOTUS)研究患者健康相关生活质量(HRQoL)的影响。方法:共322例患者,在第0周和第4周随机接受乌司奴单抗45mg(n=160)或安慰剂(n=162);第12周和第16周安慰剂组交叉使用乌司奴单抗,而乌司奴单抗组则在第16周继续使用乌司奴单抗。第12周HRQoL终点包括皮肤病生活质量指数(DLQI)评分较基线的变化、单个DLQI域的变化、DLQI评分为0分或1分的患者比例以及获得有临床意义DLQI改善(评分降低≥5分)的患者比例。结果:乌司奴单抗治疗患者12周时DLQI评分较基线的改善(-9.3分)显著优于安慰剂组(-1.9分)(P0.001)。同样,乌司奴单抗治疗后DLQI≤1分的患者比例显著高于安慰剂组(42.6%vs 10.7%,P0.001),乌司奴单抗组和安慰剂组治疗后分别有71.5%和29.6%的患者DLQI降低≥5分(P均0.001)。乌司奴单抗治疗患者12周时单个DLQI域与安慰剂相比显著改善(P0.001)。乌司奴单抗组DLQI的改善在治疗28周内持续存在。交叉接受乌司奴单抗的安慰剂组患者,与最初随机接受乌司奴单抗治疗的患者相比,HRQoL改善程度类似。结论:乌司奴单抗显著改善了中国中至重度斑块状银屑病患者的HRQoL。     

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。     

盐酸非索非那定片递减疗法治疗慢性自发性荨麻疹的疗效观察

目的：探讨盐酸非索非那定片递减疗法治疗慢性自发性荨麻疹的有效性。方法在临床病史评估和自体血清皮肤试验（ASST）的基础上,将80例慢性自发性荨麻疹患者随机分配到常规剂量组和递减剂量组。常规剂量组给予口服盐酸非索非那定片120 mg/d,连续12周;递减剂量组前4周每日给予口服盐酸非索非那定片120 mg/d,第5周和第9周时尝试逐渐减量至可控制症状的最小服药量。在治疗前（基线）和治疗后第4、8、12周时评价所有患者荨麻疹疾病活动程度（UAS）、皮肤病生活质量指数（DLQI）和抗组胺药物总服用量。结果共76例患者完成12周的治疗,包括常规剂量组37例和递减剂量组39例。治疗4、8、12周后,常规剂量组（UAS 0.64±0.82、0.37±0.68、0.27±0.56;DLQI：3.62±1.82、2.81±1.65、1.37±1.14）和递减剂量组（UAS：0.61±0.87、0.48±0.72、0.28±0.61;DLQI：3.79±2.57、2.74±2.11、1.15±1.47）UAS、DLQI评分均分别显著低于各组治疗前评分（UAS：4.08±0.79、4.07±0.81;DLQI：16.19±3.79、15.92±4.2）,差异有统计学意义（均P<0.001）,但两组在治疗后同一时间UAS和DLQI评分差异均无统计学意义（P>0.05）。递减剂量组在治疗8、12周后分别有71.79%（28/39）和82.05%（32/39）患者在原有剂量基础上减少剂量仍能控制症状,且服药总量显著低于常规剂量组对应时间段的药量（均P<0.001）。结论慢性荨麻疹患者使用盐酸非索非那定治疗4~8周后,逐步减少药物剂量可取得与常规剂量类似的临床疗效。     

司库奇尤单抗治疗中重度斑块状银屑病疗效及安全性的真实世界研究

目的 观察真实世界司库奇尤单抗治疗中重度斑块状银屑病的临床疗效及安全性。方法 本研究共纳入45例中重度斑块状银屑病患者,接受司库奇尤单抗150 mg或300 mg治疗,持续至少24周。通过银屑病皮损面积及严重程度指数(PASI)、体表受累面积(BSA)、皮肤病生活质量指数(DLQI)的变化来评估疗效,并对其安全性进行分析。结果 所有患者经过24周治疗,PASI、BSA及DLQI评分均显著下降(P<0.001)。其中16例接受150 mg治疗的患者第12周PASI75、PASI90、PASI100的应答率分别为93.75%、62.50%和12.50%,在第24周时达到100.00%、93.75%和43.75%。而29例接受300 mg治疗的患者第12周时PASI75、PASI90、PASI100应答率分别为100.00%、79.31%和34.48%,第24周时则为100%、93.10%和62.07%。而在改善患者生活质量上,150 mg组患者第12周和第24周DLQI 0/1的应答率分别为50.00%和75.00%;300 mg组患者第12、24周DLQI 0/1的应答率分别为51...     

