Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen, United Kingdom.
Adv Pharmacol. 2023;98:31-54. doi: 10.1016/bs.apha.2023.04.003. Epub 2023 Apr 27.
Severe or refractory asthma is seen in approximately 5% of asthmatic subjects who have unsatisfactory symptom control despite adherence to high-dose inhaled glucocorticoid therapies resulting in significant morbidity, reduced quality of life with attendant implications for healthcare costs. Marked heterogeneity in symptoms and at the molecular phenotypic level are hallmarks of asthma resulting in the requirement of specifically targeted treatments to block the key pathways of the disease. Monoclonal antibody (mAb)-based biologics targeted at inhibition of the type 2 cytokines IL-4, IL-5 and IL-13 have become established as effective treatments for severe asthma, with significant clinical benefit seen in carefully selected patient populations that take asthma phenotypes and endotypes into account. The further development of reproducible and straightforward discriminatory biomarkers may aid identification of those patients most likely to benefit from treatment with these interventions.
大约有 5%的哮喘患者属于严重或难治性哮喘，这些患者尽管坚持使用高剂量吸入性糖皮质激素治疗，但仍无法控制症状，导致发病率显著升高，生活质量下降，同时也增加了医疗成本。哮喘的症状和分子表型水平存在明显的异质性，这是哮喘的特征，因此需要有针对性的治疗方法来阻断疾病的关键途径。针对抑制 2 型细胞因子 IL-4、IL-5 和 IL-13 的单克隆抗体 (mAb) 生物制剂已被确立为治疗严重哮喘的有效方法，在仔细选择考虑哮喘表型和内型的患者人群中，可显著改善临床疗效。进一步开发可重复和直接的鉴别生物标志物可能有助于确定那些最有可能从这些干预措施中受益的患者。
