Wechsler Michael E, Klion Amy D, Paggiaro Pierluigi, Nair Parameswaran, Staumont-Salle Delphine, Radwan Amr, Johnson Robert R, Kapoor Upender, Khokhar Faisal A, Daizadeh Nadia, Chen Zhen, Laws Elizabeth, Ortiz Benjamin, Jacob-Nara Juby A, Mannent Leda P, Rowe Paul J, Deniz Yamo
National Jewish Health, Denver, Colo.
Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Md.
J Allergy Clin Immunol Pract. 2022 Oct;10(10):2695-2709. doi: 10.1016/j.jaip.2022.05.019. Epub 2022 May 28.
Transient increases in blood eosinophil counts have been observed in dupilumab clinical trials.
To assess eosinophil counts and eosinophilia-related treatment-emergent adverse events (TEAEs) across 11 dupilumab clinical trials, comparing adult and adolescent patients with asthma and adult patients with chronic rhinosinusitis with nasal polyps (CRSwNP), atopic dermatitis, and eosinophilic esophagitis.
Eosinophil counts, rates of eosinophilia-related TEAEs or treatment-emergent eosinophilia (>1,500 cells/μL), discontinuations, clinical symptoms, and efficacy in patients with asthma or CRSwNP with treatment-emergent eosinophilia are presented.
Transient increases in mean eosinophil counts were observed in dupilumab-treated patients with asthma (mean range across studies at baseline: 349-370 cells/μL; week 4: 515-578 cells/μL), CRSwNP (baseline: 440-448 cells/μL; week 16: 595 cells/μL), and atopic dermatitis (baseline: 434-600 cells/μL; week 4: 410-710 cells/μL), followed by a decline starting by week 24 to baseline or lower. No increases were seen in patients with eosinophilic esophagitis (baseline: 310 cells/μL; week 4: 230 cells/μL). In dupilumab-treated patients across all studies, rates of eosinophilia TEAEs were 0% to 13.6%. Clinical symptoms associated with increased eosinophils were rare (seven of 4,666 dupilumab-treated patients, including six cases of eosinophilic granulomatosis with polyangiitis) and occurred only in patients with asthma or CRSwNP. Eosinophilia was not associated with reduced dupilumab efficacy.
Transient increases in eosinophil counts with dupilumab treatment did not affect efficacy and were rarely of clinical consequence. It remains important for physicians to base judgment on individual patient history and baseline eosinophil counts and to be alert to hypereosinophilic symptoms.
在度普利尤单抗的临床试验中观察到血液嗜酸性粒细胞计数短暂升高。
评估11项度普利尤单抗临床试验中的嗜酸性粒细胞计数及与嗜酸性粒细胞增多相关的治疗中出现的不良事件（TEAE），比较成年和青少年哮喘患者、成年慢性鼻-鼻窦炎伴鼻息肉（CRSwNP）患者、特应性皮炎患者和嗜酸性粒细胞性食管炎患者。
列出了嗜酸性粒细胞计数、与嗜酸性粒细胞增多相关的TEAE发生率或治疗中出现的嗜酸性粒细胞增多（>1500个细胞/μL）、停药情况、临床症状，以及哮喘或CRSwNP患者出现治疗中出现的嗜酸性粒细胞增多时的疗效。
在接受度普利尤单抗治疗的哮喘患者（各研究基线时的平均范围：349 - 370个细胞/μL；第4周：515 - 578个细胞/μL）、CRSwNP患者（基线：440 - 448个细胞/μL；第16周：595个细胞/μL）和特应性皮炎患者（基线：434 - 600个细胞/μL；第4周：410 - 710个细胞/μL）中观察到平均嗜酸性粒细胞计数短暂升高，随后在第24周开始下降至基线或更低。嗜酸性粒细胞性食管炎患者未见升高（基线：310个细胞/μL；第4周：230个细胞/μL）。在所有研究中接受度普利尤单抗治疗的患者中，嗜酸性粒细胞增多性TEAE的发生率为0%至13.6%。与嗜酸性粒细胞增多相关的临床症状很少见（4666例接受度普利尤单抗治疗的患者中有7例，包括6例嗜酸性肉芽肿性多血管炎），且仅发生在哮喘或CRSwNP患者中。嗜酸性粒细胞增多与度普利尤单抗疗效降低无关。
度普利尤单抗治疗导致的嗜酸性粒细胞计数短暂升高不影响疗效，且很少产生临床后果。医生根据个体患者病史和基线嗜酸性粒细胞计数进行判断并警惕高嗜酸性粒细胞症状仍然很重要。
