Evaluation of real-world efficacy of mepolizumab on SNOT-22 outcomes in patients with unified airway disease

IF 4.6 2区 医学 Q2 ALLERGY Clinical and Translational Allergy Pub Date : 2024-10-31 DOI:10.1002/clt2.70006
Ruperto González-Pérez, Paloma Poza-Guedes, María Gabriela Martín-Voso, Inmaculada Sánchez-Machín
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Key inclusion criteria were a clinician-confirmed diagnosis of SA and AR with a T2 signature according to specific guidelines<span><sup>7, 8</sup></span> and a CRSwNP diagnosis based on EPOS criteria.<span><sup>9</sup></span> Pregnant and breast-feeding women were excluded. The study was approved by the local Ethical Committee of our Institution and informed consent was signed by all participants.</p><p>Data from clinical records collected between January 2021 and July 2024 were retrospectively analyzed, with a total of 102 patients screened. Among them, 71 patients—40 females and 31 males, median age 48 years (IQR 21)—were confirmed as eligible for the study (Table S1). Outcome data from all participants were gathered and compared at two time points: before (T0) and 52-weeks post-commencement (T1) of monthly mepolizumab. Quantitative variables were presented as median and interquartile range (IQR), whereas qualitative variables were expressed as number of observations and percentage. Individual SNOT-22 item scores were summed, and a median domain score was derived. Pulmonary function test, including pre- and post-bronchodilator spirometry (Datospir 600<sup>®</sup>, Sibel S.A.U., Barcelona, Spain) and a validated asthma control test (ACT) were conducted in accordance with daily practice guidelines. Comparison of findings between baseline and different follow-ups were performed using the Wilcoxon matched pairs signed rank and paired <i>t</i> tests. A <i>p</i> value of less than 0.05 was considered statistically significant. All statistical data were analyzed using GraphPad Prism version 10.2.3 for Windows, GraphPad Software, La Jolla, CA, USA.</p><p>In the present study (Table 1), patients with CRSwNP exhibited a significantly higher median baseline SNOT-22 score compared to those without CRSwNP (57 (22) versus 38 (36), <i>p</i> = 0.0136). After 52 weeks of treatment with mepolizumab 100 mg mg-q4w, patients with CRSwNP showed a marked median reduction in their SNOT-22 score (from 58 (22) to 32 (32.25), <i>p</i> = 0.0001), whereas the improvement in patients without CRSwNP was not significant (from 38 (36) to 36 (29), <i>p</i> = 0.1126) (Figure 1). Furthermore, a clinically significant improvement (more than 8.9 points) in the overall SNOT-22 score was observed in 25 out of 35 individuals from the CRSwNP group compared to 8 out of 36 patients in the non-CRSwNP group. Interestingly, 21 of the 22 SNOT-22 items -excluding “Embarrassed” from the emotional domain-significantly improved (<i>p</i> &lt; 0.05) after 52 weeks of mepolizumab 100 mg-q4w in patients with CRSwNP, unlike those without this comorbidity. Notably, while all items in the SNOT-22 nasal domain significantly enhanced only in patients with CRSwNP, the specific item “Decreased sense of smell/taste” showed significant improvement in both patients with (<i>p</i> = 0.002) and without CRSwNP (<i>p</i> = 0.012). Regarding T2-inflammation biomarkers a significant reduction (<i>p</i> &lt; 0.0001) in the absolute blood eosinophil counts after 52 weeks of treatment with mepolizumab was observed with no significant changes recorded in total IgE, specific IgE (sIgE) to dust mites, or fractional exhaled nitric oxide (FeNO) in either study group (Table S2).</p><p>Due to a lack of improvement in sino-nasal symptoms, two out of 35 (5.71%) patients with CRSwNP required functional endoscopic sinus surgery (FESS) after 24–32 weeks of mepolizumab 100 mg-q4w, continuing the treatment post-surgery. No patients experienced adverse events leading to mepolizumab discontinuation throughout the study period. 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Further research is essential to better understand the synergistic effects of precision therapy, optimize outcomes for UAD patients extrapolated from other populations, and ensure the safety of drug interventions.</p><p><b>Ruperto González-Pérez</b>: Conceptualization; investigation; funding acquisition; writing—original draft; methodology; writing—review and editing; data curation; resources. <b>Paloma Poza-Guedes</b>: Conceptualization; investigation; methodology; writing—review and editing; software; project administration; data curation; supervision. <b>María Gabriela Martín-Voso</b>: Investigation; data curation; visualization; software. <b>Inmaculada Sánchez-Machín</b>: Supervision; resources; validation; writing—review and editing.</p><p>The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.</p>","PeriodicalId":10334,"journal":{"name":"Clinical and Translational Allergy","volume":"14 11","pages":""},"PeriodicalIF":4.6000,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/clt2.70006","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Clinical and Translational Allergy","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/clt2.70006","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"ALLERGY","Score":null,"Total":0}
引用次数: 0

