Department of Otorhinolaryngology, Careggi University Hospital, Largo Brambilla, 3 - 50134, Florence, Italy.
Department of Otorhinolaryngology, Meyer Children's Hospital IRCCS, Florence, Italy.
Eur Arch Otorhinolaryngol. 2024 Oct;281(10):5023-5031. doi: 10.1007/s00405-024-08725-7. Epub 2024 May 19.
The recent approval of Dupilumab has profoundly revolutionized the management of patients affected by severe and recalcitrant Chronic Rhinosinusitis with Nasal Polyps (CRSwNP). However, a review that summarizes the results of real-life studies and compares them to phase 3 studies SINUS-24 and 52 is still lacking.
A search of all real-life studies published from 2019 to 2023 was performed. Patients characteristics at baseline and 6 and 12 months after starting Dupilumab were extracted and compared to those from phase 3 trials: age, sex, smoking habits, comorbid asthma and aspirin-exacerbated respiratory disease (AERD), previous endoscopic sinus surgery (ESS), hematic eosinophils and total IgE, NasalAQ2 Polyps Score (NPS), smell, SNOT-22, adverse events (AEs), and response to treatment.
15 papers were included with an overall number of 1658 patients. A higher rate of comorbidities and previous ESS was found in patients from real-life studies. In addition, they had worse smell and SNOT-22 at baseline compared to patients from SINUS-24 and 52. Comorbid and post-ESS patients tended to have a faster NPS and SNOT-22 improvement, although the absolute values were not clinically relevant. A more extensive surgery and a number of ESS ≥ 2 were related to worse olfactory outcomes, probably due to iatrogenic damage. No correlation was found between hematic eosinophils and outcomes. AEs were reported by 12.4% of patients and 2.2% had to discontinue dupilumab. Weight gain was an emergent AE (0.8%), probably related to the restored sense of smell and taste. Non-responders were 3.5% and they were switched to systemic steroid, ESS, or another biologic.
Despite some differences in prescription criteria between countries, dupilumab was demonstrated to be effective even in the real-life scenario. However, emerging AEs and possible unknown long-term AEs of a likely lifelong therapy should be considered.
达普单抗的最近获批极大地改变了严重和难治性慢性鼻-鼻窦炎伴鼻息肉（CRSwNP）患者的治疗模式。然而，目前仍缺乏对真实世界研究结果进行总结并与 SINUS-24 和 52 期临床试验进行比较的综述。
对 2019 年至 2023 年期间发表的所有真实世界研究进行了检索。提取并比较了开始使用达普单抗后 6 个月和 12 个月时患者的基线特征以及来自 3 期临床试验的数据：年龄、性别、吸烟习惯、合并哮喘和阿司匹林加重性呼吸道疾病（AERD）、既往内镜鼻窦手术（ESS）、血液嗜酸性粒细胞和总 IgE、鼻息肉评分（NPS）、嗅觉、SNOT-22、不良反应（AE）和治疗反应。
共纳入 15 篇文献，涉及 1658 例患者。真实世界研究中的患者合并症和既往 ESS 发生率更高。此外，与 SINUS-24 和 52 期临床试验中的患者相比，他们的嗅觉和 SNOT-22 基线评分更差。合并症和 ESS 后患者的 NPS 和 SNOT-22 改善更快，尽管绝对值无临床意义。更广泛的手术和 ESS≥2 次与嗅觉结局更差相关，可能与医源性损伤有关。血液嗜酸性粒细胞与结局无相关性。12.4%的患者报告了不良反应，2.2%的患者停止使用达普单抗。体重增加是一种新出现的不良反应（0.8%），可能与嗅觉和味觉的恢复有关。无应答者为 3.5%，他们被转为全身皮质类固醇、ESS 或另一种生物制剂治疗。
尽管各国的处方标准存在差异，但达普单抗在真实世界环境中也显示出有效性。然而，应该考虑到可能出现的新不良反应和可能未知的长期不良反应，以及可能需要终身治疗。