Omalizumab in patients with chronic spontaneous urticaria nonresponsive to H1-antihistamine treatment: results of the phase IV open-label SUNRISE study

This study from France concerned itself with the biologic drug, omalizumab, as treatment for chronic spontaneous urticaria (CSU). CSU causes troublesome, even debilitating, itchy weals like nettle stings (urticaria), together with swelling of deeper tissues (angioedema) that commonly affects the lips, tongue and eyelids. Omalizumab is licensed for severe CSU that does not respond to high-dose antihistamines. One hundred and thirty-six patients with CSU were enrolled and 124 completed the study. They were given three standard doses of omalizumab, every four weeks for 12 weeks. Half the patients also took other medication, usually an antihistamine, to treat their CSU. Researchers and participants knew that all participants were getting omalizumab, and there was no placebo group. Two scoring methods used to assess improvement – the established 7-day urticaria activity score UAS7 and the newer urticaria control test UCT – were found to correlate i.e. their scores were similar. Omalizumab was effective in two-thirds of patients as measured by the UAS7 score, and in three-quarters by the UCT score. These results were not influenced by whether the patients had angioedema. Quality of life scores improved markedly. Mean levels of a blood protein called D-dimer were increased at the beginning of the study and fell with treatment, but there was no correlation with the improvement in UAS7 or UCT scores. Eight of nine patients with very high D-dimer levels responded to treatment, so measuring D-dimer might predict response to omalizumab. Apart from this, the main conclusions were that omalizumab works for CSU and has few side-effects, and that the UCT is reliable.     

慢性自发性荨麻疹患者血清白细胞介素9、血小板活化因子水平与总IgE、病情严重程度和病程的相关性研究

【摘要】 目的 探讨慢性自发性荨麻疹（CSU）患者血清白细胞介素（IL）9、血小板活化因子（PAF）水平与血清IgE水平、病情严重程度和病程的相关性。方法 收集河北北方学院附属第一医院皮肤科2018年3月至2019年3月收治的60例活动期CSU,按7日荨麻疹活动评分（UAS7）将其分为轻度组、中度组和重度组;同时将经规范抗组胺治疗28 d后进入疾病静止期的患者纳入CSU静止期组。另选同期30例健康体检者为健康对照。采集各组受试者外周静脉血,使用酶联免疫法检测血清IL-9、PAF水平,选用免疫散射比浊法测定血清总IgE水平。分析CSU患者血清IL-9、PAF水平与血清总IgE水平、UAS7评分和病程之间的相关性。多组间比较采用单因素方差分析,组间两两比较采用LSD-t检验,相关性分析采用Pearson检验。结果 CSU活动期组男28例,女32例,年龄11 ~ 68（34.68 ± 8.62）岁,病程2个月至7年［（1.42 ± 0.41）年］。健康对照组男14例,女16例,年龄10 ~ 70（35.06 ± 7.89）岁。轻、中、重度CSU患者分别有12、26、22例,经规范治疗后22例纳入静止期组。CSU活动期组、CSU静止期组、健康对照组血清IL-9水平（144.34 ± 23.19、109.25 ± 20.77、107.23 ± 19.23 pg/ml）、PAF水平（362.45 ± 51.45、223.18 ± 32.46、221.23 ± 28.38 pg/ml）、总IgE水平（168.12 ± 32.48、24.04 ± 7.04、21.76 ± 5.95 IU/ml）差异均有统计学意义（F = 38.80、148.38、499.12,均P < 0.001）,CSU活动期组IL-9、PAF、总IgE水平均显著高于CSU静止期组与健康对照组（P < 0.05）;CSU静止期组与健康对照组差异均无统计学意义（P > 0.05）。血清IL-9水平、PAF水平与血清总IgE水平、UAS7评分均呈正相关（P < 0.05）,与病程无显著相关性（P > 0.05）。结论 CSU活动期患者血清IL-9、PAF水平均随病情严重程度的增加而明显升高,且与血清总IgE水平具有密切的相关性。     

Long‐term follow‐up effect of omalizumab in chronic spontaneous urticaria and its association with serum C‐reactive protein levels

This study aims to determine the efficacy of omalizumab, a humanized monoclonal anti‐immunoglobulin E antibody, in patients with chronic spontaneous urticaria (CSU) refractory to conventional therapy, together with the evaluation of serum CRP levels. All the patients with a diagnosis of CSU who were continuously treated with omalizumab (300 mg/mo) for at least 3 months between June 2016 and July 2019 were included in this study. Urticaria activity score (UAS‐7) was used for assessment of disease activity. Serum CRP levels were also retrospectively analyzed. When UAS‐7 scores before the initiation of therapy were compared to the week 4, 12, 24, and 36 scores after the treatment, each were significantly different from the pretreatment results (P < .01). CRP level prior to treatment was found to be strongly correlated with baseline UAS scores of the patients' (P = .00). At the 12th week of treatment, decline of CRP level was positively and strongly correlated with the decline of UAS (P = .037). In this study, mean UAS decreased, mean rescue medication use declined, and overall therapeutic response improved with omalizumab treatment. Additionally, significant correlation between the decline of CRP levels and treatment response was found.     