Abstract

To the Editor,

The unified airway hypothesis suggests that the upper and lower airways constitute a single, interconnected organ, sharing significant physiological traits such as immunology, pathophysiology, epidemiology, and clinical features.1 Allergic rhinitis (AR), various forms of chronic rhinosinusitis (CRS), including those with nasal polyposis (NP), and severe asthma (SA) share a common underlying pathogenesis known as type-2 inflammation (T2).2 These coexisting conditions represent a substantial clinical burden and significantly impact patients' quality of life (QoL) through a variety of disruptive symptoms The SNOT-22 is a validated questionary designed to assess the symptom burden of CRS and has proven effective utility in evaluating both QoL and symptom control in AR.3, 4

Mepolizumab, a monthly subcutaneous IL-5 antagonist monoclonal antibody, has been approved for treating various type 2 inflammatory conditions, including both eosinophilic SA and CRSwNP.5, 6 The performance of mepolizumab on SNOT-22 scores has not been completely assessed in patients afflicted with Unified Airway Disease (UAD).

This Phase IV, single-center observational cohort investigation, conducted at Hospital Universitario de Canarias in Tenerife, Spain, aimed to evaluate the real-world performance of mepolizumab 100 mg every 4 weeks (100 mg-q4w) over 52-weeks on SNOT-22 scores in patients aged over 18 years with UAD, including uncontrolled SA and persistent mite (Dermatophagoides spp. and/or Blomia tropicalis) AR, with or without comorbid CRSwNP. Key inclusion criteria were a clinician-confirmed diagnosis of SA and AR with a T2 signature according to specific guidelines7, 8 and a CRSwNP diagnosis based on EPOS criteria.9 Pregnant and breast-feeding women were excluded. The study was approved by the local Ethical Committee of our Institution and informed consent was signed by all participants.

Data from clinical records collected between January 2021 and July 2024 were retrospectively analyzed, with a total of 102 patients screened. Among them, 71 patients—40 females and 31 males, median age 48 years (IQR 21)—were confirmed as eligible for the study (Table S1). Outcome data from all participants were gathered and compared at two time points: before (T0) and 52-weeks post-commencement (T1) of monthly mepolizumab. Quantitative variables were presented as median and interquartile range (IQR), whereas qualitative variables were expressed as number of observations and percentage. Individual SNOT-22 item scores were summed, and a median domain score was derived. Pulmonary function test, including pre- and post-bronchodilator spirometry (Datospir 600®, Sibel S.A.U., Barcelona, Spain) and a validated asthma control test (ACT) were conducted in accordance with daily practice guidelines. Comparison of findings between baseline and different follow-ups were performed using the Wilcoxon matched pairs signed rank and paired t tests. A p value of less than 0.05 was considered statistically significant. All statistical data were analyzed using GraphPad Prism version 10.2.3 for Windows, GraphPad Software, La Jolla, CA, USA.

In the present study (Table 1), patients with CRSwNP exhibited a significantly higher median baseline SNOT-22 score compared to those without CRSwNP (57 (22) versus 38 (36), p = 0.0136). After 52 weeks of treatment with mepolizumab 100 mg mg-q4w, patients with CRSwNP showed a marked median reduction in their SNOT-22 score (from 58 (22) to 32 (32.25), p = 0.0001), whereas the improvement in patients without CRSwNP was not significant (from 38 (36) to 36 (29), p = 0.1126) (Figure 1). Furthermore, a clinically significant improvement (more than 8.9 points) in the overall SNOT-22 score was observed in 25 out of 35 individuals from the CRSwNP group compared to 8 out of 36 patients in the non-CRSwNP group. Interestingly, 21 of the 22 SNOT-22 items -excluding “Embarrassed” from the emotional domain-significantly improved (p < 0.05) after 52 weeks of mepolizumab 100 mg-q4w in patients with CRSwNP, unlike those without this comorbidity. Notably, while all items in the SNOT-22 nasal domain significantly enhanced only in patients with CRSwNP, the specific item “Decreased sense of smell/taste” showed significant improvement in both patients with (p = 0.002) and without CRSwNP (p = 0.012). Regarding T2-inflammation biomarkers a significant reduction (p < 0.0001) in the absolute blood eosinophil counts after 52 weeks of treatment with mepolizumab was observed with no significant changes recorded in total IgE, specific IgE (sIgE) to dust mites, or fractional exhaled nitric oxide (FeNO) in either study group (Table S2).

