半数以上接受杜匹单抗治疗的 CRSwNP 患者在 28 天内嗅觉得到了快速改善。

IF 12.6 1区 医学 Q1 ALLERGY
Allergy Pub Date : 2024-10-29 DOI:10.1111/all.16357
Josje Janna Otten, Rik Johannes Leonardus van der Lans, Hester Beatrice Emilie Elzinga, Gwijde Flavius Jacobus Petrus Maria Adriaensen, Linda Berendina Laurentia Benoist, Rienk D. Hoven, Sven Seys, Wytske Johanna Fokkens, Sietze Reitsma
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引用次数: 0

摘要

嗅觉功能障碍是慢性鼻炎伴鼻息肉(CRSwNP)患者的主要主诉之一,严重影响了他们的生活质量。在实际研究中,dupilumab 能在治疗后 6 个月内有效增强患者的嗅觉功能。1, 2 然而,在治疗的最初几周,这种效应对嗅觉功能的影响速度和疗效还有待确定。患者被要求使用 Galenus Health App 在健康日记中报告其主诉的视觉模拟量表 (VAS) 评分。3 关于嗅觉减退,"今天嗅觉减退对您有多大困扰?"这一问题的回答采用 VAS 评分(0-10 厘米;0 表示完全不困扰,10 表示最困扰),嗅觉功能障碍的临界值为 5.2。共有 72 名患者在基线和杜匹单抗治疗的前 28 天内至少有一天填写了嗅觉功能障碍 VAS 评分。此外,还收集了基线和治疗 28 天后的嗅棒-12 鉴定测试(SSIT-12)结果。图 1 显示了基线和随访 SSIT-12 和 VAS 测量的结果(其他结果列于表 S2)。基线时,SSIT-12 评分的中位数为 3(IQR 2-4),表明有嗅觉障碍(图 1B)。28 天后,SSIT-12 评分的中位数增加到 6(IQR 3-9),Wilcoxon 符号秩检验:P &lt; .001,50% 的患者出现嗅觉减退或正常(图 1B)。同样,93.7% 的患者在基线时报告嗅觉丧失的 VAS 评分为 &gt;5.2,表明嗅觉功能障碍。在随后的 28 天治疗中,这一比例显著下降至 44.2%(图 1:Pearson r = .924,p &lt;.001)。治疗第一周的平均 VAS 分数可显著预测治疗 4 周后的 SSIT-12 结果(线性回归 F(1,97) = 6.7,p = .01)。最后,我们对这 72 位患者的病历进行了回顾性分析,以了解患者在开始接受杜利单抗治疗之前是否曾报告在口服皮质类固醇 (OCS) 治疗期间嗅觉功能有所改善5。72 名患者中有 63 名患者的数据可用,因此分为 OCS 反应组(n = 51)(OCS-R)或 OCS 无反应组(n = 12)(OCS-U)。两组患者既往鼻窦手术次数无统计学差异(P = .60)。对 OCS 反应性进行分层后发现,OCS-R 组的杜匹单抗治疗效果更好(图 1A、B)。我们承认该研究存在局限性,包括患者群体较小、健康日记数据缺失、截断点与 SSIT-12 并不直接对应(图 S1 和 S2、表 S3 和 S4)以及研究地点位于三级中心,但我们的发现意义深远。杜比鲁单抗能逆转炎症变化,是改善 CRSwNP 患者嗅觉功能的一种快速、有效的治疗方法。我们的数据表明,有可能需要根据 OCS 反应性对治疗反应进行分层,因为如果患者同时报告使用了 OCS,他们的嗅觉功能就会得到改善。6Hester Beatrice Emilie Elzinga、Gwijde Flavius Jacobus Petrus Maria Adriaensen、Linda Berendina Laurentia Benoist、Sven Seys 和 Rienk D. Hoven 为该研究提供了资源,并参与了撰写、审阅和编辑工作。Wytske Johanna Fokkens、Sietze Reitsma 和 Rik Johannes Leonardus van der Lans 在构思、方法、资源、监督以及写作 - 评审和编辑方面做出了贡献。Josje Janna Otten 参与了写作--原稿、数据整理、正式分析和可视化。本研究报告所涉及的患者登记处 PolyREG 致力于对接受生物制剂治疗的慢性鼻炎伴鼻息肉患者进行观察性科学研究,由阿姆斯特丹大学医学院、AERO、葛兰素史克、诺华和赛诺菲共同资助。SR 还报告了赛诺菲公司、诺华公司和葛兰素史克公司提供的资助、咨询费和酬金。RL 还报告了葛兰素史克公司的咨询费。JO 曾担任赛诺菲公司的顾问成员。RL 曾担任葛兰素史克公司的顾问和/或咨询委员会成员。WF 是赛诺菲、葛兰素史克和 Dianosic 的顾问委员会成员,并从这些公司领取顾问费。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

More than half of chronic rhinosinusitis with nasal polyps (CRSwNP) patients treated with dupilumab experience early and fast olfactory improvement within 28 days

More than half of chronic rhinosinusitis with nasal polyps (CRSwNP) patients treated with dupilumab experience early and fast olfactory improvement within 28 days

Olfactory dysfunction is one of the main complaints of patients suffering from Chronic Rhinosinusitis with Nasal Polyps (CRSwNP), significantly affecting their quality of life. In real-life studies, dupilumab effectively enhances olfactory function within 6 months of treatment.1, 2 However, the speed and efficacy of this effect on olfactory function during the initial weeks of treatment has to be determined.

