抗IgE单抗治疗过敏性联合气道疾病的真实世界研究

A real world study of anti-IgE monoclonal antibody in the treatment of allergic united airway disease

目的探讨真实世界中抗IgE单抗(奥马珠单抗)治疗过敏性联合气道疾病的临床疗效及安全性。方法回顾性队列研究,选择2018年3月1日至2022年6月30日在北京大学第一医院经抗IgE单抗(奥马珠单抗)治疗16周及以上的过敏性联合气道疾病患者的病例资料。过敏性联合气道疾病定义为过敏性哮喘合并过敏性鼻炎(AA+AR)、过敏性哮喘合并慢性鼻窦炎伴鼻息肉(AA+CRSwNP)、过敏性哮喘合并过敏性鼻炎及鼻息肉(AA+AR+CRSwNP)。通过哮喘控制测试(ACT)、肺功能、呼出气一氧化氮(FeNO)对哮喘控制进行评估;通过鼻症状总分(TNSS)对过敏性鼻炎进行评估;通过鼻部视觉模拟量表(n-VAS)、鼻腔鼻窦结局测试22(SNOT-22)、鼻内镜下鼻息肉评分(TPS)、鼻窦CT扫描Lund-Mackay评分对慢性鼻窦炎伴鼻息肉进行评估;通过总体有效性评估(GETE)对抗IgE单抗的总体疗效进行评分。同时记录治疗期间患者出现的药物相关不良反应。配对t检验和Wilcoxon signed-rank检验比较奥马珠单抗治疗前后评分变化,多因素logistic回归分析判断奥马珠单抗应答的影响因素。结果共纳入117例联合气道疾病患者,年龄范围19~77岁;患者中位数年龄48.7岁;其中男性60例,年龄范围19~77岁,中位年龄49.9岁;女性57例,年龄范围19~68岁,中位数年龄47.2岁。AA+AR亚组32例,AA+CRSwNP亚组59例,AA+AR+CRSwNP亚组26例。血清总IgE水平为190.5(103.8,391.3)IU/ml。抗IgE单抗的疗程为24(16,32)周。抗IgE单抗治疗前、后比较:ACT评分由20.0(19.5,22.0)分升高到24.0(23.0,25.0)分(Z=-8.537,P<0.001),舒张前FEV1占预计值百分比由90.2(74.8,103.0)%升高至95.4(83.2,106.0)%(Z=-5.315,P<0.001),舒张前FEV1/FVC由80.20(66.83,88.38)%升高至82.72(71.26,92.25)%(Z=-4.483,P<0.001),FeNO由(49.1±24.8)ppb下降至(32.8±24.4)ppb(t=5.235,P<0.001),TNSS由(6.5±2.6)分降至(2.4±1.9)分(t=14.171,P<0.001),n-VAS由(6.8±1.2)分降至(3.4±2.0)分(t=14.448,P<0.001),SNOT-22由(40.0±7.9)分下降至(21.3±10.2)分(t=15.360,P<0.001),TPS由(4.1±0.8)分下降至(2.4±1.0)分(t=14.718,P<0.001),鼻窦CT Lund-Mackay评分由(6.0±1.3)分下降至(3.1±1.6)分(t=17.012,P<0.001)。抗IgE单抗治疗16周时总体显著应答率为67.5%(79/117),AA+AR亚组的应答率(90.6%,29/32)高于AA+CRSwNP组(61.0%,36/59)和AA+AR+CRSwNP组(53.8%,14/26)(χ2=11.144,P=0.004)。4例(3.4%,4/117)患者出现轻度不良反应。结论本项真实世界研究显示抗IgE单抗对过敏性联合气道疾病具有良好的疗效及安全性。为预防过敏性联合气道疾病进展和精准治疗提供依据。

Objective To investigate the clinical efficacy and safety of anti-IgE monoclonal antibody(omazumab)in the treatment of allergic united airway disease(UAD)in the real-wold.Methods Retrospective cohort study summarizes the case data of patients with allergic united airway disease who were treated with anti IgE monoclonal antibody(omalizumab)for more than 16 weeks from March 1,2018 to June 30,2022 in the Peking University First Hospital.The allergic UAD is defined as allergic asthma combined with allergic rhinitis(AA+AR)or allergic asthma combined with chronic sinusitis with nasal polyps(AA+CRSwNP)or allergic asthma combined with allergic rhinitis and nasal polyps(AA+AR+CRSwNP).The control of asthma was evaluated by asthma control test(ACT),lung function test and fractional exhaled nitric oxide(FeNO).The AR was assessed by total nasal symptom score(TNSS).The CRSwNP was evaluated by nasal visual analogue scale(n-VAS),sino-nasal outcome test-22(SNOT-22),nasal polyps score(TPS)and Lund-Mackay sinus CT grading system.The global evaluation of omalizumab for the treatment of allergic UADwas performed by Global Evaluation of Treatment Effectiveness(GETE).The drug-related side effects were also recorded.Matched t test and Wilcoxon signed-rank test were used to compare the score changes of IgE monoclonal antibody(omazumab)before and after treatment,and multivariate logistic regression analysis was used to determine the influencing factors of IgE monoclonal antibody(omazumab)response.Results A total of 117 patients with UAD were enrolled,ranging in age from 19 to 77 years;The median age of patients was 48.7 years;Among them,60 were male,ranging from 19 to 77 years old,with a median age of 49.9 years;There were 57 females,ranging from 19 to 68 years old,with a median age of 47.2 years.There were 32 cases in AA+AR subgroup,59 cases in AA+CRSwNP subgroup,and 26 cases in AA+AR+CRSwNP subgroup.The total serum IgE level was 190.5(103.8,391.3)IU/ml.The treatment course of anti IgE monoclonal antibody was 24(16,32)weeks.Compared with pre-treatment,omalizumab increased ACT from 20.0(19.5,22.0)to 24.0(23.0,25.0)(Z=-8.537,P<0.001),increased pre-bronchodilator FEV1 from 90.2(74.8,103.0)%predicted value to 95.4(83.2,106.0)%predicted value(Z=-5.315,P<0.001),increased FEV1/FVC from 80.20(66.83,88.38)%to 82.72(71.26,92.25)%(Z=-4.483,P<0.001),decreased FeNO from(49.1±24.8)ppb to(32.8±24.4)ppb(t=5.235,P<0.001),decreased TNSS from(6.5±2.6)to(2.4±1.9)(t=14.171,P<0.001),decreased n-VAS from(6.8±1.2)to(3.4±2.0)(t=14.448,P<0.001),decreased SNOT-22 from(40.0±7.9)to(21.3±10.2)(t=15.360,P<0.001),decreased TPS from(4.1±0.8)to(2.4±1.0)(t=14.718,P<0.001)and decreased Lund-Mackay CT score from(6.0±1.3)to(3.1±1.6)(t=17.012,P<0.001).The global response rate to omalizumab was 67.5%(79/117).The response rate in AA+AR(90.6%,29/32)was significantly higher than that in AA+CRSwNP(61.0%,36/59)and AA+AR+CRSwNP(53.8%,14/26)subgroups(χ2=11.144,P=0.004).Only 4 patients(3.4%,4/117)had mild side effects.Conclusion The real-world study showed favorable effectiveness and safety of anti-IgE monoclonal antibody for treatment of allergic UAD.To provide basis for preventing the progress and precise treatment of allergic UAD.