Due to a lack of improvement in sino-nasal symptoms, two out of 35 (5.71%) patients with CRSwNP required functional endoscopic sinus surgery (FESS) after 24–32 weeks of mepolizumab 100 mg-q4w, continuing the treatment post-surgery. No patients experienced adverse events leading to mepolizumab discontinuation throughout the study period. The size of the investigated population, and the lack of a control group should be considered potential limitations of this investigation when interpreting the overall data.

In conclusion, these findings demonstrate the long-term real-world effectiveness of mepolizumab 100 mg-q4w in enhancing all SNOT-22 domains in a selected cohort of patients with UAD. Our results confirmed that mepolizumab significantly reduces symptom severity and improves overall QoL, particularly in patients with UAD, irrespective of comorbid NERD, prior surgery, and/or systemic corticosteroid use in a specifically selected population. The interconnection between upper and lower airway T2-inflammation diseases highlights the need for a more holistic approach to patient assessment and management. Further research is essential to better understand the synergistic effects of precision therapy, optimize outcomes for UAD patients extrapolated from other populations, and ensure the safety of drug interventions.

Ruperto González-Pérez: Conceptualization; investigation; funding acquisition; writing—original draft; methodology; writing—review and editing; data curation; resources. Paloma Poza-Guedes: Conceptualization; investigation; methodology; writing—review and editing; software; project administration; data curation; supervision. María Gabriela Martín-Voso: Investigation; data curation; visualization; software. Inmaculada Sánchez-Machín: Supervision; resources; validation; writing—review and editing.

