Soler Zachary M, Patel Zara M, Mullol Joaquim, Mattos Jose, Nash Scott, Xia Changming, Wang Zhixiao, Borsos Kinga, Corbett Mark, Jacob-Nara Juby A, Sacks Harry, Rowe Paul, Deniz Yamo, Lane Andrew P
Department of Otolaryngology, Head and Neck Surgery, Medical University of South Carolina, Charleston, SC, USA.
Department of Otolaryngology, Head and Neck Surgery, Stanford University School of Medicine, Stanford, CA, USA.
Am J Rhinol Allergy. 2025 Jan;39(1):6-12. doi: 10.1177/19458924241274501. Epub 2024 Sep 19.
To evaluate the association between smell loss and other aspects of disease, and evaluate dupilumab efficacy in patients with severe chronic rhinosinusitis with nasal polyps (CRSwNP) and moderate or severe smell loss.
This post-hoc analysis of the SINUS-24/52 studies (NCT02912468/NCT02898454) analyzed nasal polyp score (NPS, 0-8), nasal congestion/obstruction (NC, 0-3), Lund-Mackay CT-scan score (LMK-CT, 0-24), rhinosinusitis severity visual analog scale (RS-VAS, 0-10), and 22-item Sinonasal Outcome Test (SNOT-22, 0-110) according to baseline monthly average patient-reported loss of smell scores (LoS, 0-3) of >1 to 2 (moderate) or >2 to 3 (severe) in patients randomized to dupilumab 300 mg or placebo every 2 weeks.
Of 724 patients randomized, baseline LoS was severe in 601 (83%) and moderate in 106 (15%). At baseline, severe versus moderate LoS was associated with 1-point greater severity of NC (odds ratio [OR] 6.01 [95% confidence interval, (CI) 3.95, 9.15]), 5-point greater severity of LMK-CT (OR 2.19 [1.69, 2.85]), and 8.9-point greater severity of SNOT-22 (OR 1.35 [1.20, 1.49]). At Week 24, least squares mean differences (95% CI) dupilumab versus placebo in change from baseline were: NPS -1.90 (-2.56, -1.25) and -1.95 (-2.20, -1.70) in the moderate and severe baseline LoS subgroups, respectively; NC -.35 (-.64, -.06) and -1.00 (-1.13, -.87); LMK-CT -6.30 (-7.88, -4.72) and -6.22 (-6.82, -5.63); RS-VAS -1.18 (-2.20, -.16) and -3.47 (-3.90, -3.03); and SNOT-22 -7.52 (-14.55, -.48) and -21.72 (-24.63, -18.82); all nominal < .05 versus placebo. Improvements with dupilumab in NC, RS-VAS, and SNOT-22 were statistically greater in patients with severe versus moderate baseline LoS.
Significant smell impairment in severe CRSwNP is associated with significant disease (NC, RS-VAS, LMK), health-related quality of life impairment (SNOT-22), asthma, and non-steroidal anti-inflammatory drug-exacerbated respiratory disease. Dupilumab significantly improved NPS, NC, LMK-CT, RS-VAS, and SNOT-22 in subjects with moderate and severe baseline smell loss.
评估嗅觉丧失与疾病其他方面之间的关联，并评估度普利尤单抗对重度慢性鼻-鼻窦炎伴鼻息肉（CRSwNP）且有中度或重度嗅觉丧失患者的疗效。
对SINUS-24/52研究（NCT02912468/NCT02898454）进行的这项事后分析，根据随机分配接受每2周一次300mg度普利尤单抗或安慰剂治疗的患者的基线每月平均患者报告的嗅觉丧失评分（LoS，0-3）>1至2（中度）或>2至3（重度），分析鼻息肉评分（NPS，0-8）、鼻充血/阻塞（NC，0-3）、Lund-Mackay CT扫描评分（LMK-CT，0-24）、鼻窦炎严重程度视觉模拟量表（RS-VAS，0-10）和22项鼻鼻窦结局测试（SNOT-22，0-110）。
在随机分组的724例患者中，601例（83%）基线LoS为重度，106例（15%）为中度。在基线时，重度与中度LoS分别与NC严重程度高1分（优势比[OR]6.01[95%置信区间，（CI）3.95，9.15]）、LMK-CT严重程度高5分（OR 2.19[1.69，2.85]）和SNOT-22严重程度高8.9分（OR 1.35[1.20，1.49]）相关。在第24周时，度普利尤单抗与安慰剂相比，从基线变化的最小二乘均值差异（95%CI）分别为：中度和重度基线LoS亚组中NPS分别为-1.90（-2.56，-1.25）和-1.95（-2.20，-1.70）；NC分别为-.35（-.64，-.06）和-1.00（-1.13，-.87）；LMK-CT分别为-6.30（-7.88，-4.72）和-6.22（-6.82，-5.63）；RS-VAS分别为-1.18（-2.20，-.16）和-3.47（-3.90，-3.03）；SNOT-22分别为-7.52（-14.55，-.48）和-21.72（-24.63，-18.82）；与安慰剂相比，所有名义P<0.05。与中度基线LoS患者相比，度普利尤单抗在NC、RS-VAS和SNOT-22方面的改善在重度基线LoS患者中具有统计学意义。
重度CRSwNP患者的显著嗅觉损害与显著的疾病（NC、RS-VAS、LMK）、健康相关生活质量损害（SNOT-22）、哮喘和非甾体抗炎药加重的呼吸道疾病相关。度普利尤单抗在基线嗅觉丧失为中度和重度的受试者中显著改善了NPS、NC、LMK-CT、RS-VAS和SNOT-22。
