抽象的
Background在临床试验中,两种抗interleukin(IL)-5单克隆抗体(MABS:mepolizumab和reslizumab)批准治疗严重的嗜酸性嗜酸性哮喘,将加剧的恶化减少了约50-60%。
ObjectiveTo observe response to anti-IL-5 mAbs in a real-life clinical setting, and to evaluate predictors of suboptimal response.
Methods在四个加拿大学术中心,预先收集了250名经过精心表征的中度至重度哮喘患者的预定义临床终点,以评估对两种抗IL-5 mAB的反应。除了持久性痰/血液嗜酸性粒细胞外,基于减少维持皮质类固醇(MCS)或哮喘症状评分(哮喘控制问卷(ACQ))或加剧的哮喘症状评分(MCS)或哮喘症状得分(MCS)或哮喘症状得分(MCS)或哮喘症状得分(MCS)或哮喘症状得分(MCS)或哮喘症状得分(MCS)或哮喘症状得分(MCS)或哮喘症状得分(MCS)或哮喘症状得分(MCS)或哮喘症状得分,确定了次优反应。根据肺功能降低25%或MCS/ACQ的增加,评估了次优应答者的恶化。通过对痰液中的炎症介质,自身抗体和补体激活评估了39例患者的代表性子集(通过ELISA)和免疫复杂沉积,通过免疫染色的福尔马林固定粉状石蜡填充的痰液塞。
结果Suboptimal responses were observed in 42.8% (107 out of 250) patients treated with either mepolizumab or reslizumab. Daily prednisone requirement, sinus disease and late-onset asthma diagnoses were the strongest predictors of suboptimal response. Asthma worsened in 13.6% (34 out of 250) of these patients. The majority (79%) of them were prednisone-dependent. Presence of sputum anti-eosinophil peroxidase immunoglobulin (Ig)G was a predictor of suboptimal response to an anti-IL-5 mAb. An increase in sputum C3c (marker of complement activation) and deposition of C1q-bound/IL-5-bound IgG were observed in the sputa of those patients who worsened on therapy, suggesting an underlying autoimmune-mediated pathology.
Conclusion在现实生活中,大量符合抗IL5 mAB的批准适应症的患者在现实生活中表现出对他们的反应,尤其是当他们使用高剂量的泼尼松时。监测血液嗜酸性粒细胞计数无助于识别这些患者。在一小部分患者中,与免疫复合介导的补体激活相关的症状恶化的关注点突出了识别气道自身免疫现象的相关性,这需要进一步评估。
抽象的
Severe asthmatics with adult-onset asthma, sinus disease and requiring daily prednisone, are at higher risk for responding suboptimally to current doses of anti-IL-5 mAbs, with further risk of worsening on an IgG1mAb if they have sputum autoantibodieshttps://bit.ly/2Ahpvsm
Footnotes
This article has supplementary material available fromwww.qdcxjkg.com
Author contributions: P. Nair and M. Mukherjee developed the concept, M. Mukherjee designed all experiments. P. Nair, J.G. Martin, C. Lemiere and L-P. Boulet recruited patients. S. Tran, M-E. Boulay, M. Bertrand, H. Al-Hayyan, J. Cherukat, M. Kjarsgaard and C. Huang collected and tabulated the data. K. Radford and M. Mukherjee performed molecular experiments. T. Javkar performed all immunostaining protocols while K. Ask, S.D. Revill and A. Ayoub did the microscopy and related validation of image analysis. A. Dvorkin-Gheva, N. Dendukuri and D.F. Forero undertook all statistical analysis. M. Mukherjee wrote the first draft. P. Nair, J.G. Martin, K. Ask, C. Lemiere, L-P. Boulet and N. Dendukuri edited and added to the development of the manuscript. All authors have read and agreed to the submitted manuscript. P. Nair and M. Mukherjee take overall guarantee of the manuscript.
Conflict of interest: M. Mukherjee reports grants from Canadian Institutes of Health Research and Canadian Allergy, Asthma, and Immunology Foundation, grants and personal fees from Methapharm Specialty Pharmaceuticals, and personal fees from Astrazeneca, outside the submitted work.
利益冲突:D.F。Forero无需披露。
利益冲突:S。Tran无话可说。
利益冲突:M-E。布莱没有什么可披露的。
Conflict of interest: M. Bertrand has nothing to disclose.
利益冲突:A。Bhalla无话可说。
Conflict of interest: J. Cherukat has nothing to disclose.
Conflict of interest: H. Al-Hayyan has nothing to disclose.
Conflict of interest: A. Ayoub has nothing to disclose.
美国南达科他州的利益冲突:Revill无关isclose.
Conflict of interest: T. Javkar has nothing to disclose.
利益冲突:K。Radford没有什么可披露的。
利益冲突:M。Kjarsgaard没有什么可披露的。
Conflict of interest: C. Huang has nothing to disclose.
Conflict of interest: A. Dvorkin-Gheva has nothing to disclose.
Conflict of interest: K. Ask reports grants from Canadian Pulmonary Fibrosis Foundation, Ontario Thoracic Society, Synairgen, GSK, Indalo, Unity, Avalyn, Canadian Institutes of Health Research and Synairgen, grants and personal fees from Boehringer Ingelheim, outside the submitted work.
利益冲突:R。Olivenstein没有什么可披露的。
利益冲突:N。Dendukuri无需披露。
Conflict of interest: C. Lemiere reports grants and personal fees for advisory board work from AstraZeneca and TEVA Innovation, personal fees for advisory board work from GlaxoSmithKline, Sanofi and Novartis, outside the submitted work.
Conflict of interest: L-P. Boulet has nothing to disclose.
Conflict of interest: J.G. Martin has nothing to disclose.
Conflict of interest: P. Nair reports grants and personal fees for lectures from AZ and Teva, grants from Novartis and Sanofi, grants and personal fees for consultancy from Roche, personal fees for lectures from Novartis, personal fees advisory board work from Merck and Equillium, outside the submitted work.
Support statement: This study was funded by a research grant awarded to P. Nair by the Canadian Institutes of Health Research. P. Nair is supported by the Frederick E. Hargreave Teva Innovation Chair in Airway Diseases. M. Mukherjee is supported by an investigator award from CIHR and Canadian Allergy, Asthma and Immunology Foundation/AllerGen NCE. Funding information for this article has been deposited with theCrossRef资助人注册表.
- ReceivedJanuary 20, 2020.
- AcceptedMay 8, 2020.
- Copyright ©ERS 2020