The data were reported in this letter stem from a prospective observational cohort (PolyREG).2 Patients from this cohort were treated with dupilumab subcutaneously (300 mg 1×/2 weeks) for CRSwNP. Patients were asked to use the Galenus Health App reporting Visual Analogue Scale (VAS) scores of their complaints in their Health Diary.3 With special regard to loss of smell, the question ‘How much does smell loss bother you today?’ was answered with a VAS score (0–10 cm; 0 being not bothersome at all, 10 being the most bothersome) with a cut-off of >5.2 for olfactory dysfunction.4 In total, 72 patients filled out a VAS score on olfactory dysfunction at baseline and at least another day during the first 28 days of dupilumab treatment. Also, the outcomes of the Sniffin' Sticks-12 Identification Test (SSIT-12) were collected at baseline and after 28 days of treatment.

Baseline demographics of these patients are shown as repository data (Table S1). Figure 1 shows the outcomes of baseline and follow-up SSIT-12 and VAS measurements (other outcomes are listed in Table S2). At baseline, the median SSIT-12 score was 3 (IQR 2–4) indicating anosmia (Figure 1B). After 28 days, the median SSIT-12 score increased to 6 (IQR 3–9), Wilcoxon signed-rank test: p < .001, with 50% of the patients having hyposmia or normosmia (Figure 1B). Similarly, 93.7% of patients reported a VAS score on the loss of smell of >5.2 at baseline, indicating olfactory dysfunction. Over the subsequent 28 days of treatment, this percentage significantly declined to 44.2% (Figure 1: Pearson r = .924, p < .001). The mean VAS score in the first week of treatment significantly predicted the outcome of the SSIT-12 after 4 weeks of treatment (linear regression F(1,97) = 6.7, p = .01). As such, the data show a rapid olfactory function improvement in more than half of the patients treated with dupilumab, starting after 1–2 injections.

Lastly, a retrospective analysis of these 72 patients' medical records was conducted to see if olfactory function improvement was previously reported by the patient during a course of oral corticosteroids (OCS) prior to initiation of dupilumab treatment.5 Data was available for 63 of 72 patients, thus giving an OCS-responsive (n = 51) (OCS-R) or OCS-unresponsive (n = 12) (OCS-U) group. The amount of previous sinus surgeries did not statistically differ between the groups (p = .60). Stratifying for OCS responsiveness showed enhanced results of dupilumab treatment in the OCS-R group (Figure 1A,B). At best, 70.8% of patients in the OCS-R group had a VAS score of ≤5.2 compared to 16.7% in the OCS-U group and 55.8% of the total cohort.

While acknowledging the study's limitations, including a small patient group, missing data in the Health Diary, a cut-off corresponding not directly to SSIT-12 (Figures S1 and S2, Tables S3 and S4) and the setting in a tertiary center, the implications of our findings are profound. Dupilumab emerges as a fast, efficacious treatment option for improving olfactory function in patients with CRSwNP as it reverses inflammatory changes. Our data suggest a potential need for stratification of treatment response based on OCS responsiveness, as more patients experience olfactory function improvement if they also report it with OCS. This might be due to a corticosteroid-resistant subset of group 2 innate lymphoid cells that are probably more prevalent in OCS-unresponsive patients.6

Hester Beatrice Emilie Elzinga, Gwijde Flavius Jacobus Petrus Maria Adriaensen, Linda Berendina Laurentia Benoist, Sven Seys, and Rienk D. Hoven contributed to resources and writing – review and editing. Wytske Johanna Fokkens, Sietze Reitsma, and Rik Johannes Leonardus van der Lans contributed to conceptualization, methodology, resources, supervision, and writing – review and editing. Josje Janna Otten contributed to writing – original draft, data curation, formal analysis, and visualization.

The patient registry PolyREG, dedicated to observational scientific research of patients treated with biologicals for chronic rhinosinusitis with nasal polyps, about which this study reports, is co-funded by the Amsterdam UMC, AERO, GSK, Novartis, and Sanofi. SR further reports grants, consulting fees, and honoraria from Sanofi and Novartis and GSK. RL further reports consulting fees from GSK. JO has acted as a consultant member for Sanofi. RL has acted as a consultant and/or advisory board member for GSK. WF is an advisory board member of and received consulting fees from Sanofi, GSK, and Dianosic. SR has acted as a consultant and/or advisory board member for Sanofi, GSK, and Novartis. The department of Otorhinolaryngology and Head/Neck Surgery of the Amsterdam UMC has received research funding from Sanofi, GSK, and Novartis. VV has acted as a consultant and/or advisory board member for GSK.

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来源期刊
Allergy
Allergy 医学-过敏
CiteScore
26.10
自引率
9.70%
发文量
393
审稿时长
2 months
期刊介绍: Allergy is an international and multidisciplinary journal that aims to advance, impact, and communicate all aspects of the discipline of Allergy/Immunology. It publishes original articles, reviews, position papers, guidelines, editorials, news and commentaries, letters to the editors, and correspondences. The journal accepts articles based on their scientific merit and quality. Allergy seeks to maintain contact between basic and clinical Allergy/Immunology and encourages contributions from contributors and readers from all countries. In addition to its publication, Allergy also provides abstracting and indexing information. Some of the databases that include Allergy abstracts are Abstracts on Hygiene & Communicable Disease, Academic Search Alumni Edition, AgBiotech News & Information, AGRICOLA Database, Biological Abstracts, PubMed Dietary Supplement Subset, and Global Health, among others.
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