Treatment of Chronic Spontaneous Urticaria with a Single Dose of Omalizumab: A Study of Four Cases

Background:Chronic spontaneous urticaria (CSU) has a detrimental effect on patients’ emotional and physical quality of life. Omalizumab, an anti-immunoglobulin E humanized monoclonal antibody, has been shown to be very effective in the treatment of refractory chronic urticaria patients but may not be an economically viable option for all CSU patients. However, we present a case series where a single dose of omalizumab gave sustained relief of symptoms in patients with CSU, which may be an economical option.Aims:The aim of this study is to assess the efficacy of a single dose of omalizumab in the treatment of CSU. Materials and Methods: Four patients of CSU whose disease was not controlled with four times the licensed dose of tablet fexofenadine 180 mg were exhibited one subcutaneous injection of omalizumab and were followed up at 4 weekly intervals for 24 weeks for Weekly Urticaria Activity Score 7 (UAS7) and Dermatology Life Quality Index (DLQI).Results:A sharp decline in UAS7 and DLQI was documented in 7–10 days. The decline was maintained up to 16 weeks in one case and 20 weeks in the other three cases. Both the scores at the end of the follow-up period of 24 weeks were better than the pre-omalizumab scores.Conclusion:The results of this case series indicate the efficacy of a single-dose omalizumab in treating moderate to severe refractory CSU. Further studies are required to identify the minimum frequency of administering omalizumab to effectively control CSU. This would greatly reduce the cost of this novel therapy.     

Omalizumab in patients with chronic spontaneous urticaria: a systematic review and GRADE assessment

Chronic spontaneous urticaria (CSU) is characterized by the occurrence of hives, angio‐oedema or both for a period of at least 6 weeks. Many patients remain symptomatic despite treatment with H₁ antihistamines, even at higher doses. This systematic review assessed the quality of the evidence for the effects of omalizumab as treatment in patients with CSU. We searched PubMed, the Cochrane Database of Systematic Reviews and the Cochrane Central Register of Controlled Trials up to 7 August 2014. Three review authors independently carried out study selection, risk of bias assessment and data extraction. Two review authors analysed the data. Five randomized controlled trials (RCTs), which included 1116 participants, were evaluated. All the RCTs were judged as having a low risk of bias. There was a statistically significant improvement in measures of disease activity and quality of life following treatment with omalizumab when compared with placebo [mean difference (MD) ?11·58, 95% confidence interval (CI) ?13·39 to ?9·77 and MD ?13·12, 95% CI ?16·30 to ?9·95, respectively]. Complete response and partial response were more frequent after treatment with omalizumab [risk ratio (RR) 6·44, 95% CI 3·95–10·49 and RR 4·08, 95% CI 2·98–5·60, respectively]. There was no difference in the proportion of participants reporting adverse events between the omalizumab and placebo treatment groups (RR 1·05, 95% CI 0·96–1·16). There was high‐quality evidence to support the effectiveness and safety of omalizumab 300 mg per month for the treatment of CSU for up to 6 months.     

Expert opinion: defining response to omalizumab in patients with chronic spontaneous urticaria

Omalizumab (a recombinant, humanized anti-immunoglobulin-E anti-body) has been shown in three pivotal Phase III trials (ASTERIA I, II and GLACIAL) and real-world studies to be effective and well-tolerated for the treatment of chronic spontaneous urticaria (CSU), and is the only licensed third-line treatment for CSU. However, the definition of response to omalizumab treatment often differs between clinical trials, real-world studies, and daily practice of individual physicians globally. As such, a consensus definition of “complete”, “partial” and “non-response” to omalizumab is required in order to harmonize treatment management and compare data. Here, it is proposed that a disease measurement tool, for example, the 7-Day Urticaria Activity Score (UAS7) or Urticaria Control Test (UCT) is required for defining response. The addition of quality of life measurements is helpful to gain insight into a patient’s disease burden and its changes during treatment. A potential omalizumab treatment approach based on speed and pattern of response at 1-3 and 3-6 months is suggested. In cases where there is no response during the first 1-3 months, physicians should consider reassessing the original CSU diagnosis. Moreover, in patients showing partial response at 12 weeks, treatment with omalizumab should be continued in order to maximize the possibility of achieving symptom control. If patients have a UAS7>6 and/or UCT<12, then continued treatment is advised, dependent on physician judgement and patient expectations. In treatment responders, omalizumab treatment can be resumed at a later stage after discontinuation with the same degree of symptom control.