Louis Renaud, Lommatzsch Marek, Jackson David J, Menzies-Gow Andrew, Shavit Anat, Cohen David, Hoyte Flavia C L, Korn Stephanie
University of Liege, GIGA I3 Research Group and Centre Hospitalier Universitaire of Liège, Department of Pneumology CHU Liege, Belgium, Liège, Belgium.
Department of Pneumology, University of Rostock, Rostock, Germany.
Clin Exp Allergy. 2025 Jul;55(7):521-531. doi: 10.1111/cea.70083. Epub 2025 May 30.
The introduction of biologics, such as benralizumab (an anti-IL-5 receptor α humanised monoclonal antibody), has made remission a feasible goal for patients with severe eosinophilic asthma (SEA). However, there are remaining research gaps and no clear consensus on the definition of remission. We consolidated post hoc remission data from clinical trials and real-world studies of benralizumab in patients with SEA to gather insights on: testing different definitions; predictors of remission; the effect of comorbidities on achieving remission; remission and background medication reduction; long-term remission patterns with benralizumab; and remission in a real-life setting. In the SIROCCO and CALIMA Phase 3 randomised studies, patients with remission had higher baseline median blood eosinophil counts, were more likely to have a FEV of ≥ 65% predicted, had fewer exacerbations within 12 months and had lower mean ACQ-6 scores. Compared with the overall population, patients with a history of nasal polyps were also more likely to achieve remission with benralizumab. Analyses of the BORA and MELTEMI extension studies showed that in the longer term, once remission is achieved with benralizumab, patients are likely to remain in remission with continued treatment. In the open-label, single-arm ANDHI-In Practice and PONENTE studies, patients achieving remission had a shorter median time since asthma diagnosis, higher median age at asthma onset and lower median ACQ-6 scores. The SHAMAL study and the Phase 3b ANDHI-In Practice substudy demonstrate that remission is maintained with benralizumab even when patients reduce their background medication. Finally, the XALOC-1 real-world study highlights how patients with lower BMI are more likely to achieve remission with benralizumab. These findings demonstrate that achieving remission in patients with SEA is feasible with benralizumab and, in turn, inform future directions for research and treatment that includes a promising shift towards a new era of treat-to-target. This manuscript was supported by AstraZeneca, the manufacturer of benralizumab.
生物制剂的引入,如贝那利珠单抗(一种抗白细胞介素-5受体α人源化单克隆抗体),使重度嗜酸性粒细胞性哮喘(SEA)患者实现缓解成为一个可行的目标。然而,仍存在研究空白,对于缓解的定义也没有明确的共识。我们整合了贝那利珠单抗治疗SEA患者的临床试验和真实世界研究中的事后缓解数据,以深入了解以下方面:测试不同的定义;缓解的预测因素;合并症对实现缓解的影响;缓解与基础药物减少;贝那利珠单抗的长期缓解模式;以及现实生活中的缓解情况。在SIROCCO和CALIMA 3期随机研究中,缓解的患者基线血液嗜酸性粒细胞计数中位数较高,FEV≥预测值65%的可能性更大,12个月内发作次数更少,ACQ-6平均得分更低。与总体人群相比,有鼻息肉病史的患者使用贝那利珠单抗实现缓解的可能性也更大。对BORA和MELTEMI扩展研究的分析表明,从长期来看,一旦使用贝那利珠单抗实现缓解,患者继续治疗时可能会维持缓解状态。在开放标签、单臂的ANDHI-In Practice和PONENTE研究中,实现缓解的患者自哮喘诊断以来的中位时间较短,哮喘发病时的年龄中位数较高,ACQ-6得分中位数较低。SHAMAL研究和3b期ANDHI-In Practice子研究表明,即使患者减少基础药物,贝那利珠单抗仍能维持缓解。最后,XALOC-1真实世界研究强调了BMI较低的患者使用贝那利珠单抗更有可能实现缓解。这些发现表明,使用贝那利珠单抗使SEA患者实现缓解是可行的,进而为未来的研究和治疗方向提供了信息,其中包括朝着治疗达标新时代的有前景的转变。本手稿得到了贝那利珠单抗制造商阿斯利康的支持。