Tran Trung N, Chen Stephanie, Emmanuel Benjamin, Altraja Alan, Bourdin Arnaud, Sheu Chau-Chyun, Tsai Ming-Ju, Hoyte Flavia C L, Quinton Anna, Cook Bill, Bulathsinhala Lakmini, Henley William, Goh Celine Yun Yi, Liu Yang, Ariti Cono, Carter Victoria, Price David B
Respiratory and Immunology, BioPharmaceuticals Medical, AstraZeneca, Gaithersburg, MD, USA.
Department of Pulmonary Medicine, University of Tartu, Tartu, Estonia.
Pragmat Obs Res. 2025 Mar 18;16:51-66. doi: 10.2147/POR.S497033. eCollection 2025.
Biologics targeting immunoglobulin E, interleukin (IL)-4/IL-13 or IL-5 signaling are effective at treating severe asthma; however, individual patients' responses may be suboptimal, leading to therapy switching or stopping. The CLEAR study aimed to assess real-world biologic use patterns and associated clinical outcomes in patients receiving care for severe asthma.
CLEAR was a multicenter, observational study that included adults (≥18 years old) from 23 countries enrolled in the International Severe Asthma Registry between December 2015 and August 2021. Patients who initiated biologic therapy were categorized as continuing the initial biologic for 6 months, switching to another biologic within 6 months or stopping biologic treatment within 6 months. Outcomes were assessed using the closest available data to 12 months after biologic initiation, using propensity score-weighted multivariable regression models.
Among 1,859 patients who initiated biologic therapy, 1,116 (60.0%) continued, 474 (25.5%) switched and 269 (14.5%) stopped treatment. Patients who switched or stopped therapy had a higher annualized asthma exacerbation rate post-initiation than those who continued (adjusted incidence rate ratio [aIRR] [95% confidence interval]: switched, 1.83 [1.51, 2.22]; stopped, 1.53 [1.19, 1.95]) and were more likely to have uncontrolled asthma at last assessment (adjusted odds ratio: switched, 5.40 [3.12, 9.33]; stopped, 4.02 [2.32, 6.98]). Compared with those who continued therapy, patients who switched had a higher long-term daily oral corticosteroid dose (adjusted β: 3.77 [1.71, 4.37] mg) and higher rates of hospitalizations (aIRR: 2.58 [1.52, 4.37]) and emergency room visits (aIRR: 2.12 [1.39, 3.24]).
Switching or stopping biologic therapy was associated with worse clinical outcomes than continuing the initial therapy.
靶向免疫球蛋白E、白细胞介素（IL）-4/IL-13或IL-5信号通路的生物制剂在治疗重度哮喘方面有效；然而，个别患者的反应可能不理想，导致治疗方案更换或停药。CLEAR研究旨在评估接受重度哮喘治疗的患者在现实世界中的生物制剂使用模式及相关临床结局。
CLEAR是一项多中心观察性研究，纳入了2015年12月至2021年8月期间登记在国际重度哮喘注册研究中的来自23个国家的成年人（≥18岁）。开始生物制剂治疗的患者被分为继续使用初始生物制剂6个月、在6个月内更换为另一种生物制剂或在6个月内停止生物制剂治疗。使用生物制剂开始后最接近12个月时的可用数据，通过倾向评分加权多变量回归模型评估结局。
在1859例开始生物制剂治疗的患者中，1116例（60.0%）继续治疗，474例（25.5%）更换治疗方案，269例（14.5%）停止治疗。更换或停止治疗的患者在开始治疗后的年化哮喘加重率高于继续治疗的患者（调整后发病率比值[aIRR][95%置信区间]：更换治疗方案者，1.83[1.51, 2.22]；停止治疗者，1.53[1.19, 1.95]），并且在最后一次评估时更有可能患有未控制的哮喘（调整后比值比：更换治疗方案者，5.40[3.12, 9.33]；停止治疗者，4.02[2.32, 6.98]）。与继续治疗的患者相比，更换治疗方案的患者长期每日口服糖皮质激素剂量更高（调整后β：3.77[1.71, 4.37]mg），住院率（aIRR：2.58[1.52, 4.37]）和急诊就诊率（aIRR：2.12[1.39, 3.24]）也更高。
与继续初始治疗相比，更换或停止生物制剂治疗与更差的临床结局相关。
