Respiratory Disease and Lung Function Unit, Department of Medicine and Surgery, University of Parma, 43126 Parma, Italy.
Unit of Respiratory Medicine, Department of Experimental Medicine, University of Rome "Tor Vergata", 00133 Rome, Italy.
Int J Mol Sci. 2021 Jul 1;22(13):7132. doi: 10.3390/ijms22137132.
Airway inflammation represents an important characteristic in asthma, modulating airflow limitation and symptom control, and triggering the risk of asthma exacerbation. Thus, although corticosteroids represent the cornerstone for the treatment of asthma, severe patients may be dependent on oral corticosteroids (OCSs). Fortunately, the current humanised monoclonal antibodies (mAbs) benralizumab, dupilumab, mepolizumab, omalizumab, and reslizumab have been proven to induce an OCS-sparing effect in randomized controlled trials (RCTs), thus overcoming the problem of OCS dependence in severe asthma. Nevertheless, a large discrepancy has been recognized between selected patients enrolled in RCTs and non-selected asthmatic populations in real-world settings. It is not possible to exclude that the OCS-sparing effect of mAbs resulting from the RCTs could be different than the real effect resulting in clinical practice. Therefore, we performed a systematic review and correlation analysis to assess whether mAbs are effective in eliciting an OCS-sparing effect and overcoming the OCS dependence in severe asthmatic patients in real-world settings. Overall, real-world studies support the evidence that OCS dependence is a real condition that, however, can be found only in a small number of really severe asthmatic patients. In most patients, the dependence on OCS can be related to modifying factors that, when adequately modulated, may lead to a significant reduction or suspension of OCS maintenance. Conversely, in severe asthmatics in whom OCS resistance is proved by a high daily dose intake, mAbs allow reversion of the OCS dependence, leading to the suspension of OCS therapy in most patients or >50% reduction in the daily OCS dose.
气道炎症是哮喘的一个重要特征,调节气流受限和症状控制,并引发哮喘恶化的风险。因此,虽然皮质类固醇是治疗哮喘的基石,但严重患者可能依赖口服皮质类固醇(OCS)。幸运的是,目前已证实人源化单克隆抗体(mAb)贝那鲁肽、度普利尤单抗、美泊利单抗、奥马珠单抗和瑞利珠单抗在随机对照试验(RCT)中可诱导 OCS 节约效应,从而克服严重哮喘中对 OCS 的依赖。然而,在 RCT 中入选的患者与真实世界环境中未选择的哮喘人群之间存在很大差异。不能排除 RCT 中 mAb 引起的 OCS 节约效应与临床实践中实际产生的效应不同。因此,我们进行了系统评价和相关性分析,以评估 mAb 是否能在真实环境中对严重哮喘患者产生 OCS 节约效应并克服对 OCS 的依赖。总的来说,真实世界研究支持这样的证据,即 OCS 依赖是一种真实存在的情况,但仅在少数真正严重的哮喘患者中发现。在大多数患者中,对 OCS 的依赖可能与可调节的因素有关,当这些因素得到适当调节时,可能会导致 OCS 维持量显著减少或停药。相反,在 OCS 抵抗已被证明需要高剂量每日摄入的严重哮喘患者中,mAb 可逆转 OCS 依赖,导致大多数患者停止 OCS 治疗或每日 OCS 剂量减少>50%。