The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

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评估mepolizumab对统一气道疾病患者SNOT-22结果的实际疗效。
致编辑:统一气道假说认为,上呼吸道和下呼吸道是一个相互关联的器官,具有重要的生理特征,如免疫学、病理生理学、流行病学和临床特征。过敏性鼻炎(AR)、各种慢性鼻窦炎(CRS)(包括鼻息肉病(NP))和严重哮喘(SA)有一个共同的潜在发病机制,即 2 型炎症(T2)。SNOT-22 是一个经过验证的问卷,旨在评估 CRS 的症状负担,已被证明可有效评估 AR 的 QoL 和症状控制情况、4每月皮下注射一次的IL-5拮抗剂单克隆抗体mepolizumab已被批准用于治疗各种2型炎症,包括嗜酸性粒细胞性SA和CRSwNP、6 在统一气道疾病(UAD)患者中,尚未对美泊利珠单抗在 SNOT-22 评分上的表现进行全面评估。这项在西班牙特内里费岛加那利群岛大学医院开展的第四阶段单中心观察性队列调查旨在评估在 52 周内每 4 周使用 100 毫克(100 毫克-q4w)的mepolizumab 对 18 岁以上 UAD 患者 SNOT-22 评分的实际效果,UAD 患者包括未控制的 SA 和持续性螨虫(皮螨和/或热带螨)AR,同时伴有或不伴有 CRSwNP。主要纳入标准是临床医生根据特定指南7、8 确诊为 SA 和 AR,并有 T2 标志,以及根据 EPOS 标准9 确诊为 CRSwNP。本研究获得了本院当地伦理委员会的批准,所有参与者均签署了知情同意书。本研究对 2021 年 1 月至 2024 年 7 月期间收集的临床病历数据进行了回顾性分析,共筛选出 102 例患者。其中,71 名患者--40 名女性和 31 名男性,中位年龄 48 岁(IQR 21)--被确认符合研究条件(表 S1)。研究人员收集了所有参与者的结果数据,并在两个时间点进行了比较:每月使用美泊利珠单抗前(T0)和使用美泊利珠单抗后 52 周(T1)。定量变量以中位数和四分位数间距 (IQR) 表示,定性变量以观察数和百分比表示。对 SNOT-22 单项得分进行加总,得出领域得分的中位数。肺功能测试包括支气管扩张剂前和支气管扩张剂后肺活量测定(Datospir 600®,Sibel S.A.U.,西班牙巴塞罗那),以及经过验证的哮喘控制测试(ACT),均按照日常实践指南进行。基线与不同随访结果之间的比较采用 Wilcoxon 配对符号秩检验和配对 t 检验。P 值小于 0.05 即为具有统计学意义。所有统计数据均使用 GraphPad Prism 10.2.3 for Windows(GraphPad Software,La Jolla,CA,USA)进行分析。在本研究中(表 1),与无 CRSwNP 患者相比,CRSwNP 患者的中位基线 SNOT-22 评分明显更高(57(22)分对 38(36)分,p = 0.0136)。在使用麦泊利单抗 100 毫克-q4w 治疗 52 周后,CRSwNP 患者的 SNOT-22 评分中位数明显降低(从 58(22)分降至 32(32.25)分,p = 0.0001),而无 CRSwNP 患者的改善并不显著(从 38(36)分降至 36(29)分,p = 0.1126)(图 1)。此外,CRSwNP 组的 35 名患者中有 25 人的 SNOT-22 总分有明显的临床改善(超过 8.9 分),而非 CRSwNP 组的 36 名患者中有 8 人的 SNOT-22 总分有明显的临床改善(超过 8.9 分)。有趣的是,CRSwNP 患者在服用甲泼尼单抗 100 mg-q4w 52 周后,22 个 SNOT-22 项目中的 21 个项目(情绪领域中的 "尴尬 "除外)都有显著改善(p &lt; 0.05),而非 CRSwNP 患者则不同。值得注意的是,虽然 SNOT-22 鼻腔领域的所有项目仅在 CRSwNP 患者中显著增强,但 "嗅觉/味觉减退 "这一特定项目在 CRSwNP 患者(p = 0.002)和非 CRSwNP 患者(p = 0.012)中均有显著改善。在T2-炎症生物标志物方面,使用美泊利珠单抗治疗52周后,血液中嗜酸性粒细胞的绝对数量明显减少(p = 0.0001),但两组患者的总IgE、尘螨特异性IgE(sIgE)或呼出一氧化氮(FeNO)均无明显变化(表S2)。由于鼻窦-鼻腔症状未见好转,35 名 CRSwNP 患者中有 2 名(5.71%)在服用甲泼尼单抗 100 毫克-q4w 24-32 周后需要进行功能性内窥镜鼻窦手术(FESS),手术后继续治疗。 在整个研究期间,没有患者出现导致停用美泊利珠单抗的不良反应。总之,这些研究结果表明,在选定的 UAD 患者队列中,美妥珠单抗 100 mg-q4w 对改善 SNOT-22 的所有领域具有长期的实际疗效。我们的研究结果证实,在经过特别筛选的人群中,无论是否合并非胃食管反流病、是否曾接受过手术和/或是否使用过全身性皮质类固醇,甲泼尼珠单抗都能明显减轻症状的严重程度并改善整体生活质量,尤其是在 UAD 患者中。上气道和下气道 T2-炎症疾病之间的相互联系凸显了对患者进行更全面评估和管理的必要性。为了更好地理解精准治疗的协同效应,优化从其他人群中推断出的UAD患者的治疗效果,并确保药物干预的安全性,进一步的研究是必不可少的。帕洛玛-波萨-盖德斯(Paloma Poza-Guedes):构思;调查;方法论;写作-审阅和编辑;软件;项目管理;数据整理;监督。María Gabriela Martín-Voso:调查;数据整理;可视化;软件。Inmaculada Sánchez-Machín:监督;资源;验证;撰写-审查和编辑。资助者在研究设计、数据收集、分析或解释、手稿撰写或结果发表的决定中均未发挥任何作用。
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来源期刊
Clinical and Translational Allergy
Clinical and Translational Allergy Immunology and Microbiology-Immunology
CiteScore
7.50
自引率
4.50%
发文量
117
审稿时长
12 weeks
期刊介绍: Clinical and Translational Allergy, one of several journals in the portfolio of the European Academy of Allergy and Clinical Immunology, provides a platform for the dissemination of allergy research and reviews, as well as EAACI position papers, task force reports and guidelines, amongst an international scientific audience. Clinical and Translational Allergy accepts clinical and translational research in the following areas and other related topics: asthma, rhinitis, rhinosinusitis, drug hypersensitivity, allergic conjunctivitis, allergic skin diseases, atopic eczema, urticaria, angioedema, venom hypersensitivity, anaphylaxis, food allergy, immunotherapy, immune modulators and biologics, animal models of allergic disease, immune mechanisms, or any other topic related to allergic disease.
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